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1
Spangenberg, Elin. "Housing laboratory dogs and rats : implications of physical and social activity /". Uppsala : Dept. of Clinical Sciences, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/2007103.pdf.
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2
Wickens, Nicolas John. "Histopathological changes in male wistar rats maintained on a water-based sutherlandia frutescens extract". Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/4742.
Testo completoAbstract (sommario):
In this study a standardized 46 week chronic drinking water toxicity protocol was used to elucidate the toxic potential of Sutherlandia frutescens (S. frutescens) using histopathologic, morphometric and transmission electron microscopic analysis. The histopathologic changes in the duodenum, heart, kidney, liver, lung, pancreas and spleen of male Wistar rats were evaluated. Fifty-four rats were randomly divided into four groups: Group 1 – Normal diet control (ND control), n=7, Group 2 – Normal diet + plant extract (ND + p), n=9, Group 3 – High fat diet control (HFD control), n=19Group 4 – High fat diet + p (HFD + p), n=19In the high fat group male Wistar rats were fed ±55 g/day of a specialised high fat diet over a 46 week period to induce obesity and an insulin resistant state. The treatment groups (groups 2 and 4) received a dose concentration of a tea extract of the S. frutescens plant in their drinking water daily. This study showed that the consumption of S. frutescens significantly reduces weight gain in male Wistar rats on a chronic high fat diet (p≤0.001 vs. HFD control group). S. frutescens appears to propagate periportal and centrilobular glycogen storage in rat hepatocytes in the experimental groups as exemplified by a significantly (p≤0.0001 vs. control groups) increased incidences of Periodic Acid Schiff (PAS) positive staining S. frutescens also reduced intracellular lipid accumulation as made evident by the significantly lower incidence of epicardial adipose tissue (EAT), hepatic steatosis and pancreatic interstitial fat. Obesity was associated with increased fibrotic lesions such as myocardial perivascular fibrosis, centrilobular hepatic fibrosis and pancreatic periductal fibrosis. Obesity associated hypertension contributed to the widespread and significant increase in the average lesion severity of arterial congestion in all organs in the HFD control group. Pulmonary infection was equally prevalent in all rats. Despite the complex histopathology in all groups, differences in the control groups, such as, the presence of a conservative polymorphonuclear leukocyte (PMNL) infiltration, substantial intra-alveolar oedema and focal arterial wall hypertrophy in the control groups was highly suggestive of Sendai viral infection. However histopathologic evidence, in the treatment groups, suggested chronic recurrent viral infection with superimposed Mycoplasma pulmonis (M. pulmonis) bacterial infection. The impact of advanced suppurative pulmonary infection was widespread and exemplified by increased lesion incidences of spontaneous murine progressive cardiomyopathy (MCP) and spontaneous chronic progressive nephropathy (CPN) among others. In conclusion S. frutescens administered for 46 weeks to male Wistar rats significantly lowered intracellular lipid accumulation and obesity associated myocardial, renal, hepatobiliary, pulmonary and pancreatic histopathology. Moreover, duodenal, cardiovascular, hepatobiliary, pulmonary, renal, pancreatic and splenic tissue did not show histopathologic evidence of direct plant extract associated toxicity or carcinogenicity.
3
Bueno, Aline [UNESP]. "Repercussões de diferentes intensidades glicêmicas no início do desenvolvimento embrionário de ratas". Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/99239.
Testo completoAbstract (sommario):
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In vitro studies suggest that maternal hyperglycemia insult impairs the early embryogenesis in the preimplantation period. In this paper, we show that streptozotocin given at birth day of life or in adulthood of rats caused hyperglycemic state. Regardless of hyperglycemic intensities (mild or severe diabetes), the embryos of these dams presented development retardation and decreased development competence. Apoptosis was detected using terminal dUTP nick end labeling (TUNEL) assays, and the morulas from mild and severe diabetic rats have a higher incidence of apoptotic cells than control embryos. Tumor necrosis factor-alpha, a cytokine whose synthesis is up-regulated in the diabetic uterus, did not alter the incidence of TUNEL-positive nuclei. The glycemic intensity is related with the increased in the apoptosis indexes in morulas. On the other hand, dams with hyperglycemia, regardless of the glycemic intensity and of the tumor necrosis factor-alpha level presented preimplantation embryos with development retardation and increase of non-viable preimplantation embryos, suggesting that the presence of the hyperglycemia leads to a decreased competence development of preimplantation embryos
4
Xu, Cen Reith Maarten E. A. "Cocaine and the dopamine transporter". Normal, Ill. Illinois State University, 1996. http://wwwlib.umi.com/cr/ilstu/fullcit?p9721400.
Testo completoAbstract (sommario):
Thesis (Ph. D.)--Illinois State University, 1996.Title from title page screen, viewed May 30, 2006. Dissertation Committee: Maarten E. A. Reith (chair), Hou Tak Cheung, John W. Dailey, Robert L. Preston, Brian J. Wilkinson. Includes bibliographical references and abstract. Also available in print.
5
Connolly, Ashley Rex. "Cytokine gene expression in a rat model of polyarthritis /". Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09phc75238.pdf.
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6
Bueno, Aline. "Repercussões de diferentes intensidades glicêmicas no início do desenvolvimento embrionário de ratas /". Botucatu : [s.n.], 2012. http://hdl.handle.net/11449/99239.
Testo completoAbstract (sommario):
Orientador: Débora Cristina DamascenoCoorientador: Yuri Karen Sinzato
Banca: Maria José Sparça Salles
Banca: Felipe Perecin
Resumo: Não disponível
Abstract: In vitro studies suggest that maternal hyperglycemia insult impairs the early embryogenesis in the preimplantation period. In this paper, we show that streptozotocin given at birth day of life or in adulthood of rats caused hyperglycemic state. Regardless of hyperglycemic intensities (mild or severe diabetes), the embryos of these dams presented development retardation and decreased development competence. Apoptosis was detected using terminal dUTP nick end labeling (TUNEL) assays, and the morulas from mild and severe diabetic rats have a higher incidence of apoptotic cells than control embryos. Tumor necrosis factor-alpha, a cytokine whose synthesis is up-regulated in the diabetic uterus, did not alter the incidence of TUNEL-positive nuclei. The glycemic intensity is related with the increased in the apoptosis indexes in morulas. On the other hand, dams with hyperglycemia, regardless of the glycemic intensity and of the tumor necrosis factor-alpha level presented preimplantation embryos with development retardation and increase of non-viable preimplantation embryos, suggesting that the presence of the hyperglycemia leads to a decreased competence development of preimplantation embryos
Mestre
7
Vetter, Courtney Suzanne. "Time-course of elevated ethanol intake in adolescent relative to adult rats under continuous, voluntary-access conditions". Diss., Online access via UMI:, 2006.
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8
Hu, Dan. "Brain cytochrome oxidase activity related to vicaroius trial-and-error behavior during Y-maze learning in the rat /". Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
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9
Kong, Hei-man Lowell, e 江希文. "Adrenomedullin: distribution in the male accessory sex glands of the rat and the effects of adrenomedullin inthe seminal fluid on the female reproductive tract". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45605671.
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10
Agnelli, Silvia. "Regulation of amino acid catabolism in rats fed diets with different protein content". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/400005.
Testo completoAbstract (sommario):
Current lifestyle with high-energy diets and characterized by sedentary is triggering an alarming growth in obesity. Obesity along with metabolic syndrome- related co-morbidities (i.e. insulin resistance, atherosclerosis, sleep apnea, depression, asthma, hypertension and the alteration of blood lipid transport) are the most apparent consequence of the excess energy. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively-adapted schemes that prevent its wastage; thus ammonia and glutamine formation and urea excretion are decreased. High lipid and energy availability limit the utilization of glucose, and high glucose spares the production of ammonium from amino acids, decreasing the synthesis of glutamine and its utilization by the intestine and kidney. In contrast, high protein diets enhance protein synthesis and growth, and the synthesis of non-protein-N-containing compounds. But these outlets are not enough; consequently, less- conventional mechanisms are activated, such as increased synthesis of NO∙ followed by higher nitrite (and nitrate) excretion and changes in the microbiota.
