Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of adding a minidose of clonidine to intrathecal sufentanil during the early first stage of a painful labour was evaluated in this preliminary open-label, non-randomised trial. Group 1 received sufentanil 5 micrograms + clonidine 30 micrograms intrathecally (n = 10) and group 2 only intrathecal sufentanil 5 micrograms (n = 11). The two groups were not statistically different regard-ing age, weight, height, primiparity (67 vs 50%), oxytocin use (37 vs 60%), initial cervical dilation (m +/- DS: 2.9 +/- 1.1 vs 2.9 +/- 1 cm) and VAS pain scores (70 +/- 14 vs 68 +/- 19 mm). In group 1, analgesia was markedly prolonged with a reduced variability in duration: 146 +/- 27 min vs 95 +/- 44 min, (P = 0.006). VAS pain scores were: 14 +/- 20 vs 19 +/- 13, 1 +/- 3 vs 9 +/- 12, 0 vs 5 +/- 7, 48 +/- 12 vs 65 +/- 15, five and fifteen minutes after intrathecal injection, during maximum efficacy, and at the time additional analgesia was required, in group 1 and group 2, respectively. Analgesia evaluated with the VAS pain scores was better in group 1 compared with group 2 (P = 0.02) and decreased somewhat slower. Side effects, such as hypotension, pruritus and sedation, were not statistically different between groups. Nausea and motor blockade did not occur. In conclusion, the addition of a minidose (30 micrograms) of clonidine to sufentanil 5 micrograms given intrathecally seems to potentiate markedly the analgesia obtained during the early first stage of labour.
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PMID:[Combined spinal and epidural analgesia for labor. Prolongation by addition of a minidose of clonidine to sufentanil. An initial study]. 918 Sep 99

We investigated the chemical and anatomical features of nitric oxide synthase (NOS)-containing neurons in the paraventricular and supraoptic nuclei in the rat hypothalamus using combinations of enzyme histochemistry, in situ hybridization and immuno-histochemistry. Neurons expressing NOS mRNA completely overlapped with NADPH-diaphorase-positive neurons. Topographical distribution of NOS was segregated from that of CRF-containing parvicellular neurons in the posterior paraventricular nucleus but overlapped with that of magnocellular neurons. In the paraventricular nucleus, 70% of oxytocin neurons contained NOS, which corresponded to one half of NOS neurons. About one third of vasopressin-immunoreactive neurons were NADPH-diaphorase-positive and the same proportion of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. In the supraoptic nucleus, 50% of oxytocin neurons were NADPH-diaphorase-positive, which corresponded to 40% of NOS neurons. About 25% of vasopressin neurons were NADPH-diaphorase-positive, and 30% of NADPH-diaphorase-positive neurons were vasopressin-immunoreactive. When NADPH-diaphorase histochemistry was performed first, subsequent immunostaining was markedly perturbed. Using fluoro-gold as a retrograde tracer, 4% of NADPH-diaphorase-positive neurons were shown to contribute to the descending projection to the spinal cord. About 40%-50% of NADPH-diaphorase-positive neurons exhibited Fos immunoreactivity after injection of lipopolysaccharide or hypertonic saline, while only 10%-15% of these neurons expressed Fos in response to immobilization or pain. Endogenous NO may be involved in the regulation of magnocellular functions, especially when the internal environment is disturbed.
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PMID:Nitric oxide synthase-containing magnocellular neurons of the rat hypothalamus synthesize oxytocin and vasopressin and express Fos following stress stimuli. 895 94

