UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cognitive disorders associated with HIV infection may be due to focal lesions (lymphoma, toxoplasmosis, progressive multifocal leukoencephalitis, etc.), metabolic encephalopathy (e.g. hepatic insufficiency) or psychiatric disorders (depression). In the absence of such causes a "cognitive and motor syndrome associated with HIV infection" has been defined on clinical criteria (Working group of the American Academy of Neurology, 1991). This syndrome is not consistently associated with any specific lesion. Neither the multifocal encephalitis of HIV or CMV infection nor the diffuse leukoencephalopathy associated with HIV are the only causes. The existence of a neocortical neuronal loss has been suggested by several retrospective studies, but our prospective study has not shown cortical or subcortical atrophy. Measurement of neuronal density in Brodmann's areas 4,9 and 40 has not revealed a significant loss either global, by layer, or by column. The only constant lesion was gliosis of the cortex and white matter. Neuronal loss, therefore, is not indispensable to the occurrence of cognitive disorders in AIDS. The mechanism of dementia might be: dysfunction of cortical neurons (dendritic abnormalities, virus/neurotransmitter competition); subcortical dysfunction, as suggested by the high density of microglial nodules in that region; white matter lesions which could be due to abnormalities in the blood-brain barrier. The expression of cell adhesion molecules (VCAM-1, VLA-4, ICAM-1 and LFA-1) by endothelial cerebral cells is not significantly different in AIDS patients, demented or not, and in patients with multiple sclerosis. In contrast, the expression of VCAM-1 by astrocytes is significantly increased in demented AIDS patients compared with non demented ones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[HIV and dementia: neuropathology]. 747 30

Fibronectin (FN), expressed primarily by macrophages, endothelial cells, and smooth muscle cells, represents an integral feature of the rejection response in transplant recipients. Here we demonstrate a unique pattern of cellular FN expression in rat recipients of cardiac allografts rendered tolerant in an infectious manner with either nondepleting CD4 mAb or regulatory spleen cells. Unlike in rejecting controls, cellular FN in tolerant hosts was restricted to the graft vessels and no vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 expression could be found, supporting the role of FN in leukocyte sequestration at the graft site. The lack of myocardial FN in tolerant rats, despite dense macrophage infiltration, correlated with profound depression of Th1 (interleukin-2 and interferon-gamma) cytokines. Treatment with CD4-depleting mAb prevented tolerance induction and restored myocardial expression of FN in parallel with marked increase in the expression of interleukin-2 and interferon-gamma mRNA/protein. Furthermore, connective segment-1 peptide-facilitated adjunctive blockade of FN-alpha4beta1 interactions in recipients conditioned with CD4 depleting mAb, significantly depressed intragraft expression of interleukin-2 and interferon-gamma mRNA/protein. Hence, the lack of FN associated with infiltrating leukocytes plays an important role in the maintenance of tolerance in transplant recipients by depressing local expression of Th1 cytokines that otherwise facilitate acute graft rejection.
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PMID:Fibronectin-mononuclear cell interactions regulate type 1 helper T cell cytokine network in tolerant transplant recipients. 1102 25

Fundamental to placental morphogenesis is union between the allantois and the chorion, two tissues initially separated in the conceptus. Results of previous studies in the mouse have suggested that chorio-allantoic union is driven by the developmental maturity of the allantois and involves molecular interactions between Vascular Cell Adhesion Molecule (VCAM-1) in the allantois and alpha4-integrin in the chorion. Little more is known about the cellular and/or molecular control of this important morphogenetic event in any species.Gross, histological, microsurgical and immunohistochemical analyses in the mouse conceptus revealed that placental ontogeny took place in three major steps. The first, chorio-allantoic contact, was not enduring and was mediated by the allantois' mesothelial surface and the mesodermal component of the chorion. Modest amounts of VCAM-1 were found in distal allantoic mesothelium, whilst levels of alpha4-integrin were high throughout chorionic mesoderm. The second step, chorio-allantoic fusion, was more enduring. During this time, the distal allantoic region contained maximal levels of VCAM-1, and all allantoises had expanded far enough to reach the posterior chorion from where they spread toward a central chorionic depression. The last step, breakdown of chorio-allantoic fusing surfaces, was dependent upon chorio-allantoic fusion and resulted in the intimate juxtaposition of allantoic endothelium and chorionic ectoderm, possibly as a result of VCAM-1-mediated interactions. The umbilical connection was thereafter fixed at its perimeter to the chorionic surface by large amounts of VCAM-1 in disto-lateral allantoic mesothelium and alpha4-integrin in the remaining peripheral mesodermal component of the chorion.Thus, chorio-allantoic union is highly regulated, taking place in multiple steps. It is dependent upon the developmental maturity of distal allantoic mesothelium and involves the mesodermal component of the chorion. Breakdown of fusing surfaces enables penetration of the allantoic vasculature into the chorion. These findings provide a secure developmental foundation in which to elucidate the genetic control of early placentation.
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PMID:Early placental ontogeny in the mouse. 1194 78