In this study we studied how the initial phase of development of metabolic syndrome can affects the function of liver as main site of amino-N metabolism, and to determine whether doubling the protein content in the diet induced significant changes in enzyme of amino acids metabolism along intestine and on liver.
The common result obtained by these studies is that, both in case of hyperlipidic or hyperproteic diets, elimination of excess N is necessary but cannot be easily carried out through the metabolic pathways/tissues we evaluated, although possible alternative pathways have been taken into consideration.L’estil de vida actual amb les dietes d'alt contingut energètic, i caracteritzat pel sedentarisme, està provocant un creixement alarmant de l'obesitat. L'obesitat, juntament amb les comorbiditats relacionades amb la síndrome metabòlica (és a dir, resistència a la insulina, aterosclerosi, apnea del son, depressió, asma, la hipertensió i l'alteració del transport de lípids en la sang) són la conseqüència més evident de l'excés d’energia. En condicions d'excés d'energia de la dieta, el cos no pot eliminar ràpidament l'excés d'amino-N contra els esquemes adaptats evolutivament i que impedeixin el seu deteriorament; així, la formació d'amoníac i de glutamina i l'excreció d'urea disminueixen. Els elevats nivells de lípids i de la disponibilitat d'energia limiten la utilització de la glucosa, i nivells elevats de glucosa estalvia la producció d'amoni a partir dels aminoàcids, disminuint la síntesi de glutamina i la seva utilització per l'intestí i el ronyó. En contrast, les dietes d’elevat contingut en proteïnes incrementen la síntesi de proteïnes i el creixement, i la síntesi de compostos que contenen N i no són proteïnes. Però aquests mecanismes no són suficients i en conseqüència, s'activen mecanismes menys convencionals, com ara augment de la síntesi de NO ∙ seguides per l’augment del nitrit (i nitrat) i la seva excreció, juntament amb canvis en la microbiota. En aquest treball es va estudiar com la fase inicial de desenvolupament de la síndrome metabòlica pot afectar la funció del fetge com lloc principal del metabolisme d'amino-N, i per determinar si la duplicació del contingut de proteïnes en la dieta induïa canvis significatius en els enzims del metabolisme d'aminoàcids al llarg intestí i al fetge. El resultat genèric obtingut per aquests estudis és que, tant en el cas de que la dieta sigui hiperlipídica o hiperproteica, l'eliminació de l'excés de N és necessària, però no es pot dur a terme fàcilment a través de les vies metabòliques / teixits que avaluem, tot i les possibles vies alternatives s'han tingut en consideració.
11
Dallison, Agnes, e University of Lethbridge Faculty of Arts and Science. "Mechanisms underlying recovery from early cortical injury in rats". Thesis, Lethbridge, Alta. : University of Lethbridge, Faculty of Arts and Science, 1999, 1999. http://hdl.handle.net/10133/98.
Testo completoAbstract (sommario):
Previous work has shown that removal of the midline frontal cortex at seven to ten days of age is followed by recovery of function correlated with apparent spontaneous generation of new tissue in the lesion cavity.
The question asked in the present thesis was whether the removal of the regrown tissue in adulthood would block normal function. Rats that received P10 frontal lesions underwent second lesions at P160, and were compared to rats with only P10 or P160 lesions. Rats with P10 + P160 lesions were severely impaired on a spatial learning task, especially relative to the P10 lesion-only rats. In a second experiment, rats with P10 + P160 lesions were given intra-ventricular infusions of a cocktail of three growth factors. The animals with growth factors showed marked behavioral recovery, although there was no cell regeneration. The results of these experiments suggest that filled-in tissue in neonatally lesioned rats is functional.viii, 74 leaves : col. ill. ; 28 cm.
12
Chung, Yee-ling Elaine. "A study on the effects of Angelica Sinensis on gastric ulcer healing in rats". Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23295120.
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13
DeClue, Amy E. "Ketamine immunomodulation during endotoxemia". Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/6276.
Testo completoAbstract (sommario):
Thesis (M.S.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "August 2007" Includes bibliographical references.
14
Brunell, Steven Craig. "Pharmacotheraphies for the treatment of alcoholism in adolescents using a rodent model". Diss., Online access via UMI:, 2006.
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15
Gao, Jing, e 高晶. "Effect of acupuncture on the spermatogenesis of heat-treated rodent testis". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41291001.
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16
Gao, Jing. "Effect of acupuncture on the spermatogenesis of heat-treated rodent testis". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41291001.
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17
Bonaventura, Leeann R. "Ontogeny of circadian and diurnal rhythms effects of light pulses on ultrasonic vocalizations, locomotor activity and Fos/pCREB expression in the suprachiasmatic nucleus and intergeniculate leaflet of the neonatal rat /". Diss., Online access via UMI:, 2006.
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18
Humm, Jennifer Leigh. "Behavior-dependent neural events and adult neurogenesis : contributions to recovery of motor function after cortical injury /". Digital version accessible at:, 2000. http://wwwlib.umi.com/cr/utexas/main.
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Volz, Kathryn Ann. "FATIGUE-RELATED CHARACTERISTICS OF THE SOLEUS AND EXTENSOR DIGITORUM LONGUS MUSCLES IN SMALL AND LARGE CAGE-REARED FEMALE RATS". Thesis, The University of Arizona, 1985. http://hdl.handle.net/10150/275378.
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20
Chan, Ying-leung. "Effect of topical green tea on subcutaneous adipocytes in rats". Click to view the E-thesis via HKUTO, 2003. http://sunzi.lib.hku.hk/hkuto/record/B31971519.
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21
Yang, Fu-Chen. "Anatomical and behavioral analysis of SCN lesion and transplantation in neonatal rats". Diss., Online access via UMI:, 2005.
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22
Barnum, Christopher John. "Repeated exposure to restraint but not social defeat leads to habituation of the pituitary-adrenal and stress-herthermic responses". Diss., Online access via UMI:, 2006.
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23
Gao, Jing, e 高晶. "Roles of VAD1.3 in spermatogenesis and fertilization". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B4852170X.
Testo completoAbstract (sommario):
Vad1.3 is an evolutionarily-conserved, testis-specific gene identified from a retinol-treated Vitamin A-deficiency (VAD) rat model. VAD1.3 is expressed throughout spermiogenesis at the acrosome of spermatids and epididymal spermatozoa, suggesting a role in acrosome biogenesis or acrosome reaction. The present study aimed to explore the functional role of VAD1.3 in spermatogenesis and sperm functions by the cellular and gene-knockout approaches.
Double immunofluorescent microscopy confirmed the co-localization of VAD1.3 and syntaxin 1 in mouse spermatids and spermatozoa. Deletion analysis of the Vad1.3 gene in transfected mouse spermatocyte GC2-spd and human cervical cancer HeLa cells revealed a polarized peri-nuclear/Golgi expression pattern for the N-terminal GFP-VAD fusion proteins which contain a bipartite nucleus localization (BNL) motif, but a nuclear expression pattern for the C-terminal GFP-VAD. The N-terminal sequences of VAD1.3 mediated its interaction with syntaxin 1, as demonstrated by both co-localization and co-immunoprecipitation studies. The full-length GFP-VAD co-localized with the Golgi markers and was redistributed into the endoplasmic reticulum after brefeldin A treatment, suggesting that VAD1.3 was recruited through the ER-Golgi-acrosome pathway.