Over the last decade, the role of visceral sensitivity has been largely recognized in the pathophysiology of functional digestive disorders, particularly in the irritable bowel syndrome. These studies have highlighted the role of afferent pathways arising from the gut as a possible target for new treatments intended to relieve pain or modify altered reflexes present in such patients. These pharmacological targets have been identified mainly by studies on animal models of visceral hyperalgesia of various origins including local inflammation. Locally, several mediators are of paramount importance for sensitization of nerve endings: 5-hydroxytryptamine, bradykinin, tachykinins, calcitonin gene-related peptide, and neurotrophins. Selective antagonists to various subtypes of their receptors are currently available and have been shown to be active in these animal models. Other substances, such as somatostatin, opiold peptides, cholecystokinin, oxytocin, and adenosine, modulate the transmission of nociceptive inputs from the gut to the brain and are of clinical interest. This article reviews the current understanding of these mediators. Although these agents seem to be promising tools for the treatment of visceral hyperalgesia and its consequences (abdominal pain and disturbed reflexes), their clinical efficacy remains to be shown. A better understanding of the nature and the location of the defect in the sensory pathways may permit the selection of subgroups of patients for treatment according to the pharmacological properties of these new therapeutic agents.
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PMID:Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. 913 53

This study aimed to investigate if pregnancy-induced hypoalgesia occurs in the sow, and to examine the role of endogenous opioids which are known to be released in response to nociception. Sixteen Large White x Landrace multiparous sows were tested in straw bedded pens (2.5 x 2.5 m) during weeks 4, 8 and 12 of pregnancy and over the farrowing period. Testing involved thermal stimulation of eight areas on the rear-quarters of the sows with a CO2 infra-red laser until a physical response was seen (tail flick, leg move or muscle twitch) or for a maximum of 16 s. Over the farrowing period testing was more frequent, and at 3.75 h after the birth of the first piglet, half the sows received an injection (i.m.) of an opioid antagonist naloxone (N) (1 mg kg(-1) body weight) with the remainder receiving a control dose of saline (S). Responses were recorded 15 and 30 min post-injection. There was no significant difference between response times over weeks 4, 8 and 12 of pregnancy (P = 0.152), however a significant rise was seen from week 12 to 5 days before parturition (P = 0.002). Response times continued to rise until the birth of the first piglet by which time the majority of sows had stopped responding within 16 s (P < 0.001). Response times fell over days 1, 2 and 7 post-partum. After administration of naloxone response times fell compared to control animals at 15 min (P < 0.001) and 30 min (P < 0.01) post-injection. These results suggest that nociceptive threshold increases during late pregnancy in the sow, perhaps as an endogenous defence against labour pain, and that during parturition this change in nociceptive threshold is, at least in part, opioid-mediated. Oxytocin is known to be inhibited by endogenous opioids at parturition, thus future research should consider the potential role of increased nociception at birth as a negative feedback to oxytocin release.
Pain 1997 Aug
PMID:Opioid-mediated changes in nociceptive threshold during pregnancy and parturition in the sow. 927 99

Membrane metalloendopeptidase EC 3.4.24.11 (Enkephalinase, neutral endopeptidase, NEP) is a cellular ectoenzyme, immunophenotypically identified as the leukocyte cluster of differentiation CD10 or CALLA (common acute lymphoblastic leukemia antigen). Immunological, biochemical and molecular biology techniques have identified tis cell membrane feature in various organs: brain, cardiovascular system, lung, placenta, kidney etc. The CD10 immunophenotype is a common feature of lymphoblasts in acute lymphoid leukemia not expressing the T- or B-markers. The enzymatic activity of CD10/NEP possibly influences normal lymphocyte ontogeny by proteolytic cleavage of the regulatory peptides. The substrates of CD10/NEP in the kidneys are (see the list of abbreviations) ANP, adrenomedullin and PAMP; in the brain, the substrates are enkephalins and oxytocin; in the lung, bombesin, BLP, GRP, neuromedin C, substance P and neurokinin A; in the cardiovascular system, angiotenisin II, bradykinin and CGRP; in the gut, VIP; on the neutrophil membrane, fMLP etc. Some substrates are not strictly tissue-specific, e.g. substance P. Preclinical and clinical trials explore possibilities of therapeutic application of the inhibitors of neutral endopeptidase, such as thiorphan in the management of pain, diarrhoea, depression, arterial hypertension and asthma. Other possibilities of application include the treatment of hyalinomembranous disease and prevention of neurotoxicosis in tetanus and botulism.
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PMID:[Membrane metalloendopeptidase (CD10/CALLA): distribution, physiologic and pathophysiologic functions and its inhibitors]. 974 92

