Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide YY (PYY) is a gut hormone localized primarily in the distal bowel. Because circulating PYY inhibits gastric acid secretion, we investigated the effects of gastric acid secretion and gastrin on gene expression and secretion of PYY. In conscious dogs, PYY release in response to oral food was inhibited (P < 0.05) by pharmacologic inhibition of gastric acid secretion (omeprazole, famotidine). In rats, omeprazole treatment resulted in a significant elevation in serum gastrin concentrations and a simultaneous decrease in PYY messenger RNA (mRNA) and peptide levels in the colon; administration of a gastrin receptor antagonist (L365, 260) prevented the inhibitory actions of omeprazole on colonic PYY mRNA levels. In athymic-nude mice, implantation of a human gastrinoma resulted in an elevation of serum gastrin concentrations and a concomitant depression of colonic PYY mRNA levels. We conclude that endogenous gastric acid secretion up-regulates PYY release and PYY mRNA expression. Circulating gastrin acts to down-regulate PYY release and PYY mRNA expression. This study provides evidence that foregut functions (i.e., gastric acid secretion and gastrin release) exert control over an antiacid signal (e.g. PYY release) emanating from the hindgut.
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PMID:Regulation of peptide YY homeostasis by gastric acid and gastrin. 862 12

The effect of capsaicin-induced stimulation of afferent neurons on peristalsis and the possible neural mediators involved in this action were examined in the guinea-pig isolated ileum. The intraluminal pressure threshold for eliciting peristaltic waves was used to quantify facilitation (decrease in threshold) or inhibition (increase in threshold) of peristalsis. Capsaicin (0.1-1 microM) caused an initial short-lasting stimulation of peristalsis followed by a prolonged inhibition of peristaltic activity. Capsaicin (1 microM) was ineffective when the gut segments had been pretreated with 3.3 microM capsaicin, which is indicative of an afferent neuron-dependent action of the drug. In contrast, the abolition of peristalsis caused by a high concentration of capsaicin (33 microM) was fully reversible on removal and reproducible on readministration of capsaicin, a feature characteristic of a nonspecific depression of smooth muscle excitability. Baseline peristalsis and the excitatory/inhibitory effect of capsaicin (1 microM) on peristalsis remained unaltered by a combination of the tachykinin NK1 receptor antagonist (+)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl piperidine (CP-99,994; 0.3 microM) and the tachykinin NK2 receptor antagonist (L(-)-N-methyl-N[4-acetylamino-4-phenyl-piperidine-2-(3,4- -dichlorophenyl)butyl]-benzamide (SR-48,968; 0.1 microM). Further experiments, performed in the presence of a low concentration of atropine (10 nM) showed that the calcitonin gene-related peptide (CGRP) antagonist human alpha-calcitonin gene-related peptide (8-37) [hCGRP(8-37); 10 microM] attenuated the delayed inhibitory effect of capsaicin on peristalsis, but did not influence baseline peristaltic activity and the capsaicin-induced facilitation of peristalsis. Blockade of nitric oxide (NO) synthesis by NG-nitro-L-arginine methylester (L-NAME, 300 microM) facilitated baseline peristaltic activity and reduced the delayed inhibition of peristalsis caused by capsaicin (1 microM) without affecting the initial peristalsis-stimulating action of capsaicin. The effects of L-NAME were prevented by L-arginine (1 mM). The data of the current study indicate that capsaicin-sensitive afferent neurons do not participate in the neural pathways subserving peristalsis in the guinea-pig small intestine, but modulate peristaltic activity upon stimulation with capsaicin. The initial stimulant action of capsaicin on peristalsis is independent of tachykinins acting via NK1 or NK2 receptors, while the delayed capsaicin-induced depression of peristalsis involves CGRP and NO.
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PMID:The inhibitory modulation of guinea-pig intestinal peristalsis caused by capsaicin involves calcitonin gene-related peptide and nitric oxide. 875 Sep 23