Vad1.3+/- mice was previously generated by the conventional knockout approach. The heterozygous mice had normal spermatogenesis during postnatal days and adulthood (6-8 weeks). At the age of 8-19 months, 6 out of 17 heterozygous mice but no wild-type exhibited a decrease in the epididymal sperm count and testicular weight (p < 0.05). Histological analyses unveiled disarrangement of the seminiferous epithelium and sloughing of germ cells, predominantly spermatids, which was mediated partially by apoptosis as a higher percentage of TUNEL-positive cells were detected in these heterozygous mice (p < 0.05). This phenotype was associated with a decrease in the mRNA (p < 0.05) and protein levels of VAD1.3 in the testis.
Crossing of the Vad1.3+/- mice produced wild-type and heterozygous offspring in a ratio of 1:3, but no Vad1.3-/- mice were found. There was no significant difference between the heterozygous intercrosses and the wild-type intercrosses in the number of oocytes ovulated, the developmental rate of embryos from zygotes to blastocysts, the number of implantation site, resorption site or the offspring could result from defective fertilization between Vad1.3 null gametes rather than developmental lethality. The role of VAD1.3 in fertilization was supported by the inhibitory effects of the anti-VAD1.3 antibody on in vitro fertilization and progesterone-induced acrosome reaction. Immuno-staining revealed that VAD1.3 was present in the acrosome-intact spermatozoa but not in acrosome-reacted spermatozoa, indicating a role of VAD1.3 in ZP-binding or acrosome reaction rather than sperm-egg fusion. In oocytes VAD1.3 was distributed in the cytoplasm near the cortex. litter size. Only a few Vad1.3-/- embryos were found at the zygotic (3.7%) and 2-cell (3%) stages in the heterozygous intercrosses. These findings suggested that the absence of the Vad1.3-/-
In sum, VAD1.3 may play important roles in fertilization and spermatogenesis in mice. The BNL motif of VAD1.3 directs its Golgi expression and the N-terminal sequence of the protein mediates its interaction with syntaxin 1. The use of tissue-specific knockout approach may help to answer the functional role of VAD1.3 in future.published_or_final_version
Obstetrics and Gynaecology
Doctoral
Doctor of Philosophy
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Stoodley, Marcus A. "Pathophysiology of Syringomyelia /". Title page, contents and abstract only, 1996. http://web4.library.adelaide.edu.au/theses/09PH/09phs882.pdf.
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Estruel, Amades Seila. "Efectes immunomoduladors de l’exercici físic intens i extenuant i de l’hesperidina en rates". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667434.
Testo completoAbstract (sommario):
En els darrers anys, la influència de l’exercici físic intens i extenuant ha guanyat molt d’interès, per una banda, pels efectes perjudicials que pot causar tant al sistema immunitari innat com a l’adaptatiu, i per altra banda per l’increment de les persones que participen en competicions esportives d’alt nivell. Tanmateix, s’ha demostrat que una dieta que conté components bioactius, com els polifenols, poden tenir un paper clau en la prevenció o en el retard d’aparició d’aquests efectes negatius.
En aquest sentit, l’objectiu principal de la tesi va ser determinar la influència de l’exercici físic intens i extenuant i del polifenol hesperidina sobre el sistema immunitari de la rata.
Per tal d’assolir el primer propòsit, es van utilitzar rates Wistar de quatre setmanes d’edat. Els animals van realitzar un entrenament curt (de dues setmanes, que va incloure dues sessions d’entrenament al dia i una prova d’extenuació final) o un entrenament llarg (de cinc setmanes, que va incloure dues proves d’extenuació a la setmana i tres entrenaments regulars la resta de setmana, i a més a més, una prova d’extenuació final). Es va determinar diferents variables del sistema immunitari innat i adaptatiu abans, immediatament després i a les 24 h de la prova d’extenuació final.
Pel que fa als resultats, els monòcits sanguinis obtinguts després de l’entrenament de cinc setmanes van mostrar una menor capacitat fagocítica i va disminuir la secreció de citocines proinflamatòries per part dels macròfags peritoneals. Aquests canvis van desaparèixer després de l’extenuació final. A més a més, l’entrenament llarg va reduir la proporció de cèl·lules NK esplèniques, però en va incrementar la seva activitat citotòxica. Pel que fa al sistema immunitari adaptatiu, l’entrenament de cinc setmanes va induir la disminució de la capacitat proliferativa dels limfòcits T i la secreció de l’interferó . Tanmateix, l’entrenament llarg, però no l’extenuació final, va incrementar la capacitat de síntesi de la immunoglobulina G esplènica.
Per tal d’aconseguir la segona part de l’objectiu, rates Lewis de tres setmanes d’edat van rebre hesperidina per via oral a dues dosis diferents (100 o 200 mg/kg) tres vegades a la setmana durant quatre setmanes. Els resultats van mostrar que l’administració de 200 mg/kg d’hesperidina incrementava el nombre total de bactèries cecals, principalment per l’increment del grup Lactobacillus. A més, l’hesperidina també va incrementar el nombre de bacteris units a IgA en el contingut cecal i el contingut d’IgA intestinal.
Finalment, es va avaluar l’impacte de l’hesperidina sobre l’estrès oxidatiu derivat de l’entrenament llarg. En aquest cas, els animals entrenats van rebre hesperidina per via oral a una dosi de 200 mg/kg tres dies a la setmana durant cinc setmanes. L’hesperidina va millorar el rendiment esportiu dels animals i va evitar l’increment de les espècies reactives d’oxigen produïdes per la prova d’extenuació final. A més, va evitar la disminució de l’activitat dels enzims superòxid dismutasa i catalasa en el timus i en la melsa derivades de la prova d’extenuació final.
En resum, l’entrenament de cinc setmanes aplicat en rates va induir alteracions en el sistema immunitari innat i adaptatiu. A més, l’hesperidina va ser capaç d’evitar l’estrès oxidatiu induït per l’exercici, alhora que va millorar el rendiment esportiu dels animals.The influence of intensive and exhausting exercise on the innate and adaptive immune system is gaining attention due to the described harmful effects on the functionality of the immune system and the high number of people participating in intense sport competitions. Nevertheless, diet containing bioactive compounds such as polyphenols can play a key role in preventing these effects. Based on these factors, the aim of this thesis was to study in depth the influence of both the intensive and exhausting exercise and the polyphenol hesperidin on the rat immune system. For this, rats were intensively trained in a short (two weeks, which included two daily trainings plus a final exhaustion test) or a longer (five weeks, which included two exhaustion tests and three regular trainings per week plus a final exhaustion test) exercise training. Results show that blood monocytes collected after the longer training exhibited a lower phagocytic activity and the ability of peritoneal macrophages to secrete pro-inflammatory cytokines decreased. In addition, the longer training reduced the spleen NK cell proportion but increased their cytotoxic activity. Moreover, the longer training decreased T-cell proliferation and interferon secretion, although it was an increase in immunoglobulin G synthesis. On the other hand, rats orally administrated with 200 mg/kg hesperidin three times/week for four weeks showed an increased caecal total bacteria number, mainly due to an increase in the Lactobacillus group. Hesperidin also enhanced the number of caecal IgA-coated bacteria and the amount of intestinal IgA. Finally, rats trained for five weeks were similarly treated with 200 mg/kg of hesperidin. The flavanone improved exercise performance, prevented the increase in reactive oxygen species induced by the final exhaustion test and inhibited the decrease in superoxide dismutase and catalase activities in the thymus and spleen derived from the final exhaustion test. In conclusion, the applied longer exercise training in rats induced alterations in the innate and acquired immune system. Moreover, hesperidin was able to prevent oxidative stress, while improving exercise performance.
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Escoda, Francolí Jaume. "Efecto de la matriz de beta-fosfato tricálcico con fibronectina en la reparación de defectos óseos críticos: estudio experimental del potencial de regeneración ósea y su aplicabilidad clínica". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/667962.