Severe sepsis is accompanied by a profound depression of myocardial contractility. Leukocyte adhesion with subsequent local excess nitric oxide and reactive oxygen species production play major roles for this deleterious effect. We hypothesized that 3-deazaadenosine (c3Ado), an adenosine analogue with anti-inflammatory properties, prevents endotoxin-induced myocardial dysfunction. Wistar rats (8 per group) were treated with Escherichia coli lipopoly-saccharide (LPS, 1 mg/kg, i.p., strain 0111:B4) +/- c3Ado (10 mg/kg, i.p.) 8 h before their hearts were harvested for isolated perfusion, histochemical analysis, or electrophoretic mobility shift assay. LPS induced a marked depression of left ventricular contractility. Immunohistochemistry revealed an upregulation of the adhesion molecules VCAM-1, ICAM-1, and P-selectin within the postcapillary venules. c3Ado inhibited VCAM-1 and ICAM-1 upregulation, but not P-selectin, and prevented cardiodepression. Electrophoretic mobility shift assay revealed inactivation of the transcription factor nuclear factor-kappaB and immunohistochemical staining for gp91phox, ED1, and CD11b demonstrated that c3Ado prevented local recruitment of monocytes and polymorph nuclear neutrophils to the myocardium. Accordingly, significantly fewer leukocytes producing nitric oxide or reactive oxygen species accumulated within the myocardium. Intravital microscopy of intestinal venules confirmed that LPS-induced adhesion of leukocytes was prevented by c3Ado. Additionally, c3Ado prevented LPS-induced elevation of serum tumor necrosis factor-alpha levels. Our results imply that c3Ado may prove to have clinical relevance for inflammatory disease processes.
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PMID:Protective effect of 3-deazaadenosine in a rat model of lipopolysaccharide-induced myocardial dysfunction. 1263 May 24

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.
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PMID:Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials. 1296 Jun 10

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

Depression is recognized as a predictor of increased cardiac morbidity and mortality. In addition, depressed patients exhibit an increase in the serum markers of endothelial dysfunction and platelet activation involved in the cascade of events leading to atherosclerosis. The purpose of this study was to determine the early and late-onset expression of various vascular markers in a rodent model of depression. Male DBA (an inbred strain of mice)/2J mice were exposed to either 7 weeks of controlled living conditions or unpredictable chronic mild stress (UCMS), and subsequently given daily fluoxetine (10 mg/kg) or NaCl (9%) during the last 5 weeks of the experiment. Depressive-like behavior was evaluated by using motivational and self-care behavior, including the assessment of the animal's coat state and grooming behavior. Enzyme-linked immunoassay was used to quantify matrix metalloproteinase-9 (MMP-9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and plasminogen activator inhibitor-1 (PAI-1) expression either immediately after the end of the UCMS procedure (short term condition) or 10 months later (long-term condition). Results indicate that 1) UCMS procedure induces a short-term depressive-like behavior in mice, defined as coat state deterioration, an effect that is prevented by fluoxetine treatment; 2) UCMS procedure has no effect on the short-term expression of the studied markers; however, UCMS increases expression of plasminogen activator inhibitor-1 only in the long-term group; 3) fluoxetine treatment is unable to counteract this UCMS-induced change; 4) aging induces behavioral perturbation, defined as a decrease in grooming motivation, and an increase of all the vascular markers in both control and UCMS groups and 5) pretreatment with fluoxetine has no protective effects on aging-induced behavioral and vascular alterations. Thus, in this model of depression-like behavior, UCMS appears to induce late-onset physiological changes, which are consistent with human studies indicating that depression is a risk factor for the development of heart disease.
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PMID:Early and late-onset effect of chronic stress on vascular function in mice: a possible model of the impact of depression on vascular disease in aging. 2142 42

