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)

Epidemiological studies have shown that cigarette smoking is associated with peptic ulceration. This study aims to investigate the mechanisms by which cigarette smoking delays ulcer healing in rats. Gastric ulcers were induced by applying acetic acid to the luminal surfaces in rats. Twenty-four hours later, rats were exposed to different concentrations of cigarette smoke (0, 2, or 4%) for a 1-h period once daily for 3 or 6 days. Cigarette smoke exposure delayed ulcer healing and decreased gastric blood flow and angiogenesis at the ulcer margin. These changes were accompanied by a significant reduction of constitutive nitric oxide synthase (cNOS) activity but not PGE2 production and vascular endothelial growth factor levels. Administration of L-arginine (10 mg/kg iv) completely reversed the adverse actions on ulcer healing, gastric blood flow, and angiogenesis in the mucosa at the ulcer margin but partially restored angiogenesis in granulation tissues. In conclusion, cigarette smoke exposure delays ulcer healing through depression of gastric blood flow and angiogenesis at the ulcer margin. Reduction of cNOS expression and activity is suggested to be involved in these ulcerogenic processes.
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PMID:Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach. 988 1

To gain insight into the glomerular capillary repair mechanisms in immunoglobulin A (IgA) nephropathy, we focused on vascular endothelial growth factor (VEGF-A) and nitric oxide (NO). Because abnormal glycosylation of serum IgA has been shown in IgA nephropathy, we examined whether VEGF-A and NO production by mesangial cells (MCs) could be modulated by aberrantly glycosylated (desialylated or degalactosylated) IgA. VEGF-A and NO synthase (NOS) gene expression were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis, and VEGF-A peptide, by capture enzyme-linked immunosorbent assay and NOS activity as production of tritium ([(3)H]) citrulline from [(3)H] arginine. Semiquantitative densitometric analysis of RT-PCR experiments showed a significant downregulation of VEGF-A messenger RNA (mRNA) in MCs incubated with aberrantly glycosylated IgA. This resulted in decreased release of VEGF-A in culture medium (P: < 0. 01). NOS activity and inducible NOS (iNOS) mRNA were enhanced by aberrantly glycosylated IgA (both P: < 0.01). No modulation of constitutive NOS mRNA was found. The depression of the VEGF-A production induced by aberrantly glycosylated IgA was mediated by NO because it was completely reversed by the NOS inhibitor, N:omega-nitro-L-arginine methyl ester. The NO donor, sodium nitroprusside, induced a bimodal modulation of VEGF; although low concentrations (0.0001 nmol/L) increased VEGF-A synthesis, greater concentrations (1,000 nmol/L) depressed it. In conclusion, we report negative control of VEGF-A synthesis in MCs by aberrantly glycosylated IgA, mediated by enhanced iNOS activity. We speculate that both increased iNOS activity and depressed VEGF-A synthesis might have a role in impairing vascular repair and favor sclerosis in IgA nephropathy.
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PMID:Aberrantly glycosylated IgA molecules downregulate the synthesis and secretion of vascular endothelial growth factor in human mesangial cells. 1109 49

