Journal articles on the topic 'Substance P Physiological effects'
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1
Drazen, J. M., S. A. Shore, and N. P. Gerard. "Substance P-induced effects in guinea pig lungs: effects of thiorphan and captopril." Journal of Applied Physiology 66, no. 3 (March 1, 1989): 1364–72. http://dx.doi.org/10.1152/jappl.1989.66.3.1364.
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The effects of the neutral metalloendopeptidase inhibitor, thiorphan, and the angiotensin-converting enzyme inhibitor, captopril, on the changes in airway opening pressure (PaO), pulmonary arterial pressure (Ppa), and weight induced by intravascular administration of substance P were examined in isolated perfused and ventilated guinea pig lungs. Administration of 1 nmol substance P without enzyme inhibitors resulted in a significant (P less than 0.01) increase in the peak PaO during ventilation from 12.4 +/- 0.5 to 22.4 +/- 2.2 cmH2O; there were small statistically insignificant increases in Ppa. The changes in PaO peaked approximately 30 s after peptide infusion and returned to preinfusion values by 5 min. In the presence of combined thiorphan (5.6 microM) and captopril (7.7 microM) the magnitude of the Pao response at 30 s (41.5 +/- 3.8 cmH2O) and at 5 min (40.0 +/- 3.6 cmH2O) after peptide infusion was significantly greater than in control lungs (P less than 0.05). The effects of substance P on PaO in the presence of the various inhibitors were not related to amount of peptide recovered in the lung effluent. Reverse-phase high-performance liquid chromatographic analysis of [3H]Pro2,4 substance P perfused through the lungs demonstrated that the major products were consistent with intact substance P, substance P 1–4, and smaller peptides; only minor amounts of products consistent with substance P 1–7, 1–9, or 3–11 were identified. These data support our previous findings showing that the physiological effects of intravascular substance P are limited by peptide degradation; the latter process, once begun, proceeds rapidly to nearly complete peptide degradation.
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Oz, E., E. Aydemir, A. F. Korcum, and K. Fiskin. "The effects of substance P fragments on breast cancer cells." Journal of Clinical Oncology 29, no. 27_suppl (September 20, 2011): 295. http://dx.doi.org/10.1200/jco.2011.29.27_suppl.295.
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295 Background: Substance P (SP), a neuropeptide, is known to induce tumor cell proliferation. In contrast with intact peptide, the fragments of SP are suggested to inhibit the growth of various cancer cells. The aim of the present study was to determine cytotoxic effects of physiological fragments of SP either alone or in combination with radiotherapy on mouse breast cancer cells. Methods: In this study, we tested the physiological fragments of SP such as SP (4-11), SP (6-11) and SP (1-7). Dose-response and time-course studies were carried out with various concentrations (100-0.001 nM) of SP fragments and the intact peptide. 4T1 mouse breast cancer cell lines were used in this study. The cytotoxic effect of SP fragments alone or in combination with radiotherapy was determined via WST-1 assay. Changes in substance P amounts in cells and in mediums determined by SP EIA kit. Results: SP(4-11) and SP(6-11), but not SP(1-7), inhibited the proliferation of breast cancer cells and potentiated antitumor effects of radiotherapy. Moreover, the intact peptide alone did not alter the proliferation rate of 4T1 cells and the cytotoxic effects of the fragments were not inhibited by SP. Conclusions: These results demonstrate that combined treatment with 2 fragments of SP (4-11 and 6-11) and radiotherapy induce cytotoxic effects. These data may provide the basis for a strategy, in which it is possible to use SP fragments and radiotherapy together to improve the efficiency of the independent therapies.
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Worthen, G. S., R. S. Gumbay, D. T. Tanaka, and M. M. Grunstein. "Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits." Journal of Applied Physiology 59, no. 4 (October 1, 1985): 1098–103. http://dx.doi.org/10.1152/jappl.1985.59.4.1098.
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Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002–0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15–20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5–10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.
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Bost, K. L., and D. W. Pascual. "Substance P: a late-acting B lymphocyte differentiation cofactor." American Journal of Physiology-Cell Physiology 262, no. 3 (March 1, 1992): C537—C545. http://dx.doi.org/10.1152/ajpcell.1992.262.3.c537.
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The peptide substance P has been recognized for years as having dramatic effects on such diverse physiological responses as blood pressure regulation, peristalsis of the gut, and salivation. More recently, demonstration of substance P receptors on leukocytes and modulation of leukocyte functions by this peptide suggested that it might also have a role in immune regulation. This review focuses on the growing body of evidence that demonstrates substance P-induced effects on one population of leukocytes, namely B lymphocytes. Despite the diversity of experimental techniques used, there is surprisingly good agreement as to the role substance P has in modulating B lymphocyte responses. In vivo treatments of rodents, which increase substance P concentrations in the periphery, increase the number of immunoglobulin-secreting cells in these animals. Conversely, infusion of substance P antagonists or depletion of substance P-containing neurons in rodents substantially reduces the animals' ability to synthesize immunoglobulins. With the use of cultures of B lymphocytes it was possible to demonstrate similar results. In the presence of polyclonal B cell activators, substance P augmented immunoglobulin secretion in cultures of purified B lymphocytes or B cell clones. The absence of accessory cells in these cultures suggested that substance P could act directly on activated B lymphocytes, and in fact these B cells were shown to express specific receptors for this peptide. It appears that the substance P receptors expressed by leukocytes are similar or identical to those expressed by neurons as evidenced by radioreceptor binding assays and detection of the gene encoding the substance P receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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Fox, J. E., and E. E. Daniel. "Substance P: a potent inhibitor of the canine small intestine in vivo." American Journal of Physiology-Gastrointestinal and Liver Physiology 250, no. 1 (January 1, 1986): G21—G27. http://dx.doi.org/10.1152/ajpgi.1986.250.1.g21.
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Intra-arterially administered substance P inhibited neurally activated contractions of the circular muscle of canine small intestine in vivo (lowest effective dose approximately 10(-13) mol). Excitation of intestine required higher (10(-10) mol) doses. The inhibitory effect required functioning nerves, since tetrodotoxin treatment eliminated it. However, inhibition of neurogenic contraction by substance P was unaffected by nicotinic or opiate receptor antagonists or by catecholamine depletion but was reduced by a selective substance P antagonist. Since the inhibition by substance P was also greatly reduced by treatment with atropine or pirenzepine and acetylcholine given intra-arterially produced a similar inhibitory response, stimulation of release of acetylcholine to inhibitory muscarinic receptors on nerves appeared to be the mechanism of this action. Direct smooth muscle effects were ruled out; substance P did not inhibit contractions to intra-arterial acetylcholine or those following tetrodotoxin. In vitro in ileal strips, no inhibition by substance P of any contractile response was found. We propose that the local release of substance P into the myenteric plexus produces inhibition and suggest that this constitutes a physiological function of the neuropeptide. This action may be absent in vitro.
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Makowska, Krystyna, Kamila Szymańska, Jarosław Całka, and Sławomir Gonkowski. "The Influence of Bisphenol A (BPA) on the Occurrence of Selected Active Substances in Neuregulin 1 (NRG1)-Positive Enteric Neurons in the Porcine Large Intestine." International Journal of Molecular Sciences 22, no. 19 (September 24, 2021): 10308. http://dx.doi.org/10.3390/ijms221910308.
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Bisphenol A (BPA) is a substance used in the manufacture of plastics which shows multidirectional adverse effects on living organisms. Since the main path of intoxication with BPA is via the gastrointestinal (GI) tract, the stomach and intestine are especially vulnerable to the impact of this substance. One of the main factors participating in the regulation of intestinal functions is the enteric nervous system (ENS), which is characterized by high neurochemical diversity. Neuregulin 1 (NRG1) is one of the lesser-known active substances in the ENS. During the present study (performed using the double immunofluorescence method), the co-localization of NRG1 with other neuronal substances in the ENS of the caecum and the ascending and descending colon has been investigated under physiological conditions and after the administration of BPA. The obtained results indicate that NRG1-positive neurons also contain substance P, vasoactive intestinal polypeptide, a neuronal isoform of nitric oxide synthase and galanin and the degree of each co-localization depend on the type of enteric plexus and the particular fragment of the intestine. Moreover, it has been shown that BPA generally increases the degree of co-localization of NRG1 with other substances.
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Wiese, Ashley J., Michael Rathbun, Mark T. Butt, Shelle A. Malkmus, Philip J. Richter, Kent G. Osborn, Qinghao Xu, et al. "Intrathecal Substance P-Saporin in the Dog." Anesthesiology 119, no. 5 (November 1, 2013): 1163–77. http://dx.doi.org/10.1097/aln.0b013e3182a95164.
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Abstract Background: Neurokinin-1 receptors (NK1-rs) located on superficial dorsal horn neurons are essential for integration of nociceptive input. Intrathecal injection of substance P-saporin (SP-SAP) leads to local loss of spinal NK1-r (+) neurons suggesting its potential as a therapeutic agent for chronic pain. The authors determined, in a canine model, effects of lumbar intrathecal SP-SAP. Methods: Distribution of SP-SAP and Saporin was determined in plasma, lumbar cerebrospinal fluid, and tissue. Safety of intrathecal SP-SAP was determined in four groups (six dogs each) administered 0 (0.9% saline), 1.5, 15, or 150 µg SP-SAP through lumbar intrathecal catheters. Behavioral, physiologic, and biochemical variables were assessed. Spinal tissues were collected at 7 and approximately 90 days, or earlier if significant morbidity developed, and analyzed for NK1-r (+) neuron loss and histopathology. Results: SP-SAP and Saporin were detectable in lumbar cerebrospinal fluid for up to 4 and 24 h, respectively. Animals receiving intrathecal saline, 1.5, or 15 µg of SP-SAP showed no persistent neurologic deficits. Three animals receiving 150 µg of SP-SAP developed pelvic limb paraparesis and were euthanized prematurely. Immunohistochemistry and in situ hybridization cell counts confirmed a significant reduction in NK1-r (+) in superficial dorsal horn neurons from lumbar spinal cord after intrathecal administration of 15 and 150 µg of SP-SAP. A significant loss of NK1-r neurons in the lumbar ventral horn occurred only with 150-µg SP-SAP. Conclusion: Intrathecal 15-µg SP-SAP reduced dorsal, but not ventral, NK1-r (+) neurons at the spinal level of delivery with minimal side effects, whereas 150-µg SP-SAP resulted in motor neuron toxicity.