Arachidonic acid ethanolamide (anandamide) is a brain constituent that binds to the brain cannabinoid receptor (CB1). It produces many of the pharmacological effects caused by delta 9-tetrahydrocannabinol (delta 9-THC) in mice. Anandamide parallels delta 9-THC in its specific interaction with the cannabinoid receptor and in inhibition of adenylate cyclase. Two additional fatty acid ethanolamides that bind to the cannabinoid receptor, homo-gamma-linolenylethanolamide and docostetraenylethanolamide, have been identified in the brain. We believe that the anandamides are involved in the coordination of movement and short term memory. Depression of ambulation in an open field and the analgetic response to anandamide are not fully developed until adulthood, possibly due to an age-related increase in the CB1 receptor concentration. This observation has clinical implications in pediatrics. A second cannabinoid receptor (CB2) is present in the spleen. A monoglyceride, 2-arachidonyl-glycerol which binds to both CB1 and CB2 in transfected cells and inhibits andenylate cyclase in spleen cells was found in the gut. Its role is apparently associated with the immune system. These fatty acids amides and esters represent a new family of chemical modulators in the body.
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PMID:Endogenous cannabinoid ligands--chemical and biological studies. 890 44

Echinococcosis is a human disease caused by the larval form of Taenia echinococcus, which lives in the gut of the dog, wild canides and other carnivorous animals which represent the definitive hosts and involves as intermediate hosts both domestic and wild animals. Humans become accidental intermediate hosts by ingesting Taenia eggs. The main species pathogenic for man are E granulosus causing cystic echinococcosis with worldwide distribution and endemic in sheep and cattle breeding countries, and E multilocularis causing alveolar echinococcosis, with preferential distribution in the northern hemisphere. After ingestion of contaminated food, hexacanth embryos migrate by the portal system to liver and later lung, brain and other tissues. Symptoms are related to both cyst location and size. E granulosus infection of the central nervous system (CNS) may be primary or secondary and has been estimated to be low (2%). Sharply demarcated, spherical and intraparenchymal, cysts may reach a large size causing neurological symptoms. Spilling of cyst fluid due to trauma or surgery may trigger anaphylaxis as well as disseminated infection. Host reaction is minimal in the brain but a foreign giant cell reaction may develop. E multilocularis develops within the liver as a rapid invasive pseudomalignant growth and may metastasize to the CNS, where estimated incidence reaches 5%. Hydatid antigens induce an immune reaction in the host which is helpful for the diagnosis. DNA probes and PCR may be applied to differentiate between Echinococcus spp. Although the host develops an immunological protection from reinfection, the parasite evades host immune attack. A wide range of evasion mechanisms have been advanced, including a barrier for host cells due to hydatid cyst laminated cuticle, polyclonal activation of lymphocytes by parasite soluble antigens, and depression of host cell immune responses. Chronic stimulation of the host by cyst fluid antigens leads to increased specific IgG4 production, which might act as blocking antibodies against anaphlaxis suggestive of host response immunomodulation.
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PMID:Echinococcosis. 903 73

Advances in ventilator technology and recent findings in pathophysiological mechanisms have resulted in a remarkable decrease in classical volume controlled and pressure controlled ventilation modes as treatment for severe acute respiratory insufficiency. New modes of ventilatory support enabling and encouraging patients' spontaneous breathing, such as Biphasic Positive Airway Pressure (BIPAP) and Airway Pressure Release Ventilation (APRV), make it possible to adapt ventilatory support better and more easily to suit patients' needs than conventional modes of controlled ventilation. Preservation and support of patients' spontaneous breathing improves pulmonary gas exchange and reduces stress imposed by mechanical ventilation. The 'invasiveness' of mechanical ventilation is reduced and patients' comfort is less disturbed. Through this, the need for sedation and analgesia is considerably reduced and this may minimize systemic side-effects and complications from analgo-sedation and mechanical ventilation. The drugs should be administered in an adequate, individually adapted manner. Routinely-ordered and fixed combinations of drugs administered continuously are not adequate adequate as they further carry the risk of overdosing a different single drug with the corresponding side-effects (depression of respiratory drive, gut motility, etc.).
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PMID:[Ventilation modes and strategies in intensive care medicine]. 917 39