Testo completoAbstract (sommario):
Estudio experimental, prospectivo y controlado en el que se incluyeron 30 ratas Sprague-Dawley, machos adultos, ex-reproductivos, de 14 semanas de edad y peso entre 250 y 300 g. Los animales se distribuyeron de forma aleatoria a los grupos de estudio mediante una tabla de aleatorización y se recogieron datos en situación basal y a las 6 y 8 semanas de la colocación de los injertos. Se utilizó un defecto de tamaño crítico en la calota craneal de la rata, ya que se trata de un modelo estándar, ventajoso desde el punto de vista económico y adecuado para evaluar la formación ósea en defectos óseos craneales. Las trepanaciones craneales de 5 mms de diámetro se efectuaron en cada lado del cráneo y se les injertaba según la tabla de aleatorización β-FTC con o sin Fn en un lado y nada en el lado contralateral (control); siempre junto a una membrana de colágeno de bovino nativo para evitar el colapso del espacio por el rápido crecimiento del tejido blando. Todos los animales recibieron fluorocromos de oxitetraciclina una semana más tarde, además de 1 dosis de 10 mg/kg de calceina 1 día antes de la eutanasia ambas por via subcutánea, con el fin de estudiar las muestras mediante microscopia de fluorescencia. Los animales fueron sacrificados por exposición a CO2 a las 6 y 8 semanas tras la intervención quirúrgica en función del grupo al que fueron asignados aleatoriamente.
Se evaluó histomorfométricamente a las 6 y 8 semanas con microscopio óptico, cámara digital, lápiz óptico y análisis de la imagen por medición digitalizada con dos programas informáticos de su potencial regenerativo óseo en el área aumentada. Los análisis se efectuaron con el paquete estadístico R v3.12 (Development Core Team 2008). Se estableció un nivel de significación estadística de P < 0,05.
En los resultados destacamos que el tejido ganado (TG) en el área diana era significativamente mayor en los dos grupos de tratamiento que en los controles. No se observaron diferencias estadísticamente significativas entre ambos grupos de tratamiento activo, excepto en el tejido ganado global a las 8 semanas. En la comparación en mm2 entre los grupos β-FTC-Fn y β-FTC a las 8 semanas se observa una diferencia estadísticamente significativa a favor del grupo β-FTC-Fn.
En el grupo de β-FTC-Fn, el porcentaje de TG, definido como la suma de matriz de hueso mineralitzada (MHM) y sustituto óseo (SO), mostraba un aumento significativo en el área diana a lo largo del estudio, en tanto que en el grupo de β-TCP sin Fn parecía estabilizarse a las 6 semanas, sin que se detectara ningún aumento significativo posterior.
Los cambios en la regeneración ósea según los biomateriales utilizados para el relleno de los defectos y el tiempo de exposición, también indican un efecto más favorable para la matriz con Fn, ya que el porcentaje de MHM en el área diana continuaba aumentando de la semana 6 a la semana 8 hasta doblar su cifra mientras que la matriz sin fibronectina mantenía prácticamente el mismo valor.
El uso de β-FTC recubierto con Fn mostró un efecto no significativo y levemente más efectivo que el ß-FTC sin Fn respecto al incremento del volumen de hueso regenerado en los defectos de tamaño crítico de calota de rata como modelo experimental, posiblemente permitiendo un proceso más eficiente de remodelado (mayor ganancia de tejido y mayor mineralización del tejido ganado a igualdad de tiempo).
No se encontraron diferencias claras entre β-FTC y β-FTC-Fn. Se necesitan estudios adicionales en que se extienda el período de seguimiento a más de 8 semanas o en períodos más cortos de 6 semanas para evaluar la capacidad osteogénica de β-FTC-Fn en la reconstrucción de defectos de calota de rata de tamaño crítico, así como estudiar la razón de crecimiento óseo de los defectos tratados mediante microscopio de fluorescencia.OBJECTIVE: This histomorphometric study compared bone regeneration potential of beta-tricalcium phosphate with fibronectin (β-TCP-Fn) in critical-sized calvarial defects (CSDs) in rats to assess whether fibronectin (Fn) improved new bone formation. MATERIAL AND METHODS: CSDs were created in 30 adult male Sprague Dawley rats, which were divided into four groups according to the time of euthanasia (6 or 8 weeks [wks] of healing) and type of filling (β-TCP-Fn/6 wks, β-TCP/6 wks, β-TCP-Fn/8 wks, β-TCP/8 wks). The primary variables related to new bone formation were augmented area (AA) and gained tissue (GT) (sum of mineralized bone matrix [MBM] and bone substitute [BS]). Secondary variables were the diameter of the defect, MBM, non-mineralized tissue (NMT), and BS. RESULTS: A total of 29 rats and 58 histological samples were evaluated, 28 (48.3%) samples obtained at 6 wks and 30 (51.7%) at 8 wks, homogeneously distributed between right and left sides. Thirteen (22.4%) were treated with β-TCP-Fn, 16 (27.6%) with β-TCP and 29 (50%) were controls. At 8 wks, histomorphometric analysis showed significant differences in AA using β-TCP and β-TCP-Fn vs controls (P = 0.001 and P = 0.005, respectively). Bone turnover expressed as % within the target area was slightly higher but not statistically significant in the β-TCP-Fn than in β-TCP (MBM) at 6 wks vs 8 wks (P = 0.067 and P = 0.335, respectively). Finally, total GT area in mm2 was higher using β-TCP-Fn as compared to β-TCP (P = 0.044). CONCLUSIONS: β-TCP-Fn was slightly but non-significantly more effective than β-TCP without Fn for improving the volume of regenerated bone in CSDs of rats, possibly allowing a more efficient bone remodeling process. This effect however should continue being investigated.
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Al-Kushi, Abdullah Glil. "Pathological changes in mesostriatal neurons in a PKC-gamma mutant rat". Connect to e-thesis, 2007. http://theses.gla.ac.uk/149/.
Testo completoAbstract (sommario):
Thesis (Ph.D.) - University of Glasgow, 2007.Ph.D. thesis submitted to the Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, University of Glasgow, 2007. Includes bibliographical references.
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Fitch, Thomas E. (Thomas Edward) Carleton University Dissertation Psychology. "The periodicity of chronic cocaine self-administration". Ottawa, 1992.
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Li, Zhuoming, e 李卓明. "Heme oxygenase-1 and endothelial dysfunction in the spontaneously hypertensive rat". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48521735.
Testo completoAbstract (sommario):
The endothelium is important for the regulation of vascular tone. In diseases like hypertension, the endothelial cells become dysfunctional. This dysfunction is characterized by nitric oxide (NO) deficiency, impairment of endothelium-dependent hyperpolarization (EDH) and the overwhelming production of endothelium-derived contracting factor (EDCF). Heme oxygenase (HO) is the rate-limiting enzyme in the catabolism of heme, producing carbon monoxide(CO), bilirubin and free iron. Up-regulation of the inducible isoform (HO-1) of the enzyme lowers blood pressure in animals. The purpose of the present study was to investigate whether or not up-regulation of HO-1by the pharmacological agent hemin improves endothelial function in arteries of spontaneously hypertensive rats(SHR).
Twenty four hours after intraperitoneal injection of hemin (50mg/kg) in 36 weeks old SHR, the expression and activity of HO-1 were augmented, in both the endothelium and vascular smooth muscle. Hemin-treatment potentiated endothelium-dependent relaxations to the muscarinic agonist acetylcholine in both the aorta and the mesenteric artery, whereas the HO inhibitor protoporphyrin IX zinc (II) (ZnPP; 30 mg/kg) prevented the beneficial effect of hemin, suggesting that HO-1 induction improves endothelial function.
Hemin-treatment did not augment acetylcholine-induced NO-mediated relaxations, and did not alter the expression level of either phosphorylated eNOS (Ser1177) or total eNOS, suggesting that the improvement of endothelial function by HO-1 induction cannot be attributed to an increased bioavailability of NO.