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Jing, Xiong, Chunju Cai, Shaohui Fan, Guanglu Liu, Changming Wu, and Benxue Chen. "Effects of Rhizome Integration on the Water Physiology of Phyllostachys edulis Clones Under Heterogeneous Water Stress." Plants 9, no. 3 (March 18, 2020): 373. http://dx.doi.org/10.3390/plants9030373.
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Water is crucial to plant growth and development. Under heterogeneous environmental water deficiency, physiological integration of the rhizomatous clonal plant triggers a series of physiological cascades, which induces both signaling and physiological responses. It is known that the rhizome of Phyllostachys edulis, which connects associated clonal ramets, has important significance in this physiological integration. This significance is attributed to the sharing of water and nutrients in the vascular bundle of clonal ramets under heterogeneous water conditions. However, the physiological characteristics of physiological integration under heterogeneous water stress remain unclear. To investigate these physiological characteristics, particularly second messenger Ca2+ signaling characteristics, long-distance hormone signaling molecules, antioxidant enzyme activity, osmotic adjustment substance, and nitrogen metabolism, ramets with a connected (where integration was allowed to take place) and severed rhizome (with no integration) were compared in this study. The vascular bundle structure of the rhizome was also observed using laser confocal microscopy. Overall, the results suggest that interconnected rhizome of P. edulis can enhance its physiological function in response to drought-induced stress under heterogeneous water deficiency. These measured changes in physiological indices serve to improve the clonal ramets’ drought adaptivity through the interconnected rhizome.
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Hoover, Donald B. "Effects of capsaicin on release of substance P-like immunoreactivity and physiological parameters in isolated perfused guinea-pig heart." European Journal of Pharmacology 141, no. 3 (September 1987): 489–92. http://dx.doi.org/10.1016/0014-2999(87)90571-1.
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Holstein, B., and C. Cederberg. "Effects of tachykinins on gastric acid and pepsin secretion and on gastric outflow in the Atlantic cod, Gadus morhua." American Journal of Physiology-Gastrointestinal and Liver Physiology 250, no. 3 (March 1, 1986): G309—G315. http://dx.doi.org/10.1152/ajpgi.1986.250.3.g309.
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Gastric acid and pepsin responses to substance P, physalaemin, eledoisin, and an eledoisin-related peptide, [Lys6]eledoisin-(6-11), were measured in gastrically and intestinally perfused cods. The intestinal perfusion maintains water balance and inhibits drinking. During basal conditions acid secretion was stimulated (approximately equal to 25%) by low doses (less than 0.13 nmol X kg-1 X h-1) of physalaemin and eledoisin. High doses (greater than 16 nmol X kg-1 X h-1) were inhibitory. Median and very high doses of substance P and eledoisin-related peptide, respectively, tended to stimulate acid secretion. All tachykinins were extremely efficacious pepsigogues. Physalaemin and eledoisin were the most potent (D50 approximately 10(-10) mol X kg-1 X h-1) but produced fading and submaximal responses at high doses. The fading persisted despite endogenous acidification produced by histamine stimulation. Relative to physalaemin, the potencies of substance P and eledoisin-related peptide were 0.04 and 0.001. The results suggest that some tachykinin may be a physiological stimulator of pepsin secretion and that the effect on acid secretion results from activation of both stimulatory and inhibitory pathways. The inhibitory component probably includes a cholinergic link. Gastric volume outflow increased during infusion of physalaemin, eledoisin, and (slightly) substance P. The response, which was not related to acid secretory rate (and conceivably not to volume secretion), suggests that a tachykinin may be involved also in the regulation of drinking.
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Moss, I. R., and J. G. Inman. "Neurochemicals and respiratory control during development." Journal of Applied Physiology 67, no. 1 (July 1, 1989): 1–13. http://dx.doi.org/10.1152/jappl.1989.67.1.1.
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During ontogeny, the central nervous system undergoes neuronal growth, regression, and remodeling. The development of neurotransmitter and modulator systems is a plastic process with individual temporal characteristics for each system. These characteristics include the synthesis, degradation, or uptake of neurochemicals and, largely independently, the appearance of their receptors. Message transmission during ontogeny is compounded by the variable development of these systems and by the coexistence and cofunction among these chemicals. Nine neurochemical systems are discussed: adenosine, gamma-aminobutyric acid, opioids, prostaglandins, serotonin, progesterone, substance P, thyrotropin-releasing hormone, and the catecholamines. The possible role of each of these in natural perinatal respiratory control is evaluated according to predetermined criteria. These include the presence of a substance system in respiratory-related regions, physiologically appropriate changes in its concentration in these regions, elicitation of respiratory effects by agonists and antagonists, and abolition with an antagonist of the effect of a substance during its presumed activation by a physiological process. It is suggested that excessive levels of suppressant neuromodulators or an imbalance among neurochemicals can partly explain the special features of respiratory control in the perinatal period.
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Thompson, Caitlin, and Martin L. Williams. "Review of the physiological effects of Phyllomedusa bicolor skin secretion peptides on humans receiving Kambô." Toxicology Research and Application 6 (January 2022): 239784732210857. http://dx.doi.org/10.1177/23978473221085746.
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Kambô is an Amazonian ritual which includes the application of the defensive secretion of the Phyllomedusa bicolor frog to superficial burns made on the skin of human participants. The secretion, which contains a range of biologically active linear peptides, induces a short purgative experience that is extensively reported by participants to leave them with positive physical, emotional and spiritual after-effects. Various peptides identified in the secretion exert analgesic, vascular, and gastric effects in vivo, and antimicrobial and anti-cancer effects, among others, in vitro. While there has been some investigation into the physiological effects of various individual peptides isolated from the P. bicolor secretion, very little is known about the putative synergistic effects of concurrent administration of the complete substance through the transdermal methods used traditionally in the Kambô ritual. In this review and commentary, the authors summarize the existing biological information from animal research on peptides from the P. bicolor secretion, then consider the evidence in the context of Kambô administration to humans. The presented information suggests that specific peptides are likely to contribute to analogous physiological effects of Kambô in humans. The possibility that beyond their physiological action, the experiential or phenomenological component of these effects may have therapeutic applications is discussed, concluding with a consideration of the feasibility of human clinical research.
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Huston, Joseph P., and Mary-S. Oitzl. "The relationship between reinforcement and memory: Parallels in the rewarding and mnemonic effects of the neuropeptide substance P." Neuroscience & Biobehavioral Reviews 13, no. 2-3 (June 1989): 171–80. http://dx.doi.org/10.1016/s0149-7634(89)80027-2.
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Ding, Ting, and Yong Li. "Quorum sensing inhibitory effects of vanillin on the biofilm formation of Pseudomonas fluorescens P07 by transcriptome analysis." SDRP Journal of Food Science & Technology 5, no. 7 (2021): 275–92. http://dx.doi.org/10.25177/jfst.5.7.ra.10686.
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Pseudomonas fluorescens is an important psychrotrophic food-spoilage bacterium. Quorum sensing (QS) enables bacteria to control various physiological processes. Hence, targeting bacterial QS would be a novel method to improve food quality. In this study, P. fluorescens P07 was treated with vanillin, which showed strong QS inhibitory activity, and its resultant effects on swarming motility, biofilm formation, and extracellular polymeric substance (EPS) secretion were measured. The mechanisms underlying the inhibitory effects were then explored by transcriptomic analysis. The results showed that vanillin had inhibitory effects on swarming motility, biofilm formation, N-acyl-L-homoserine Lactone (AHLs) and EPS secretion of P. fluorescens P07. The result of transcriptionomic tests indicated that the decrease in bacterial biofilm formation was probably due to the influence of vanillin on mobility, adhesion, chemotaxis, EPS secretion, and QS system of the bacteria. Keywords: Pseudomonas fluorescens, quorum sensing, biofilm formation, transcriptome analysis, swarming motility
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Ichikawa, S., S. P. Sreedharan, R. L. Owen, and E. J. Goetzl. "Immunochemical localization of type I VIP receptor and NK-1-type substance P receptor in rat lung." American Journal of Physiology-Lung Cellular and Molecular Physiology 268, no. 4 (April 1, 1995): L584—L588. http://dx.doi.org/10.1152/ajplung.1995.268.4.l584.
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Peptidergic nerves in the respiratory tract release vasoactive intestinal peptide (VIP) and substance P (SP), which mediate physiological and immune functions. Antipeptide antibodies to type I VIP receptor (VIPR) and NK-1-type SP receptor (SPR) were used to identify these receptors in normal rat lungs. VIPRs and SPRs were detected on airway epithelium from the trachea to the respiratory bronchioles but not in alveoli, submucosal glands, or pulmonary smooth muscle, except for that of some pulmonary veins. VIPRs also were expressed on macrophages around capillaries, in tracheal and bronchial connective tissue, in alveolar walls, and in the subintima of pulmonary veins and some arterioles. The absence of receptors from airway smooth muscle and submucosal glands implies that mediation of some known effects of SP and VIP may be epithelial or macrophage dependent. Other types of VIPRs and SPRs on airway glands and smooth muscle may transduce direct effects. The similar localization of VIPRs and SPRs in rat lung suggests that VIP and SP may coordinately regulate some pulmonary functions.