Parturition is a natural event that involves stress and pain for the mother. We thus hypothesized that levels of stress hormones measured during parturition could reflect levels reached in response to severe discomfort and pain of other kinds as well. The aim of this study was therefore to determine whether plasma concentrations of cortisol, adrenaline, noradrenaline, beta-endorphin, met-enkephalin, vasopressin and oxytocin vary depending on the phase and severity of labour in dairy heifers (ten) and dairy goats (six), and how these hormones interact with each other. Blood samples were taken once a day for 3 days before labour and for 3 days afterwards and at predetermined phases during labour. All heifers delivered one calf and five of them needed obstetrical assistance. Two of the goats delivered one kid, and four had twins; all kidded without help. The cortisol concentration peaked when the calf and the first kid were born. In the heifers, plasma adrenaline increased after delivery, while the noradrenaline concentration did not change significantly in heifers that needed assistance, but increased during expulsion in heifers calving without help. In the goats, adrenaline and noradrenaline concentrations increased in association with expulsion of the first kid. The beta-endorphin concentration increased during labour in goats. In heifers that needed assistance, beta-endorphin concentration increased 1 h after labour but there was no change in heifers that did not need assistance. The met-enkephalin concentration was elevated during expulsion in heifers and fluctuated in the goats. Both oxytocin and vasopressin increased during expulsion in both groups of heifers, but vasopressin increased four times more in heifers needing assistance. In the goats, oxytocin reached its highest levels just as the feet of the first kid became visible, and vasopressin peaked as the head emerged. Parturition took longer in heifers that needed assistance than in those that did not. It is concluded that, even though the pattern of change differed between hormones during labour, the changes were related to the phases of labour. A longer labour therefore meant that the hormone concentrations stayed elevated for longer. Vasopressin reached high levels in goats and was the only hormone for which plasma concentrations were higher in heifers that needed assistance than in those that did not, indicating that this hormone is released in order to deal with the pain-related stress associated with labour.
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PMID:Hormonal changes during parturition in heifers and goats are related to the phases and severity of labour. 985 79

Exposure to hostile conditions initiates the secretion of several hormones, including corticosterone/cortisol, catecholamines, prolactin, oxytocin, and renin, as part of the survival mechanism. Such conditions are often referred to as "stressors" and can be divided into three categories: external conditions resulting in pain or discomfort, internal homeostatic disturbances, and learned or associative responses to the perception of impending endangerment, pain, or discomfort ("psychological stress"). The hormones released in response to stressors often are referred to as "stress hormones" and their secretion is regulated by neural circuits impinging on hypothalamic neurons that are the final output toward the pituitary gland and the kidneys. This review discusses the forebrain circuits that mediate the neuroendocrine responses to stressors and emphasizes those neuroendocrine systems that have previously received little attention as stress-sensitive hormones: renin, oxytocin, and prolactin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABAA, histamine, and serotonin receptors alter the neuroendocrine stress response. The effects of these drugs are discussed in relation to their effects on forebrain neural circuits that regulate stress hormone secretion. For psychological stressors such as conditioned fear, the neural circuits mediating neuroendocrine responses involve cortical activation of the basolateral amygdala, which in turn activates the central nucleus of the amygdala. The central amygdala then activates hypothalamic neurons directly, indirectly through the bed nucleus of the stria terminalis, and/or possibly via circuits involving brainstem serotonergic and catecholaminergic neurons. The renin response to psychological stress, in contrast to those of ACTH and prolactin, is not mediated by the bed nucleus of the stria terminalis and is not suppressed by benzodiazepine anxiolytics. Stressors that challenge cardiovascular homeostasis, such as hemorrhage, trigger a pattern of neuroendocrine responses that is similar to that observed in response to psychological stressors. These neuroendocrine responses are initiated by afferent signals from cardiovascular receptors which synapse in the medulla oblongata and are relayed either directly or indirectly to hypothalamic neurons controlling ACTH, prolactin, and oxytocin release. In contrast, forebrain pathways may not be essential for the renin response to hemorrhage. Thus current evidence indicates that although a diverse group of stressors initiate similar increases in ACTH, renin, prolactin, and oxytocin, the specific neural circuits and neurotransmitter systems involved in these responses differ for each neuroendocrine system and stressor category.
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PMID:Forebrain pathways mediating stress-induced hormone secretion. 988 35