In the mesenteric arteries, hemin treatment potentiated acetylcholine-evoked EDH-mediated relaxations in the presence of L-NAME and indomethacin. The IKCa channel blocker TRAM-34andthe Na+-K+-ATPase blocker ouabain significantly impaired these hemin-potentiated relaxations. NS309-induced TRAM-34-and ouabain-sensitive relaxations were enhanced by hemin-treatment. K+-induced ouabain-sensitive relaxations and the expression of Na+-K+-ATPase were increased by hemin-treatment. Taken in conjunction, these observations imply that the improved EDH-mediated relaxations by HO-1 induction is due to an improvement of IKCa-Na+-K+-ATPase pathway. Treatment with an antioxidant apocynin (50mg/kg) showed a similar effect as hemin, and the combined treatment with hemin and apocynin did not cause a greater improvement. In vitro treatment with bilirubin, enhanced EDH responses and K+-induced ouabain-sensitive relaxations. These observations suggest that the effect of HO-1 induction on EDH-mediated relaxations is possibly due to its antioxidant properties and the production of bilirubin.
In the aortae, hemin-treatment reduced endothelium-dependent contractions in response to acetylcholineor to a calcium ionophoreA23187. Production of reactive oxygen species (ROS) was suppressed by hemin-treatment, judging from the results of 2’,7’-dichlorodihydrofluoresein diacetate staining, dihydroethidium staining and lucigenin chemiluminescence, which was attributed to the decreased expressions of NADPH oxidase-2 (Nox2) and cyclooxygenase-1(COX-1). The production of prostacyclin was decreased, which was explained by a lower expression of COX-1. Contractions to vasoconstrictor concentrations of prostacyclin and its mimetic iloprost were attenuated, suggesting that the responsiveness of thromboxane-prostanoid receptors (TP receptors) to prostacyclin was decreased by hemin-treatment. The effects of HO-1 on the suppressed production of ROS and prostacyclin, and the decreased responsiveness of TP receptors, contribute to its inhibitory role on EDCF-mediated response.
Thus, up-regulation of HO-1 improves endothelial function in the SHR by potentiating EDH response and impairing EDCF.published_or_final_version
Pharmacology and Pharmacy
Doctoral
Doctor of Philosophy
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Gamieldien, Kareemah. "The influence of maternal nicotine exposure on selected glycolytic and cytochrome P450 enzymes in developing neonatal rat lung". Thesis, University of the Western Cape, 2005. http://etd.uwc.ac.za/index.php?module=etd&.
Testo completoAbstract (sommario):
The structural and functional integrity of a developing and maturing fetal and neonatal lung is critically dependent on carbohydrate metabolism. The energy derived from carbohydrate metabolism is utilized during the processed of cell growth and development. It is reported that maternal nicotine exposure during pregnancy and lactation results in the irreversible inhibition of glycolysis, for which no mechanism is currently proposed and a significant increase in glucose turnover. The principal objective of this thesis was to determine the influence of maternal nicotine exposure during gestation and lactation on the isoenzyme patterns and transcript levels of the selected enzymes in developing neonatal rat lung, in an attempt to elucidate the mechanism of inhibition of glycolysis observed.
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Malago, Rodolfo. "Autotransplante experimental de baço". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311399.
Testo completoAbstract (sommario):
Orientadores: Nelson Adami Andreollo, Norair Salviano dos ReisDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-11T12:24:09Z (GMT). No. of bitstreams: 1 Malago_Rodolfo_M.pdf: 3465635 bytes, checksum: 3dc7b9920d1c43468cd3be71172c3771 (MD5) Previous issue date: 2008
Resumo: O baço é um órgão linfóide que tem importante papel na defesa dos organismos, participando no processo de filtração, fagocitose e produção de imunoglobulinas. Histologicamente é formado pelo estroma e o parênquima, sendo seu arranjo celular diferenciado em polpas branca e vermelha. Os principais tipos celulares na estrutura esplênica são: linfócitos T e B, macrófagos, plasmócitos, fibrócitos, reticulócitos e células dendríticas. Os doentes vítimas de traumatismos esplênicos e esplenectomizados assumem um estado de asplenia e consequentemente adquirem grande susceptibilidade à sepse a qual pode ser rapidamente progressiva e fatal. Assim, têm surgido opções terapêuticas após as esplenectomias, utilizando técnicas cirúrgicas conservadoras (tratamento conservador, esplenectomia parcial e esplenorrafias com ou sem aplicação de agentes hemostáticos) e por fim as técnicas de autotransplante esplênico. Os objetivos desta pesquisa experimental foram analisar macro e microscopicamente a evolução tardia do autotransplante de fragmentos de baço na cavidade peritoneal, epíplon e mesentério, após 24 semanas de observação. Foram utilizados 52 ratos Wistar, machos e adultos, submetidos a esplenectomia total e divididos em quatro grupos. O grupo I (controle) foi formado por oito animais escolhidos aleatoriamente entre os três grupos estudados. O grupo II por dezessete animais com implante de fragmento de baço solto na cavidade peritoneal; grupo III por dezoito animais com implante no epíplon e o grupo IV por dezessete animais com implante fixado na raiz do mesentério. Na avaliação histológica foram adotados critérios qualitativos e quantitativos, com a contagem de elementos celulares e não celulares. Os resultados mostraram que se formaram aderências aos tecidos adjacentes e neovascularização em todos os fragmentos transplantados. O grupo II apresentou polpa branca e vascularização preservadas. No grupo III foram observados polpa branca com formações folicular e bainha linfóide, e a polpa vermelha em aspecto cordonal apesar de hemorrágica. No grupo IV foram observados alguns cortes histológicos com depleção de polpa branca e vermelha, enquanto outros evidenciavam melhor preservação das polpas. A contagem de linfócitos revelou diferença significativa entre os grupos I e II e o grupo I e IV (p<0,05). A contagem de macrófagos ativos revelou diferença significativa entre os grupos III e IV (p<0,05) e similaridade entre I e III (p>0,05). Os outros elementos: macrófagos ativos fagocitando hemossiderina, plasmócitos, fibroblastos, fibrócitos, células gigantes, monócitos, espaços intersticiais e fibras de colágeno, não apresentaram diferença significativa entre os grupos. O autotransplante esplênico é factível, sendo o grande epíplon o melhor local para a sua fixação. Esta pesquisa demonstrou por meio de análise histológica qualitativa e quantitativa que o tecido esplênico autotransplantado no epíplon preserva sua função de defesa dos organismos
Abstract: The spleen is a lymphoid organ that plays important part in the organism defense, participating in filtration processes, phagocytosis and immunoglobulin production. Histologically, is formed by a stroma and the parenquima being its cellular arrangement differentiated in white and red pulps. The main cellular types in the splenic structure are: T and B lymphocytes, macrophages, plasmocytes, fibrocytes, reticulocytes and dendritic cells. The patients victims of spleen traumatisms and splenectomized assume an asplenia state and consequently they acquire a larger susceptibility to the sepses, which can be quickly progressive and fatal. Thus, it has appeared therapeutic options after the splenectomies, using techniques of conservative surgery (conservative treatment, partial splenectomies and splenorrhaphies with or without application of haemostatics agents), as well as techniques of splenic autotransplantation. The objectives of the research were to evaluate macro and microscopically the late evolution of the fragments of spleen autotransplanted in the greater omentum, mesenterium and peritoneal cavity, after 24 weeks of observation. To perform the experimental study, were employed fifty two Wistar rats, males and adults, submitted to total splenectomy and divided in four groups. The group (control) I was formed by eight animals chosen aleatorily among the three groups studied. The group II - seventeen animals with implant of spleen fragment in the peritoneal cavity; group III - eighteen animals with implant in the omentum and group IV - seventeen animals with implant fixed in mesenterium root. In the histological analysis were adopted qualitative and quantitative criteria, with the counting of no cellular e cellular elements. The results showed adherences to the adjacent tissues and vascularization in all of the fragments transplanted. The group II presented white pulp and preserved vascularization. The group III showed white pulp with follicular formations and lymphoid tissue preserved, and the red pulp in cordon aspect and hemorrhagic. The group IV presented depletion of white and red pulp, while others evidenced better preservation of the pulps. The counting of lymphocytes revealed significant difference between the groups I and II and the group I and IV (p < 0.05). The counting of active macrophages revealed significant difference between the groups III and IV (p < 0.05) and similarity between I and III (p > 0.05). The other elements: active macrophages phagocyting hemosiderine, plasmocytes, fibroblasts, fibrocytes, giant cells, monocytes, interstitial spaces and fibers of collagen, did not show significant difference among the groups. The splenic autransplantation is feasible, being the better place the greater omentum. This research demonstrated through qualitative and quantitative histological analysis that the splenic tissue autotransplanted in the omentum of Wistar rats preserves its function of defense of the organisms
Mestrado
Pesquisa Experimental
Mestre em Cirurgia
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Dodridge, M. E. "The effects of variable dose methotrexate infusion in the laboratory rat /". Title page, contents and precis only, 1987. http://web4.library.adelaide.edu.au/theses/09DM/09dmd641.pdf.