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Rameshwar, P., D. Ganea, and P. Gascon. "In vitro stimulatory effect of substance P on hematopoiesis." Blood 81, no. 2 (January 15, 1993): 391–98. http://dx.doi.org/10.1182/blood.v81.2.391.391.
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Abstract The neuropeptide Substance P (SP) is widely distributed in the peripheral nervous system. Its biologic effects have been extensively studied in the immune system. However, even though the bone marrow (BM) is innervated with SP-immunoreactive fibers and some of its cells not only express SP receptors (T and B cells, endothelial cells, and macrophages) but also produce SP (macrophages, eosinophils, and endothelial cells), the effects of SP on hematopoiesis are scanty. Furthermore, SP induces the production of hematopoietic growth factors (HGFs) (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) from human monocytes. In this study, we have found a potent in vitro stimulatory effect of SP (10(-8) to 10(-12) mol/L) on hematopoiesis for both erythroid and granulocytic progenitors in short-term methyl- cellulose BM cultures. SP alone, in the absence of exogenous HGFs, is able to sustain hematopoiesis in vitro. This stimulatory effect of SP is: (1) mostly mediated by the adherent cells; (2) completely abrogated by two SP receptor (SP-R) antagonists; and (3) partially reduced by anti-IL-1, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, it appears that the stimulatory effect of SP may be mediated by IL-3 and GM-CSF because we have also found that SP induces the release of these two cytokines from BM mononuclear cells. Considering that the SP effect occurs at concentrations as low as 10(-11) mol/L, and via a specific receptor, it appears that SP may play a physiologic role in regulating hematopoiesis, at least partially through the adherent BM cells and the release of HGFs, and may place SP, a neuropeptide, in a new category of hematopoietic regulators.
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Rameshwar, P., D. Ganea, and P. Gascon. "In vitro stimulatory effect of substance P on hematopoiesis." Blood 81, no. 2 (January 15, 1993): 391–98. http://dx.doi.org/10.1182/blood.v81.2.391.bloodjournal812391.
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The neuropeptide Substance P (SP) is widely distributed in the peripheral nervous system. Its biologic effects have been extensively studied in the immune system. However, even though the bone marrow (BM) is innervated with SP-immunoreactive fibers and some of its cells not only express SP receptors (T and B cells, endothelial cells, and macrophages) but also produce SP (macrophages, eosinophils, and endothelial cells), the effects of SP on hematopoiesis are scanty. Furthermore, SP induces the production of hematopoietic growth factors (HGFs) (interleukin-1 [IL-1], IL-6, and tumor necrosis factor alpha) from human monocytes. In this study, we have found a potent in vitro stimulatory effect of SP (10(-8) to 10(-12) mol/L) on hematopoiesis for both erythroid and granulocytic progenitors in short-term methyl- cellulose BM cultures. SP alone, in the absence of exogenous HGFs, is able to sustain hematopoiesis in vitro. This stimulatory effect of SP is: (1) mostly mediated by the adherent cells; (2) completely abrogated by two SP receptor (SP-R) antagonists; and (3) partially reduced by anti-IL-1, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, it appears that the stimulatory effect of SP may be mediated by IL-3 and GM-CSF because we have also found that SP induces the release of these two cytokines from BM mononuclear cells. Considering that the SP effect occurs at concentrations as low as 10(-11) mol/L, and via a specific receptor, it appears that SP may play a physiologic role in regulating hematopoiesis, at least partially through the adherent BM cells and the release of HGFs, and may place SP, a neuropeptide, in a new category of hematopoietic regulators.
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Panettieri, R. A., R. K. Murray, L. R. DePalo, P. A. Yadvish, and M. I. Kotlikoff. "A human airway smooth muscle cell line that retains physiological responsiveness." American Journal of Physiology-Cell Physiology 256, no. 2 (February 1, 1989): C329—C335. http://dx.doi.org/10.1152/ajpcell.1989.256.2.c329.
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We report the development of a nontransformed line of human airway smooth muscle cells retaining smooth muscle-specific contractile protein expression and physiological responsiveness to agonists implicated in inflammatory airway diseases. Specific responses to histamine, leukotrienes, bradykinin, platelet-activating factor, substance P, and thromboxane analogues are demonstrated as well as functional coupling to beta-adrenergic receptors. The cell line was characterized using indirect immunofluorescence, as well as electrophoretic separation and immunoblot analysis of smooth muscle-specific actin. Functional responses were assessed by measurements of cytosolic calcium and stimulation of adenosine 3',5'-cyclic monophosphate production. The cells retain their responsiveness over many population doublings and should be a useful model to examine specific receptor-effector mechanisms, as well as the effects of neurohumoral agents on the regulation of airway smooth muscle growth and differentiation.
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Zhao, Jiantao, Rongzheng Huang, Kaixin Yang, Chunhui Ma, and Qianbing Zhang. "Effects of Nitrogen and Phosphorus Fertilization on Photosynthetic Properties of Leaves and Agronomic Characters of Alfalfa over Three Consecutive Years." Agriculture 12, no. 8 (August 9, 2022): 1187. http://dx.doi.org/10.3390/agriculture12081187.
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The present study aimed to investigate the nitrogen (N) and phosphorus (P) fertilization of continuous addition effects plant biomass, the physiological properties of leaves and the antioxi-dant enzyme activities of alfalfa (Medicago sativa L) in the northern Xinjiang region; including the no fertilization (CK), nitrogen fertilization (N, 120 kg·ha−1), phosphorus fertilization (with low amount of N) (P, 100 kg·ha−1 P and 23.5 kg·ha−1 N) and combined nitrogen and phosphorus fertilization (NP, 120 kg·ha−1 N and 100 kg·ha−1 P) on the K well supplied soil. After three consecutive years of the supply of N and P fertilization, samples were taken at the first flowering of alfalfa (four clippings in the total year) to determine its pigment concentration, stomatal aperture, antioxidant enzyme activity and hay yield. The results showed that NP fertilization promoted growth with a higher number of branches and hay yield of alfalfa, while N or P fertilization alone had a positive effect on the growth of alfalfa. However, P fertilization significantly increased the carotenoid (Car) content at the early flowering stage of alfalfa leaves (during four clippings) (p < 0.05), In addition, NP ferti-lization enhanced stomatal aperture, increased the antioxidant enzyme activity and decreased the oxidized substance at the early flowering stage of alfalfa leaves. The results showed that a N and P balance rather than an absolute amount of either enhanced the growth of alfalfa, and N or P fertili-zation affects physiological traits differently. We propose that NP fertilization increases the nutri-tional characteristics and physiological characteristics, enhancing the adaptive capacity of alfalfa and making it better adapted to external environmental changes.
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Duverger, D., L. Edvinsson, E. T. MacKenzie, A. Oblin, L. Rouquier, B. Scatton, and B. Zivkovic. "Concentrations of Putative Neurovascular Transmitters in Major Cerebral Arteries and Small Pial Vessels of Various Species." Journal of Cerebral Blood Flow & Metabolism 7, no. 4 (August 1987): 497–501. http://dx.doi.org/10.1038/jcbfm.1987.93.
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The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced. 5-Hydroxytryptamine concentrations in rats, cats, and rabbits were significantly greater in the small pial vessels, although measurable concentrations existed in the circle of Willis. In cats and monkeys, substance P was found in major arteries, but was not detectable at the level of the small pial vessels. The differences in the regional distribution of the various neurotransmitter candidates in the cerebrovascular bed may reflect their physiological significance.
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Yoo, Seon Pil, Myunggi Baik, Hyeok Joong Kang, Seung Ju Park, Da Jin Sol Jung, Beak Seok-Hyeon, and Inhyuk Jeong. "312 Effects of castration stress on behaviors and leukocyte cytokine gene expression in Korean cattle bull calves." Journal of Animal Science 97, Supplement_3 (December 2019): 8–9. http://dx.doi.org/10.1093/jas/skz258.015.
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Abstract This study investigated behavioral, physiological, and inflammatory responses, as well as leukocyte cytokine gene expression, of Korean cattle calves following surgical castration. Nineteen Korean cattle bull calves (average body weight, 254.5 kg; average age, 8.2 months) were assigned to one of two treatment groups: control (n = 9) and surgical castration (n = 10). Castration was performed surgically using Newberry knives and a Henderson castrating tool. Blood was collected immediately before castration and at 0.5 h, 6 h, 1 d, 3 d, 7 d, and 14 d after castration, and analyzed cortisol and substance P concentrations and leukocyte cytokine gene expression by quantitative real-time PCR. Behaviors were observed for 3 h, from 0.5 to 3.5 h after castration. Feed intake was recorded daily, and body weight was measured 1 d prior to the experiment and 14 d after castration. Castration decreased average daily gain (P = 0.005) and gain-to-feed ratio (P = 0.003). Castration reduced the time spent eating (P < 0.001) and the frequency of eating (P = 0.003) and increased (P < 0.001) the frequency of lying during the 3 h after castration. Castration temporarily increased circulating plasma cortisol (P < 0.001) and salivary cortisol concentrations (P = 0.03) at 0.5 h after castration. Castration temporarily increased (P < 0.05) plasma substance P concentration at 1 d after castration. Castration increased plasma haptoglobin concentration at 1 d and 3 d after castration. With regard to leukocytes, castration increased (P < 0.05) mRNA levels of inflammatory cytokine interleukin-1-beta and interleukin-1 receptor antagonist (IL1RA) genes at 6 h after castration, and increased (P < 0.05) IL1RA, interleukin-1-alpha, and interleukin-6 mRNA levels at 1 d after castration. In conclusion, castration of Korean cattle bull calves temporarily induced stress, retarded growth, and affected behaviors and inflammatory cytokine gene expression.