We determined the dose-dependent effects of central mu-opioid receptor stimulation on rates of tissue protein synthesis. Chronically catheterized conscious rats received an intracerebroventricular injection of [D-Ala2, N-Me-Phe4,Gly5-ol]enkephalin (DAGO, 0.5, 2, or 8 nmol/rat) or water (5 microliters) 45 min before determination of protein synthesis by the flooding dose technique. DAGO produced a significant decrease in tissue protein synthesis in liver (57%), spleen (54%), gut mucosa (36%), gut serosa (23%), kidney (48%), gastrocnemius (33%), and plantaris muscle (27%), but it did not alter rates of protein synthesis in the brain, heart, and soleus muscle. DAGO produced an acute dose-dependent respiratory depression 30 min after intracerebroventricular injection; this depression resulted in acidosis, hypoxia, and hypercapnia (pH 7.19 +/- 0.04, arterial partial O2, pressure 44.2 +/- 3.4 Torr, arterial O2 saturation 65.3 +/- 5.5%, and PCO2 66.3 +/- 4.4 Torr). Intracerebroventricular DAGO increased circulating levels of catecholamines, corticosterone, and growth hormone but did not alter those of insulin and insulin-like growth factor I. Significant positive correlations between protein synthesis and pH were observed in the tissues studied (i.e., liver protein synthesis vs. pH, P < 0.0001, r = 0.902; gastrocnemius protein synthesis vs. pH, P < 0.0001, r = 0.830). Our results indicate that mu-receptor stimulation inhibits tissue protein synthesis, and this effect appears to be secondary to respiratory depression and the resulting acidosis and/or hypoxia. Furthermore, our findings suggest differential sensitivity in tissue response to alterations in pH, hypoxia, and stress hormone elevation.
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PMID:Central opiate mu-receptor-mediated suppression of tissue protein synthesis. 932 68

Murine studies have demonstrated that, as with other nematodes, infection with the intestinal nematode Trichinella spiralis is associated with a pronounced intestinal mastocytosis, eosinophilia and an elevation in serum levels of total IgE. Both interleukin (IL)-4 and IL-5 are clearly important in the generation of IgE responses and eosinophilia, respectively, but the control of mucosal mastocytosis in vivo is not as well defined. Mucosal mast cells appear to be particularly important with regard to T. spiralis infections as there is good evidence to suggest their involvement in expulsion of the parasite from the host. In this study we examined the effect of the overproduction of the Th2 cytokine IL-9 on infection with this nematode. We demonstrate that naive IL-9-transgenic mice have an intense intestinal mastocytosis and high serum levels of mouse mast cell protease-1. Moreover, upon infection high titers of parasite-specific IgG1 were observed with a heightened mast cell response, which was associated with the rapid expulsion of T. spiralis from the gut. Furthermore, as depression of this mast cell response, using anti-c-kit antibodies, resulted in the inability of these mice to expel the parasite, this study clearly demonstrates an activity of IL-9 on mucosal mastocytosis and the host protective immune response in vivo.
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PMID:Interleukin-9 is involved in host protective immunity to intestinal nematode infection. 936 7

