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1

Nguyen, Andrew D. "Evolutionary Innovations In Ants To Thermally Stressful Environments." ScholarWorks @ UVM, 2017. http://scholarworks.uvm.edu/graddis/739.

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Temperature is a fundamental environmental force shaping species abundance and distributions through its effects on biochemical reaction rates, metabolism, activity, and reproduction. In light of future climate shifts, mainly driven by temperature increases, how will organisms persist in warmer environments? One molecular mechanism that may play an important role in coping with heat stress is the heat shock response (HSR), which protects against molecular damage. To prevent and repair protein damage specifically, Hsps activate and become up-regulated. However, the functional diversity and relevance of heat shock proteins (Hsps) in extending upper thermal limits in taxonomic groups outside marine and model systems is poorly understood. Ants are a good system to understand the physiological mechanisms for coping with heat stress because they have successfully diversified into thermally stressful environments. To identify and characterize the functional diversity of Hsps in ants, I surveyed Hsp orthologues from published ant genomes to test for signatures of positive selection and to reconstruct their evolutionary history. Within Hymenoptera, ants utilize unique sets of Hsps for the HSR. Stabilizing selection was the prevailing force among Hsp orthologues, suggesting that protein activity is conserved. At the same time, regulatory regions (promoters) governing transcriptional up-regulation diversified: species differ in the number and location of heat shock elements (HSEs). Therefore, Hsp expression patterns may be a target for selection in warm environments. I tested whether Hsp expression corresponded with variation in upper thermal limits in forest ant species within the genus Aphaenogaster. Whole colonies were collected throughout the eastern United States and were lab acclimated. There was a positive relationship between upper thermal limits (Critical Thermal maxima, CTmax) and local temperature extremes. Upper thermal limits were also higher in ant species that lived in open habitats (shrub-oak and long-leaf pine savannah) than species occupying closed habitats (deciduous forest). Ant species with higher CTmax expressed Hsps more slowly, at higher temperatures, and at higher maximum levels than those with low CTmax. Because Hsps sense and repair molecular damage, these results suggest the proteomes of open relative to closed canopy forests are more stable. Although deciduous forest ant species may be buffered from temperature stress, it is likely that temperature interacts with other environmental stressors such as water and nutrient availability that may impact upper thermal limits. I measured the influence of dehydration and nutrition stress on upper thermal limits of forest ants from a single population. Ants that were initially starved were much less thermally tolerant than controls and ants that were initially desiccated. Because ants are likely to experience similar combination of stressors in the wild, upper thermal limits may be severely overestimated in single factor experiments. Therefore, realistic forecasting models need to consider multiple environmental stressors. Overall, adaptive tuning of Hsp expression that reflects better protection and tolerance of protein unfolding may have facilitated ant diversification into warm environments. However, additional stressors and mechanisms may constrain the evolution of upper thermal limits.
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2

Muncy, Nathan McKay. "A Semi-Automated Algorithm for Segmenting the Hippocampus in Patient and Control Populations." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6421.

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Calculating hippocampal volume from Magnetic Resonance (MR) images is an essential task in many studies of neurocognition in healthy and diseased populations. The `gold standard' method involves hand tracing, which is accurate but laborious, requiring expertly trained researchers and significant amounts of time. As such, segmenting large datasets with the standard method is impractical. Current automated pipelines are inaccurate at hippocampal demarcation and volumetry. We developed a semi-automated hippocampal segmentation pipeline based on the Advanced Normalization Tools (ANTs) suite of programs to segment the hippocampus. We applied the semi-automated segmentation pipeline to 70 participant scans (26 female) from groups that included participants diagnosed with autism spectrum disorder, healthy older adults (mean age 74) and healthy younger controls. We found that hippocampal segmentations obtained with the semi-automated pipeline more closely matched the segmentations of an expert rater than those obtained using FreeSurfer or the segmentations of novice raters. Further, we found that the pipeline performed best when including manually- placed landmarks and when using a template generated from a heterogeneous sample (that included the full variability of group assignments) than a template generated from more homogeneous samples (using only individuals within a given age or with a specific neuropsychiatric diagnosis). Additionally, the semi-automated pipeline required much less time (5 minutes per brain) than manual segmentation (30-60 minutes per brain) or FreeSurfer (8 hours per brain).
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3

Geerdes, Bastiaan Petrus. "Dynamic graciloplasty (patho)physiology of failure and success /." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=6789.

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4

Bhavaraju, Kamala. "MOLECULAR PHYSIOLOGY OF THROMBOXANE A2 GENERATION IN PLATELETS." Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/92746.

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Molecular and Cellular Physiology
Ph.D.
Cardiovascular diseases are a major cause of mortality and morbidity in the developed countries. Anti-platelet therapy is a cornerstone treatment for patients with cardiovascular diseases. Patients are routinely managed with a combination therapy consisting of aspirin and clopidogrel. Aspirin inhibits cyclooxygenase 1 (COX 1) a crucial intermediate enzyme involved in thromboxane biosynthesis. Clopidogrel on the other hand antagonizes ADP receptor P2Y12. ADP is a weak platelet agonist stored in platelet dense granules and is released upon platelet activation. ADP activates platelets through two purinergic receptors namely P2Y1 and P2Y12 these receptors couple to Gq and Gi class of G-proteins, respectively. P2Y1 causes calcium mobilization through activation of PLC-β. P2Y12 inhibits adenylyl cyclase, causes activation of Rap1B and Akt. Signaling from both the receptors is required for complete integrin activation, thromboxane generation and Erk activation. Previous studies have shown that P2Y12 potentiates fibrinogen receptor activation, secretion, thrombi stabilization, thrombin generation, platelet leukocyte aggregation formation. ThromboxaneA2 (TXA2) is a potent platelet agonist generated through arachidonic acid metabolism in platelets. TXA2 thus, generated after platelet activation acts as a positive feedback mediator along with ADP. Under physiological conditions, platelet activation leads to thrombin generation through coagulation cascades. Generated thrombin activates PAR receptors and ADP is released from dense granules, which further potentiates thromboxane generation downstream of PARs. Current anti-platelet therapy regimens often include P2Y12 antagonists and aspirin in management of patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI) with stent implantation. However, there still exists a need for improved treatment strategies as not all patients benefit from this dual combination therapy. Reasons include, poor responders either to P2Y12 antagonists or to aspirin, or if aspirin is contraindicated in these patient populations. In the current study we evaluated the role of P2Y12 in thromboxane generation under physiological conditions. We studied serum thromboxane generation in a model system wherein P2Y12 was antagonized or deficient. Using pharmacological approaches we show that dosing mice with 30mg/Kg/body weight clopidogrel or 3mg/Kg/body weight prasugrel decreased serum thromboxane levels when compared to the control mice. Pre-treatment of human blood ex vivo with active metabolites of clopidogrel (R361015) or prasugrel (R138727) also led to reduction in thromboxane levels. We also evaluated serum thromboxane levels in P2Y receptor null mice, serum thromboxane levels in P2Y1 null mice were similar to those in wild type littermates, and were inhibited in P2Y12 null mice. Furthermore, serum thromboxane levels in P2Y12 deficient patients, previously described in France and Japan, were also evaluated and these patients had lower serum thromboxane levels compared to normal controls. In a pilot study, serum thromboxane levels were radically reduced in healthy human volunteers upon dosing with clopidogrel, compared to the levels before dosing. In conclusion, P2Y12 antagonism alone can decrease physiological thromboxane levels. Thus P2Y12 regulates physiological thromboxane levels. Further it is known that ADP-induced thromboxane generation is integrin-dependent. However it is not clear if other potent platelet agonists like thrombin require outside-in signaling for thromboxane generation. Our results show that thrombin-induced thromboxane generation was independent of integrins i.e. when platelets were stimulated with PAR agonists in presence of fibrinogen receptor antagonist thromboxane generation was not affected. Since PAR agonists, unlike ADP, activate G12/13 signaling pathways. Hence, we hypothesized that these pathways might play a role in TXA2 generation. Our results show, that inhibition of ADP-induced thromboxane generation by fibrinogen receptor antagonist SC57101 was rescued by costimulation of G12/13 pathways with YFLLRNP. This observation suggested an existence of a common signaling effector downstream of integrins and G12/13 pathways. Next, we evaluated role of three potential tyrosine kinases; c-Src, Syk and FAK (Focal Adhesion Kinase) that are known to be activated by integrins. Our results showed that c-Src and Syk kinase did not play a role in ADP-induced functional responses in platelets. We observed differential activation of FAK downstream of integrins and G12/13 pathways. ADP-induced activation of FAK was integrindependent and SFK-independent. On the other hand selective activation of G12/13 pathway lead to FAK activation, in SFK and Rho dependent manner. We also evaluated specificity of new FAK inhibitor TAE-226 to understand the role of FAK in TXA2 generation. Our results showed that TAE-226 exhibited non-specific effects at higher concentrations. Furthermore, in comparison to WT mice, FAK null mice did not show any difference in TXA2 generation. Therefore, we concluded that differential activation of FAK occurs downstream of Integrins and G12/13 pathways. However, the common effector molecule downstream of integrins and G12/ 13 pathways contributing to TXA2 generation in platelets remains elusive.
Temple University--Theses
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5

Ronca, Rich Daniel. "The Cannabinoid-2 Receptor Agonist O-1966 Reverses Postischemic Learning and Memory Deficits Through Anti-Inflammatory Processes." Diss., Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/253154.

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Pharmacology
Ph.D.
Ischemic stroke is the third leading cause of death and the leading cause of morbidity in the United States. Cognitive deficits, specifically with respect to learning and memory, are a significant contributor to morbidity in stroke patients. Unfortunately, current treatment options must be administered within a thin therapeutic window of the initial infarct. This requirement results in less than 10% of stroke patients being eligible for treatment. There are currently no treatment options that are effective in the subacute phase of the disease and no treatments that are effective in reversing postischemic learning and memory deficits. We sought to examine the potential efficacy of the anti-inflammatory Cannabinoid-2 Receptor Agonist, O-1966, in attenuating infarct expansion and reversing cognitive deficits in the subacute phase of the disease using a photothrombosis model of stroke. Additionally, we sought to characterize the inflammatory response in photothrombosis. Mice were treated with repeated doses of O-1966 or vehicle and were sacrificed at 24 hours and 7 days to study the acute and subacute phase of the disease respectively. Learning and memory testing, immunohistochemistry, and polymerase chain reaction were used to measure the effect of O-1966 on infarct expansion, inflammatory gene expression, and cognitive function. In addition to PCR, flow cytometry was used to characterize the temporal dynamics of inflammation following photothrombosis. Our studies show that O-1966 is effective in the subacute phase in attenuating infarct expansion and proinflammatory gene expression and reversing learning and memory deficits.
Temple University--Theses
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6

Washington, N. "In vitro and in vivo evaluation of antacid and anti-reflux formulations." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376161.

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7

Shimizu, Manabu. "Acid-base balance in arterial plasma of white Pekin duck (Anas platyrhynchos) during forced submergence and recovery." Thesis, University of British Columbia, 1985. http://hdl.handle.net/2429/25044.

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Acid-base balance in plasma was studied in forcibly submerged Pekin ducks (Anas platyrhynchos). All important variables determining acid-base balance (arterial CO₂ tension (PαCO₂) strong ion difference ([SID]) and total protein content which approximates total weak acid concentration in plasma) were measured. During forced submergence PαCO₂ increased and pHa steadily decreased with time. There was also an increase in [lactate⁻], which was accompanied by an increase of equal magnitude in [Na⁺]. There were no significant changes in the concentrations of other strong ions (K⁺, Ca²⁺, Mg²⁺ and Cl⁻). Strong ion difference did not change during the first two minutes of submergence, but there was about a 4 mequiv/L increase by the end of the four-minute dive. Theoretically an increase in [SID] should cause plasma to be alkaline, but since plasma became progressively acidic, this condition can only be due to the increase in PαCO₂. During recovery from dives, the plasma remained as acidic one minute after emersion as at the end of the dives. On the other hand, arterial pH slowly increased towards the pre-dive level during recovery. Arterial CO₂ tension decreased much more rapidly and was already at or below the pre-dive level one minute after emersion. Therefore, PαCO₂ could no longer affect plasma pH. There was, however, a great increase in [lactate-] in the first minute of recovery. Although [Na⁺] and [K⁺] were elevated, from pre-dive values after the four minute dive, the increase in [lactate⁻] resulted in a marked reduction in [SID]. Since there was no change in the total plasma protein content, the acidic condition observed in recovery could only be due to decreased [SID]. Breathing 0₂ before diving prevented circulatory adjustments and pH returned to pre-dive levels one minute after emersion, confirming that the acidic condition observed in recovery is a consequence of the lactate produced in the hypoperfused tissues during submergence.
Science, Faculty of
Zoology, Department of
Graduate
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8

Lopez, Tapia Francisco Javier. "A general approach to the total synthesis of yeuhchukene and its analogues : a novel anti-implantation agent." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/29013.