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Bouras, C., P. Schulz, J. Constantinidis, and R. Tissot. "Differential Effects of Acute and Chronic Administration of Haloperidol on Substance P and Enkephalins in Diverse Rat Brain Areas." Neuropsychobiology 16, no. 4 (1986): 169–74. http://dx.doi.org/10.1159/000118321.
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Cantó, Antolin, Teresa Olivar, Francisco Javier Romero, and María Miranda. "Nitrosative Stress in Retinal Pathologies: Review." Antioxidants 8, no. 11 (November 11, 2019): 543. http://dx.doi.org/10.3390/antiox8110543.
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Nitric oxide (NO) is a gas molecule with diverse physiological and cellular functions. In the eye, NO is used to maintain normal visual function as it is involved in photoreceptor light transduction. In addition, NO acts as a rapid vascular endothelial relaxant, is involved in the control of retinal blood flow under basal conditions and mediates the vasodilator responses of different substances such as acetylcholine, bradykinin, histamine, substance P or insulin. However, the retina is rich in polyunsaturated lipid membranes and is sensitive to the action of reactive oxygen and nitrogen species. Products generated from NO (i.e., dinitrogen trioxide (N2O3) and peroxynitrite) have great oxidative damaging effects. Oxygen and nitrogen species can react with biomolecules (lipids, proteins and DNA), potentially leading to cell death, and this is particularly important in the retina. This review focuses on the role of NO in several ocular diseases, including diabetic retinopathy, retinitis pigmentosa, glaucoma or age-related macular degeneration (AMD).
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Okoli, Chizimuzo, Jonathan Kodet, and Heather Robertson. "Behavioral and Physiological Responses to Nicotine Patch Administration Among Nonsmokers Based on Acute and Chronic Secondhand Tobacco Smoke Exposure." Biological Research For Nursing 18, no. 1 (April 15, 2015): 60–67. http://dx.doi.org/10.1177/1099800415579261.
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Introduction: Despite the large amount that is known about the physical health effects of secondhand tobacco smoke (SHS) exposure, little is known about the behavioral health effects. Nicotine, the principle psychoactive substance in SHS, elicits subjective mood and physiological responses in nonsmokers. However, no studies have examined the subjective mood or physiological responses to nicotine in nonsmokers while accounting for prior chronic or acute SHS exposure. Methods: A 7-mg nicotine patch was administered to 17 adult nonsmokers for 2 hr. Main outcome measures obtained at ½ hr, 1 hr, and 2 hr were subjective behavioral drug effects (based on eleven 10-cm Visual Analog Scales [VASs]) and the physiological measures of heart rate, blood pressure, and serum nicotine levels. Analysis of outcome data was based on participants’ chronic (using hair nicotine) or acute (using saliva cotinine) SHS exposure. Results: Greater chronic SHS exposure was negatively associated with pleasurable responses to nicotine administration (“drug feels good” score at 2-hr time point, Spearman’s ρ = −.65, p < .004), whereas greater acute SHS exposure was associated with positive responses (“like feeling of drug” score at 2-hr time point, Spearman’s ρ = .63, p < .01). There were no associations between chronic or acute exposure and physiological changes in response to nicotine administration. Discussion: The findings of this study may be useful in providing preliminary empirical data for future explorations of the mechanism whereby SHS exposure can influence behavioral outcomes in nonsmokers. Such studies can inform future interventions to reduce the physical and behavioral health risks associated with SHS exposure.
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Colombo, Eduardo, Reinaldo F. Cooke, Alice Brandão, Jacob Wiegand, Kelsey Schubach, CiCi A. Sowers, Glenn Duff, Vinicius N. Gouvea, and Bruno I. Cappellozza. "268 Administering an appeasing substance to optimize welfare and performance of receiving cattle." Journal of Animal Science 98, Supplement_4 (November 3, 2020): 193. http://dx.doi.org/10.1093/jas/skaa278.355.
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Abstract This experiment evaluated the impacts of bovine appeasing substance (BAS) administration on performance, health, and physiological responses of feedlot cattle during a 45-d receiving period. A total of 342 recently-weaned Angus-influenced steers, originating from 16 cow-calf operations, were obtained from an auction yard on d -1 and road-transported (12 h) to the feedlot. Upon arrival on d 0, body weight (BW) was recorded and steers were ranked by BW and source and assigned to receive BAS (Nutricorp, Araras, SP, Brazil; n = 171) or placebo (diethylene glycol monoethyl ether; CON; n = 171). Treatments (5 mL) were topically applied to the nuchal skin area of each animal. Within treatment, calves were allocated to 1 of 24 drylot pens (12 pens/treatment) and received a free choice total-mixed ration from d 1 to 45. Calves were assessed for bovine respiratory disease (BRD) signs and feed intake was recorded from each pen daily. Steer BW was again recorded on d 1, 7, 17, 31, and 45, whereas blood samples were collected from 5 steers/pen concurrently with each BW assessment. Average daily gain was greater (P = 0.05) in BAS vs. CON calves, although final BW did not differ (P = 0.36) between treatments. No treatment effects were detected for feed intake (P = 0.95), resulting in greater (P = 0.05) feed efficiency in BAS vs. CON steers. No treatment effects were detected (P ≥ 0.37) for plasma concentrations of haptoglobin, whereas plasma cortisol concentrations were greater (P = 0.05) in CON vs. BAS steers on d 7 (treatment × day; P = 0.07). Incidence of BRD was greater (P ≤ 0.05) in BAS vs. CON on d 6 to 10 and d 18 to 21 (treatment × day; P < 0.01), although overall BRD incidence did not differ (P = 0.24) between treatments. The number of antimicrobial treatments required per steer diagnosed with BRD symptoms to recover from sickness was greater (P = 0.04) in CON vs. BAS calves. No treatment differences were detected (P ≥ 0.41) for mortality incidence, or proportion of steers removed from the experiment due to extreme sickness. Results from this experiment indicate BAS administration upon feedlot entry improved average daily gain by enhancing feed efficiency. Administration of BAS facilitated earlier detection of BRD and reduced the need for antimicrobial treatments. Collectively, these results suggest BAS administration as a promising strategy to benefit performance and immunocompetence of feedlot receiving cattle.
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Schmid, H. A., L. Jansky, and F. K. Pierau. "Temperature sensitivity of neurons in slices of the rat PO/AH area: effect of bombesin and substance P." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 264, no. 2 (February 1, 1993): R449—R455. http://dx.doi.org/10.1152/ajpregu.1993.264.2.r449.
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The effects of bombesin (Bom) and substance P (SP) were investigated in 156 temperature-sensitive and -insensitive neurons in slices of the preoptic and anterior hypothalamic area (PO/AH) of rats. Application of Bom increased the firing rate (FR) in 68% (n = 38) of the warm-sensitive and in 62% (n = 39) of the temperature-insensitive neurons. One cold-sensitive neuron was excited; a second was not affected by the peptide. No neuron decreased its activity after Bom application. SP excited 80% (n = 15) of the warm-sensitive neurons and 48% (n = 29) of the temperature-insensitive neurons. Two cold-sensitive neurons were inhibited by SP, a third one was not affected. The opposite effect on thermoregulation in vivo caused by the two peptides cannot be explained simply by their relatively similar excitatory effects on the FR of PO/AH neurons. After Bom application the temperature coefficient (TC) was significantly elevated in 7 out of 11 warm-sensitive neurons and in 19 out of 21 temperature-insensitive neurons. After SP application the TC was significantly reduced in 6 out of 7 warm-sensitive and 1 out of 12 temperature-insensitive neurons. Bom caused grouped discharges (bursts) in 7 out of 42 PO/AH neurons; SP never produced bursts in the discharge pattern. The increase of the TC of warm-sensitive and the transformation of temperature-insensitive into warm-sensitive neurons by Bom might be regarded as the neurophysiological basis for the decreased body temperature after Bom application. It is concluded that the temperature sensitivity of PO/AH neurons is not an unchangeable inherent property of certain cells but may be altered or even evoked by physiological processes like the release of neuromodulators.
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Wang, Tobias, Michael Axelsson, Jorgen Jensen, and J. Michael Conlon. "Cardiovascular actions of python bradykinin and substance P in the anesthetized python, Python regius." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 2 (August 1, 2000): R531—R538. http://dx.doi.org/10.1152/ajpregu.2000.279.2.r531.
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The cardiovascular actions of python bradykinin (BK) and substance P (SP) have been investigated in the anesthetized ball python, Python regius. Bolus intra-arterial injections of python BK (0.03–3 nmol/kg) produced concentration-dependent increases in arterial blood pressure, heart rate (HR), and cardiac output concomitant with small decreases in systemic resistance and stroke volume. Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in circulating concentration of norepinephrine, but epinephrine levels did not change. BK-induced tachycardia was attenuated (>90%) by the β-adrenergic receptor antagonist sotalol, and the hypertensive response was attenuated (>70%) by the α-adrenergic receptor antagonist prazosin, indicating that effects of python BK are mediated at least in part by activation of the extensive network of adrenergic neurons present in vascular tissues. Bolus intra-arterial injections of python SP in the range 0.01–30 pmol/kg produced concentration-dependent decreases in arterial blood pressure and systemic peripheral resistance concomitant with increases in cardiac output and stroke volume but with only minor effects on HR. The data suggest that kinins play a physiologically important role in cardiovascular regulation in the python.