The association of posttraumatic stress disorder (PTSD) with cardiovascular disease risk may be mediated by inflammation. Our objective was to examine the association between PTSD and measures of inflammation and to determine whether these associations are due to shared familial or genetic factors. We measured lifetime history of PTSD using the Structured Clinical Interview for DSM-IV in 238 male middle-aged military veteran twin pairs (476 individuals), selected from the Vietnam Era Twins Registry, who were free of cardiovascular disease at baseline. We assessed inflammation using levels of high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), fibrinogen, white blood cells, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 (ICAM-1). Geometric mean levels and percent differences by PTSD were obtained from mixed-model linear regression analyses with adjustment for potential confounders. Within-pair analysis was conducted to adjust for shared family environment and genetics (monozygotic pairs). Overall, 12.4% of participants had a lifetime history of PTSD. Adjusted mean levels of hsCRP and ICAM-1 were significantly higher among those with vs. without PTSD [hsCRP: 1.75 vs. 1.31mg/l (33% difference); ICAM-1: 319 vs. 293ng/ml (9% difference)]. Adjustment for depression rendered the association of PTSD with hsCRP non-statistically significant. For IL-6, no consistent association was seen. Within-pair analysis produced associations that were similar in direction for all three markers but lesser in magnitude for hsCRP and IL-6. There was no evidence of interaction by zygosity. Elevated hsCRP and ICAM-1 are associated with PTSD, and these associations may be confounded by shared non-genetic, antecedent familial and environmental factors.
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PMID:Association between posttraumatic stress disorder and inflammation: a twin study. 2337 97

Atherosclerosis is one of the most common disorders among the elderly. Depression may be associated with the development of atherosclerosis. Thus, the aim of this study is to evaluate and compare the effects of escitalopram (a selective serotonin reuptake inhibitor) with atorvastatin (a well known antihyperlipidemic drug) on high fat diet induced atherosclerosis in rats. The results of this study showed that the administration of either escitalopram or atorvastatin for 6 weeks was associated with a significant decrease in serum levels of total cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins, and serum malondialdehyde, and a significant increase in high density lipoproteins when compared with the atherosclerosis model group. Histopathological examination of the aortas from the test rats revealed significant regression of atherosclerotic changes, together with a significant decrease in vascular cell adhesion molecule-1 (VCAM-1) expression in the media of both the escitalopram group and the atorvastatin group when compared with the atherosclerosis model group. This study has shown that escitalopram reduced atherosclerotic changes, thus its use as an antidepressant in elderly patients should be considered.
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PMID:Comparison of the effects of escitalopram and atorvastatin on diet-induced atherosclerosis in rats. 2459 87

Serotonin (5-HT) is an important neurotransmitter involved in the control of neural and vascular responses. 5-HT depletion can induce several neurological disorders, including migraines. Studies on a cortical spreading depression (CSD) migraine animal model showed that the cortical neurons sensitivity, vascular responses, and nitric oxide (NO) production were significantly increased in 5-HT depletion. However, the involvement of NO in the cerebrovascular responses in 5-HT depletion remains unclear. This study aimed to investigate the role of NO in the CSD-induced alterations of cerebral microvessels in 5-HT depletion. Rats were divided into four groups: control, control with L-NAME treatment, 5-HT depleted, and 5-HT depleted with L-NAME treatment. 5-HT depletion was induced by intraperitoneal injection with para-chlorophenylalanine (PCPA) 3 days before the experiment. The CSD was triggered by KCl application. After the second wave of CSD, N-nitro-l-arginine methyl ester (L-NAME) or saline was intravenously injected into the rats with or without L-NAME treatment groups, respectively. The intercellular adhesion molecules-1 (ICAM-1), cell adhesion molecules-1 (VCAM-1), and the ultrastructural changes of the cerebral microvessels were examined. The results showed that 5-HT depletion significantly increased ICAM-1 and VCAM-1 expressions in the cerebral cortex. The number of endothelial pinocytic vesicles and microvilli was higher in the 5-HT depleted group when compared to the control. Interestingly, L-NAME treatment significantly reduced the abnormalities observed in the 5-HT depleted group. The results of this study demonstrated that an increase of NO production is one of the mechanisms involved in the CSD-induced alterations of the cerebrovascular responses in 5-HT depletion.
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PMID:Serotonin depletion can enhance the cerebrovascular responses induced by cortical spreading depression via the nitric oxide pathway. 2467 Feb 56

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