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This thesis concerns a general approach to the total synthesis of yuehchukene 2 and its analogues. Yuehchukene has a potent anti-implantation activity. It also lacks the estrogenic side effect of most compounds with similar biological activity. However, it is somewhat unstable and this could bring some problems when administered to humans. Development of a versatile synthesis of yuehchukene capable of producing a variety of analogous structures in order to fully exploit the pharmacological properties of this novel molecular system and/or to make a more stable product without losing its biological properties was the central objective of this project. Specifically, the total synthesis of yuehchukene 2 and its analogue 6a-ep/-yuehchukene 25 are described. After some preliminary studies, it was found that a kinetic carboxylation (lithium 2,6-di-tert-butyl-4-methylphenoxide, CO₂) of isophorone 26 followed by a reduction (NaBH₄) produced stereoselectively cis-hydroxyacid 46 in good yield. The latter was transformed into indoleacid 48 by dibenzoylation (PhCOCI, DMAP) and treatment with indolylmagnesium iodide. The key intermediate trans-ketone 60 was obtained by treatment of 48 with oxalyl chloride followed by indolylmagnesium iodide. Epimerization of 60 to the more stable cis-ketone 24 was accomplished quantitatively under basic conditions (MeONa/MeOH, reflux). Reduction (LiAlH₄) and dibenzoylation (PhCOCI, DMAP, Et₃N) of 24 furnished the benzoate 68 which was subjected to a nucleophilic substitution with indolylmagnesium iodide to give N-benzoylyuehchukene 69. The latter transformation also gave the interesting compound 75 which was submitted to an X-Ray diffraction analysis. The total synthesis of yuehchukene 2 was then achieved by methanolysis (NaOMe/MeOH) of 69. As far as the synthesis of 6a-epi-yuehchukene 25 is concerned, it was found that, after a thorough study, it was best to transform trans-ketone 60 into its SEM-derivative 85 (SEM-CI,NaH). The latter was reduced (DIBAL) and acetylated (Ac₂O, DMAP, Et₃N) to produce stereoselectively the acetate 87 which, by treatment with indolylmagnesium iodide, furnished SEM-trans-yuehchukene 88. The newly incorporated indole group bears a 1,3-diaxial-like interaction with the β-methyl group at C-7. Unlike 88, tosylacetate 82 gave the compound 84. Finally, the total synthesis of 6a-epi-yuehchukene was accomplished by deprotection of the indole system. Various compounds from this study are now under investigation at WHO and in Hong Kong but, unfortunately, biological results are unavailable at present. [Formula Omitted]
Science, Faculty of
Chemistry, Department of
Graduate
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9

Hoggatt, April Marie. "Mab anti-type I and Mab anti-zebrin II labelling in two siluriform fishes : the role of shared lineage versus shared function in polypeptide co-distributions." Virtual Press, 1994. http://liblink.bsu.edu/uhtbin/catkey/902481.

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Two monoclonal antibodies (mabs), the newly generated mab anti-type I and the previously documented mab anti-zebrin II, were reacted with brainstem sections of two ostariophysan siluriforms, the gymnotoid Rhamphichthys rostratus and the siluroid Ictalurus punctatus. Mab anti-type I recognizes a 47 kD polypeptide present in the dendrites and soma of projection neurons. Mab anti-zebrin II recognizes a 36 kD polypeptide present throughout the neuronal cytoplasm, including the axon. Strongly type I immunopositive cells include all cerebellar Purkinje cells, pyramidal cells of the nucleus medialis, electrosensory lateral line lobe, and tectum, pacemaker relay cells, Mauthner neurons, lateral line ganglion cells, and cells of the reticular formation, lateral reticular nucleus, and inferior olive. Weakly reactive type I cells include neurons in the torus semicircularis, medial and efferent octavolateralis nuclei, magnocellular and lateral tegmentum, and motor neurons of the Vth, V I Ith, and Xth cranial nerves. All type I positive cells are projection neurons. Zebrin II expression is restricted to subsets of two cell types which also express the type I antigen -- Purkinje cells and developing acousticolateralis pyramidal cells. Both of these neurons develop from the region of the rhombic lip. Thus, the mutual expression of the type I antigen can be explained by the shared function of projection neurons, while the common expression of the zebrin II antigen may be due to a shared embryological lineage.
Department of Physiology and Health Science
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10

Totton, Rebecca. "Examining Anti-Transgender Prejudice: Identity-Confusion and Deception as Aspects ofDistrust." Ohio University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1597060574652936.

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11

Claes, Anthony N. J. "ANTI-MÜLLERIAN HORMONE IN STALLIONS AND MARES: PHYSIOLOGICAL VARIATIONS, CLINICAL APPLICATIONS, AND MOLECULAR ASPECTS." UKnowledge, 2014. http://uknowledge.uky.edu/gluck_etds/18.

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Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein that is best known for its role in regression of the Müllerian duct in the male fetus. Accumulating evidence indicates that AMH also has an important role during different physiological processes after birth. In contrast to other species, relatively little is known about AMH in the horse. In chapter one, developmental and seasonal changes in serum AMH concentrations in male horses were determined, and the use of AMH for determination of retained cryptorchid testes was established. In chapter two, the interrelationship between plasma AMH concentrations, antral follicle counts (AFC), and age in mares was evaluated. Molecular and hormonal changes in the equine follicle with regard to variations in antral follicle count and follicular development were examined in chapter three. In chapter four, the effect of AFC on age-related changes in follicular parameters in light-type horse mares was examined. Peripheral AMH concentrations were significantly higher in prepubertal colts than in postpubertal stallions and varied with season in mature stallions with higher concentrations during the physiological breeding season. Furthermore, serum AMH concentrations were significantly higher in cryptorchid stallions compared to intact stallions or geldings. Circulating AMH concentrations varied widely amongst mares of the same age while the repeatability of AMH was high within and between estrous cycles. More importantly, AMH concentrations were positively associated with AFC, and this relationship increased with mare age. In addition, variations in AMH concentrations or AFC were associated with molecular differences in granulosa cells of growing follicles, and the expression of AMH and genes co-expressed with AMH in the equine follicle as well as intrafollicular AMH concentrations decreased during follicular development. Finally, the inter-ovulatory interval and length of the follicular phase is increased in aged mares with low AFC. In conclusion, AMH is a useful biomarker for cryptorchidism in stallions and ovarian reserve in mares. Furthermore, follicular function was interrelated to AFC or AMH based upon molecular differences in growing follicles, while age-related changes in follicular parameters are linked to differences in AFC.
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12

McKay, Allison E. "Gastroduodenal motility during the development of experimental duodenal ulceration: The effects of enteric transmitters and anti-ulcer drugs." Thesis, University of Ottawa (Canada), 1993. http://hdl.handle.net/10393/6809.

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13

Lacombe, A. M. A. "Effects of circulating catecholamines on diving in ducks (Anas platyrhynchos)." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/30724.

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Plasma catecholamines have been measured in chronically adrenalectomised (ADX) ducks, in chronically adrenal denervated ducks (DNX), in their respective sham-operated controls (SH-adx, SH-dnx) as well as in intact ducks after 3 minutes forced submergence. The results showed that 100% of the plasma Epinephrine (EP) and 40 to 80% of plasma Norepinephrine (NE) released during the dive came from the adrenal glands. 20 to 60% of plasma NE came from endings of the autonomic vascular sympathetic nerves which are strongly stimulated during diving. Adrenal catecholamines were released by nerve activation only; non neural mechanisms did not play any role in their release. Maximum dive times (MDT) in chronically adrenalectomised ducks (ADX: 5 min. 19 ± 20 sec.) and in chronically adrenal denervated ducks (DNX: 7 min. 10 ± 13 sec.) were significantly lower than in sham-operated controls (respectively SH-adx: 9 min. 58 ± 45 sec., SH-dnx: 12 min. 10 ± 28 sec). Venous infusion of catecholamines in ADX and DNX during the dive increased MDT: MDT of DNX ducks perfused with catecholamines (9 min. 46 ± 20 sec.) were significantly higher than in DNX perfused with saline (7 min. 21 ± 17 sec.), but did not reach the MDT observed in the SH-dnx: other adrenal products must be involved. Diving heart rates of ADX and DNX (at 4 min. dive respectively: 62 ± 16 and 31 ± 2 beats/min.) were significantly higher than in their sham-operated controls (23 ± 3 and 17 ± 2 beats/min.) . Blood pressure during the dive was signifi- cantly lower in ADX and DNX (at 4 min. dive respectively: 93 ± 8 and 98 ± 4 mmHg) compared with their sham-operated controls (131 ± 12 and 118 ± 6 mmHg). Infusion of catecholamines in DNX raised blood pressure towards SH-dnx values, but there was no change in heart rate. PaO₂, CaO₂, pHa and lactate levels in DNX (respectively: 42 ± 2 mmHg, 4.5 ± 0.8 ml 02 /100ml blood, 7.233 ± 0.016, 3.1 + 0.3 mM) were significantly lower than in SH-dnx after 5 minutes submergence (53 ± 1 mmHg, 6.8 ± 0.4 ml 02 /100 ml blood, 7.301 ± 0.007, 4.8 + 0.4 mM). There was also a significant increase of plasma N⁺ (+ 5.4 ± 1.7 mEq/L) in SH-dnx after 5 minutes submergence, but this was not the case in DNX where it was K⁺ (+ 1.1 ± 0.4 mEq/L) which increased. This suggested that adrenal catecholamines increase tolerance to underwater submersion by enhancing peripheral vasoconstriction, thus preserving the O₂ stores for the heart and brain. Moreover, they may affect the acid-base equilibrium during diving by increasing the activity of the Na⁺K⁺ pump and may also have a direct effect on the rate of glycogenolysis. Preventing the actions of catecholamines on the heart by injecting beta-blocker during forced submersion did not decrease MDT; however the cardiovascular response was markedly affected. During beta-blockade, diving heart rate rose steadily from 24 ± 6 beats/minute after 2 minutes to 52 ± 8 beats/minute after 6 minutes diving. In contrast, heart rates remained close to the levels reached at 2 minutes (17 ± 3 and 19 ± 4 beats/minute) throughout the control dives. Perfusion pressure and blood flow have been recorded simultaneously in both hind limbs of ducks. One leg was perfused with different blood mixtures devoid of catecholamines (Test leg) and compared with the other, perfused with the ducks'own blood (autoperfused leg). This showed that hyper-capnia has a depressant effect on the neural component of the peripheral vasoconstriction. Perfusion of test legs with hypoxic-hypercapnic blood to which catecholamines were added, showed that circulating catecholamines are needed to increase peripheral vasoconstriction during diving. In summary, during forced submergence circulating catecholamines, released mainly by the adrenal glands, compensate for the depressant action of hypercapnia on the neural component of peripheral vasoconstriction. Maintenance of this peripheral vasoconstriction during forced diving ensures that O₂ stores are not wasted on peripheral tissues, and this explains how MDT is prolonged.
Science, Faculty of
Zoology, Department of
Graduate
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14

Chen, Qixuan, and 陳起萱. "Anti-obesity effect of bitter melon (Momordica charantia)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31048778.

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Million, Laurence. "Proposition d'un bioréactif stable pour le dépistage et l'identification des anticorps irréguliers anti-érythrocytaires." Nancy 1, 1997. http://www.theses.fr/1997NAN19006.

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La sécurité transfusionnelle passe par les progrès des techniques de recherche et d'identification des anticorps irréguliers anti-érythrocytaires. Notre travail porte sur la mise au point d'un bioréactif stable pour le dépistage et d'identification des anticorps irréguliers en phase solide. Pour cela, nous préparons des suspensions de membranes et des «lyophilisats» de globules rouges sur lesquels nous vérifions la présence et l'intégrité des antigènes des principaux groupes sanguins. Les techniques d'électrophorèse et de microscopie électronique à transmission permettent d'observer la modification des protéines membranaires au cours de leur conservation et de démontrer la spécificité antigénique des suspensions membranaires. La révélation des anticorps s'effectue à l'aide d'un système original et stable, constitué de particules de latex couplées à des immunoglobulines anti-lgG et IgM humaines. Après sa mise au point, le bioréactif proposé fait l'objet d'une validation en plusieurs étapes. Tout d'abord nous validons le test avec le dépistage d'anticorps présents dans des sérums-tests commerciaux afin d'évaluer sa sensibilité ainsi que la plage de détection pour chaque anticorps. La seconde phase de la validation du dispositif s'effectue dans les conditions réelles de laboratoire avec le dépistage et l'identification des anticorps issus de sérums de patients. L'ensemble de ces travaux permettent de présenter un bioréactif stable appliqué au dépistage et à l'identification des anticorps irréguliers anti-érythrocytaires afin de pallier les contraintes d'un panel de globules rouges.
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Hornsey, Crystal A. "The function of extensive structured RNA in the evasion of host anti-virus responses." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/56672/.

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Genome scale ordered RNA structure (GORS) is found throughout the genome of many single stranded positive sense RNA viruses, including plant viruses. It was hypothesised that GORS may function to help evade RNAi either by preventing the generation of siRNAs or by stopping RNAi-mediated cleavage of the target. This project used Potato Leafroll Virus (PLRV) to investigate the function of GORS in plant viruses. The RNA structure of a 750nt region of the genome was modified to have less, more or the same energy as the WT sequence. The physical structure of these sequences was shown to be different using two distinct methods. Viral infectivity was tested and although all four viruses were able to replicate and spread to distal leaves, the WT virus was always able to outcompete the variant viruses in competition assays. This suggests GORS provides a distinct selective advantage to the WT virus. The effect on the siRNA response was tested using a dedicated siRNA assay. In plants, this showed that the WT sequence was more resistant to degradation by siRNAs than the variant sequences in the presence of their specific inducers. The WT inducer was also not able to cause suppression of the other targets indicating that this inducer failed to produce siRNAs or that they were not effective. The siRNA populations generated during infections were sequenced and the profiles compared. This showed that all four viruses stimulated the production of siRNAs but the location of siRNA hotspots differed. It is therefore hypothesised that GORS may function to evade the RNAi response by directing the generation of less effective siRNAs. The data presented in this thesis not only informs current work on GORS and RNA structure in viral genomes but also has wider implications for research on siRNAs and food biosecurity.
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17

Bizumukama, Leonidas. "Contribution à l'étude du mécanisme d'action anti-drépanocytaire du cromoglycate disodique." Doctoral thesis, Universite Libre de Bruxelles, 2011. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209805.