Human and macaque retinae have similar retinal vascular anatomy. The general features of the retinal vascular anatomy of these two primates have much in common with more widely studied animal models such as rat and cat. However, primates are unique amongst mammals in having a region in temporal retina specialized for high visual acuity, which includes the fovea centralis (or 'fovea'). Several features distinguish the fovea from other parts of the retina, including a very high local density of cone photoreceptors, a high density of inner retinal cells during development, and an absence of retinal blood vessels. The retinal vascular complex comprises a number of cell types, in addition to vascular endothelial cells, including pericytes, microglia, astrocytes-none of which is intrinsic to the retina. In addition, amacrine-like cells make bouton-like associations with retinal vessels and may be involved in the autoregulation of blood flow. During development endothelial cells 'invade' the retina, accompanied by a population of microglial cells; glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes are also seen associated with the developing vasculature, and are in advance of the vascular front by a few hundred microns. Recent findings indicate that astrocytes at the vascular front proliferate in response to factors released by endothelial cells, including leukemia inhibitory factor. Better understood is the role of GFAP-immunoreactive astrocytes just in advance of the developing vessels. These astrocytes are sensitive to hypoxia and in response release vascular endothelial growth factor (VEGF) which in turn promotes the migration, differentiation and proliferation of vascular endothelial cells. This hypoxia/VEGF-mediated process of migration, proliferation and differentiation appears common to the retinae of a variety of species, including human. However, in human and macaque retina, different mechanisms appear to govern the development of the retinal vessels growing along the horizontal meridian of the retina towards the central area, which contains the fovea. Despite the relatively advanced state of differentiation and maturation of cells in the central area compared with the periphery, the growth of retinal vessels into the central area has been described as 'retarded', and the incidence of cell proliferation associated with these vessels is lower than in peripheral vessels. Furthermore, neither retinal vessels nor their accompanying astrocytes grow into a circumscribed region which, at a later stage, develops into the foveal depression. These observations suggest that molecular markers define the foveal region and inhibit cell proliferation and vascular growth at the fovea and, perhaps, along the horizontal meridian. The findings also suggest that at the fovea, the retina is adapted morphologically to its blood supply, since in the vicinity of the fovea, the development of retinal vessels is retarded or inhibited. The limitations on vascularization of central retina has implications for its vulnerability to degenerative changes, as seen in age-related macular degeneration.
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PMID:Development of the primate retinal vasculature. 1158 18

Electroconvulsive seizure therapy (ECS) is a clinically proven treatment for depression and is often effective even in patients resistant to chemical antidepressants. However, the molecular mechanisms underlying the therapeutic efficacy of ECS are not fully understood. One theory that has gained attention is that ECS and other antidepressants increase the expression of select neurotrophic factors that could reverse or block the atrophy and cell loss resulting from stress and depression. To further address this topic, we examined the expression of other neurotrophic-growth factors and related signaling pathways in the hippocampus in response to ECS using a custom growth factor microarray chip. We report the regulation of several genes that are involved in growth factor and angiogenic-endothelial signaling, including neuritin, stem cell factor, vascular endothelial growth factor (VEGF), VGF (nonacronymic), cyclooxygenase-2, and tissue inhibitor of matrix metalloproteinase-1. Some of these, as well as other growth factors identified, including VEGF, basic fibroblast growth factor, and brain-derived neurotrophic factor, have roles in mediating neurogenesis and cell proliferation in the adult brain. We also examined gene expression in the choroid plexus and found several growth factors that are enriched in this vascular tissue as well as regulated by ECS. These data suggest that an amplification of growth factor signaling combined with angiogenic mechanisms could have an important role in the molecular action of ECS. This study demonstrates the applicability of custom-focused microarray technology in addressing hypothesis-driven questions regarding the action of antidepressants.
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PMID:Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. 1464 77

Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic-pituitary-adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a 'somatic regulator' of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.
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PMID:VEGF is necessary for exercise-induced adult hippocampal neurogenesis. 1465 29

Although it has been postulated that adult neurogenesis, i.e. the generation of functional neurons from progenitor cells in the mammalian brain, is involved in both the pathogenesis of depressive disorders and the therapeutic effect of antidepressant drugs, its regulation is still poorly understood. Nitric oxide, a gaseous messenger molecule, represents a possible modulating agent as it is involved in learning and memory formation as well as synapto- and morphogenesis. Here we investigated whether adult neurogenesis is altered in mice lacking endothelial nitric oxide synthase (NOS-III). Compared to wild-type littermates, NOS-III-deficient mice showed a significant reduction in neuronal progenitor cell proliferation in the dentate gyrus, suggesting a role for NOS-III in the stimulation of neuroneogenesis. NeuN, beta-III-tubulin and GFAP double-immunolabelling demonstrated that proliferating progenitor cells differentiate preferentially into neurons but not into astrocytes. However, when the survival rate of newly formed cells was examined no difference between wild-type and NOS-III knockout mice was found, suggesting that NOS-III selectively exerts its effects on the proliferation of progenitor cells. This might be mediated by a decrease in vascular endothelial growth factor (VEGF) transcripts in the hippocampus of knockout animals. At the behavioural level, while NOS-III knockout mice displayed better and faster learning in a learned helplessness paradigm, no depression-like behaviours were observed. In conclusion, our results indicated that NOS-III is involved in the proliferation of neuronal progenitor cells, although behavioural analysis does not provide evidence for a pro-depressive effect of reduced neuroneogenesis.
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PMID:Differential effect of endothelial nitric oxide synthase (NOS-III) on the regulation of adult neurogenesis and behaviour. 1530 57