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Frase, Sibylle, Franziska Löffler, and Jonas A. Hosp. "Enhancing Post-Stroke Rehabilitation and Preventing Exo-Focal Dopaminergic Degeneration in Rats—A Role for Substance P." International Journal of Molecular Sciences 23, no. 7 (March 31, 2022): 3848. http://dx.doi.org/10.3390/ijms23073848.
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Dopaminergic signaling is a prerequisite for motor learning. Delayed degeneration of dopaminergic neurons after stroke is linked to motor learning deficits impairing motor rehabilitation. This study investigates safety and efficacy of substance P (SP) treatment on post-stroke rehabilitation, as this neuropeptide combines neuroprotective and plasticity-promoting properties. Male Sprague Dawley rats received a photothrombotic stroke within the primary motor cortex (M1) after which a previously acquired skilled reaching task was rehabilitated. Rats were treated with intraperitoneal saline (control group, n = 7) or SP-injections (250 µg/kg) 30 min before (SP-pre; n = 7) or 16 h (SP-post; n = 6) after rehabilitation training. Dopaminergic neurodegeneration, microglial activation and substance P-immunoreactivity (IR) were analyzed immunohistochemically. Systemic SP significantly facilitated motor rehabilitation. This effect was more pronounced in SP-pre compared to SP-post animals. SP prevented dopaminergic cell loss after stroke, particularly in the SP-pre condition. Despite its proinflammatory propensity, SP administration did not increase stroke volumes, post-stroke deficits or activation of microglia in the midbrain. Finally, SP administration prevented ipsilesional hypertrophy of striatal SPergic innervation, particularly in the SP-post condition. Mechanistically, SP-pre likely involved plasticity-promoting effects in the early phase of rehabilitation, whereas preservation of dopaminergic signaling may have ameliorated rehabilitative success in both SP groups during later stages of training. Our results demonstrate the facilitating effect of SP treatment on motor rehabilitation after stroke, especially if administered prior to training. SP furthermore prevented delayed dopaminergic degeneration and preserved physiological endogenous SPergic innervation.
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Kuprash, Liana, Tetyana Panteleymonova, Ludmila Sharabura, Sergiy Mykhalskiy, Pavlo Klymenko, Sergey Lugovskoy, Valentyn Nepomnyashchy, Nina Sykalo, and Vladislav Bezrukov. "Pharmacology-based toxicity assessment of molsidomine and ATP-LONG combination with singular and repetitive injections under experimental conditions." Ageing & Longevity 2, no. 3 2021 (October 6, 2021): 1–13. http://dx.doi.org/10.47855/jal9020-2021-3-1.
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Abstract. The aim of the work was to study toxic properties of the new combined drug which comprise nitrovasodilator molsidomine and adenosine- 5’-triphosphate in a form of coordination compound with histidine, magnesium, and potassium (ATP-LONG). The drug was examined for its acute and subacute toxicity on Balb/c mice and Wistar rats of reproductive age with peroral (p/o) and sublingual (s/l) administrations. It has been established that LD50 of the substance contains over 10000 mg/kg (p/o) and 5010 mg/kg (s/l), which corresponds to the category of Practically non-toxic substances. The repetitive administrations within a 28 day period of the conditionally therapeutic dose of 260 mg/hg (s/l) did not cause any negative impact on physiological, biochemical, histological values in male and female rats. In doses 1300 and 2080 mg/kg, which exceed conditionally therapeutic doses by 5 and 8 times, the combination was not changing clinical laboratory urine and blood values but induced histological changes such as dilation and plethora of capillaries along with edema of smooth muscle cells of the brain, myocardium, liver, spleen, kidneys, and adrenal glands in rats. Additionally, the particular dosages of the combined substance provoked irritation of the mucous membrane of the tongue. Detected effects of the drug do not carry any pathological character and can be viewed as a specific reaction of the organism to high doses of nitrovasodilator. However, the duration and reversibility of unwanted consequences of molsidomine overdose, particularly in its combined form, need further investigation. Keywords: combination of molsidomine and ATP-LONG, acute and subacute toxicity
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Esteban, Francisco, Pablo Ramos-García, Miguel Muñoz, and Miguel Ángel González-Moles. "Substance P and Neurokinin 1 Receptor in Chronic Inflammation and Cancer of the Head and Neck: A Review of the Literature." International Journal of Environmental Research and Public Health 19, no. 1 (December 30, 2021): 375. http://dx.doi.org/10.3390/ijerph19010375.
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Head and neck cancer is a growing worldwide public health problem, accounting for approximately 1,500,000 new cases and 500,000 deaths annually. Substance P (SP) is a peptide of the tachykinin family, which has roles related to a large number of physiological mechanisms in humans. The implications of SP in carcinogenesis have recently been reported through the stimulation of the neurokinin 1 receptor (NK1R), or directly, through the effects derived from the constitutive activation of NK1R. Consequently, SP/NK1R seems to play relevant roles in cancer, upregulating cell proliferation, cell migration and chronic inflammation, among other oncogenic actions. Furthermore, there is growing evidence pointing to a central role for SP in tumour progression, singularly so in laryngeal and oral squamous cell carcinomas. The current narrative review of the literature focuses on the relationship between the SP/NK1R system and chronic inflammation and cancer in the head-and-neck region. We described a role for SP/NK1R in the transition from chronic inflammation of the head and neck mucosa, to preneoplastic and neoplastic transformation and progression.
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LANGENFELD, M. R., S. NAKHLA, A. K. DEATH, W. JESSUP, and D. S. CELERMAJER. "Endothelin-1 plus oxidized low-density lipoprotein, but neither alone, increase human monocyte adhesion to endothelial cells." Clinical Science 101, no. 6 (November 21, 2001): 731–38. http://dx.doi.org/10.1042/cs1010731.
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Endothelin-1 is a potent vasoconstrictor and mitogenic peptide that is implicated in the atherosclerosis of apolipoprotein E-deficient mice and may promote atherogenesis in humans. We hypothesized that endothelin-1 might promote the adhesion of monocytes to endothelial cells, a key early event in atherosclerosis. We investigated the adhesion of primary human monocytes (isolated by elutriation) to human umbilical vein endothelial cell cultures after incubation with endothelin-1 (0.1 and 0.01nM; approximately physiological concentrations), copper-oxidized low-density lipoprotein (LDL) (0.1mg/ml) and a combination of the two. After a 4h incubation with 0.1 or 0.01nM endothelin-1 combined with oxidized LDL, adhesion was increased to 120±4% (P < 0.001 compared with control) and 118±4% (P < 0.002) respectively, whereas neither substance alone increased adhesion (92-104% of control values; not significant). Neither endothelin receptor A blockade nor co-incubation with anti-fibronectin antibody inhibited the pro-adhesive effects of endothelin-1 plus oxidized LDL (115±7% and 115±3% of control compared with 120±4% respectively; not significant). Endothelial cell expression of intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin were unchanged throughout the experiment. Therefore physiological concentrations of endothelin-1 and oxidized LDL may act synergistically to increase the adhesion of human monocytes to endothelial cells, contributing in part to the observed pro-atherogenic effects of endothelin-1.
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CELLAT, Mustafa, and Cafer Tayer İŞLER. "Ratlarda intravenöz kontrast madde uygulamasının göz içi basıncı, göz yaşı miktarı ve oksidatif stres üzerine etkileri." Journal of Advances in VetBio Science and Techniques 7, no. 2 (August 31, 2022): 169–78. http://dx.doi.org/10.31797/vetbio.1087898.
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Although iodinated radiocontrast agents, which are frequently used in radiological procedures such as indirect radiography, angiography, intravenous urography and computed tomography, are generally safe, they can cause serious side effects. In this study, it was aimed to investigate the effect of intravenous ionic high osmolar contrast agent administration on intraocular pressure, tear amount and oxidant and antioxidant parameters of eye tissue. Study groups consisted of 2 groups, Group 1 (Control) and Group 2 (Urographin), and a total of 16 Wistar albino female rats were used. On the first day of the experiment, 6 ml/kg of physiological saline was administered intravenously to the control group, and the same dose of contrast agent was administered to group 2. Intraocular pressure and tear amounts were measured at 1, 6, 12, 24 and 48 hours after intravenous administration. After measurements were made at the 48th hour of the experiment, all rats were euthanized and their eye tissues were removed. In order to reveal the oxidative damage and antioxidant activity in the eye tissue, malondialdehyde and reduced glutathione levels, catalase and glutathione peroxidase enzyme activities were measured spectrophotometrically. Schimer tear test (STT-1) strip was used for tear amount measurements, and rebound tonometer Tonovet® was used as tonometer for intraocular pressure measurements. No statistically significant difference was found between the control and urographin groups in terms of intraocular pressure and tear amounts in the measurements performed at 1,6,12,24 and 48th hours after urographin administration. It was observed that the same application significantly increased the malondialdehyde level (P<0.005) in the eye tissue. There was no significant difference between the groups in terms of reduced glutathione level and catalase and glutathione peroxidase enzyme activities in eye tissue. It was evaluated that intravenous contrast agent administration causes oxidative stress in the eye tissue and this may have a long-term ocular effect
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Osório, F. L., A. E. M. Barbar, M. F. Donadon, and J. A. S. Crippa. "A Single Dose of Oxytocin on Music Performance Anxiety: Results Involving a Situation of Simulated Performance." European Psychiatry 41, S1 (April 2017): S110. http://dx.doi.org/10.1016/j.eurpsy.2017.01.1882.