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La drépanocytose est une maladie génétique touchant l'hémoglobine, de transmission autosomique récessive, caractérisée par trois grandes manifestations cliniques :anémie hémolytique chronique, phénomènes vaso-occlusifs et susceptibilité accrue aux infections. Dans diverses régions du monde et particulièrement en Afrique subsaharienne, cette maladie est très fréquente et constitue un problème crucial de santé publique. Sa physiopathologie complexe est basée sur la polymérisation de l’hémoglobine anormale (Hb S) qui provoque une falciformation et une déshydratation du globule rouge. Les hématies falciformées sont impliquées dans les phénomènes de vaso-occlusion. Le traitement et la prise en charge de la maladie reste toujours problématique. A l’heure actuelle, le seul traitement curatif est la transplantation de moelle osseuse mais les donneurs compatibles sont assez rares et les coûts élevés. Des traitements symptomatiques et préventifs (principalement la transfusion et l’hydroxyurée) existent toutefois.

Des études in vitro et in vivo ont démontré les possibilités thérapeutiques de certaines molécules dont les cibles sont les transports membranaires impliqués dans la déshydratation cellulaire.

Depuis les années 1990, le cromoglycate de sodium, un médicament anti-allergique et anti-asthmatique, a montré un intérêt potentiel dans le traitement de la drépanocytose. Néanmoins, son mode d’action n’est actuellement pas connu. Notre travail a pour but de contribuer à l’étude du mécanisme d’action anti-drépanocytaire de la molécule.

Dans un premier temps, des globules rouges drépanocytaires préincubés en absence ou présence de cromoglycate ont été désoxygénés par un flux d’azote. Ensuite, les concentrations intracellulaires en Na+ et en K+ ont été mesurées. Les résultats de ces investigations ont montré un effet inhibiteur du cromoglycate sur l’efflux de K+ et l’influx du Na+ provoqués par la désoxygénation.

Sur base de ces observations, des expériences testant l’action du cromoglycate sur le canal K+ dépendant du Ca2+ (canal de Gardos) ont été effectuées. Dans des globules rouges normaux et drépanocytaires, ce canal a été activé par augmentation de la concentration intra-cellulaire en Ca2+. L'effet du cromoglycate a été comparé à celui d'un inhibiteur connu, le clotrimazole. Les résultats ont montré que 1e cromoglycate n'exerce pas d'effet inhibiteur sur le canal de Gardos, au contraire du clotrimazole. Il est également sans effet significatif sur la Ca2+-ATPase.

Nous avons ensuite investigué l’implication du Ca2+ dans les perturbations du flux des ions K+ et Na+. Des globules rouges drépanocytaires ont été incubés en absence et présence d’EGTA 5 mmol/l ou de BAPTA 10 µmol/l, respectivement chélateurs du Ca2+ extra et intracellulaire. Après désoxygénation, les concentrations intracellulaires en Na+ et K+ ont été mesurées. Les résultats de ces expériences montrent que seul le chélateur du Ca2+ extracellulaire bloque les perturbations ioniques causées par la désoxygénation. Ces résultats viennent donc confirmer les observations d’autres auteurs quant à l’implication du Ca2+ extracellulaire dans la fuite de K+ des globules drépanocytaires soumis à la désoxygénation.

Enfin, l’effet du cromoglycate sur l’influx de Ca2+ extracellulaire et sur la falciformation induits par le métabisulfite a été mesuré et comparé à celui du clotrimazole. Des globules rouges drépanocytaires, prélablement chargés en Fura Red, un indicateur fluorescent du Ca2+, ont été exposés au métabisulfite, un puissant réducteur provoquant une falciformation rapide. L’influx de Ca2+ a été mesuré par la diminution de la fluorescence du Fura Red. Parallèlement, la falciformation a été suivie en mesurant la lumière diffractée à 90° par les cellules. Les résultats de ces investigations montrent que le cromoglycate (1 µmol/l) et le clotrimazole (10 µmol/l) ont des effets inhibiteurs comparables sur la falciformation mais que le cromoglycate freine significativement plus l'influx de Ca2+ au cours de ce processus.

En conclusion, sur base de ces différents tests in vitro, le cromoglycate inhibe la falciformation induite par la désoxygénation. Cette inhibition résulte du blocage des perturbations ioniques induites par la désoxygénation en empêchant l’influx du Ca2+ extracellulaire et secondairement la fuite du K+ intracellulaire, ce qui inhibe la déshydratation cellulaire.

La diminution des crises vaso-occlusives observée chez les patients drépanocytaires traités par le cromoglycate s’expliquerait donc par ces effets. En présence de cromoglycate, les globules rouges sont moins déshydratés et falciforment moins rapidement. Ils sont dès lors moins impliqués dans les phénomènes de vaso-occlusion, ce qui améliore l’état des patients.


Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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18

Hubert, Terrence L. "Effect of rhCC10 on the Pro/Anti-Inflammatory Profile of the Immature Lung." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/240379.

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Physiology
Ph.D.
There is a gap in the treatment of preterm infants with respiratory distress syndrome. Despite addressing surfactant insufficiency and mechanical instability, currently available exogenous surfactant does not reduce the inflammation that results from aggressive ventilation and hyperoxia. Preterm infants are also deficient in anti-oxidant and anti-inflammatory defenses. All of these factors predispose the infant to bronchopulmonary dysplasia. Recombinant human Club Cell Secretory Protein 10 (rhCC10), known to inhibit sPLA2, has been used to reduce ventilator induced lung inflammation. The long-term goal of this study is to understand the impact of rhCC10 on the pro/anti-inflammatory balance during early development. We will interrogate the link between Toll-Like Receptors (TLR 4) and rhCC10 because TLRs are integral to lung inflammation. By measuring the mRNA expression, protein, and downstream signaling activity in rhCC10 treated preterm lamb lung and then in A549 cells, an alveolar epithelial cell-like system, the anti-inflammatory effect of rhCC10 will be differentiated. This research is significant because it will improve understanding of the effect of rhCC10 on pro/anti-inflammatory regulation and provide insight regarding potential co-therapies when treating with rhCC10.
Temple University--Theses
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19

Schneider, Verena. "Association of selective and conventional nonsteroidal anti-inflammatory drugs with acute renal failure." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98793.

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The safety of the novel class of nonsteroidal anti-inflammatory drugs (NSAIDs), the COX-2 inhibitors, is currently debated, with the focus on their cardiovascular toxicity. Here, the association of NSAIDs with acute renal failure (ARF) was assessed in a nested case-control study using the administrative databases of Quebec.
The risk of ARF for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) 2.05, 95% confidence interval (CI) 1.61 - 2.60) and receded thereafter. After at least 30 days without an NSAID-prescription, the risk had returned to baseline. The associations with ARF were comparable for rofecoxib (RR 2.31, 95%CI 1.73 - 3.08), naproxen (RR 2.42, 95%CI 1.52 - 3.85) and non-selective, non-naproxen NSAIDs (RR 2.30, 95%CI 1.60 - 3.32), but lower for celecoxib (RR 1.54, 95%CI 1.14 - 2.09). They were dose-dependent for celecoxib, naproxen, and rofecoxib. Results were confirmed when using an alternative exposure definition. Interactions between NSAIDs and aspirin, and NSAIDs and nephrotoxic drugs could not be demonstrated conclusively.
There is a significant association for both selective and non-selective NSAIDs with ARE Celecoxib appears to have a more favorable renal safety profile but confirmatory studies are required.
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20

Adams, Katherine Jane. "Redirected T cell activity by high affinity TCR-ANTI-CD3 bispecific candidate therapeutics." Thesis, Cardiff University, 2013. http://orca.cf.ac.uk/47578/.

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T cell antigen receptors (TCRs) on CD8+ T cells recognise endogenously processed peptides bound to major histocompatibility complex (pMHC) antigens presented on the cell surface on almost all types of cells in the body, including tumour cells. The majority of tumour-associated peptide antigens (TAPAs) are derived from non-mutated self-proteins and are therefore subject to immunological tolerance, mainly through negative selection of high avidity T cells in the thymus. In addition, there is low presentation of pMHC on the surface of cancer cells. As a result, T cell responses tend to be weak and ineffective at killing tumour cells. ImmTACs (Immune mobilising monoclonal T cell receptors Against Cancer) are bispecific soluble biologics comprising a soluble TCR with an enhanced affinity for tumour-associated pMHCI fused to a humanised anti-CD3 single-chain antibody fragment (scFv) which redirect and activate T cells to lyse tumour cells. In this study, the potency, sensitivity, and specificity of ImmTACs was investigated for pMHCI epitopes derived from four tumour associated antigens (TAAs): (1) gp100, (2) MAGE-A3, (3) Melan-A/MART-1, and (4) NY-ESO-1/LAGE-1. A comprehensive range of assays and methodologies have been established to characterise the ImmTAC reagents. Cytokine release assays such as IFN-γ and Granzyme B ELISpot were used to evaluate the specificity and biological activity of ImmTACs. In concentration-response experiments, all four ImmTACs produced EC50 values in the range of 100 picomolar or lower demonstrating a high degree of sensitivity despite low epitope numbers. Killing assays, including LDH-release for assessing short-term lysis and IncuCyte technology to visualise long-term killing kinetics in real time, show that redirected T cells potently kill their targets. Furthermore, in vitro screening against a panel of antigen negative, primary human cell lines have shown that ImmTACs are highly specific and only activate T cells against target cells presenting their cognate pMHC. The potency of ImmTACs was also investigated using tumour infiltrating lymphocytes (TILs) extracted from tumour specimens and with tumour-derived cancer cells as targets. An HLA-A2, gp100 specific ImmTAC has received phase I clinical trial regulatory approval in the UK and in the US on the basis of this in vitro data, which has been used to determine minimal anticipated biological effect level (MABEL). The clinical trial is currently in progress.
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21

England, Ross N. "Cellular Mechanisms of the Anti-Inflammatory Effects of Interleukin-19." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/216875.

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Physiology
Ph.D.
BACKGROUND: Atherosclerotic vascular disease is a significant medical and socioeconomic problem and contributes to mortality in multiple diseases including myocardial infarction (MI), stroke, renal failure, and peripheral vascular disease. Atherosclerosis, as well as other vascular diseases including post-intervention restenosis and allograft vasculopathy, is known to be driven by chronic inflammation and, consequently, pro- and anti-inflammatory cell signaling molecules have been an important target of cardiovascular research. Interleukin (IL)-19 is a recently discovered member of the IL-10 family of anti-inflammatory cytokines. IL-19 is expressed in injured vascular cells, including vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), where it exerts an anti-inflammatory effect. In VSMCs, IL-19 signaling results in inhibition of proliferation, migration, spreading, production of reactive oxygen species (ROSs), and expression of pro-inflammatory genes. In ECs, IL-19 signaling is pro-angiogenic and results in increased EC proliferation, migration, and spreading. AIMS and HYPOTHESIS: The goal of the present study was to explore the hypothesis that IL-19 mediates anti-inflammatory effects on vascular cells by inhibiting the expression of pro-inflammatory genes, such intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, IL-1β, IL-8, and monocyte chemotactic protein (MCP)-1, through modulation of the mRNA stability factor HuR by post- transcriptional (e.g., microRNA) and post-translational (e.g., serine phosphorylation) mechanisms. METHODS and RESULTS: We found that IL-19 can significantly inhibit tumor necrosis factor (TNF)-α-driven ICAM-1 and VCAM-1 mRNA and protein abundance in cultured human coronary artery ECs (p < 0.01). IL-19 treatment of ECs, but not monocytes, significantly inhibited monocyte adhesion to cultured EC monolayers (p < 0.01). In wild-type mice, systemic administration of IL-19 significantly reduced TNF-α-induced leukocyte rolling and adhesion as quantitated by intravital microscopy (p < 0.05). IL-19 failed to inhibit TNF-α-induced nuclear factor (NF)-κB activation in ECs. IL-19 inhibited nuclear-to-cytoplasmic translocation of HuR and significantly reduced mRNA stability of ICAM-1 and VCAM-1 (p < 0.01 ). IL-19 significantly inhibited serine-phosphorylation of HuR, which is required for its translocation, and significantly increased expression of the putative HuR regulator microRNA (miR)-133 in VSMCs. CONCLUSIONS: These data are the first to report that IL-19 can reduce leukocyte-EC interactions, and to propose reduction in HuR-mediated mRNA stability of ICAM-1 and VCAM-1 as a mechanism. We conclude that expression of IL-19 by ECs and VSMCs may represent an auto-regulatory mechanism to promote resolution of the vascular response to inflammation. These results suggest that IL-19 is anti-inflammatory in vascular cells and, therefore, may be of therapeutic value in atherosclerotic vascular disease.
Temple University--Theses
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22

Autefage, André. "Les anti-inflammatoires chez le cheval : étude pharmacocinétique et pharmacodynamique." Toulouse, INPT, 1990. http://www.theses.fr/1990INPT006A.

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Une etude du rythme circadien de la cortisolemie et du taux de production du cortisol a mis en evidence un rythme circadien bien marque avec un zenith situe a 9,190,59 h. Le taux de production du cortisol a ete estime a 0,4590,084 mg/kg/24 h et le profil instantane de secretion a ete reconstitue. La pharmacocinetique et l'action sur la glande surrenale de l'acetate de methylprednisolone ont ete abordees apres injection intra-articulaire (100 mg) puis injection intramusculaire (1 mg/kg). Lors de l'injection intra-articulaire, il a ete constate une hydrolyse rapide de l'acetate de methylprednisolone et une persistance de la methylprednisolone au sein du liquide synovial pendant un delai variant de 5 a 39 jours. Par voie intramusculaire, l'acetate de methylprednisolone a des effets systemiques maximaux 3 semaines apres l'administration. L'etude de l'elimination urinaire de l'acetate de methylprednisolone et de la methylprednisolone a egalement ete menee lors de l'utilisation de ces deux voies d'administration. Si aucune detection n'a ete possible pour l'injection intra-articulaire, en revanche lors de l'injection intramusculaire, la methylprednisolone a ete decelee dans les urines pendant 28 jours. L'interet de la lyophilisation des urines dans le cadre du controle antidopage a ete avance, aucune difference n'ayant ete notee lors des dosages entre les urines lyophilisees et les urines congelees. Enfin, une etude pharmacocinetique et pharmacodynamique de quelques anti-inflammatoires non steroidiens (dont la phenylbutazone) et steroidiens (la dexamethasone) a ete conduite apres declenchement d'une arthrite experimentale
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23

Hill, Cindy. "The efficacy of Diavite tm (Prosopis glandulosa) as anti-diabetic treatment in rat models of streptozotocin-induced type 1 diabetes and diet-induced-obese insulin resistance." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/4173.