Hypocretin (orexin) is synthesized by neurons in the lateral hypothalamus and has been reported to increase food intake and regulate the neuroendocrine system. In the present paper, long descending axonal projections that contain hypocretin were found that innervate all levels of the spinal cord from cervical to sacral segments, as studied in mouse, rat, and human spinal cord and not previously described. High densities of axonal innervation are found in regions of the spinal cord related to modulation of sensation and pain, notably in the marginal zone (lamina 1). Innervation of the intermediolateral column and lamina 10 as well as strong innervation of the caudal region of the sacral cord suggest that hypocretin may participate in the regulation of both the sympathetic and parasympathetic parts of the autonomic nervous system. Double-labeling experiments in mice combining retrograde transport of diamidino yellow after spinal cord injections and immunocytochemistry support the concept that hypocretin-immunoreactive fibers in the cord originate from the neurons in the lateral hypothalamus. Digital-imaging physiological studies with fura-2 detected a rise in intracellular calcium in response to hypocretin in cultured rat spinal cord neurons, indicating that spinal cord neurons express hypocretin-responsive receptors. A greater number of cervical cord neurons responded to hypocretin than another hypothalamo-spinal neuropeptide, oxytocin. These data suggest that in addition to possible roles in feeding and endocrine regulation, the descending hypocretin fiber system may play a role in modulation of sensory input, particularly in regions of the cord related to pain perception and autonomic tone.
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PMID:Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. 1019 30

This study aimed to compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labor at term. 211 women were assigned to receive vaginal administration of either misoprostol or dinoprostone gel doses. Results showed that there were no maternal demographic differences between the two groups and no cases in which labor could not be induced. In the misoprostol group, the induction interval was 14.4 hours, and more women delivered after a single dose (77% vs. 49%, P 0.0001; or 3.51, 95% CI 1.94-6.35) within 12 or 24 hours. In the dinoprostone group, the induction interval was 22.9 hours; the median induction interval of the two groups was U = 3238, P 0.00001. The oxytocin augmentation requirement of labor was significantly less in the misoprostol group (21% vs. 47%, P 0.0001; OR 0.30, 95% CI 0.16-0.54), and in those cases requiring oxytocin, the median total dose used was less (0.96 U) compared to the dinoprostone group (1.86 U) (U = 3886, P = 0.002). There were no differences between the groups in analgesia used during labor or in mode of delivery. Median patient pain scores were higher in the misoprostol group. Findings indicate that 50 mcg misoprostol vaginally is a highly effective induction agent with no apparent adverse effects on the outcome of labor. There is a need for further studies to establish the safety of misoprostol.
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PMID:Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel. 1075 84

This study examined the relationship between method of pain management during labor and birth outcomes. A retrospective comparative chart review of 233 primiparous deliveries was conducted and group assignment was based on method of pain control (nonnarcotic, narcotic, or epidural). Epidural analgesia or anesthesia was associated with increased rates of instrumental and cesarean delivery. Augmentation of labor using a synthetic oxytocin was reported in more charts than expected, and the length of the second stage of labor was longer in those who received epidural analgesia or anesthesia. Apgar scores for those who received early epidural analgesia or anesthesia were lower than for those who received late or no epidural analgesia or anesthesia, although Apgar scores were satisfactory across all groups. Between-groups differences were unrelated to time of epidural placement or maternal temperature. Findings are relevant for maternal child nurses who serve as a resource for families wishing to make informed decisions about pain management in labor.
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PMID:The relationship between method of pain management during labor and birth outcomes. 1088 65


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