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IntroductionMusic performance anxiety (MPA) is a persistent and distressing experience that involves apprehension linked with musical performance in public (individual or collective). Anxious individuals concentrate their anxiety in situations that involve social scrutiny, favoring distorted, dysfunctional, and negative interpretations of that situation followed by experiences of physiological symptoms associated with the exposure. The most commonly used substances in the pharmacological management of MPA are beta-blockers and benzodiazepines. However, these options are not fully efficient and cause relevant side effects that interfere mainly with performance. Therefore, investigations on alternative substances to treat MPA are highly opportune.ObjectiveTo assess the acute effects of oxytocin (OT) on physiological and cognitive variables during an experimental model of simulated performance.MethodsWe assessed 12 musicians with MPA pre-treated with intranasal OT (24 UI) or placebo in a crossover trial involving an experimental situation of public performance. Cognitive and physiological measures (heart rate, blood pressure, salivary cortisol) were recorded before/during performance (anticipatory performance anxiety). Statistical analyses were made using Stata Direct.ResultsThe results showed no effects of OT on physiological symptoms (P > 0.190). In respect to anticipatory anxiety, however, we found a tendency for OT to reduce negative cognitions associated with music performance (P = 0.06). No side effects were reported by musicians throughout the trial.ConclusionThese tendencies, if confirmed through the expansion of the sample, have important implications for the practice of amateur and professional musicians who could benefit from interventions as the one described, possibly with a lesser impact of side effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Joad, J. P., K. S. Kott, and A. C. Bonham. "Exposing guinea pigs to ozone for 1 wk enhances responsiveness of rapidly adapting receptors." Journal of Applied Physiology 84, no. 4 (April 1, 1998): 1190–97. http://dx.doi.org/10.1152/jappl.1998.84.4.1190.
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Acute exposure to ozone causes changes in breathing pattern and lung function which may be caused in part by stimulation of rapidly adapting receptors (RARs). The consequences of repeated daily ozone exposure on RAR responsiveness are unknown, although ozone-induced changes in pulmonary function diminish with repeated exposure. Accordingly, we investigated whether repeated daily ozone exposure diminishes the general responsiveness of RARs. Guinea pigs ( n = 30) were exposed to 0.5 parts/million ozone or filtered air (8 h/day for 7 days). The animals were then anesthetized, and RAR impulse activity, dynamic compliance (Cdyn), and lung resistance were recorded at baseline and in response to four stimuli: substance P, methacholine, hyperinflation, and removal of positive end-expiratory pressure. Repeated daily ozone exposure exaggerated RAR responses to substance P, methacholine, and hyperinflation without causing physiologically relevant effects on baseline or substance P- and methacholine-induced changes in Cdyn and lung resistance. Because agonist-evoked changes in RAR activity preceded Cdyn changes, the data suggest that repeated daily ozone exposure enhances RAR responsiveness via a mechanism other than changes in Cdyn.
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Kawsar, Sarkar M. A., Khaleda Mymona, Refat Asma, Mohammad A. Manchur, Yasuhiro Koide, and Yasuhiro Ozeki. "Infrared, <sup>1</sup>H-NMR Spectral Studies of some Methyl 6-O-Myristoyl-α-D-Glucopyranoside Derivatives: Assessment of Antimicrobial Effects." International Letters of Chemistry, Physics and Astronomy 58 (September 2, 2015): 122–36. http://dx.doi.org/10.56431/p-v4hx32.
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This study was carried out to regioselective myristoylation of methyl α-D-glucopyranoside (1) using the direct acylation method gave the corresponding methyl 6-O-myristoyl-α-D-glucopyranoside (2) in fair yield. A number of 2,3,4-tri-O-acyl derivatives (3-15) of this 6-O-substitution product using a wide variety of acylating agents were also prepared in order to obtain newer derivatives of synthetic and biological importance. The reaction conditions are reasonably simple and yields were very good. The structures of the title compounds (2-15) were established by using analytical, physicochemical techniques and spectroscopic data (IR and 1H-NMR). All the synthesized compounds were employed as test chemicals for in vitro antimicrobial functionality test against Gram-positive Bacillus subtilis, Staphylococcus aureus, Gram-negative Escherichia coli, Pseudomonas aeruginosa bacteria and plant pathogenic fungi Aspergillus niger and Candida albicans. For comparative studies, antimicrobial activity of standard antibiotics, Ampicillin and Nystatin were also carried out against these microorganisms. The study revealed that the tested samples exhibited moderate to good antibacterial and antifungal activities. It was also observed that the test substances were more effective against fungal phytopathogens than those of the human bacterial strains. Encouragingly, a number of tested chemicals showed nearest antibacterial and antifungal activities with the standard antibiotics employed.
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Marques, Rodrigo S., Keenan Kvamme, Vinicius Cruz, Eduardo Colombo, and Reinaldo Cooke. "2 Effects of Multiple Bovine Appeasing Substance Administration During a 42-Day Preconditioning Program on Physiologic, Health, and Performance Responses of Feeder Cattle." Journal of Animal Science 100, Supplement_4 (October 22, 2022): 14–16. http://dx.doi.org/10.1093/jas/skac313.020.
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Abstract This experiment evaluated the effects of multiple bovine appeasing substance administration during a 42-day preconditioning program followed by feedlot receiving period on productivity, health, and physiological variables of feeder cattle. Ninety recently weaned calves were obtained from Red Bluff Ranch (Norris, MT). All calves were weaned and weighed (prior to transport). Calves were loaded into a livestock trailer, transported for 70 km, and unloaded at the Bozeman Agricultural Research and Teaching Farm for a 42-day preconditioning program. Upon arrival, calf body weight was recorded, and both pre- and post-transport body weight were averaged and used as calf weaning initial body weight. Calves were sorted by body weight, sex, and age, and assigned to receive 1) multiple administration of bovine appeasing substance at weaning (d0), d 14, 28, and before transport and feedlot entry (d 42; BAS; RSEA Group, Quartier Salignan, France), or 2) placebo (diethylene glycol monoethyl ether; CON). Treatments (5 mL) were applied topically to the nuchal skin area of each animal every 14 d during the preconditioning period. Calves within treatment groups were ranked by initial BW, sex, and age, and allocated to 1 of 18 drylot pens. On day 42, calves were combined within treatment group, loaded into 2 different single double-deck commercial livestock trailers, and transported for 1000 km (approximately 16 h). Upon arrival (day 43), calves were unloaded at the same feedyard and with the same pen distribution used prior to transport and fed ad libitum a TMR diet. Blood samples were collected on day 0 (weaning), 3, 7, 14, 21, 28, 42 (prior transport), 43 (feedlot arrival), 46, 50, 57, 64 and 90. Average daily gain and final BW did not differ (P > 0.52) between BAS and CON calves in both the preconditioning and receiving phases. No treatment effects were also detected (P > 0.44) for daily TMR intake in any of the phases. Overall feed efficiency did not differ between BAS and CON calves (P > 0.54). No treatment effects were detected (P = 0.98) for plasma concentrations of cortisol. A treatment × day interaction was detected (P < 0.001) for plasma haptoglobin concentrations, which was greater (P < 0.01) in CON on day 3 and 7 vs. BAS calves. Therefore, multiple applications of BAS mitigated an acute-phase response associated with accumulative stress caused by weaning, transport, and vaccination.
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Mori, Takahide, Minoru Irahara, Haruhiko Saito, Yoshio Ohno, and Eiji Hosoi. "Inhibitory action of somatostatin on meiotic maturation of cultured porcine follicular ova." Acta Endocrinologica 110, no. 3 (November 1985): 408–12. http://dx.doi.org/10.1530/acta.0.1100408.
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Abstract. To investigate the physiological importance of somatotrophin release-inhibiting factor (SRIF), effects in vitro of synthetic SRIF 14 on germinal vesicle breakdown (GVB) of cultured porcine follicular ova were studied. The proportion of ova with GVB decreased gradually and significantly with increasing concentrations of SRIF 14 in the range from 6 × 10−12 to 6 × 10−7 m during a 22 h period of culture. The inhibitory effect was apparent for the period between 14 and 22 h in the course of culture but was reversed by a concomitant addition of anti-SRIF to the medium. Neither synthetic oxytocin, vasoactive intestinal polypeptide nor substance P exerted any inhibitory or stimulatory action on GVB. These results suggest a limited but definite inhibitory action of SRIF on GVB of porcine ova.
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Kanazawa, H., H. Kamoi, T. Kawaguchi, S. Shoji, T. Fujii, S. Kudoh, K. Hirata, and J. Yoshikawa. "PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs." American Journal of Physiology-Lung Cellular and Molecular Physiology 272, no. 6 (June 1, 1997): L1066—L1069. http://dx.doi.org/10.1152/ajplung.1997.272.6.l1066.
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Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.
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Joborn, Henrik, Rolf Larsson, Jonas Rastad, Peter Nygren, Göran Åkerström, and Sverker Ljunghall. "Vasoactive intestinal polypeptide stimulates parathyroid hormone release by interaction with cyclic adenosine monophosphate production of bovine parathyroid cells." Acta Endocrinologica 124, no. 1 (January 1991): 54–59. http://dx.doi.org/10.1530/acta.0.1240054.
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Abstract. Influence of vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and substance P was investigated on dispersed parathyroid cells of adult cattle. At a physiological concentration of extracellular calcium, vasoactive intestinal polypeptide stimulated the parathyroid hormone release in a dose-dependent manner, whereas no effects were noted for the other peptides. The dependency of PTH secretion upon extracellular calcium was shifted to the right by vasoactive intestinal polypeptide at 10−6 mol/l, with a tendency for greater effects at low (0.5 mmol/l) than high concentrations (2.0-3.0 mmol/l) of the cation. Vasoactive intestinal polypeptide significantly enhanced cAMP release of the parathyroid cells, whereas no influence was noted on cytoplasmic calcium or pH within the cells. The results suggest that vasoactive intestinal polypeptide stimulates the PTH release by interaction with cAMP production of the parathyroid cells. This effect may contribute to the development of hypercalcemia in patients with neuroendocrine tumours secreting vasoactive intestinal polypeptide.
