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)

A central position in the development of systemic inflammation is played by activation of the vascular endothelium and monocyte- macrophage system. Both are associated with the formation of inflammatory cytokines, the primary mission of which is mobilization of the organism to cope with the infection. The so-called acute stage response develops with typical clinical manifestations and laboratory values. When it is impossible to stop the inflammation the syndrome of systemic inflammatory response develops with excessive activity of inflammatory cytokines and immune mechanisms. This apparently favourable system can be highly toxic for the organism and can lead to the syndrome of multiorgan failure, to disseminated intravascular coagulation, to depression of the myocardium, refractory vasodilatation, hypertension and septic shock. The compensatory antagonistic mechanism which develops due to the formation of anti-inflammatory cytokines leads sometimes to the development of a balanced state of immunity which is most favourable from the prognostic aspect. In case of their excess however immunodepression develops which is equally dangerous for the patient as excessive cytokine activity. From what has been said ensues the need of regular monitoring of patients with sepsis and thus also detailed investigation of their immune system.
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PMID:[Role of cytokines in the development of local and systemic inflammation and septic shock]. 1242 7

When male rats were given a single dose of cadmium (Cd) (3.58 mg CdCl2 x H2O/kg, i.p.) 72 hr prior to sacrifice, the testicular 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP), and cumene hydroperoxide (CHPx) decreased significantly as compared to controls. Cd also inhibited reduced glutathione (GSH) level while increasing the lipid peroxidation (LP) level significantly. When the animals were given a single dose of nickel (Ni) (59.5 mg NiCl2 x 6H2O/kg, i.p.) 16 hr prior to sacrifice, significant decreases were observed in EROD and GST activities toward CDNB, EAA, EPNP, and CHPx, and GSH level. No significant alterations were noted in DCNB GST activity and LP level by Ni. For the combined treatment, rats received the single dose of Ni 56 hr after the single dose of Cd and were killed 16 hr later. In these animals, lesser depressions were observed on EROD activity and LP level than those of Cd alone. The combination of metals significantly inhibited GST activities and GSH level but not to a greater degree than noted by Cd or Ni alone. Plasma testosterone levels of Cd-, Ni-, and combination-treated rats decreased significantly compared to controls. The strongest depression was achieved by Cd alone. Cd, both alone and in combination with Ni, increased the tissue Ni uptake significantly. Ni, however, did not produce such an effect on the tissue uptake of Cd in either case. Cd treatment caused interstitial edema and coagulation necrosis in seminiferous tubules and also caused fibrinoidal necrosis in vascular endothelium. Ni treatment did not produce any pathological testicular alterations compared to controls. Combined treatment produced fewer pathological alterations (i.e., only interstitial edema) than that of Cd treatment. These results reveal that the combination of Cd and Ni does nothave a synergistic effect on testicular xenobiotic metabolizing enzymes, and in contrast, Ni has an ameliorating effect on pathological disturbances caused by Cd alone in the rat testis.
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PMID:Combined effects of cadmium and nickel on testicular xenobiotic metabolizing enzymes in rats. 1244 41

Chickens were intranasally inoculated with Chilean H7N3 avian influenza (AI) viruses of low pathogenicity (LP) (H7N3/LP), high pathogenicity (HP) (H7N3/HP), and a laboratory derivative (02-AI-15-#9) (H7N3/14D) from the LPAI virus to determine pathobiologic effects. All chickens inoculated with H7N3/HP AI virus became infected and abruptly died 2 or 3 days postinoculation, but a few showed moderate depression before death. The H7N3/HP AI virus produced focal hemorrhages of the comb, petechial hemorrhage at the esophageal-proventricular junction and proventricular mucosa, edema and congestion of the lung, petechiation of the spleen, and generalized decrease in body fat. Histologically, severe necrosis, hemorrhage, and inflammation were primarily identified in lungs and the lymphoid tissues. All tissues sampled from the H7N3/HP AI group were positive for the AI viral antigen, predominantly in endothelium of blood vessels throughout most tissues and less frequently in histiocytes and cellular debris of lymphoid tissues. Even less consistently, cardiac myocytes, hepatocytes, Kupffer cells, glandular epithelial cells, microglial cells, and neurons became infected. These studies suggest the Chilean H7N3/LP AI virus was poorly infectious for chickens and may have been recently introduced from a nongalliform host. By contrast, the H7N3/HP AI virus was highly infectious and lethal for chickens. The H7N3/HP AI virus had a strong tropism for the cardiovascular system, principally vascular endothelium, which is similar to the viral tropism demonstrated previously with other H5 and H7 HPAI viruses. Interestingly, the H7N3/LP AI virus on intravenous inoculation replicated in cardiac myocytes, a feature of HPAI and not LPAI viruses, which further supports the theory that the H7N3/LP AI virus was in transition from LP to HP.
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PMID:Comparative pathobiology of low and high pathogenicity H7N3 Chilean avian influenza viruses in chickens. 1507 5