Infection with gastrointestinal nematodes, particularly Ostertagia species in domestic ruminants, continues to represent an important cause of impaired productivity in temperate parts of the world. The mechanisms responsible for such losses include changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and body composition, and were described in detail at the last Ostertagia Workshop (Fox, M.T. 1993. Pathophysiology of infection with Ostertagia ostertagi in cattle. Vet. Parasitol. 46, 143-158). Since then, research into the pathophysiology of infection has focused on three main areas: mechanisms of appetite depression; changes in gastrointestinal function; and alterations in protein metabolism. Studies on the mechanisms responsible for appetite depression in Ostertagia-infected cattle have continued to support a close association between impaired feed intake and elevated blood gastrin concentrations. Alternative explanations will have to be sought, however, to account for the drop in feed intake associated with intestinal parasitism in which blood gastrin levels normally remain unaltered. Such work in sheep, and more recently in laboratory animals, has shown that central satiety signals are associated with inappetance accompanying intestinal infections, rather than changes in peripheral peptide levels. Changes in gastrointestinal function have also attracted attention, particularly the mechanisms responsible for increases in certain gut secretions, notably pepsinogen and gastrin. Elegant experimental studies have established that the gradient in pepsinogen concentration between abomasal mucosa and local capillaries could alone account for the increase in blood concentrations seen in Type 1 ostertagiosis. Additional factors, such as increases in capillary permeability and in surface area, probably contribute to such responses in cases of Type 2 disease. The increase in blood gastrin concentrations that accompanies Ostertagia infections in cattle is associated with the concurrent rise in abomasal pH. However, in sheep, additional factors appear to contribute to the hypergastrinaemia which may occur independent of parasite-induced changes in gastric pH. Alterations in protein metabolism have been well documented in ruminants harbouring monospecific infections with either abomasal or intestinal nematodes. More recently, however, the effects of dual abomasal and intestinal infections have been investigated and demonstrated that the host is able to compensate for impaired abomasal digestion provided that the intestinal parasite burden does not occupy the main site of digestion and absorption in the latter organ. An alternative method of improving the host's protein balance, dietary supplementation, has been shown not only to improve productivity, but also to enhance the innate resistance of susceptible breeds of sheep to Haemonchus and to accelerate the development of immunity to Ostertagia in lambs.
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PMID:Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments. 946 Feb 3

This study examined the effects of arginine supplement of fluid resuscitation from burn injury on cardiac contractile performance and bacterial translocation after a third-degree burn comprising 43% of the total body surface area in adult rats. Before burn injury, rats were instrumented to measure blood pressure; after burn (or sham injury), paired groups of sham-burned and burned rats were given vehicle (saline), L-arginine, D-arginine, or N-methyl-L-arginine (300 mg/kg in 0.3 ml of saline 30 min, 6 h, and 23 h postburn) plus fluid resuscitation; sham-burned rats received drug only. Twenty-four hours after burn trauma, hemodynamics were measured; the animals were then killed and randomly assigned to Langendorff heart studies or to studies examining translocation of gut bacteria. Burn rats treated with vehicle, D-arginine, or N-methyl-L-arginine had well-defined cardiocirculatory responses that included hypotension, tachycardia, respiratory compensation for metabolic acidosis, hypocalcemia, cardiac contractile depression, and significant bacterial translocation. Compared with values measured in vehicle-treated burn rats, L-arginine given after burn improved blood pressure, prevented tachycardia, reduced serum lactate levels, improved cardiac performance, and significantly reduced bacteria translocation, confirming that L-arginine administration after burn injury provided significant cardiac and gastrointestinal protection. Circulating neutrophil counts fell after burn trauma and serum glucagon levels rose, but these changes were not altered by pharmacological intervention. Our finding of significantly higher coronary perfusate guanosine 3',5'-cyclic monophosphate concentration in L-arginine-treated burn rats suggests that the beneficial effects of L-arginine were mediated by nitric oxide production.
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PMID:Arginine in burn injury improves cardiac performance and prevents bacterial translocation. 947 82

The pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally derived peptide, neuropeptide Y (NPY). All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into the circulation from neuroneal stores in response to stress. These peptides have broad peripheral actions on a number of organs. Not surprisingly, PYY and PP are believed to play an important role in the function of the gastrointestinal tract while NPY is a potent vasconstrictor and may have effects on the gut through the enteric nervous system. In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine function, and metabolism. Recent advances in the molecular biology of the receptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compared to other G-protein coupled receptor families, the PP-fold peptide receptors exhibit a relatively low level of sequence identity. Further advances in the development of selective agonists and antagonists for individual receptor subtypes will be needed to understand further their role in physiological function.
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PMID:Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications. 957 48


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