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Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010.
ENGLISH ABSTRACT: Introduction: Obesity and its associated complications, such as the metabolic syndrome, hypertension and cardiovascular disease, are escalating worldwide. In recognition of this, untested remedies advertised as anti-diabetic agents are flooding the market. Many of these products have limited efficacy, limited tolerability and significant side-effects. One remedy, claiming to have anti-diabetic properties, is DiaviteTM. DiaviteTM, a herbal product, consisting solely of the dried and ground pods of the Prosopis glandulosa tree, which is currently marketed as a food supplement with blood glucose and blood pressure stabilizing properties, as well as having the ability to enhance glucose utilization. It is already freely available from agents as well as sold over the counter at pharmacies. The producers of DiaviteTM are now seeking registration for their product from the Medicines Control Council (MCC) and, therefore, require solid scientific evidence of its effects. Aims: The aims of our study were, on request of the producing company, to determine the efficacy of DiaviteTM (P. glandulosa) as an anti-diabetic agent and possible mechanisms of action of this plant product. Methology: We utilized rat models of streptozotocin (STZ)-induced type 1 diabetes and diet-induced obese (DIO) insulin resistance. Male Wistar rats were rendered (a) type 1 diabetic after a once-off intra-peritoneal injection of STZ at a dose of 40 mg/kg and (b) insulin resistant after being on a high caloric diet (DIO) for 16 weeks. Half the animals of the type 1 diabetes model as well as the insulin resistant model were placed on DiaviteTM treatment (25 mg/kg/day) for a period of 4 – 8 weeks, depending on the model. The STZ-induced type 1 diabetic rats were sacrificed and the pancreata harvested for histological analysis. Animals on the DIO diet were sacrificed and (i) intra-peritoneal fat weight determined (ii) isolated hearts subjected to ischaemia/reperfusion to determine infarct size and protein expression profiles and (iii) cardiomyocytes prepared to determine insulin sensitivity. At the time of sacrifice blood was collected for blood glucose and serum insulin level determination, for both models. In addition, a standard toxicology study was performed in Vervet monkeys over a 3 month period. Results: In our type 1 diabetic model (blood glucose > 10 mmol/L) with a β-cell reserve, DiaviteTM treatment lead to increased serum insulin levels (p < 0.001) in both control and STZ groups as well as increased small β-cell (0 - 2500 μm2) formation (p < 0.001) in the pancreas of the STZ animals. Hearts from DiaviteTM treated control and DIO insulin resistant animals presented with smaller infarct sizes (p < 0.05) after ischaemia/reperfusion compared to their controls. DiaviteTM treatment lead to the increase of basal (p < 0.01) and insulin-stimulated (p < 0.05) glucose uptake in cardiomyocytes prepared from DIO insulin resistant animals. DiaviteTM treatment also led to significantly suppressed PTEN expression and activity (p < 0.01) in the DIO insulin resistant animals. In addition, DiaviteTM treatment had (i) no obvious detrimental effects in our rat models and (ii) no toxicity over a 3 month period in vervet monkeys. Conclusion: Our present study has shown that DiaviteTM treatment lowers fasting blood glucose levels, stimulates insulin secretion and leads to the formation of β-cells. In addition, oral consumption of DiaviteTM elicits cardioprotection against an ischaemic incident. DiaviteTM treatment improves insulin sensitivity of cardiomyocytes. Furthermore, it has been established that DiaviteTM treatment has no obvious detrimental effects in either of our rat models and no short-term toxic effects over a 3 month period in Vervet monkeys (data not shown). We thus conclude that in our models, DiaviteTM proved safe and it seems as if DiaviteTM, after short-term use, is beneficial as a dietary supplement.
AFRIKAANSE OPSOMMING: Inleiding: Vetsug, en die gepaardgaande komplikasies, soos die metaboliese sindroom, hipertensie en kardiovaskulêre siektes, neem wêreldwyd toe. Daar is tans verskeie middels op die mark wat as anti-diabetiese middels geadverteer word. Baie van hierdie geadverteerde produkte het beperkte effektiwiteit en het verskeie newe-effekte. Een so ‘n middel, is DiaviteTM. DiaviteTM is 'n plantproduk, wat slegs uit die gedroogte en fyngemaakte peule van die P. glandulosa boom bestaan. Hierdie produk word tans bemark as 'n voedselaanvulling met beide bloedglukose en bloeddruk stabiliserende eienskappe, asook die vermoë om glukose gebruik te verbeter. DiaviteTM is reeds vrylik beskikbaar van agente sowel as verkrygbaar by verskeie apteke. Die produsente van DiaviteTM wil aansoek doen om registrasie vir hul produk by die Medisynebeheerraad (MCC) en hulle vereis daarom wetenskaplike bewyse van die gevolge van die gebruik van hierdie produk. Doel: Die doel van ons studie was om op versoek van die produksie maatskappy, die doeltreffendheid van DiaviteTM (P. glandulosa) as 'n anti-diabetiese behandeling te evalueer, sowel as die moontlike meganismes van werking van hierdie plantproduk. Metodes: Ons het gebruik gemaak van rot modelle van (i) streptozotocin (STZ)-geïnduseerde tipe 1 diabetes en (ii) dieet-geïnduseerde vetsugtig (DIO) insulienweerstandigheid. Manlike Wistar rotte was as (a) tipe 1 diabeties geklassifiseer na 'n eenmalige, intra-peritoneale inspuiting van STZ teen 'n dosis van 40 mg/kg en as (b) insulienweerstandig geklassifiseer, nadat hulle op 'n hoë kalorie dieet (DIO) vir 16 weke was. Die helfte van beide die tipe 1 diabetes en die insulienweerstandige groep diere was met DiaviteTM behandel (25 mg/kg/dag) vir 'n tydperk van 4 - 8 weke, afhangende van die model. Die STZ-geïnduseerde tipe 1 diabetes rotte is geslag en die pankreata geoes vir histologiese analise. Diere op die DIO dieet is geslag en (i) die intra-peritoneale vet gewig bepaal, (ii) die geïsoleerde harte blootgestel aan isgemie/herperfusie om die infarkt groottes vas te stel, sowel as die proteïenuitdrukkingsprofiele te bepaal en (iii) kardiomiosiete was berei om die insulien sensitiwiteit te bepaal. Ten tyde van die slagting is bloedmonsters geneem vir bloedglukose en serum insulien vlak bepaling, vir beide modelle. Additioneel, is 'n standaard toksologie studie met Vervet apies oor 'n 3 maande tydperk uitgevoer. Resultate: In die model van tipe 1 diabetes (bloed glukose > 10 mmol/L), met 'n β-sel reserwe, is gevind dat DiaviteTM behandeling tot verhoogde serum insulien vlakke (p < 0.001) in beide kontrole en STZ groepe lei. DiaviteTM behandeling lei ook tot ‘n hoër vlak van klein β-sel (0 - 2500 μm2) vorming (p < 0.001) in die pankreas van die STZ diere. Die harte van die DiaviteTM behandele kontrole en DIO groep het kleiner infarkt groottes (p < 0.05) getoon na isgemie/herperfusie in vergelyking met hul kontrole groepe. DiaviteTM behandeling het ook gelei tot verhoogde basal (p < 0. 01) en insulin-gestimuleerde (p < 0. 05) glukose opname in kardiomiosiete wat berei was van DIO insulinweerstandige diere. DiaviteTM behandeling het PTEN uitdrukking en aktiwiteit aansienlik onderdruk (p < 0.01) in die DIO insulienweerstandige groep diere. Daar is dus gevind dat DiaviteTM behandeling (i) geen duidelike nadelige invloed in ons rot-modelle en (ii) geen toksisiteit oor 'n 3 maande tydperk in Vervet apies getoon nie. Gevolgtrekking: Ons huidige studie toon dus dat DiaviteTM behandeling vastende bloedglukosevlakke verlaag, insulien sekresie stimuleer en die proses van β-sell vorming bevorder. Additioneel, is gewys dat wanneer DiaviteTM mondelings gebruik word, dit die hart beskerm teen isgemiese insidente. Ons het ook getoon dat DiaviteTM behandeling insuliensensitiwiteit van kardiomiosiete verhoog. Verder is daar vasgestel dat DiaviteTM behandeling geen ooglopende nadelige gevolge in beide ons rot-modelle getoon het nie en daar geen korttermyn-toksiese effekte oor 'n 3 maande tydperk in Vervet apies (data nie getoon) is nie. Ons kan dus aflei dat Diavite TM in ons modelle veilig is en na kort termyn gebruik, voordelig is as 'n dieetaanvulling.
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24

Beaubien, Eliot R. "Non-steroidal anti-inflammatory drugs and the risk of end stage renal disease in hypertensive individuals." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81593.

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Objective. To examine the association between non-steroidal anti-inflammatory drug (NSAID) use and end stage renal disease (ESRD) among hypertensive subjects.
Study design. We conducted a nested case-control study within a cohort of 77,887 hypertensive adult subjects within the province of Saskatchewan, Canada.
Outcome. The primary outcome was ESRD, defined by chronic dialysis or renal transplantation.
Exposure. NSAID exposure was determined using prescription records, for various time windows up to 10 years preceding the onset of end stage renal disease.
Statistical analysis. Rate ratios (RR) were estimated with 95% confidence intervals using conditional logistic regression, adjusting for potential confounding variables and stratified for effect modifiers.
Results. We identified 397 cases and 7,399 controls. In subjects followed for at least 10 years continuous NSAID use was observed in 20.8% of cases and 17.9% of controls (RR = 1.18, 95% CI 0.68--2.05). Additionally, neither early (RR = 1.10, 95% CI 0.50--2.41) nor late (RR = 0.81, 95% CI 0.32--2.04) NSAID exposure was associated with ESRD during this time period. Evaluation of other time windows (0--2 years, 2--5 years and 5--10 years) and NSAID dosing provided similar results. Results were not modified by loop diuretic and angiotensin converting enzyme inhibitor use.
Conclusion. Up to 10 years of non-steroidal anti-inflammatory drug use does not appear to influence the development of end stage renal disease. These results however may be influenced by unmeasured co-morbidities and confounding by "contra-indication".
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25

AL-Thabhani, Hanaa A. "Steriods Protect Against Doxorubicin-Induced Cytotoxicity in Rat Cardiac Myoblastic H9C2 Cells." VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd_retro/18.

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Doxorubicin is one of the most potent anticancer drugs used in the treatment of wide spectrum of neoplastic diseases including breast, thyroid, colon and liver cancer. However, doxorubicin use is associated with undesirable side effects including cardiomyopathy and congestive heart failure. In the present study we have established that treatment of rat cardiac myoblasts (H9c2 cells) with doxorubicin resulted in H9c2 cell injury in a dose and time dependent manner with almost 50% cell death obtained at 5 μM of doxorubicin treatment for 24 hours. We have selected about 50% cell injury as optimum doxorubicin-induced cell injury because once this threshold is reached, cells became irreversibly injured and could not respond to protective treatment. Another potent antineoplastic drug cyclophosphamide had no cardiotoxic effects on H9c2 cells even at 35 μM concentration and up to 72 hours of treatment. Pretreatment of H9c2 cells for 24 hours with dexamethasone, cortisol, corticosterone or progesterone, significantly protect H9c2 myoblasts against subsequent 5 μM doxorubicin treatment for 24 hours in a concentration dependent manner with maximum protection obtained at 100 nM dexamethasone, 100 nM progesterone, 500 nM cortisol and 500 nM corticosterone. However, testosterone or dehydroepiandrosterone had no protective effects even at 10 μM concentration. It is concluded that both glucocorticoids and progesterone protect H9c2 cells against doxorubicin-induced cell injury.
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26

Richards, Jamie Madison. "The Potential of IL-19 As a Therapeutic Anti-inflammatory and Angiogenic Cytokine." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/345114.