Testo completo
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李蕾 e Lei Li. "Adrenomedullin in female reproductive system: gene expression and actions in cycling and pregnant rats". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44891799.
Testo completo
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Gwayi, Noluzuko. "The effects of melatonin on the testis, epididymis and sperm physiology of the Wistar rat". Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1005366.
Testo completoAbstract (sommario):
Melatonin is a product of the pineal gland and is postulated to play an antigonadotropic role in the reproductive system of mammals. The reproductive system of non-seasonally breeding mammals is believed to be not as responsive to melatonin treatment as that of seasonally breeding mammals. Recently, there has been increasing support from in vivo and in vitro studies, for the hypothesis that melatonin has negative effects on sperm physiology, especially on sperm motility. High and/or low seminal concentrations of melatonin have been associated with abnormalities in human sperm motility and concentration. In this study, I examined the effects of melatonin on the testis, epididymis and sperm physiology, using in vivo and in vitro experiments, in a non-seasonally breeding mammal. Treatment, in vivo, with exogenous melatonin for six weeks did not inhibit testosterone production or spermatogenesis, nor did it affect the mass of the testes and epididymides at dissection, the concentration the morphology of speimatozoa. However, melatonin in vivo had a small, but significant negative effect on sperm motility and sperm motility index. In vitro incubation of spermatozoa Fith melatonin reduced the percentage (%) of forward progressive movement (fpm), increased the % reduction in fpm, reduced the vigor or quality of sperm motility, reduced the sperm motility index, and delayed and/or prolonged the transition of one pattern of sperm motility to the subsequent patterns. Melatonin increased the pH of the culture medium, and the increased pH, and the ethanol utilized as a solvent for melatonin, both negatively affected all the sperm motility parameters that were assessed in my study. The effects of ethanol increased with time, and the effects of pH increased with both time and increasing pH. Melatonin in vitro did not inhibit capacitation and the acrosome reaction, but it delayed the onset and the progression of capacitation and the acrosome reaction. These results suggest that while melatonin did not inhibit spermatogenesis in the Wistar rat, it may influence sperm motility. Therefore, the presence of high concentrations of melatonin in the reproductive fluids may inhibit sperm motility. With further detailed research, melatonin may have a potential use as a contraceptive drug.
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Ng, Kwok-chai Kelvin, e 吳國際. "Local and systemic effects of hepatic radiofrequency ablation in animal models". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B29434920.
Testo completo
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Xiong, Hui, e 熊暉. "Condylar adaptation to active mandibular forward positioning in non-growing rats". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31374220.
Testo completo
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Piette, Etienne. "Scanning electron microscopic studies of the rat mandibular joint : angioarchitecture and surface morphology /". Thesis, Click to view the E-thesis via HKUTO, 1993. http://sunzi.lib.hku.hk/HKUTO/record/B38627978.
Testo completo
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Lai, Ka-wai, e 黎嘉慧. "An in vitro study of ovarian folliculogenesis in galactosemic rats". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B3015134X.
Testo completo
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Lacosta, Susan Carleton University Dissertation Psychology. "The effects of MDL 72222, Ketanserin and Methysergide pretreatments on cocaine self-administration in rats". Ottawa, 1992.
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40
Lee, Chun-kei, e 李鎮基. "Development of an in vivo animal model for testing of endodontic medicaments on pulp tissue". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31954182.
Testo completo
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Lee, Chun-kei. "Development of an in vivo animal model for testing of endodontic medicaments on pulp tissue". Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23300462.
Testo completo
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Jornada, Daniela Hartmann. "Efeito da associação da taurina e do 5-fluorouracil em câncer de cólon induzido por DMH. Planejamento e síntese de pró-fármacos derivados /". Araraquara, 2018. http://hdl.handle.net/11449/157230.
Testo completoAbstract (sommario):
Orientador: Man Chin ChungCoorientador: Cleverton Roberto de Andrade
Banca: Luiz Fernando Takase
Banca: Cíntia Duarte de Freitas Milagre
Banca: Renato Farina Menegon
Banca: Jean Leandro dos Santos
Resumo: O câncer colorretal (CCR) é um dos 10 tipos de câncer mais incidentes no Brasil. A terapia consiste na remoção cirúrgica e em alguns casos, a quimioterapia adjuvante, composta de 5-fluorouracil e outros fármacos associados. O 5-FU, apesar de amplamente utilizado, provoca uma série de efeitos adversos, relacionados à toxicidade renal, cardíaca, hepática e mucosite. Nesse contexto, a ferramenta do planejamento de pró fármacos é uma alternativa para a redução das propriedades indesejadas dos fármacos. Assim, o objetivo deste trabalho foi comprovar a hipótese da diminuição da toxicidade do 5-FU pela taurina, aminoácido com propriedades anti-inflamatórias e antioxidante, para a obtenção de pró-fármacos derivados. Para isso, ratos Wistar foram submetidos ao modelo de carcinogênese de cólon induzida por1,2-dimetilhidrazina (DMH), e tratados com a associação (5-FU+TAU) por 8 dias, na 20° semana pós indução. Os resultados demonstraram que a taurina inibe a formação de criptas aberrantes e atua sinergicamente com 5-FU reduzindo a quantidade das mesmas. Além disso, o grupo tratado com 5-FU isolado apresentou aumento de 28% no número de tumores, enquanto a TAU isolada promoveu 64% menos neoplasias que o controle. Na associação a redução na incidência alcança 86%, sendo nenhuma das neoplasias classificados como adenocarcinomas (tumor invasivo), enquanto TAU isolada apresenta 50%, e 5-FU 70% de adenocarcinomas entre as neoplasias. Os resultados demonstram que a TAU e o 5-FU apresentam efei... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Colorectal cancer is one of the ten most incident types of cancer in Brazil. Its treatment consists of surgical intervention and, in some cases, adjuvant chemotherapy, using 5-fluorouracil (5-FU) associated with other drugs. Although extensively used, 5-FU presents several adverse effects, related to renal, cardiac and hepatic toxicity and mucositis. In this context, the search of new drugs is an alternative to reduce some undesired properties of the drug. Thus, the objective of this work was to prove the hypothesis of the reduction of toxicity of 5-FU by taurine, amino acid with anti-inflammatory and antioxidant properties, to obtain derivative prodrugs. For this, Wistar rats were submitted to the colon carcinogenesis model induced by 1,2-dimethylhydrazine (DMH) and treated with the combination (5-FU + TAU) for 8 days at the 19th week post induction. The results have demonstrated that taurine inhibits the formation of aberrant crypts foci and acts synergistically with 5-FU. In addition, the group treated with 5-FU alone showed a 28% increase in the number of tumors, whereas the isolated TAU promoted 64% fewer neoplasms than the control. In the association, the reduction in incidence reaches 86%, none of the neoplasms classified as adenocarcinomas (invasive tumor), while isolated TAU presents 50%, and 5-FU 70% of adenocarcinomas between neoplasms. Thus, the association results have demonstrated that the two substances presented a chemotherapic effect and can be used to obtent... (Complete abstract click electronic access below)
Doutor
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Sham, Ngai-fung. "Study of the protective mechanisms of cigarette smoke and nicotine on experimental ulcerative colitis in rats /". Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B2342459x.