Betamethasone is frequently administered to pregnant women at risk of premature labor to accelerate fetal lung maturation. Maternally administered betamethasone produces pronounced changes in the fetal peripheral vasculature, raises fetal blood pressure and produces fetal growth restriction. Endothelial nitric oxide synthase (eNOS) plays an important role in regulating vascular tone. We hypothesized that effects of betamethasone on the fetal vasculature include decreased eNOS activity. We determined a significant depression of total placental eNOS protein measured by ELISA (betamethasone treated vs control, 0.48 +/- 0.28 vs 1.57 +/- 0.45, p < 0.05) and immunohistochemistry in both syncytiotrophoblast and vascular endothelium. Following betamethasone exposure, eNOS mRNA and enzyme activity showed decreasing trends which were not statistically significant. eNOS protein was higher in the placentas of both control and betamethasone treated baboons in the presence of a female fetus compared with a male fetus. The same effect of the sex of the fetus was observed in the betamethasone group for eNOS mRNA. In conclusion, maternally administered betamethasone produces a consistent decrease in several indices of placental eNOS function that may play a role in the altered cardiovascular dynamics and fetal growth retardation produced by betamethasone administration in late pregnancy.
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PMID:Effect of betamethasone administration to the pregnant baboon at 0.75 gestation on placental eNOS distribution and activity. 1545 Nov 92

Many clinic investigations support the relation between coronary heart disease (CAD) and psychosocial factors (PFs) and how these two entities influence each other. On one hand, FPs like depression, anxiety, social isolation, stress and some types of personality, contribute significantly to the pathogenesis and expression of CAD. Pathophysiological mechanisms underly in this interrelation, can be divided between FPs conditions that contribute to a higher frequency of adverse health behaviors (eg. smoking) or directly increasing the platelets and neuroendocrine activity. In this review there is information relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. Recent data also indicate that the foregoing effects are in part a result of the endothelial dysfunction and injury induced by acute stress. The complex interactions among vascular endothelium, platelets, serotonin and blood components are one of the most exciting research areas today. The importance of maximizing the efficacy of psychological and psychopharmacology interventions is in part because of the knowledge that psychosocial stresses tend to cluster together and when this takes place, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia. Thus, to know about these mechanisms, helps to widen the view and use therapeutic strategies that go beyond symptomatic effects and commit us to an interdisciplinary work.
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PMID:[Stress, anxiety and cardiovascular disease: an interdisciplinary approach]. 1550 91

Expression of the drug transport proteins, including P-glycoprotein (Pgp), in the brain vascular endothelium represents a challenge for the effective delivery of drugs for the treatment of several central nervous system (CNS) disorders including depression, schizophrenia and epilepsy. It has been hypothesized that Pgp plays a major role in drug efflux at the blood-brain barrier, and may be an underlying factor in the variable responses of patients to CNS drugs. However, the role of Pgp in the transport of many CNS drugs has not been directly demonstrated. To explore the role of Pgp in drug transport across an endothelial cell barrier derived from the central nervous system, the expression and activity of Pgp in bovine retinal endothelial cells (BRECs) and the effects of representative CNS drugs on Pgp activity were examined. Significant Pgp expression in BRECs was demonstrated by western analyses, and expression was increased by treatment of the cells with hydrocortisone. Intracellular accumulation of the well-characterized Pgp-substrate Taxol was markedly increased by the non-selective transporter inhibitor verapamil and the Pgp-selective antagonist PGP-4008, demonstrating that Pgp is active in these endothelial cells. In contrast, neither verapamil nor PGP-4008 affected the intracellular accumulation of [3H]paroxetine, [14C]phenytoin, [3H]clozapine or [14C]carbamazapine, indicating that these drugs are not substrates for Pgp. Paroxetine, clozapine and phenytoin were shown to be Pgp inhibitors, while carbamazapine did not inhibit Pgp at any concentration tested. These results indicate that Pgp is not likely to modulate patient responses to these drugs.
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PMID:Evaluation of the role of P-glycoprotein in the uptake of paroxetine, clozapine, phenytoin and carbamazapine by bovine retinal endothelial cells. 1596 Nov 25