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Physiology
Ph.D.
Our lab has recently shown that IL-19 is expressed in angiogenic ECs, opening the possibility for its use as a medicine to increase perfusion in patients with PAD. The first aim of the current study is to show IL-19’s ability to increase perfusion in vivo using C57BL/6 wild type and IL-19 KO mice in the hindlimb ischemia (HLI) model. Wild-type mice injected with 10ng/g/day of rmIL-19 after being subject to hindlimb ischemia showed significantly greater levels of perfusion than PBS injected littermates. Immunohistochemistry of harvested gastrocnemius muscle showed a greater level of capillary density in IL-19 injected mice as well. IL-19-/- mice also showed a slower recovery of perfusion in a ligated limb in addition to less CD31 positive cells in gastrocnemius muscle when compared to C57BL/6 wild type mice. IL-19 -/- mice also showed increased perfusion when injected with rmIL-19. The second aim of the study is to show more precisely if IL-19 increases angiogenesis by increasing angiogenic cytokine production, polarizing macrophage phenotype, or by influencing angiogenic and anti-angiogenic factors. Spleen, serum, and bone marrow derived macrophage (BMDM) from mouse models used in Aim 1 showed increased levels of angiogenic cytokines, decreased anti-angiogenic cytokines, and markers of M2 macrophage polarization when IL-19 was injected i.p. or present genetically. The third aim of the study examines whether or not IL-19 can increase perfusion within an atherosclerotic background. It also addresses whether IL-19 can both simultaneously reduce atherosclerosis and increase perfusion. This aim also uses mice lacking LDLR-/- genes to further evaluate these questions. LDLR-/- mice fed a high fat diet for 12 weeks underwent HLI and had perfusion levels measured using Doppler imaging in addition to four weeks of 10ng/g/day of IL-19 or PBS injections. Upon sacrifice mice also had their aortas harvested and stained for plaque measurement. This experiment seeks to demonstrate if IL-19 can increase perfusion on an atherosclerotic background. Additionally, a second set of experiments addresses if LDLR-/- mice injected with recombinant mouse IL-19 (rmIL-19) or PBS for 16 weeks on a HFD in addition to HLI being performed at week 12 showed decreased levels of plaque and increased levels of hindlimb perfusion. These experiments seek to demonstrate if IL-19 can simultaneously reduce atherosclerosis while increasing perfusion. A third set of experiments attempts to evaluate the hypothesis that double knock out mice (DKO) lacking both LDLR and IL-19 genes will have increased plaque after being fed a HFD for 16 weeks. These aims all support the overall hypothesis that IL-19 can increase angiogenesis while additionally proving to be anti-inflammatory and anti-atherogenic in vivo
Temple University--Theses
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27

Aindongo, Wilhelmina Vulikeni. "Postharvest physiology and effects of modified atmosphere packaging and anti-browning treatment on quality of pomegranate arils and aril-sac (CV. Bhagwa)." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/86395.

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Thesis (MScFoodSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: Knowledge of postharvest quality attributes of minimally processed packaged fruit is essential in order to establish the optimum shelf life period. The aim of this study was to investigate the effects of Passive-modified atmosphere packaging (MAP) on the quality of minimally processed pomegranate (cv. Bhagwa) arils and aril-sacs. These began by understanding the physiological processes i.e. respiration and transpiration rates of the whole fruit, arils and aril-sacs. The respiration rates (RR) of whole fruit, aril-sacs and arils were studied at 5, 10, 15 and 22°C, and comparisons were made among these fruit fractions. A high RR was observed in aril-sacs compared to whole fruit and arils across all storage temperatures. A 74.5% decrease in RR was observed when storage temperature was reduced from 22°C to 5°C. A significant increase in RR occurred from day 3 of storage across all fruit fractions and storage temperatures. The transpiration rates (TR) of arils and aril-sacs were studied at storage conditions of 5, 10 and 15°C and 76, 86 and 96% relative humidity (RH), and was found to increase with increase in temperature and decrease in relative humidity, with lowest TR occurring in fruit fractions stored at 5°C and 96% RH showing lower TR. Arils had high TR compared to aril-sacs, and this may be related to high surface area to volume ratio of exposed arils. The effects of modified atmosphere packaging and application of anti-browning agents on quality of arils and aril-sacs stored at 5°C were studied. Compared to clamshell packaging, Passive-MAP using POLYLID® 107 polyethylene (PE) polymeric film showed greater positive effects in maintaining the quality and extends the shelf life of the arils and aril-sacs. Furthermore, the anti-browning agents used controlled browning on the cut-surfaces of the peel of the aril-sacs and reduced microbial growth in both arils and aril-sacs. When the effects of MAP and anti-browning were combined, aril-sacs stored better than arils. These treatments extended the shelf life of aril-sacs to 12 days while arils lasted up to 9 days. The water vapour transmission rate (WVTR) of pomegranate fruit membrane was evaluated at cold storage (5°C, 90% RH) and room condition (18.7°C, 70% RH). A high WVTR occurred in membranes stored at room condition, compared to those stored at cold storage. Further studies are warranted to improve our understanding of the biophysical properties of pomegranate membranes in relation to possible exchange of water vapour and gases between the aril-sacs. In summary, the use of MAP in combination with anti-browning agents showed a high potential in maintaining the quality of pomegranate arils and aril-sacs and consequently increase their shelf-life.
AFRIKAANSE OPSOMMING: Kennis van naoes- gehalte-eienskappe van minimaal geprosesseerde verpakte vrugte is essensieel ten einde optimum rakleeftyd te bepaal. Die doel van hierdie studie was om die gevolge van passiewe gemodifiseerde atmosfeerverpakking (GAV) op die gehalte van arils en arilsakkies van minimaal geprosesseerde granaat (kv. Bhagwa) te ondersoek. ʼn Aanvang is gemaak deur die fisiologiese prosesse, m.a.w. respirasie- en transpirasietempo’s van die hele vrugte, arils en arilsakkies, te begryp. Die respirasietempo’s (RT) van hele vrugte, arilsakkies en arils is by 5, 10, 15 en 22°C bestudeer, en vergelykings is getref tussen hierdie vrugdele. ʼn Hoë RT is waargeneem by arilsakkies in vergelyking met hele vrugte en arils oor alle bergingstemperature heen. ʼn Afname van 74.5% RT is waargeneem toe bergingstemperatuur van 22°C na 5°C verminder is. ʼn Beduidende toename in RT het van dag 3 van berging af oor alle vrugdele en bergingstemperature heen voorgekom. Die transpirasietempo’s (TR) van arils en arilsakkies is by bergingstoestande van 5, 10 en 15°C en 76, 86 en 96% relatiewe humiditeit (RH) bestudeer, en daar is bevind dat dit verhoog met ’n toename in temperatuur en ʼn afname in relatiewe humiditeit, met die laagste TR wat voorkom by vrugdele geberg by 5°C en 96% RH wat dus laer TR toon. Arils het hoë TR gehad in vergelyking met arilsakkies, en dit kan verband hou met die verhouding van hoë oppervlakarea tot volume blootgestelde arils. Die gevolge van gemodifiseerde atmosfeerverpakking en aanwending van middels vir die voorkoming van verbruining op gehalte van arils en arilsakkies geberg teen 5°C is bestudeer. In vergelyking met verpakking in toeknipbakkies (clamshell packaging), het passiewe GAV waarby POLYLID® 107 poliëtileen- (PE) polimeriese film gebruik is, groter positiewe gevolge by die behoud van gehalte getoon, en die rakleeftyd van die arils en arilsakkies is verleng. Daarbenewens het die middels vir die voorkoming van verbruining beheerde verbruining op die sny-oppervlakke van die skil van die arilsakkies gebruik en mikrobiese groei in beide arils en arilsakkies verminder. Toe die gevolge van GAV en die voorkoming van verbruining gekombineer is, het arilsakkies beter as arils geberg. Hierdie behandelings het die rakleeftyd van arilsakkies tot 12 dae verleng terwyl arils tot 9 dae gehou het. Die waterdamptransmissiespoed (WDTS) van granaatvrugtemembraan is geëvalueer by koel berging (5°C, 90% RH) en kamertoestande (18.7°C, 70% RH). ʼn Hoë WDTS het voorgekom by membrane wat by kamertoestande geberg is in vergelyking met dié wat in koelbewaring geberg is. Verdere studies is geregverdig vir verbetering van ons begrip van die biofisiese eienskappe van granaatmembrane in verhouding met moontlike uitruiling van waterdamp en atmosfere tussen die arilsakkies.
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28

黃穎康 and Wing-hong Wong. "The anti-ulcer mechanisms of Cortex moutan against stress-induced gastric mucosal damage in rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31221981.

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29

Billinghurst, Robert Clark. "The identification of collagenase-generated cleavage products of type II collagen using anti-neoepitope antibodies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0004/NQ36955.pdf.

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30

Siproudhis, Laurent. "Distensions rectales isobariques : un modele d'etude dynamique de la physiologie anorectale chez l'homme (doctorat : biologie et sciences de la sante)." Rennes 1, 1998. http://www.theses.fr/1998REN1B031.

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31

Blake, Crystal. "Anti-Depressive and Anti-Obesity Changes Following Either Dietary Isoflavone Treatment or Injection Treatment with the Isoflavonoid Equol: Positive Response Dependent on Animal Age and Ovarian Status in Female Long Evans Rats." BYU ScholarsArchive, 2010. https://scholarsarchive.byu.edu/etd/3036.

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Two conditions associated with ovarian depletion are increased potential for depressive episodes and increased abdominal weight gain. In five different experiments we examined the effect of soy-containing diets or equol injections on depression, serotonin levels, weight gain (BW) and white adipose tissue (WAT) deposition of female Long-Evans rats in various stages of life. Rats were intact, ovariectomized or experienced natural ovarian failure (NOF). While this paper will present each experiment, only experiment 5 is outlined here due to space limitations. From conception the rats were exposed to either a soy-rich (Phyto-600) or low-soy diet (Phyto-low). Animals experienced NOF at approximately 300 days. At 330 days-old animals underwent the Porsolt forced swim test (PFST). One month later (following 1 week of equol injections in Phyto-low fed animals) the animals were again tested in the PFST. Serum was collected before the first PFST and following the second PFST for serotonin and isoflavone analysis. This experiment demonstrated that animals fed a soy-rich diet have decreased BW and WAT compared to a low-soy diet. At the first PFST, the Phyto-low fed NOF females displayed increased immobility and lower serotonin levels compared to the Phyto-600 NOF females indicating the Phyto-low animals were more depressed than the Phyto-600 females. The second PFST demonstrated equol injection significantly increased both time mobile and serum serotonin levels in the Phyto-low fed rats suggesting that equol has antidepressant effects. This experiment demonstrated that isoflavone exposure has antiobesity-like effects. Furthermore, isoflavones (particularly equol) appear to have antidepressant potential in NOF females.
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32

Jambois, Anne. "Dialogue moléculaire au cours de l'ontogénèse ectomycorhizienne : accumulation et activité anti-auxinique de l'hypaphorine, approches physiologique et génomique." Nancy 1, 2004. http://docnum.univ-lorraine.fr/public/SCD_T_2004_0190_JAMBOIS.pdf.

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Certaines étapes de l'ontogenèse ectomycorhizienne nécessiteraient un subtil équilibre entre des molécules actives telles que l'AIA et des molécules régulatrices telles que l'hypaphorine, un alcaloi͏̈de indolique synthétisé et accumulé en grande quantité dans les hyphes de Pisolithus au contact de la plante hôte. Ici, l'activité stimulatrice des jasmonates sur la synthèse d'hypaphorine a été mise en évidence ; une nouvelle classe d'antagonistes spécifiques et compétitifs de l'activité auxinique a été identifiée, les alcaloi͏̈des indoliques. L'activité de l'hypaphorine et/ou de l'AIA sur l'expression de plus de 4000 gènes de peuplier a été suivie. Parmis les 121 transcrits différentiellement exprimés, un seul d'entre eux codant pour une Extensine-like-Protein est régulé de façon opposée par les deux molécules antagonistes. Avec l'hypaphorine et certains alcaloi͏̈des indoliques, s'ouvre un champ nouveau d'étude des modes d'action des auxines
Some steps of the ectomycorrhizae ontogenesis would require a subtle balance between active molecules such as IAA and regulating molecules such as hypaphorine, an indolic alkaloid synthesised and accumulated in large quantities by Pisolithus in contact with the host plant. Here the up-regulating activity of jasmonates on hypaphorine synthesis in Pisolithus hyphae was evidenced; a new class of IAA competitive-antagonists has been identified, the indole alkaloids. The activity of hypaphorine or/and IAA on gene expression in poplar roots, has been folowed. Amongst121 EST differentially expressed, only one coding for an extensinlike protein was regulated the opposite ways by both antagonist molecules. With hypaphorine, and some indole alkaloids, opens a new range of investigation of IAA activities
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33

Grönkvist, Mikael. "Ventilation distribution in the lung periphery measured by inert gas washout : influence of increased gravity, anti-G suit pressure, body posture, and breathing pattern /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/tek896s.pdf.

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34

Africa, Luan Dane. "HIV-1 associated neuroinflammation : effects of two complimentary medicines illustrated in an in vitro model of the blood-brain barrier." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/95869.