To address the role of follicular angiogenesis in the determination of ovulatory follicles and the effects of different vascular endothelial growth factor (VEGF) isoforms on follicular angiogenesis and development, mature female rats were treated with an angiogenic inhibitor (TNP-470), and also with VEGF 120 or 164 at different dosages (0.4, 0.8, 4.0 or 8.0 microg/kg body weight) for 3 days during the estrous cycle. Ovarian follicular angiogenesis, the population of large follicles and ovulation were examined. VEGF 120 (0.8 microg/kg) and 164 (8.0 microg/kg) treatments stimulated follicular angiogenesis in the theca interna layer, while TNP-470 treatment showed severe depression of follicular angiogenesis, and completely inhibited ovulation. After administration of VEGF 120 or 164, the number of healthy preovulatory follicles and ovulated oocytes increased significantly, concomitantly with a decrease in the number of atretic preovulatory follicles. The oocytes ovulated had normal fertilizability and developed to term with the same litter size as in the control rats. Our findings suggest that follicular angiogenesis may be a determinant of follicular development during the periovulatory phase, and that VEGF isoforms may play different important roles in regulating follicular angiogenesis.
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PMID:Acceleration of follicular development by administration of vascular endothelial growth factor in cycling female rats. 1575 Mar 8

The characterization of depression as a treatable disease has led to very significant research aimed at understanding disease mechanisms and treatments. Antidepressant therapy, employing chemical and non-chemical antidepressants are quite successful in treatment of the disorder although their mechanism of action is not well understood. Basic research with rodent models is providing vital evidence concerning the molecules and mechanisms involved in antidepressant action. The regulation of neurotrophic and growth factors observed after antidepressant administration is seen as playing an important role in modulating the therapeutic effects of antidepressants. Recently, adult neurogenesis or the birth of new neurons has emerged as a physiological phenomenon necessary for the behavioral response of antidepressant treatment. Equally interesting are correlative associations between neurogenesis and angiogenesis or the birth of new vasculature. Growth factors such as brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) play vital roles in both these phenomena making the interplay of neurogenesis and angiogenesis an exciting avenue of brain research. This review will focus on the research that has led us to this current understanding of antidepressant action in context with the pathophysiology of depression using examples from basic, preclinical and clinical investigations.
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PMID:Regulation of neurogenesis and angiogenesis in depression. 1618 Oct 76

Diazepam and chlorpromazine - psychotropic agents widely used for the amelioration of anxiety, depression, and psychosis, have been found to affect cell proliferation. We have checked whether these drugs influence proliferation of endothelial cells and probably angiogenesis process. We have studied the effect of diazepam and chlorpromazine on proliferative activity and vascular endothelial growth factor (VEGF) release from murine endothelial HECa10 cells cultured in vitro. In conclusion, diazepam at concentration of 10(-4)M had inhibitory action on the proliferation of endothelial cells in cultures. Chlorpromazine at concentrations from 10(-7) to 10(-4)M diminished the proliferative activity and secretion of VEGF into supernatants of cultured cells.
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PMID:Effect of diazepam and chlorpromazine on proliferative activity and vascular endothelial growth factor (VEGF) secretion from cultured endothelial HECa10 cells in vitro. 1622 52

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.
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PMID:Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. 1679 Dec 87

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