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Rizo, Roca David. "Efectos de la hipoxia hipobárica intermitente en la recuperación del daño muscular inducido por ejercicio excéntrico en ratas entrenadas". Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/402828.
Testo completoAbstract (sommario):
En esta tesis se explora la posibilidad de aplicar la hipoxia hipobárica intermitente (HHI) como herramienta terapéutica no farmacológica para tratar el daño muscular que aparece como consecuencia del ejercicio excéntrico en individuos entrenados. Debido a la necesidad de realizar pruebas invasivas, se escogió un modelo animal. Se entrenaron ratas Sprague-Dawley en un tapete rodante y se sometieron posteriormente a un protocolo de daño muscular inducido por ejercicio excéntrico (EEIMD). Como grupo Control se sacrificó un subgrupo de ratas entrenadas antes del protocolo de EEIMD. El resto de animales fue aleatoriamente dividido en tres grupos en función del tratamiento que se les aplicó: 1) animales con recuperación pasiva (grupo PNR), 2) animales sometidos a una sesión diaria de 4 horas de hipoxia hipobárica a una presión barométrica equivalente a 4000 m de altitud (grupo PHR); y 3) animales sometidos a HHI que inmediatamente después realizaron una sesión de ejercicio aeróbico ligero (grupo AHR). Estos tres grupos comenzaron sus respectivas intervenciones el día siguiente al EEIMD, y fueron sacrificados 1, 3, 7 y 14 días después. El análisis de los biomarcadores plasmáticos creatina quinasa y mioglobina confirmó la presencia de daño muscular en los animales sometidos al protocolo de EEIMD. Además, se observaron infiltraciones por mononucleares, fibras anómalas y distensión del tejido conectivo en cortes histológicos del músculo de sóleo. También se observó, en este músculo, una disminución en la capilarización de las fibras, consecuencia de una disrupción parcial de la red capilar y del aumento del tamaño medio de las fibras. Estos eventos fueron acompañados por un declive de la red mitocondrial, como reflejó el análisis de diversas proteínas relacionadas con este orgánulo. El EEIMD indujo la disminución de diferentes marcadores de biogénesis mitocondrial (PGC-1a y Tfam) y aumentó el marcador de fisión Drp-1. En conjunto, estos resultados sugieren una disrupción de la red mitocondrial. De hecho, y en consonancia con esta hipótesis, la actividad de la enzima citrato sintasa (CS) se encontró significativamente reducida una y dos semanas después del protocolo de EEIMD. El análisis de las proteínas Bax y Bcl-2 indica un posible aumento de la señalización apoptótica, en tanto que la expresión de Sirtuina 3 disminuyó, sugiriendo un aumento del estrés oxidativo. En general, la HHI, especialmente en combinación con el ejercicio aeróbico ligero, atenuó o revertió la mayoría de estos efectos deletéreos, siendo especialmente destacable el aumento de la capilarización debido a un proceso de angiogénesis (en tanto se observó un aumento del recuento de capilares y de VEGF) y a la conservación del tamaño de las fibras. Además, en comparación con el grupo no tratado, los animales AHR mostraron niveles significativamente mayores de proteínas marcadoras de biogénesis y fusión mitocondrial, mayor actividad de la enzima CS y menos indicadores de estrés oxidativo. La adición de una sesión leve de ejercicio aeróbico resultó fundamental para la obtención de muchos de estos resultados, probablemente debido a que tuvo un efecto de refuerzo sobre el estímulo hipóxico, tal y como se deduce del aumento de la expresión de las proteínas VEGF y GLUT1 en el grupo AHR. En conclusión, estos resultados sugieren que la HHI, en la intensidad y duración adecuada y combinada con ejercicio aeróbico ligero, puede acelerar la recuperación de determinados parámetros afectados por el EEIMD.This work explores the potential use of intermittent hypobaric hypoxia (IHH) as a non-pharmacological tool to treat muscle damage in trained subjects. Here we applied a recovery protocol consisting of 4 hour-daily sessions of hypobaric hypoxia (≈4000m), alone or immediately followed by light aerobic exercise. Because invasive analyses were needed, we opted for a rodent model. Sprague-Dawley rats were trained in a treadmill for a month and then were subjected to downhill running, a well-known method of eccentric exercise-induced muscle damage (EEIMD). After that, rats were divided in three groups: 1) passive normobaric recovery (PNR); 2) passive hypobaric recovery (PHR); and 3) active hypobaric recovery (AHR), rats that immediately after each daily session of hypobaric hypoxia performed light aerobic exercise. These groups were subdivided in four subgroups according to the following sampling days: 1, 3, 7 or 14 days after the EEIMD protocol. Additionally, a group of rats was euthanized before the EEIMD protocol (CTRL). Histopathological and histomorphometric analysis of transversal sections of soleus muscle were carried out. Additionally, the protein expression of mitochondrial biomarkers related to biogenesis, fusion and fission, apoptosis signaling, bioenergetics and oxidative stress was semiquantified. As expected, EEIMD induced a number of alterations at the histopathological level, such as mononuclear infiltrates, presence of abnormal fibers and connective tissue distension. Furthermore, a decrease in the muscle capillarization and an apparent hypertrophy were also reported. The biogenesis biomarker PGC-1α was found reduced 3 days after the EEIMD protocol, while Drp-1, a marker of mitochondrial fission, and the Bax/Bcl-2 ratio, a marker of apoptosis signaling, were increased. Maybe as a consequence, the citrate synthase activity decreased. Interestingly, HHI combined with light aerobic exercise attenuated or reversed most of these findings: after two weeks of recovery, AHR rats showed a fiber size and muscle capillarization similar to CTRL animals, as well as decreased percentage of abnormal fibers, higher levels of biomarkers related to mitochondrial biogenesis and fusion and reduced apoptosis signaling markers when compared to PNR and PHR groups.
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Izquierdo, Castro Cristina. "Estudio de terapias antígeno-específicas para la prevención de la diabetes tipo 1 en el ratón nod". Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/386436.
Testo completoAbstract (sommario):
La diabetes tipo 1 (DT1) es una patología autoinmunitaria causada por la destrucción de los islotes β pancreáticos encargados de la producción de insulina. Actualmente, no existe cura alguna para la enfermedad más allá de la administración de insulina exógena a los pacientes, lo cual no permite el control de los efectos nocivos provocados a largo plazo. Por este motivo resulta de relevancia el desarrollo de nuevas terapias que permitan la reversión o prevención de los mecanismos implicados en la dolencia. Dado el papel principal del sistema inmunitario en el avance de la DT1 su modulación resulta clave en el diseño de novedosos sistemas de tratamiento, en concreto, la modulación antígeno-específica de las poblaciones T responsables del ataque contra el páncreas se postula como aproximación terapéutica segura y efectiva. Más aún, la capacidad supresora de células T reguladoras las convierte en una diana celular ideal para el desarrollo de terapias capaces de recuperar la tolerancia inmunológica.