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Thesis (MSc)--Stellenbosch University, 2014.
ENGLISH ABSTRACT: Background: Neuroinflammation is central to the aetiology of HIV-associated neurocognitive disorders (HAND) that are prevalent in late stage AIDS. ARV treatments are rolled out relatively late in the context of neuroinflammatory changes, so that their usefulness in directly preventing HAND is probably limited. It is common practice for HIV+ individuals in developing countries to make use of traditional/complimentary medicines. One such medicine is Sutherlandia frutescens - commonly consumed as a water infusion. We have also identified a new candidate complimentary medicine for use in this context - grape seed-derived proanthocyanidolic oligomers (PCO) have significant anti-inflammatory action in the peripheral compartment in the context of e.g. skeletal muscle injury, but have not been investigated in the context of either neuroinflammation or HIV/AIDS. Here the efficacy of these two substances as an anti-inflammatory modality in this context was investigated in an in vitro co-culture model of the blood-brain barrier (BBB). Methods: Single cultures of human astrocytes, HUVECs and primary human monocytes, as well as co-cultures (BBB), were stimulated with HIV-1 subtype B & C Tat protein and/or HL2/3 cell secretory proteins after pre-treatment with S. frutescens or PCO extracts. Effects of this pre-treatment on pro-inflammatory mediator expression and monocyte migration across the BBB were assessed. Results: In accordance with others, B Tat was more pro-inflammatory than C Tat, validating our model. S. frutescens decreased IL-1β secretion significantly (P<0.0001), but exacerbated both monocyte chemoattractant protein-1 (P<0001) – a major role player in HIV-associated neuroinflammation – and CD14+ monocyte infiltration across the BBB (P<0.01). PCO pre-treatment resulted in a significantly dampened IL-1β (P<0.0001) response to stimulation with HIV-associated proteins. In contrast to S. frutescens, PCO modulated monocyte chemoattractant protein-1 (P<0001) response and decreased capacity for CD14+ monocytes to migrate across the simulated BBB (P<0.0001). Additionally, PCO pre-treatment decreased both GFAP (P<0.001) and HSP-27 (P<0.001) expression in the astrocytes of the BBB. Conclusions: Current data illustrates that the combined use of HL2/3 cells and the simulated BBB presents an accurate, disease relevant in vitro model with which to study neuroinflammation in the context of HIV/AIDS. In addition, our results caution against the use of S. frutescens as anti-inflammatory modality at any stage post-HIV infection. Novel data presented here illustrate that PCO is able to blunt the MCP-1 and IL-1β response to HIV-1 proteins in single cultures of human astrocytes and HUVECs, as well as in an in vitro simulation of the BBB. In addition, PCO was able to limit monocyte transmigration across the simulated BBB in response to HIV-1 proteins generated by HL2/3 cells. This suggests that grape seed-derived PCO could be considered as complimentary anti-neuroinflammatory drug in the context of HIV/AIDS.
AFRIKAANSE OPSOMMING: Agtergrond: Neuroinflammasie staan sentraal in die ontwikkeling van MIV-verwante toestande wat gekenmerk word deur neurokognitiewe afteruitgang, veral in die later stadia van die siekte. Aangesien anti-virale middels relatief laat toegedien word in die konteks van neuroinflammasie, is hul rol in die voorkoming van neuroinflammatoriese veranderinge heel moontlik weglaatbaar. MIV+ individue, veral in ontwikkelende lande, gebruik algemeen natuurlike medisinale preparate. Sutherlandia frutescens is een so „n middel wat as „n tee ingeneem word. Verder het ons ook „n nuwe kandidaat komplimentêre medisyne identifiseer – druiwepitekstrak wat polifenole bevat (PCO) het aansienlike anti-inflammatoriese eienskappe in die periferie, bv. in die konteks van skeletspierskade, maar die middel is nog nie voorheen in die konteks van neuroinflammasie of MIV/VIGS ondersoek nie. Hier word die anti-inflammatoriese effektiwiteit van beide middels in hierdie konteks ondersoek deur gebruik te maak van „n in vitro simulasie van die bloedbreinskans (BBS). Metodes: Kulture van menslike astrosiete, menslike naelstring endoteelselle (HUVECs) en primêre menslike monosiete, sowel as gesamentlike kulture (BBS) is met MIV-1 subtipe B en C Tat proteïen en/of HL2/3 selprodukte gestimuleer na voorafbehandeling met S. frutescens of PCO ekstrakte. Effekte op pro-inflammatoriese mediator uitdrukking sowel as monosiet migrasie oor die BBS is ondersoek. Resultate: In ooreenstemming met die literatuur was B Tat meer inflammatories as C Tat, wat die akkuraatheid en gepastheid van ons model bevestig. . S. frutescens het afskeiding van IL-1β betekenisvol verminder (P<0.0001), maar het afskeiding van beide monosiet chemoaantrekkingsproteïen-1 – „n groot rolspeler in MIV-verwante neuroinflammasie – en CD14+ monosiet migrasie oor die BBS vererger (P<0.0001 en P<0.01 onderskeidelik). PCO behandeling het „n betekenisvolle demping van die IL-1β reaksie (P<0.0001) op stimulasie met MIV-geassosieerde proteïene tot gevolg gehad. Anders as S. frutescens het PCO die MCP-1 reaksie, asook CD14+ monosiet migrasie betekenisvol inhibeer. Verder het PCO ook beide GFAP en HSP-27 uitdrukking in astrosiete van die BBS verminder (beide P<0.001). Gevolgtrekkings: Huidige data wys dat die gekombineerde gebruik van HL2/3 selle en die gesimuleerde BBS „n akkurate en fisiologies relevante in vitro model daarstel, waarmee neuroinflammasie in die konteks van MIV/VIGS bestudeer kan word. Ons resultate waarsku verder teen die gebruik van S. frutescens as anti-inflammatoriese middel in selfs die vroeë stadium na MIV infeksie. Oorspronklike data wat hier aangebied word illustreer dat PCO die pro-inflammatoriese reaksie op MIV-proteïene in kulture van astrosiete en HUVECs, asook die in vitro simulasie van die BBS, effektief demp. Verder het PCO die vermoë getoon om monosiet migrasie oor die BBS, in reaksie op MIV-1 proteïene wat hul oorsprong uit HL2/3 selle het, te beperk. Hierdie bevindings beteken dat PCO dus eerder as S. frutescens oorweeg moet word as komplimentêre anti-inflammatoriese medisyne in die konteks van MIV/VIGS.
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35

Vadapalli, Vatsala. "Role of N-Acylethanolamines in Plant Defense Responses: Modulation by Pathogens and Commercial Antimicrobial Stressors." Thesis, University of North Texas, 2010. https://digital.library.unt.edu/ark:/67531/metadc30521/.

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N-acyl ethanolamines (NAEs) are a class of lipids recently recognized as signaling molecules which are controlled, in part, by their degradation by fatty acid amide hydrolase (FAAH). On the basis of previous studies indicating increased NAE levels in a tobacco cell suspension-xylanase elicitor exposure system and the availability of FAAH mutants, overexpressor and knockout (OE and KO) genotypes in Arabidopsis thaliana, further roles of NAEs in A. thaliana plant defense was investigated. The commonly occurring urban antimicrobial contaminant triclosan (TCS) has been shown to suppress lipid signaling associated with plant defense responses. Thus, a second objective of this study was to determine if TCS exposure specifically interferes with NAE levels. No changes in steady state NAE profiles in A. thaliana-Pseudomonas syringae pv. syringae and A. thaliana-flagellin (bacterial peptide, flg22) challenge systems were seen despite evidence that defense responses were activated in these systems. There was a significant drop in enoyl-ACP reductase (ENR) enzyme activity, which catalyzes the last step in the fatty acid biosynthesis pathway in plants, on exposure of the seedlings to TCS at 10 ppm for 24 h and decreased reactive oxygen species (ROS) production due to flg22 in long term exposure of 0.1 ppm and short term exposure of 5 ppm. However, these responses were not accompanied by significant changes in steady state NAE profiles.
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36

Smith, Aaron P. "Tissue Specific Porcupine Deletion Reveals a Novel Role for Ectodermal Wnts in Musculotendon Development." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3323.

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The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the limbs of these mice have several similarities with En1 mutant mice which have a double-dorsal phenotype. however, we show that appropriate dorsoventral limb pattern is maintained at the molecular level and that the observed defects are due to a failure to appropriately execute ventral pattern. Additionally, newborn mice lack ventral digital tendons and the most superficial musculature in the regions of strongest and earliest deletion. Molecular analysis indicates that tendons are lost downstream of the absent musculature and are initially patterned correctly. Thus we show a role for ectodermal Wnts in the development of underlying musculature. We additionally examine the role of limb mesenchymal Wnts in the development of deeper limb musculature utilizing the Prx1Cre deleter. The deep musculature of the autopod and zeugopod is reduced or absent in mutants and the development of superficial musculature appears to proceed normally. Hence we show that superficial muscles require only ectodermal Wnts and deeper muscles require only mesenchymal Wnts.
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37

Bouarrata, Abderrachid. "Contribution à l'étude du comportement de prise de risque et de l'attitude observée à l'égard du risque chez l'enfant de 13-14 ans." Bordeaux 2, 1987. http://www.theses.fr/1987BOR28158.

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Nous avons relevé dans nos mesures d'appréciation des niveaux de prise de risque (attitude et comportement), mesures réalisées auprès d'enfants algériens âgés de 13-14 ans, issus d'un milieu rural et d'un milieu urbain, des deux sexes, des rapports qui présentent une certaine différence. Au vu de ces résultats, l'impression globale prévalente est celle d'une tendance à la prise de risque largement connotée de masculinité et aussi celle d'une ascendance rurale. S'il est vrai que les valeurs présentement observées ne peuvent être généralisables à toutes les formes de situations, il est non moins vrai que nous prenons conscience de la difficulté de mesurer un phénomène dont les indices d'appréciation sont multiples et si fluctuants. Derrière cette difficulté de mesure, la prise de risque laisse apparaitre un caractère polymorphe qui détermine les méthodes de son approche, lesquelles doivent être diversifiées. Une approche qui découle de l'analyse pluridimensionnelle
In our study on algerian children of both sexes, whose age is 13-14 years, some of them issued from an rural milieu and the others from an urban one, we have got some conclusions which show a difference concerning the level of facing danger in these children (their attitude and behaviour). In the light of these results, the main feeling we have is that of a predisposition to face risks widely prevailing among boys (male predominance) and also among these who have a rural ancestry. Even if we know that the values actually observed cannot be applied to all kinds of cases, we are aware, nevertheless, of the difficulty to measure a phenomen when the ways to examine it are so numerous and so capricious. Near the difficulty to measure this phenomen, facing risks also shows a polymorphous aspect since the methods of studying it ought to be diversified and since this study derives from a multidimensional analysis
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38

Oliary, Juliette. "Pénétration salivaire des antiinfectieux. Une application à l'étude du fluconazole." Paris 5, 1990. http://www.theses.fr/1990PA05P066.

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39

Maillet, Alain. "Comparaison des effets endocriniens, métaboliques et cardio-vasculaires observés lors d'expériences d'alitement anti-orthostatique et de confinement." Lyon 1, 1997. http://www.theses.fr/1997LYO1T243.

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40

Ekström, Andreas. "Effects of the NO donors Sodium Nitroprusside andS-nitrosoglutathione on oxygen consumption and embryonic organ growth in the domestic broiler chicken,Gallus gallus domesticus." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-59567.

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Nitric oxide (NO) is an important chemical factor that controls vascular tone in the cardiovascular system. NO is a vasodilatory molecule that plays a role in blood pressure and blood flow regulation as well as vessel formation and tissue cell proliferation. NO influences the flow by which nutrients and other metabolites required for growth are transported to the tissues. The aim of this study was to investigate if NO, through mediation by the NO donors Sodium Nitroprusside (SNP) and S-Nitrosoglutathione (GSNO) affect growth and oxygen consumption of prenatal broiler chicken. The results indicate that, although the treatments did not have clear significant effects on the embryos or the organs examined, a slight delay in development can be observed in the GSNO treatment embryos. The study could not conclude, however, if this was due to effects of NO donors

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41

Hanin, Véronique. "Utilisation d'immunogènes synthétiques de type "résine polyacrylique-peptide" pour l'obtention d'anticorps anti-peptides : caractérisation et application à l'étude de quelques protéines." Montpellier 2, 1990. http://www.theses.fr/1990MON20106.

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Une nouvelle methode de production d'anticorps anti-peptides a ete mise au point, a partir d'immunisations chez l'animal contre des peptides lies a une resine polyacrylamide sur laquelle la synthese peptidique est effectuee. Les anticorps obtenus ont ete caracterises, compares (pour certains) aux anticorps produits contre le meme peptide couple a une proteine porteuse et utilises pour l'etude immunochimique des proteines correspondantes: actine, interferon gamma humain, dystrophine et recepteur d2 de la dopamine. Cette nouvelle procedure s'avere simple, rapide, efficace et tout a fait comparable aux techniques d'immunisation anti-peptides classiques. Elle presente plusieurs avantages d'ordre chimique: specificite et stabilite de la liaison resine-peptide, connaissance et modulation possible du rapport resine/peptide et absence d'etapes fastidieuses de clivage, purification et couplage du peptide a un porteur proteique
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42

Contreras, Garces Andrea Maud. "Physiological Effects and Biotransformation of Paralytic Shellfish Toxins in New Zealand Marine Bivalves." Thesis, University of Canterbury. School of Biological Sciences, 2010. http://hdl.handle.net/10092/5181.

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Although there are no authenticated records of human illness due to PSP in New Zealand, nationwide phytoplankton and shellfish toxicity monitoring programmes have revealed that the incidence of PSP contamination and the occurrence of the toxic Alexandrium species are more common than previously realised (Mackenzie et al., 2004). A full understanding of the mechanism of uptake, accumulation and toxin dynamics of bivalves feeding on toxic algae is fundamental for improving future regulations in the shellfish toxicity monitoring program across the country. This thesis examines the effects of toxic dinoflagellates and PSP toxins on the physiology and behaviour of bivalve molluscs. This focus arose because these aspects have not been widely studied before in New Zealand. The basic hypothesis tested was that bivalve molluscs differ in their ability to metabolise PSP toxins produced by Alexandrium tamarense and are able to transform toxins and may have special mechanisms to avoid toxin uptake. To test this hypothesis, different physiological/behavioural experiments and quantification of PSP toxins in bivalves tissues were carried out on mussels (Perna canaliculus), clams (Paphies donacina and Dosinia anus), scallops (Pecten novaezelandiae) and oysters (Ostrea chilensis) from the South Island of New Zealand. Measurements of clearance rate were used to test the sensitivity of the bivalves to PSP toxins. Other studies that involved intoxication and detoxification periods were carried out on three species of bivalves (P. canaliculus, P. donacina, P. novaezelandiae), using physiological responses (clearance and excretion rate) and analysis of PSP toxins in the tissues over these periods. Complementary experiments that investigated other responses in bivalves fed with the toxic cells were also carried out. These included byssus production, and the presence of toxic cells in the faeces of mussels, the siphon activity and burrowing depth in clams and the oxygen consumption in scallops. The most resistant species to PSP toxins were the mussel, Perna canaliculus and the clam, Dosinia anus. Both species fed actively on toxic dinoflagellates and accumulated toxins. The intoxication and detoxication rate of the mussel was faster than the other species of bivalve studied (P. donacina and P. novaezelandiae) which confirm mussels as a good sentinel species for early warning of toxic algal blooms. The clearance rate of the clam, Paphies donacina decreased when fed on Alexandrium species but the effect of the PSP toxins on this physiological response was not confirmed. Over the detoxification period of 8 days, this clam did not detoxify which suggests that its ability to retain high level of toxins for an extensive period may be critical for public health management. The scallop, Pecten novaezelandiae was clearly the most sensitive species to the PSP toxins and the clearance rate was significantly lower in the presence of the toxic dinoflagellate A. tamarense. Although the clearance rate was low, the scallops still fed on the toxic dinoflagellate and accumulated PSP toxins in the tissues. The scallops detoxified slowly which would affect the market for this bivalve in the presence of a toxic algal bloom. This bivalve would retain PSP toxins for longer period of time than other species such as mussels. The oyster, Ostrea chilensis, had erratic clearance rate and did not respond clearly to any of the variables tested over the time. Oysters accumulated more toxins than the sensitive species, but they had been exposed to two more days of feeding with A. tamarense; therefore this species may actually have a similar intoxication responses to P. novaezalandiae and P. donacina. The results from this thesis suggest further directions for the aquaculture sector and ongoing research in this field, which in future will lead to a better selection of suitable species for culture as well as species for monitoring of PSP toxins. In the future, research that integrates field and controlled laboratory studies will expand to other species of interest and a more complete record will in time be available in order to manage more efficiently the negative effects that harmful algal blooms may have in New Zealand.
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43

Palenske, Nicole Marie. "Effects of Triclosan, Triclocarban, and Caffeine Exposure on the Development of Amphibian Larvae." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc11016/.