Increased blood pressure induces functional and structural changes of the vascular endothelium. Depression of endothelium-dependant vasodilatation is an early manifestation of endothelial dysfunction due to hypertension. It can be demonstrated by pharmacological or physiological tests. Decreased availability of nitric oxide (NO) is a major determinant of the depression of vasodilatation. It may be caused by a reduction in the activity of NO-endothelial synthase (NOSe) related to: 1) a deficit in substrate (L-arginine), 2) an inhibition by asymmetrical dimethylarginine, 3) a deficit in the cofactor tetrahydrobiopterin (BH4). However, the increase in oxidative stress, a producer of superoxide radicals which combine with NO to form peroxynitrates (ONOO-), is the determining factor. It is related to activation of membranous NAD(P)H oxidases initiated by the stimulation of activating mecanosensors of protein C kinase. The message is amplified by oxidation of BH4 which transforms the NOSe into a producer of superoxide radicals. A cascade of auto-amplification loops leading to atherosclerosis and its complications is then triggered. The superoxide radicals and the peroxynitrates oxidise the LDL-cholesterol. They activate the nuclear factor-kappaB which controls the genes stimulating the expression of many proteins: angiotensinogen and AT1 receptors which stimulate the sympathetic system, receptors of oxidised LDL, adhesion and migration factors (ICAM-1, VCAM-1, E-selectin and MCP-1), pro-inflammatory cytokins (interleukines and TNF-alpha), growth factors (MAP kinases), plasminogen activator inhibitor 1. The monocytes and smooth muscle cells produce metalloproteinases and pro-inflammatory cytokins which destabilise the atheromatous plaque and favourise vascular remodelling. Inshort, the endothelial dysfunction due to hypertension plays a role in a complex physiopathological process and is a marker of future cardiovascular events.
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PMID:[Hypertension, endothelial dysfunction and cardiovascular risk]. 1710 Jan 43

In septic shock, systemic vasodilation and myocardial depression contribute to the systemic hypotension observed. Both components can be attributed to the effects of mediators that are released as part of the inflammatory response. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression that develops in a canine model of septic shock. Lzm-S binds to the endocardial endothelium, resulting in the production of nitric oxide (NO), which, in turn, activates the myocardial soluble guanylate cyclase (sGC) pathway. In the present study, we determined whether Lzm-S might also play a role in the systemic vasodilation that occurs in septic shock. In a phenylephrine-contracted canine carotid artery ring preparation, we found that both canine and human Lzm-S, at concentrations similar to those found in sepsis, produced vasorelaxation. This decrease in force could not be prevented by inhibitors of NO synthase, prostaglandin synthesis, or potassium channel inhibitors and was not dependent on the presence of the vascular endothelium. However, inhibitors of the sGC pathway prevented the vasodilatory activity of Lzm-S. In addition, Aspergillus niger catalase, which breaks down H(2)O(2), as well as hydroxyl radical scavengers, which included hydroquinone and mannitol, prevented the effect of Lzm-S. Electrochemical sensors corroborated that Lzm-S caused H(2)O(2) release from the carotid artery preparation. In conclusion, these results support the notion that when Lzm-S interacts with the arterial vasculature, this interaction results in the formation of H(2)O(2), which, in turn, activates the sGC pathway to cause relaxation. Lzm-S may contribute to the vasodilation that occurs in septic shock.
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PMID:Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation. 1826 14

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.
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PMID:Beta-blockers in the management of hypertension: focus on nebivolol. 1840 37

The results of prospective study of the stage of vascular endothelium and neutrophil phagocytic activity (NPA) in patients with chronic calculous cholecystitis (CCC) in perioperative period, who had anxious depressive disturbances (ADD), were represented. 61 patients were examined 3 weeks before cholecystectomy (CE). Intensity of anxiety and depression, vegetative tonus, desquamated endotheliocytes (DE) in blood and phagocytosis degree were assessed. The patients were randomized into 2 groups. The patients of 1st group (n = 30) received antidepressant coaxil during perioperative period (6 weeks); 2nd group (the control) was composed of 31 patients and was treated without coaxil. In 1st group significant decrease in AAD and symptoms of vegetative dystonia (VD) in 3 weeks after CE was detected; number of DE in blood was considerable reduces, and NPA was significantly increased vs. control group. Correlation analysis made possible to show that the higher AAD and VD intensity, the more frequently epithelium desquamation was detected, and percentage of phagocytes was reduced at increase in DE in blood. Use of balanced antidepressant coaxil in perioperative period in CCC patients makes possible to reduce occurrence and intensity of AAD and VD after operation, improve vascular endothelium state, increase NPA and adaptive reserves of organism.
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PMID:[Influence of antidepressant therapy on psychovegetative disorders in patients with chronic calculous cholecystitis in perioperative period]. 1872 Jul 13


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