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Hinson, J. P., and S. Kapas. "Effects of sodium depletion on the response of rat adrenal zona glomerulosa cells to stimulation by neuropeptides: actions of vasoactive intestinal peptide, enkephalin, substance P, neuropeptide Y and corticotrophin-releasing hormone." Journal of Endocrinology 146, no. 2 (August 1995): 209–14. http://dx.doi.org/10.1677/joe.0.1460209.
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Abstract There are several neuropeptides, present in nerves supplying the rat adrenal zona glomerulosa, which have been shown to stimulate aldosterone secretion in the intact perfused rat adrenal preparation. The purpose of the present study was twofold: first, to determine whether these peptides acted directly on adrenocortical cells by examining their effects on collagenase-dispersed rat zona glomerulosa cells, and second, to investigate the likely physiological significance of these actions, by determining whether the responses of zona glomerulosa cells to neuropeptides were changed by prior sodium depletion. Of the peptides tested, neuropeptide Y (NPY) and substance P had only a minor effect on aldosterone secretion, which was not substantially affected by sodium depletion. Corticotrophin-releasing hormone (CRH) had a significant stimulatory effect on aldosterone secretion, but neither the threshold concentration for significant stimulation nor the maximal response to stimulation were altered by prior sodium depletion. Vasoactive intestinal peptide (VIP), on the other hand, had little effect on aldosterone secretion by cells from normal animals, but was a potent stimulus to aldosterone secretion in cells obtained from sodium-depleted animals. The response to the Met-enkephalin analogue, [d-Ala2-Met2]-enkephalinamide (DALA), was also significantly enhanced by prior sodium depletion. Experiments using the angiotensin II receptor blocker, saralasin, were carried out to determine whether the enhanced actions of DALA and VIP seen in sodium depletion may be a result of activation of angiotensin II receptors, known to be increased in sodium depletion. Saralasin did not affect the response to either peptide. These data suggest that all the peptides tested may be able to stimulate aldosterone secretion. However, the data obtained with substance P, NPY and CRH do not support a major role for these peptides in the regulation of aldosterone secretion either under control conditions, or in sodium depletion. The finding that the responses to VIP and DALA were altered by sodium depletion suggests that the actions of VIP and opioid peptides may have physiological significance in the regulation of aldosterone secretion in response to sodium depletion. Furthermore, the observation that saralasin does not inhibit the responses to these peptides strongly suggests that they are not acting through angiotensin II receptors, and may indicate altered VIP- and opioid-receptor regulation in sodium depletion. Journal of Endocrinology (1995) 146, 209–214
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Nevadunsky, Nicole S., and Ursula A. Matulonis. "Chemotherapy-induced Nausea and Vomiting." Oncology & Hematology Review (US) 05, no. 01 (2009): 10. http://dx.doi.org/10.17925/ohr.2009.05.1.10.
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Nausea and vomiting are commonly observed and feared side effects of chemotherapy. Understanding of the physiological mechanisms of chemotherapy-induced nausea and vomiting (CINV) has led to the development of several classes of anti-emetic, including substance P antagonists, serotonin antagonists, and dopamine antagonists. The newest of these agents include aprepitant and palonosetron, which are very effective in treating emesis in highly emotegenic chemotherapies. Several organizations, including the Multinational Association of Supportive Care in Cancer (MASCC), the National Comprehensive Cancer Network (NCCN), and the American Society of Clinical Oncology (ASCO), have developed guidelines for classification and treatment of CINV. The aim of this article is to summarize current gold standards of anti-emetics and treatment guidelines, as well as introducing innovations such as approaches to breakthrough and refractory nausea and vomiting, alternative therapies, and transdermal delivery systems.
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Gokbayrak, Zeliha, and Hakan Engin. "Brassinosteroids and gibberellic acid: effects on in vitro pollen germination in grapevine." OENO One 51, no. 3 (September 22, 2017): 303. http://dx.doi.org/10.20870/oeno-one.2017.51.4.1862.
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<p style="text-align: justify;">Many physiological processes related to plant growth and development are under the influence of growth regulators, which also have an impact on pollen germination. In this study, the effects of two brassinosteroid compounds, epibrassinolide and 22S,23S-homobrassinolide, and gibberellic acid (GA<sub>3</sub>) on <em>in vitro</em> pollen germination of two table grape cultivars, ‘Italia’ and ‘Cardinal’ (<em>Vitis vinifera</em> L.), were determined. A total of 28 treatments, alone and in combination, were applied to freshly collected pollens which were sown on a basic medium with 1% agar and 20% sucrose. Petri dishes were kept at 26±1°C for 24 hours. Counting of the germinated pollens revealed that the effects of these plant hormones were cultivar- and substance-specific. The cultivar ‘Italia’ was not influenced by the treatments (the highest germination ratio being 44.4% from 0.001 mg L<sup>-1</sup> epibrassinolide) as opposed to the cultivar ‘Cardinal’. The highest germination ratio in ‘Cardinal’ was about 50% in pollens treated with 25 mg L<sup>-1</sup> GA<sub>3</sub> + 0.01 mg L<sup>-1</sup> epibrassinolide. The control group resulted in 32.38% germination. Combining GA<sub>3</sub> with epibrassinolide provided slightly higher germination ratios compared to combining GA<sub>3</sub> with 22S,23S-homobrassinolide. </p>
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Drake, Matthew G., Gregory D. Scott, Emily D. Blum, Katherine M. Lebold, Zhenying Nie, James J. Lee, Allison D. Fryer, Richard W. Costello, and David B. Jacoby. "Eosinophils increase airway sensory nerve density in mice and in human asthma." Science Translational Medicine 10, no. 457 (September 5, 2018): eaar8477. http://dx.doi.org/10.1126/scitranslmed.aar8477.
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In asthma, airway nerve dysfunction leads to excessive bronchoconstriction and cough. It is well established that eosinophils alter nerve function and that airway eosinophilia is present in 50 to 60% of asthmatics. However, the effects of eosinophils on airway nerve structure have not been established. We tested whether eosinophils alter airway nerve structure and measured the physiological consequences of those changes. Our results in humans with and without eosinophilic asthma showed that airway innervation and substance P expression were increased in moderate persistent asthmatics compared to mild intermittent asthmatics and healthy subjects. Increased innervation was associated with a lack of bronchodilator responsiveness and increased irritant sensitivity. In a mouse model of eosinophilic airway inflammation, the increase in nerve density and airway hyperresponsiveness were mediated by eosinophils. Our results implicate airway nerve remodeling as a key mechanism for increased irritant sensitivity and exaggerated airway responsiveness in eosinophilic asthma.
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Sun, Yunfeng, Yinling Zhang, Ning He, Xufeng Liu, and Danmin Miao. "Caffeine and Placebo Expectation." Journal of Psychophysiology 21, no. 2 (January 2007): 91–99. http://dx.doi.org/10.1027/0269-8803.21.2.91.
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Abstract. Caffeine placebo expectation seems to improve vigilance and cognitive performance. This study investigated the effect of caffeine and placebo expectation on vigilance and cognitive performance during 28 h sleep deprivation. Ten healthy males volunteered to take part in the double-blind, cross-over study, which required participants to complete five treatment periods of 28 h separated by 1-week wash-out intervals. The treatments were no substance (Control); caffeine 200 mg at 00:00 (C200); placebo 200 mg at 00:00 (P200); twice caffeine 200 mg at 00:00 and 04:00 (C200-C200); caffeine 200 mg at 00:00 and placebo 200 mg at 04:00 (C200-P200). Participants were told that all capsules were caffeine and given information about the effects of caffeine to increase expectation. Vigilance was assessed by a three-letter cancellation test, cognitive functions by the continuous addition test and Stroop test, and cardiovascular regulation by heart rate and blood pressure. Tests were performed bihourly from 00:00 to 10:00 of the second day. Results indicated that C200-P200 and C200-C200 were more alert (p < .05) than Control and P200. Their cognitive functions were higher (p < .05) than Control and P200. Also, C200-P200 scored higher than C200 in the letter cancellation task (p < .05). No test showed any significant differences between C200-P200 and C200-C200. The results demonstrated that the combination of caffeine 200 mg and placebo 200 mg expectation exerted prolonged positive effects on vigilance and cognitive performance.
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Sembries, Sabine, Gerhard Dongowski, Gisela Jacobasch, Katri Mehrländer, Frank Will, and Helmut Dietrich. "Effects of dietary fibre-rich juice colloids from apple pomace extraction juices on intestinal fermentation products and microbiota in rats." British Journal of Nutrition 90, no. 3 (September 2003): 607–15. http://dx.doi.org/10.1079/bjn2003925.
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Effects of colloids isolated from apple pomace extraction juices (so-called B-juices) produced by enzymic liquefaction on food intake, body and faecal weights, short-chain fatty acid (SCFA) profile and selected intestinal microbiota were investigated in rats. Ten male Wistar rats per group were fed diets without any apple dietary fibre (DF) (control) or supplement with 5 % B-juice colloids or an alcohol-insoluble substance (AIS) from apples for 6 weeks. Rats fed with apple DF (5 % B-juice colloids or AIS) gained less weight than control rats (P<0·05). B-juice colloids did not affect food intake, whereas feeding AIS resulted in a 10% higher food consumption than in control rats. Both juice colloids and AIS increased the weight of caecal contents in rats and lowered luminal pH values (P<0·05). In addition, SCFA concentrations and total yields were also raised (P<0·05) in caecum of these rats indicating good fermentability of apple substrates by gut microflora. Distinctly higher concentrations of acetate and propionate were found in intestinal contents of juice colloid-fed rats (P< 0·05), whereas AIS also increased butyrate yield. Changes in microbiota due to apple DF in diets were restricted in the caecum to theEubacterium rectalecluster (AIS;P<0·05) and in faeces to theBacteroidaceae(juice colloids and AIS;P<0·05). The present study shows the physiological effects of apple DF isolated from pomace extraction juices produced by enzymic liquefaction on intestinal fermentation. Results may be helpful for the development of such innovative juice products that are rich in DF of fruit origin.