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Triclosan and triclocarban are antimicrobials found in numerous consumer products, while caffeine is the most commonly consumed stimulant by humans. This study was undertaken to determine the effects of triclosan, triclocarban, and caffeine on the development and physiology of amphibian larvae. LC50 values of triclosan and triclocarban were determined after 96 hours for three North American larval species: Acris crepitans blanchardii, Bufo woodhousii woodhousii, Rana sphenocephala, and for a common amphibian developmental model: Xenopus laevis. Amphibian larvae were most sensitive to triclosan and triclocarban exposure during early development based upon 96-hour LC50 values. Heart rates for X. laevis and North American larvae exposed to triclosan were variable throughout development. However, significantly lower heart rates were observed in all larvae exposed to triclocarban. Metabolic rates of X. laevis and R. sphenocephala larvae exposed to triclosan were significantly affected in larvae exposed to ½ LC50 and the LC50 concentration. Metabolic rates of X. laevis larvae exposed to triclocarban were significantly affected by exposure to ½ LC50 concentrations in three of four stages investigated. No significant differences were observed in North American larvae exposed to triclocarban. Tissue uptake, lipid uptake, tissue bioconcentration factor (BCF) and lipid BCF of triclosan and triclocarban were investigated in three developmental stages of X. laevis, and in one developmental stage of B. woodhousii woodhousii, and R. sphenocephala. For most tissue and lipid uptake values, a significant increase was observed as exposure concentration increased. Tissue and lipid BCF values were dependent upon both stage and species. Chronic and acute effects of caffeine were determined in X. laevis larvae. Acute 96-hour LC50 values in four developmental stages were > 75,000 ug L-1 caffeine and heart rates were significantly different at the two earliest developmental stages. Larvae chronically exposed to caffeine reached metamorphosis at the same time as controls. Changes in chronic heart rate were dependent upon stage of development and exposure concentration. This research indicates that the toxicity of amphibian larvae exposed to triclosan, triclocarban, and caffeine appears to be dependent upon species and developmental stage, with early developmental stages being most sensitive to contaminant exposure.
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44

Darrasse-Jèze, Guillaume. "Lymphocytes T régulateurs naturels de l'autoimmunité : nature, bienfaits et méfaits : étude de leur physiologie et leur rôle dominant dans les réactions immunitaires materno-foetales et anti-tumorales." Paris 6, 2006. http://www.theses.fr/2006PA066160.

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Au cours de cette thèse, nous avons étudié la physiologie, le rôle et les mécanismes établissant la tolérance dominante des lymphocytes T régulateurs naturels de l’autoimmunité (Tregs), qui jouent un rôle majeur dans le maintien de la tolérance au soi et la régulation immunitaire. Nous avons démontré leur apparition précoce pendant le développement fœtal, précisé leur ontogénie thymique, étudié leur homéostasie in vivo et caractérisé une sous-population de Tregs stimulée en permanence localement par les antigènes du soi. Nous avons aussi mis en évidence le rôle des Tregs dans la tolérance materno-fœtale et élucidé le mécanisme qui leur permet d’établir une tolérance dominante aux cellules tumorales. Le statut immunologique et la cinétique d’activation respectifs des T effecteurs anti-tumoraux et des Tregs mémoire lors de l’émergence d’une tumeur favorise inéluctablement ces derniers. Ces découvertes modifient notre vision du sytème immunitaire et ouvrent des perspectives thérapeutiques
Natural regulatory T cells (Tregs) play a key role in self-tolerance and immune regulation. We have studied their physiology and the obtained results encouraged us to evaluate their functions in the control of immune responses during pregnancy and cancer. The demonstration of their emergence together with the first T cells during human fetal development and their thymic ontogeny indicated that the generation of Tregs is consubstantial to the generation of the immune system. Study of their homeostasis in normal mice revealed the existence of a Treg subset continuously activated, locally, by self-antigens. We also observed that Tregs play a major role in maternal-fetal and tumor immune tolerance. The memory Tregs overwhelm anti-tumor effector responses by a very early and brisk response that pre-empt the slower activation of effector T cells at the very time of tumor emergence. These results have profound implications in fundamental comprehension of immune system and in cancer therapy
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45

Boscolo, Rita Aurélia [UNIFESP]. "Análise da relação entre a taxa metabólica basal, a composição corporal e o sono em idosos antes e após o treinamento resistido." Universidade Federal de São Paulo (UNIFESP), 2009. http://repositorio.unifesp.br/handle/11600/8908.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Associação Fundo de Incentivo à Psicofarmacologia (AFIP)
Centros de Pesquisa, Inovação e Difusão (CEPID)
Durante o processo de envelhecimento ocorrem alterações neuroquímicas, morfológicas e funcionais, como a redução de algumas das características do sono, da quantidade da massa livre de gordura e da taxa metabólica basal. Estes fatores podem estar relacionados uma vez que a diminuição da taxa metabólica basal ocorre em conseqüência da diminuição da massa livre de gordura. O treinamento físico provavelmente pode minimizar tais efeitos e/ou trazer resultados positivos ao padrão do sono, assim como aos parâmetros da composição corporal e ao metabólico. O objetivo deste estudo foi avaliar os efeitos do treinamento resistido na taxa metabólica basal (TMB), na composição corporal e nos parâmetros do sono, verificando as suas possíveis relações em homens idosos. A amostra foi composta por 37 homens idosos com uma idade entre os 65 e os 75 anos, distribuídos aleatoriamente em dois grupos: o controle (GC) e o resistido (GR). O protocolo incluiu 72 sessões de treinamento resistido progressivo realizado três vezes semanais; e avaliações do metabolismo basal, da composição corporal, do sono (objetiva e subjetiva) e do consumo alimentar. Os resultados demonstraram que a força muscular aumentou em todos os grupos musculares no GR. Nas variáveis morfológicas, somente o GC aumentou a massa gorda e diminuiu a livre de gordura na avaliação final, enquanto que o GR manteve todas as variáveis da composição corporal. A TMB e o consumo energético diário não sofreram alterações em ambos os grupos ao longo das avaliações. Nas variáveis do sono, o GC aumentou o tempo total de sono, os microdespertares e o valor da escala de Pittsburgh, enquanto que o GR reduziu significativamente o percentual do estágio 1 do sono NREM. Houve associação de causa e efeito da massa livre de gordura (kg) e do estágio 1 sobre a TMB com o modelo final de regressão (TMB= 539,81 + 21,99 massa livre de gordura – 26,01 estágio 1), o que explica os 34% da variação da TMB. Em conclusão, os resultados sugeriram que o treinamento resistido, apesar de não alterar as relações entre a TMB, o sono e a composição corporal, foi efetivo para aumentar a força muscular, manter a massa livre de gordura e a TMB, e ainda melhorar a qualidade do sono em idosos saudáveis, refletindo numa qualidade de vida mais ativa para uma longevidade saudável.
During the process of aging, neurochemical, morphological and functional changes occur such as the decline of some characteristics of sleep, the amount of fat free mass and basal metabolic rate. These factors may possibly be related because the decrease in basal metabolic rate is due to the decrease in fat free mass. Physical training can possibly minimize such effects and / or bring positive results to sleep pattern, body composition and metabolism. The objective of this study was to evaluate the effects of resistance training on basal metabolic rate (BMR), body composition and parameters of sleep and to verify their possible relationship in elderly men. The sample consisted of 37 elderly men age 65 to 75 years randomly assigned into two groups: control (CG) and resisted (RG). The protocol included 72 sessions of progressive resistance training performed three times weekly, the evaluation of basal metabolism, body composition, sleep (objective and subjective) and food consumption. The results showed that muscle strength increased in all muscle groups in the RG. In the morphological variables, only the CG had the fat mass increased and decreased fat free mass in the final evaluation, in the other hand the RG remained with the same variables of body composition. The BMR and daily energy consumption remained unchanged in both groups during the evaluations. As far as sleep variables are concerned, the CG increased total sleep time, arousals and score of the scale of Pittsburgh, while the RG significantly reduced the percentage of stage 1 of NREM sleep. There was a chance association of the fat free mass (kg) and stage 1 for the BMR with the final model of regression (BMR = 539.81 + 21.99 mass free of fat - 26.01 stage 1), explaining 34% change in BMR. In conclusion, the results suggest that resistance training, although not altering the relationships between BMR, the sleep and body composition was effective in increasing muscle strength, keep free of fat mass and BMR and to improve the quality of sleep in healthy elderly, reflecting a quality of life more active for a healthy longevity.
FAPESP: 06/05210-0
CEPID: 98/14303-3
TEDE
BV UNIFESP: Teses e dissertações
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46

Lario, Fábio de Cerqueira. "Estudo da reserva de perfusão miocárdica pelo ecocardiograma com contraste em tempo real, em indivíduos com hipercolesterolemia grave, antes e após tratamento com inibidores da HMG-CoA redutase." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-31082009-160424/.

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INTRODUÇÃO: A hipercolesterolemia provoca alterações inflamatórias no sistema cardiovascular, induzindo disfunção endotelial e mudanças estruturais na microcirculação, com alterações significativas da homeostase vascular, processo este reversível com o tratamento hipolipemiante. Clinicamente, tais fenômenos podem ser demonstrados pela avaliação da reserva de fluxo coronário e da reatividade vascular periférica. A ecocardiografia de perfusão miocárdica em tempo real (EPMTR) possui características que a tornam ideal para a avaliação da microcirculação coronária, como a utilização de contrastes intravasculares, além de ótimas resoluções temporal e espacial. MÉTODOS: 16 pacientes com hipercolesterolemia e sem lesões coronárias obstrutivas (grupo HF) e 10 indivíduos saudáveis, sem doença arterial coronária obstrutiva estabelecida (grupo controle) foram avaliados por EPMTR e por ultrassonografia da artéria braquial em dois momentos: pré-tratamento com atorvastatina no grupo HF (período livre de medicação >6 semanas) e 12 semanas após o primeiro exame. A análise do fluxo miocárdico foi realizada nos 17 segmentos do ventrículo esquerdo obtendo-se índices de volume de sangue relativo no miocárdio (AN), da velocidade do fluxo () e do fluxo miocárdico absoluto (ANx) na condição de repouso e durante a vasodilatação com adenosina. A reserva de fluxo foi definida como a razão entre o fluxo durante vasodilatação e o fluxo do repouso. Para estudo da reatividade vascular periférica, todos os indivíduos foram submetidos à ultrassonografia da artéria braquial, com avaliação dos diâmetros da artéria braquial antes e depois de um período de isquemia de 5 minutos. RESULTADOS: Os dois grupos foram comparáveis quanto à idade, sexo, peso, superfície corpórea, índice de massa corpórea, índice de massa do VE, frequência cardíaca e pressões arteriais sistólica e diastólica, tanto no repouso quanto durante a infusão de adenosina. Os valores evolutivos de LDL-C (mg.dL-1) nos dois momentos foram 106±36 e 107±35; p=NS para o grupo controle vs 278±48 e 172±71; p<0,001 para o grupo HF. Na avaliação inicial, a dilatação braquial estava reduzida nos pacientes do grupo HF 0,08±0,04 vs 0,15±0,02; p<0,001 relativamente ao grupo controle, com aumento do diâmetro arterial basal (mm): 3,42±0,63 vs 3,07±0,53; p<0,001. O grupo HF, quando comparado ao grupo controle na avaliação inicial, apresentava valores mais altos de AN: (dB) 0,56±0,08 vs 0,49±0,05; p=0,02, de (s-1) 0,56±0,14 vs 0,45±0,04; p=0,02 e ANx: (dB.dB-1 s-1) 0,28±0,06 vs 0,20±0,02; p<0,001, maiores valores de AN: durante infusão de adenosina 0,64±0,08 vs 0,57±0,06; p=0,001 e menores reservas de : 2,59±0,61 vs 3,25±0,45; p=0,001 e de ANx: 2,78±0,71 vs 3,43±0,66; p=0,03. Após o uso de atorvastatina, as alterações foram revertidas, tanto na circulação periférica quanto na coronária. CONCLUSÕES: A EPMTR monstrou que em indivíduos com hipercolesterolemia e sem doença coronária obstrutiva existe aumento do fluxo microvascular em repouso e redução da reserva de fluxo miocárdico. Após o tratamento com atorvastatina houve normalização do fluxo em repouso. Adicionalmente, alterações similares ocorreram na circulação periférica dos indivíduos hipercolesterolêmicos, revertidas por utilização da atorvastatina.
BACKGROUND: Hypercholesterolemia induces inflammatory changes on the cardiovascular system, causing endothelial dysfunction and structural alterations of microcirculation, with substantial imbalance of vascular homeostasis. Reduction of blood cholesterol levels can stop these processes. These circulation alterations can be demonstrated by coronary flow reserve and peripheral vascular reactivity evaluation. Real time myocardial perfusion echocardiography (EPMTR) is an excellent method to demonstrate coronary microcirculation alterations, as ultrasound contrast agent has rheological properties close to red cells. Additionally, EPMTR has optimal spatial and temporal resolutions. METHODS: 16 patients with hypercholesterolemia (group-HF) without overt obstructive coronary disease and 10 healthy volunteers (group-C) were evaluated by EPMTR and vascular ultrasound in 2 moments: before atorvastatin treatment (group-HF, >6 weeks free of statin) and 12 weeks after beginning medication (group-HF), or 12 weeks after the first evaluation (group-C). For myocardial blood flow evaluation, the left ventricle was divided into 17 segments, and indexes of myocardial blood volume (AN), blood flow velocity (), and myocardial blood flow (ANx) were obtained for each myocardial segment at rest condition and after adenosine infusion. Myocardial flow reserve was calculated as the hyperemic to rest values of AN, e ANx. Peripheral vascular reactivity was evaluated by vascular ultrasound. Measures of braquial artery diameter were obtained before and after 5 minutes of arterial flow occlusion. RESULTS: Both groups were comparable for age, sex, body weight, body surface area, body mass index, left ventricular mass index, heart rate, and systolic and diastolic arterial blood pressure. These variables were also comparable, under basal or adenosine stress conditions. LDL-C values (mg.dL-1) in different moments (intra-group) were 106±36 and 107±35; p=NS for group-C vs 278±48 and 172±71; p<0,001 for group-HF. Group-HF as compared to group-C had higher initial resting values of AN (dB): 0,56±0,08 vs 0,49±0,05; p=0,02, (s-1): 0,56±0,14 vs 0,45±0,04; p=0,02, and ANx (dBdB-1s-1): 0,28±0,06 vs 0,20±0,02; p<0,001, and higher hyperemic value of AN 0,64±0,08 vs 0,57±0,06; p=0,04, and lesser reserves of 2,59±0,61 vs 3,25±0,45; p=0,01 and of ANx: 2,78±0,71 vs 3,43±0,66; p=0,03. After atorvastatin treatment no difference was observed at rest, hyperemic and reserve values of AN, and ANx between the groups. CONCLUSION: In patients with hypercholesterolemia and without coronary obstruction, there was augmented myocardial blood flow and reduced coronary flow reserve at rest, compared to healthy volunteers. After atorvastatin treatment at rest myocardial blood flow was normalized in those patients. Additionally, similar alterations in peripheral circulation could be demonstrated in hypercholesterolemia, and were reverted with atorvastatin.
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47