En el presente trabajo se ha abordado la prevención de la DT1 desarrollada en el modelo murino espontáneo NOD a través de dos estrategias terapéuticas distintas. Ambas se encuentran centradas en la inmunomanipulación péptido-específica de la población autorreactiva T CD4+ 2.5mi+. En una primera aproximación, mediante la administración de tratamientos combinados de tetrámeros de pMHC y complejos de IL-2, se ha conseguido la expansión in vivo de células T reguladoras Foxp3+ antígeno-específicas, las cuales muestran un fenotipo altamente activado, demuestran una capacidad supresora incrementada y cuentan con una efectiva capacidad de migración a islote. La aplicación de los tratamientos combinados diseñados a hembras NOD jóvenes ha propiciado en ellas la prevención de la aparición de diabetes autoinmune prácticamente en un 100% de los animales estudiados. En segundo término, se ha planteado la modulación del conjunto T CD4+ 2.5mi+ a través de la administración de una vacuna de ADN péptido-específica denominada pCMV-CTLA4-Fc-2.5mi. Dada la efectiva prevención de la DT1 inducida por la vacuna al aplicarla a hembras NOD jóvenes se continuó con el estudio del mecanismo celular implicado en el control autoinmune. Así, ha podido determinarse que pCMV-CTLA4-Fc-2.5mi es responsable del incremento selectivo de una población T CD4+ 2.5mi+ Foxp3- con propiedades supresoras in vitro y con capacidad de secreción de la citocina antiinflamatoria IL-10. Asimismo, el plásmido induce también la activación específica de linfocitos T CD4+ 2.5mi+ Foxp3+, promoviendo en ellos el aumento de su función inhibidora. Ambas poblaciones, activadas y/o expandidas, podrían ser las mediadoras del freno del ataque autoinmune centrado en páncreas.
En conjunto, los resultados obtenidos a lo largo del estudio aportan nuevos conocimientos que podrían ser de utilidad en el desarrollo y optimización de terapias antígeno-dirigidas contra la DT1. Hemos podido demostrar que la modificación de una pequeña población T autorreactiva, mediante dos mecanismos de acción distintos, puede resultar efectiva para el control autoinmune de respuestas Th1 órgano-específicas evitándose con ello la manipulación general del sistema inmunitario, cuyo completo funcionamiento es esencial para la protección del individuo contra desafíos externos mediados por patógenos.Type 1 diabetes (T1D) is an autoimmune disorder caused by the selective destruction of insulin-producing islet β cells in the pancreas. Currently, no cure capable to revert or prevent the deleterious effects of the disease is available. Therefore there is a compelling need to identify new therapies that may safely restore the immune tolerance against pancreas. Due to their key role in the development of T1D, the modulation of antigen-specific T cell populations responsible for the autoimmune attack of islets may represent an interesting approach for the design of novel therapeutic strategies against diabetes. In fact, the unique suppressive capacity of regulatory T cells makes them an ideal target for the development of treatments designed to reestablish immunological tolerance against self. The main goal of this study was to generate an antigen-specific immunotherapy to avoid pancreatic damage based on the modulation of the autoreactive T CD4+ 2.5mi+ population in NOD mice, a murine model used in T1D research. We have addressed the prevention of the autoimmune disease through two different therapeutic strategies. Firstly, by the administration of combined treatments of pMHC tetramers and IL-2 complexes we achieved a vast in vivo expansion of a Foxp3+ 2.5mi+Treg cell population which prevented autoimmune diabetes in NOD females that received the combined treatment. Secondly, we have engineered a novel antigen-specific DNA vaccine named pCMV-CTLA4-Fc-2.5mi which also effectively prevented diabetes in NOD mice. The vaccine mediates its therapeutic effect through the expansion and/or activation of two different autoreactive Treg cell populations: T CD4+ Foxp3+ 2.5mi+, which exhibits a potent suppressive phenotype in vitro, and T CD4+ Foxp3- 2.5mi+ which also exerts enhanced anti-inflammatory properties. Overall, the results obtained throughout our study provide new insights that could be useful for the development and optimization of antigen-targeted therapies against T1D. We have shown that the alteration of a single autoreactive T cell population via two different ways may be effective in the control of organ-specific autoimmune damage without systemic interventions that mediate general immune suppression.
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Tili, Siphokazi Pamphilia. "Observed pathological changes in male Wistar rats after co-treatment of Type II Diabetes with metformin and sutherlandia frutescens". Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1012644.
Testo completoAbstract (sommario):
Diabetes is a serious condition that affects all the body’s systems including kidneys, heart, eyes and limbs. This alone makes type II diabetes a life threatening disease; an expensive disease and economic burden that many individuals struggle to cope with.The rapid growth type II diabetes in South Africa is associated with the change of life style, and environmental factors brought by westernized way of life living in rural areas. Despite the technical advances in diagnosis and therapy of diabetes many people still use alternative forms of therapy due to the cost, traditional reasons and religion. Some of the people use the conventional medication together with the alternative therapy without informing their doctor and knowing the pathological changes. The aim of the study was to investigate pathological changes in male Wistar rats after co-treatment of type II diabetes with metformin and Sutherlandia frutescens and the possible synergistic and antagonistic effects. The thirty five rats were divided into five groups, seven in each group. There were two control groups and three test groups. Only the first control group was on a low fat diet (normal rat pellets) and second control group and test groups were on a high fat diet which induces obesity, insulin resistance and leads a typical prediabetic state for 12 weeks (Buettner et al., 2006). After 11.5 weeks medication was administered by oral gavaging to the test groups for 4 weeks and control groups received water. Blood was collected for determination of glucose, insulin, lipid profile and the concentrations of the liver enzymes. Pancreas, liver and kidney tissue were removed and used for histology. Urine was collected from the bladder for creatinine analyses. The plant + metformin group co-treatment was better in managing hyperglycemia, liver damages were minimal and also weight control was better when compared to metformin alone.
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Chadwick, Wayne. "Observed metabolic changes in male Wistar rats after treatment with an antidepressant implied in undesirable weight gain, or Sutherlandia frutescens for Type II diabetes". Thesis, University of Port Elizabeth, 2003. http://hdl.handle.net/10948/313.
Testo completoAbstract (sommario):
Type II diabetes is fast becoming a growing problem in developed countries worldwide. Traditionally the median age for diagnosis was around sixty, but recent surveys have shown that the entire age distribution curve has shifted to the left. Western countries boast the worst statistics in which type II diabetes is being reported in children under the age of ten. At such a young age the disease often goes undiagnosed for long periods of time allowing considerable damage to occur. The incidence of type II diabetes is thought to be parallel with the growing rate of obesity associated with a characteristically unhealthy western diet. Type II diabetes is an extremely expensive disease to manage, and with the rapid growth of this pandemic our country will soon feel the economic burden of this disease. It is for this reason that cheaper medication needs to be investigated in the form of traditional plants, such as Sutherlandia frutescens. Prescription medication, such as tricyclic antidepressants, may also increase body weight or appetite thereby playing a role in obesity. The cause of weight gain in such cases may go unrecognized or lead to cessation of the medication with or without the practitioner’s knowledge or approval. It is therefore necessary to investigate the causative agents responsible for the excessive weight gain. Drinking water containing extracts of the S. frutescens, metformin (a well known type II diabetes medication) and amitriptyline (a common tricyclic antidepressant) was administered to three groups of ten male Wistar rats. The control group received water without any medication. The rat’s weight and food consumption was monitored throughout the trial and their oxygen consumption was also determined. Rats were sacrificed after four months of medicinal compliance and glucose uptake, in the presence and absence of insulin, was tested in epididymal fat, liver and muscle. Fasting plasma glucose levels, lipoprotein, cholesterol and triglyceride concentrations were also determined.
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Wong, Shu-hing Louise. "Replicating mesenchymal cells in the glenoid fossa in response to mandibular advancement". Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/hkuto/record/B31973140.
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Guilhardi, Paulo. "A unified approach to the study of choice, conditioning, and timing /". View online version; access limited to Brown University users, 2005. http://wwwlib.umi.com/dissertations/fullcit/3174614.
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Froc, David John Racine Ronald J. "Neocortical long-term depression and depotentiation in the adult, freely moving rat /". *McMaster only, 2002.
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