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De Sanctis, G. T., E. M. App, J. K. Trask, B. I. De Sanctis, J. E. Remmers, F. H. Green, S. F. Man, and M. King. "Resorptive clearance and transepithelial potential difference in capsaicin-treated F344 rats." Journal of Applied Physiology 68, no. 5 (May 1, 1990): 1826–32. http://dx.doi.org/10.1152/jappl.1990.68.5.1826.
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The long-term effects of substance P (SP) depletion on epithelial integrity were assessed by measurements of airway transepithelial potential difference (PD) and resorptive clearance. Both techniques are highly sensitive to differences in epithelial permeability. PD (mV) was assayed with a KCl-saturated agar bridge technique in the lower trachea of Fischer 344 rats depleted of SP by neonatal capsaicin treatment. Capsaicin treatment is known to ablate a subpopulation of primary afferent fibers containing SP. Resorptive clearance (clearance in 1 h) was measured with 99mTc-labeled diethylenetriaminepentaacetic acid administered as a 100-microliters (100 microCi) bolus. Depletion of SP by neonatal treatment with capsaicin resulted in a highly significant increase in resorptive clearance (P less than 0.001). There was also a significant difference in PD in the lower trachea, the values being less negative for the capsaicin-treated rats (P less than 0.005). The increase in resorptive clearance may reflect the leakiness of the epithelial membrane, as also suggested by the decrease in PD. Aside from its known involvement as a neurotransmitter in neurogenic inflammation, SP may, under normal physiological conditions, have an additional role in the maintenance of epithelial barrier function.
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Wegerer, M., S. Adena, A. Pfennig, D. Czamara, U. Sailer, T. Bettecken, B. Müller-Myhsok, S. Modell, and M. Ising. "Variants within the GABA transaminase (ABAT) gene region are associated with somatosensory evoked EEG potentials in families at high risk for affective disorders." Psychological Medicine 43, no. 6 (January 9, 2012): 1207–17. http://dx.doi.org/10.1017/s0033291711002923.
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BackgroundDepression frequently co-occurs with somatization, and somatic complaints have been reported as a vulnerability marker for affective disorders observable before disease onset. Somatization is thought to result from an increased attention to somatic sensations, which should be reflected in long-latency somatosensory evoked electroencephalogram (EEG) potentials (SSEPs) at the physiological level. Previous studies revealed that SSEPs are altered in depressed patients and suggested late SSEP components as vulnerability markers for affective disorders. Neurotransmitters such as serotonin, γ-aminobutyric acid (GABA) and the neuropeptide substance P may play an important role for both affective disorders and somatosensory processing.MethodWe investigated the associations between SSEPs and polymorphisms within candidate genes of the serotonergic, GABAergic as well as the substance P system in subjects at high risk for affective disorders. The sample was composed of high-risk families participating in the Munich Vulnerability Study and genetic association analyses were calculated using qfam (family-based association tests for quantitative traits) implemented in PLINK 1.05.ResultsWe observed significant associations (false discovery rate <0.05) withstanding correction for multiple testing between late SSEP components (response strength 170–370 ms after stimulation) and four single nucleotide polymorphisms within the GABA transaminase (ABAT) gene region coding for a protein responsible for GABA degradation. No effects were found with the classical disease trait approach, suggesting SSEP marker specificity of the observed associations.ConclusionsOur findings point to a possible role of ABAT gene-regulated GABA catabolism for an altered processing of somatosensory stimuli as a potential vulnerability marker for affective disorders.
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Rauner, Martina, Claudia Goettsch, Nicola Stein, Sylvia Thiele, Martin Bornhaeuser, Karolien De Bosscher, Guy Haegeman, Jan Tuckermann, and Lorenz C. Hofbauer. "Dissociation of Osteogenic and Immunological Effects by the Selective Glucocorticoid Receptor Agonist, Compound A, in Human Bone Marrow Stromal Cells." Endocrinology 152, no. 1 (January 1, 2011): 103–12. http://dx.doi.org/10.1210/en.2010-0456.
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Abstract Glucocorticoids (GCs) regulate various physiological processes, including bone remodeling. Whereas physiological amounts of GCs are required for proper human osteoblast differentiation, prolonged exposure to GCs leads to substantial bone loss in vivo predominantly by inhibiting osteoblast functions. Compound A (CpdA) is a novel GC receptor modulator with the potential of an improved benefit/risk profile. Here we tested the osteoimmunological effects of CpdA on primary human osteoblasts and their paracrine interactions with osteoclasts. To assess the antiinflammatory potential of CpdA in human bone marrow stromal cell (BMSC)-derived osteoblasts, cells were stimulated with lipopolysaccharide and cytokine expression was determined. Similar to dexamethasone (DEX), CpdA profoundly suppressed lipopolysaccharide-induced TNF-α (−63%), IL-1β (−38%), and IL-6 (−36%) (P < 0.05) mRNA levels. Of note, CpdA failed to induce osteogenic differentiation of BMSCs, whereas DEX and budesonide enhanced matrix mineralization an d increased runt-related transcription factor 2 and alkaline phosphatase mRNA levels up to 5-fold in a dose-dependent manner. Interestingly, each substance promoted cell proliferation by 7–10% and suppressed apoptosis by 25–30% at low concentrations and early differentiation stages, whereas high concentrations (1 μm) suppressed proliferation and stimulated apoptosis in mature osteoblasts. Finally, CpdA did not increase the receptor activator of nuclear factor-κB ligand to osteoprotegerin mRNA ratio as compared with DEX and did not stimulate the formation of osteoclasts in coculture with BMSCs. In summary, CpdA displays dissociated osteogenic and immunological effects in human BMSCs that are distinct from those of conventional GCs. Whether the specific osteoimmunological profile of CpdA translates into a relevant in vivo effect needs to be further explored.
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Costa, Joana, Vanessa Almonti, Ludovica Cacopardo, Daniele Poli, Simona Rapposelli, and Arti Ahluwalia. "Investigating Curcumin/Intestinal Epithelium Interaction in a Millifluidic Bioreactor." Bioengineering 7, no. 3 (August 26, 2020): 100. http://dx.doi.org/10.3390/bioengineering7030100.
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Multidrug resistance is still an obstacle for chemotherapeutic treatments. One of the proteins involved in this phenomenon is the P-glycoprotein, P-gp, which is known to be responsible for the efflux of therapeutic substances from the cell cytoplasm. To date, the identification of a drug that can efficiently inhibit P-gp activity remains a challenge, nevertheless some studies have identified natural compounds suitable for that purpose. Amongst them, curcumin has shown an inhibitory effect on the protein in in vitro studies using Caco-2 cells. To understand if flow can modulate the influence of curcumin on the protein’s activity, we studied the uptake of a P-gp substrate under static and dynamic conditions. Caco-2 cells were cultured in bioreactors and in Transwells and the basolateral transport of rhodamine-123 was assessed in the two systems as a function of the P-gp activity. Experiments were performed with and without pre-treatment of the cells with an extract of curcumin or an arylmethyloxy-phenyl derivative to evaluate the inhibitory effect of the natural substance with respect to a synthetic compound. The results indicated that the P-gp activity of the cells cultured in the bioreactors was intrinsically lower, and that the effect of both natural and synthetic inhibitors was up modulated by the presence of flow. Our study underlies the fact that the use of more sophisticated and physiologically relevant in vitro models can bring new insights on the therapeutic effects of natural substances such as curcumin.
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Whatnall, Megan, Janelle Skinner, Antonio Verdejo-Garcia, Adrian Carter, Robyn M. Brown, Zane B. Andrews, Chris V. Dayas, et al. "Symptoms of Addictive Eating: What Do Different Health Professions Think?" Behavioral Sciences 11, no. 5 (April 26, 2021): 60. http://dx.doi.org/10.3390/bs11050060.
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The symptoms of addictive eating are often debated, with some overlap in symptoms with substance addictions or other disorders such as binge eating disorder. This study explored the levels of agreement with symptoms of addictive eating among different health professions, the conditions they provide advice for, and the population group/s they work with. An online cross-sectional survey was conducted in February–April 2020 including 142 health professionals (87% female, 65% residing in Australia, 28% each working in private practice/hospital settings). Of these, 47% were dietitians, 20% psychologists/psychotherapists/counsellors, 16% other health practitioners (e.g., social workers), 13% health researchers, and 5% medical professionals. Agreement with 11 statements relating to addictive eating symptoms was assessed on a scale of 1/strongly disagree to 5/strongly agree (e.g., certain foods produce physiological effects in the brain rewards system). Differences in agreement by health profession were assessed by one-way analysis of variance. There were significant differences in agreement with individual statements between health professions. Psychologists, psychotherapists, and counsellors reported lower agreement to statements relating to physiological effects in the reward system, withdrawal symptoms, and over-eating to alleviate stress/anxiety, than other professions (p < 0.05). Those providing advice for disordered eating only reported lower agreement across statements compared with those providing advice for overweight/obesity or both (p < 0.001). There were minimal differences based on the population group/s that health professionals work with. There is some agreement among health professionals regarding addictive eating symptoms, however, this differs by profession and the conditions they treat. This study provides a novel perspective on health professionals’ views on addictive eating symptoms, and there is a need for more research to explore the concepts further.