Calistro, Neto José Pedro [UNESP]. "Interferência do parecoxibe sobre a função renal e lesão de rins submetidos ao estresse isquêmico: trabalho experimental em ratos com uso de NGAL como marcador da função renal." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/123691.

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Justificativas e objetivos: os anti-inflamatórios não esteroidais (AINEs) têm mostrado sua eficácia na abordagem multimodal da dor, reduzindo o consumo de opioides na dor aguda pós-operatória. Embora os AINEs possam afetar a função renal, existem poucos dados da utilização de AINEs coxibes disponíveis nesse contexto. Os biomarcadores precoces de lesão renal aguda, como o NGAL (neutrophil gelatinase-associated lipocalin), podem ser importantes aliados na determinação de lesão real associada ao uso de AINEs coxibes no período perioperatório. Materiais e métodos: após aprovação pelo Comitê de Ética em Pesquisa Experimental, 40 ratos Wistar foram distribuídos aleatoriamente em quatro grupos. Sob anestesia geral, e dependendo do grupo a qual os animais foram incluídos, eles foram submetidos a isquemia e reperfusão renal. Dois grupos receberam parecoxibe para avaliar a influência deste medicamento na função renal. Dosagem de NGAL e histologia renal bilateral foram realizadas para a avaliação da existência e grau da lesão renal. Resultados: o grupo isquemia (que não recebeu injeção de parecoxibe) apresentou os maiores níveis de NGAL e maior frequência de lesão renal. O grupo que sofreu isquemia e recebeu parecoxibe apresentou níveis de NGAL e frequência de lesão renal similares aos outros grupos que não sofreram tal injúria. Conclusão: neste modelo experimental, parecoxibe exibiu propriedades em promover proteção renal
Background and aims: nonsteroidal anti-inflammatory drugs (NSAIDs) have been proved to be effective, in a multidimensional approach, at reducing the opioid consumption during the postoperative acute pain. Although the NSAIDs may affect the renal function, there are few published data related to the use of coxibs and the kidney function. The early biomarkers of acute renal injury (EBARI) may be important tool to determining the actual risk associated with the use of coxibs NSAIDs in the perioperative period. Methods: after approval by Experimental Ethics Committee, 40 male Wistar rats were randomly assigned into four groups. Under general anesthesia, and depending on the assigned group, rats underwent renal ischemia and reperfusion. Parecoxib was injected in two of the groups to evaluate the coxib intluence on the renal function. Parametric data, serum neutrophil gelatinase-associated lipocalin (NGAL), an EBARI, and right and left renal histology were used to evaluate there renal function. Results: the animals of ischemia group which did not receive parecoxib showed the highest NGAL serum level, as well as the most severe tubular injury. The animals on ischemia group which received parecoxib showed NGAL plasmatic levels and tubular injury similar to the groups not subjected to renal ischemia. Conclusion: on this experimental model, parecoxib showed protective renal properties
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48

Calistro, Neto José Pedro. "Interferência do parecoxibe sobre a função renal e lesão de rins submetidos ao estresse isquêmico : trabalho experimental em ratos com uso de NGAL como marcador da função renal /." Botucatu, 2014. http://hdl.handle.net/11449/123691.

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Orientador: Guilherme Antonio Moreira de Barros
Banca: Eliana Marisa Ganen
Banca: Eunice Sizue Hirata
Resumo: Justificativas e objetivos: os anti-inflamatórios não esteroidais (AINEs) têm mostrado sua eficácia na abordagem multimodal da dor, reduzindo o consumo de opioides na dor aguda pós-operatória. Embora os AINEs possam afetar a função renal, existem poucos dados da utilização de AINEs coxibes disponíveis nesse contexto. Os biomarcadores precoces de lesão renal aguda, como o NGAL (neutrophil gelatinase-associated lipocalin), podem ser importantes aliados na determinação de lesão real associada ao uso de AINEs coxibes no período perioperatório. Materiais e métodos: após aprovação pelo Comitê de Ética em Pesquisa Experimental, 40 ratos Wistar foram distribuídos aleatoriamente em quatro grupos. Sob anestesia geral, e dependendo do grupo a qual os animais foram incluídos, eles foram submetidos a isquemia e reperfusão renal. Dois grupos receberam parecoxibe para avaliar a influência deste medicamento na função renal. Dosagem de NGAL e histologia renal bilateral foram realizadas para a avaliação da existência e grau da lesão renal. Resultados: o grupo isquemia (que não recebeu injeção de parecoxibe) apresentou os maiores níveis de NGAL e maior frequência de lesão renal. O grupo que sofreu isquemia e recebeu parecoxibe apresentou níveis de NGAL e frequência de lesão renal similares aos outros grupos que não sofreram tal injúria. Conclusão: neste modelo experimental, parecoxibe exibiu propriedades em promover proteção renal
Abstract: Background and aims: nonsteroidal anti-inflammatory drugs (NSAIDs) have been proved to be effective, in a multidimensional approach, at reducing the opioid consumption during the postoperative acute pain. Although the NSAIDs may affect the renal function, there are few published data related to the use of coxibs and the kidney function. The early biomarkers of acute renal injury (EBARI) may be important tool to determining the actual risk associated with the use of coxibs NSAIDs in the perioperative period. Methods: after approval by Experimental Ethics Committee, 40 male Wistar rats were randomly assigned into four groups. Under general anesthesia, and depending on the assigned group, rats underwent renal ischemia and reperfusion. Parecoxib was injected in two of the groups to evaluate the coxib intluence on the renal function. Parametric data, serum neutrophil gelatinase-associated lipocalin (NGAL), an EBARI, and right and left renal histology were used to evaluate there renal function. Results: the animals of ischemia group which did not receive parecoxib showed the highest NGAL serum level, as well as the most severe tubular injury. The animals on ischemia group which received parecoxib showed NGAL plasmatic levels and tubular injury similar to the groups not subjected to renal ischemia. Conclusion: on this experimental model, parecoxib showed protective renal properties
Mestre
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49

Nicoláo, Ana Lúcia Anauate [UNIFESP]. "Associação entre maturação sexual e limiar de lactato em meninas de 10-15 anos." Universidade Federal de São Paulo (UNIFESP), 2010. http://repositorio.unifesp.br/handle/11600/8988.

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Os limiares de lactato são utilizados para a avaliação da capacidade aeróbia em diferentes idades. Estudos demonstraram que crianças e adolescentes apresentam menores concentrações sanguíneas de lactato ([la]) para mesma carga de esforço do que adultos. Existem evidências de que isto está relacionado ao desenvolvimento maturacional das mesmas. Objetivo: Verificar a associação entre a maturação sexual e o limiar de lactato de atletas de futebol de 12 a 15 anos de idade. Método: A amostra foi do tipo intencional, não probabilística, com um total de 36 meninas, entre 12 e 15 anos, participantes de escolinhas de futebol da prefeitura da cidade de São Paulo. Foram obtidas da amostra a massa corporal, a estatura e a tomada de dobras cutâneas triciptal e subescapular. A maturação sexual foi feita através da observação direta, por uma médica, do desenvolvimento de órgãos genitais e de pilosidade púbica, por meio de planilhas propostas por Tanner. Para determinação do limiar de lactato foi realizado teste progressivo em pista, onde as jovens realizaram três corridas de 800 metros, com a intensidade do esforço sendo controlada por zonas de frequência cardíaca pré-estabelecidas, com mensurações das [la] no final de cada corrida. Através da interpolação linear foi encontrada a velocidade correspondente a [la] de 2,5 mmol.L-1 (V2,5). Para compreender melhor a natureza das associações entre as variáveis foi utilizada a regressão linear múltipla, tendo como variável dependente o limiar de lactato (V2,5) e como variáveis independentes idade (anos), IMC (kg/m2), estatura (cm) e somatório de dobras cutâneas (mm). Resultados: Em mais jovens, pré-púbere, as variáveis de crescimento e a maturação sexual tem pouca associação com o limiar de lactato. Sendo importante uma ponderação sobre a influência da maturação sexual no limiar de lactato. Conclusão: Levando em consideração a homogeneidade do grupo e o fato de a idade entre 12 e 15 anos ser um período de diversas modificações, o desenvolvimento maturacional, e não a idade cronológica, mostrou uma diferença significante nas variáveis analisadas.
The lactate thresholds are used to assess the aerobic capacity in different ages. Studies show that children and adolescents present less lactate blood concentrations [la] than adults under certain effort loads. There are evidences that this is related to their maturational development. Objective: To verify the association between the sexual maturation and the lactate threshold in some adolescent soccer players ranging from 12 to 15 years old. Method: The sample was related to the intentional and not probabilistic type involving 36 girls, from 12 to 15 years old, members of the soccer schools held by the Mayority of São Paulo. The body weight, height and the sum of two skinfolds – calf and triceps were obtained from the sample. A physician directly observed the sexual maturation of the genitals and pubic hair development through the Tanner index. To determine the lactate threshold a progressive test, a 3 x 800 m in running track, was performed by adolescents, their effort intensity was controlled by pre-established heart rate zones and the [la] were measured at the end of each run. The velocity corresponding to [la] of 2,5 mmol.L-1 (V2,5) was obtained through the linear interpolation. The multiple linear regression was used to better understand the nature of these associations between the variables, considering the lactate threshold (V2,5) as a dependent variable and the age (years), the body weight index (kg/m2), height (cm) and the sum of the skinfolds (mm) as independent variables. Result: The growth variables and the sexual maturation have little association with the lactate threshold in the youngest and pre-adolescent girls. It is important to take in consideration the sexual maturation influence on the threshold lactate. Conclusion: Taking in account the group homogeneity and being the range between 12 and 15 years old a period susceptible to many modifications, the maturational development and not the chronological age showed to be responsible for a significant difference in the analyzed variables.
TEDE
BV UNIFESP: Teses e dissertações
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Parent, Véronique. "Rendement en lecture et vitesse du traitement de l'information chez les enfants de 6 à 8 ans." Master's thesis, Université Laval, 2003. http://hdl.handle.net/20.500.11794/62073.

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Abstract:
La présente étude vise à éprouver des mesures de vitesse du traitement de l'information (VTI) en vérifiant leurs relations potentielles avec le rendement en lecture chez des enfants de 6 à 8 ans. Cent cinq enfants participent à l'étude. Les mesures de vitesse sont tirées de trois instruments, soit les Tests de rendement cognitif pour adultes présentant une déficience intellectuelle (TRCA ; Loranger & Pépin, 1997), le test Temps de réaction des Tests de rendement cognitif pour enfants (TRCE ; Loranger & Pépin, 1998) et le Rapid automatized naming test (RAN ; Denckla & Rudel, 1976). Le rendement en lecture est quant à lui évalué par le Test d'habiletés en lecture (THAL ; Pépin & Loranger, 1999) et par le Test phonologique (Melançon, Ziarko & Gagnon, 1996, dans Melançon, 1997). Les résultats des analyses de corrélation canonique indiquent I'existence de relations modérées (.66 et .55) entre les différents regroupements de mesures de vitesse et le rendement en lecture. Les résultats démontrent donc que la VTI entretient des relations significatives avec le rendement en lecture.
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