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

There are several findings on the action of magnesium ions supporting their possible therapeutic potential in affective disorders. Examinations of the sleep-electroencephalogram (EEG) and of endocrine systems point to the involvement of the limbic-hypothalamus-pituitary-adrenocortical axis as magnesium affects all elements of this system. Magnesium has the property to suppress hippocampal kindling, to reduce the release of adrenocorticotrophic hormone (ACTH) and to affect adrenocortical sensitivity to ACTH. The role of magnesium in the central nervous system could be mediated via the N-methyl-D-aspartate-antagonistic, gamma-aminobutyric acidA-agonistic or a angiotensin II-antagonistic property of this ion. A direct impact of magnesium on the function of the transport protein p-glycoprotein at the level of the blood-brain barrier has also been demonstrated, possibly influencing the access of corticosteroids to the brain. Furthermore, magnesium dampens the calciumion-proteinkinase C related neurotransmission and stimulates the Na-K-ATPase. All these systems have been reported to be involved in the pathophysiology of depression. Despite the antagonism of lithium to magnesium in some cell-based experimental systems, similarities exist on the functional level, i.e. with respect to kindling, sleep-EEG and endocrine effects. Controlled clinical trials examining the effect of Mg in affective disorder are warranted.
 ...
PMID:Magnesium and affective disorders. 1250 67

Complex disturbances in hemostasis characterise chronic renal insufficiency. Defect of primary hemostasis is a common cause of bleeding complications. The hemodialysis procedure (HD), by itself, influences platelet function (the key part of primary hemostasis) which is compromised after the procedure. Many functional defects of thrombocytes have been described in end stage renal failure (ESRF) patients; one of them is adhesion defect where the pivotal role plays the complex of glycoprotein Ib (GP Ib) and IX. The aim of the study was to determine the extent of activation, reactivity of platelets and expression of GP Ib in ESRF patients. The flow cytometry method was used, and thrombin was used for stimulation of thrombocytes. Membrane expression of GP Ib and selectin P was assessed in 14 hemodialysed patients before and after stimulation with thrombin, before and after HD and in 10 healthy persons. The patient group had lower expression of GP Ib on resting platelets and significantly lower expression of selectin P after stimulation with thrombin when compared to the control group. After HD, thrombocytes had much lower expression of GP Ib; however there was no difference in expression of selectin P when compared to the state before HD. A lower reduction of GP Ib expression after stimulation with thrombin was observed after and before HD. On the basis of the results the following conclusions may be drawn: hemo-dialysed ESRF patients have lower expression of platelet GP Ib and reactivity of thrombocytes; the HD results in further depression in expression of GP Ib and reactivity of thrombocytes. It is plausible that nitric oxide (NO) released during HD modulates the expression of selectin P, but it remains to be confirmed.
 ...
PMID:[Influence of hemodialysis on expression of glycoprotein lb platelets reactivity in patients with the end stage renal failure]. 1263 21

Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.
 ...
PMID:A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs. 1277 11

Clusterin is a sulfated glycoprotein produced by neurons and by resting and activated astrocytes that has several putative functions, including protective responses to brain injury. Cortical spreading depression (CSD) is a powerful yet largely benign stimulus that acutely is capable of providing long-lasting ischemic tolerance. The current study investigated possible alterations in expression of clusterin mRNA in the cerebral cortex of the rat at various times after unilateral CSD. Using semiquantitative in situ hybridization histochemistry, significant increases (30-100%; P< or =0.05) in clusterin mRNA were detected in layers I-III and IV-VI of the ipsilateral cortex at 1, 2, 7 and 14 (layers I-III only) days after CSD. Transcript levels in the ipsilateral cortex were again equivalent to contralateral (control) levels at 28 days after CSD. These molecular anatomical studies also revealed that both neurons and nonneuronal cells (presumed reactive astrocytes) increased their expression of clusterin mRNA following CSD. Notably the time-course of increases in clusterin mRNA after CSD (1-14 days) overlaps that during which CSD reportedly provides neuroprotection against subsequent cerebral ischemia. These findings along with other evidence suggest that increased clusterin production and secretion, particularly by astrocytes, could be neuroprotective-perhaps via one or more of its putative actions that include inhibition of complement activation and cytolysis, effects on chemotaxis and apoptosis, and actions as an anti-stress protein chaperone.
 ...
PMID:Delayed, but prolonged increases in astrocytic clusterin (ApoJ) mRNA expression following acute cortical spreading depression in the rat: evidence for a role of clusterin in ischemic tolerance. 1278 89

This study was designed to evaluate how new treatment guidelines of acute coronary syndrome (ACS) without ST elevation have been implemented in clinical practice especially in diabetic patients. A prospective follow-up was performed on 501 consecutive patients with suspected ACS without ST elevation admitted to nine hospitals in Finland between 15 January and 11 March 2001. The study group included 143 (29%) diabetic patients. Their risk profile was more severe than in non-diabetic patients; ST-depression on admission electrocardiography 57 versus 38%; P<0.0001, elevated troponin levels 66 versus 56%; P<0.05. Six months composite incidence of death, new myocardial infarction (MI), refractory angina or readmission for unstable angina was 39% in diabetic patients and 20% in non-diabetic patients (P<0.0001). In spite of this more severe risk profile, glycoprotein (GP) IIb/IIIa receptor antagonists and statins were used with similar frequency in non-diabetic and diabetic patients (15 vs. 19 and 48 vs. 54%, respectively; P=NS for both). In diabetic patients mean delay for in hospital coronary angiography was longer (6.4 vs. 4.2 days, P<0.05) and it was performed less often (32 vs. 45% P<0.05). Our results show that diabetic patients with ACS have higher risk profile and worse outcome than non-diabetic patients. Despite their indisputable benefits in diabetic patients, statins, GP IIb/IIIa receptor antagonists and invasive strategy were underused or often neglected. Further education is needed to change attitudes and to better implement new guidelines into clinical practice.
 ...
PMID:Underuse of evidence-based treatment modalities in diabetic patients with non-ST elevation acute coronary syndrome. A prospective nation wide study on acute coronary syndrome (FINACS). 1284 22

Bitiscetin, a platelet adhesion inducer isolated from venom of the snake Bitis arietans, activates the binding of the von Willebrand factor (VWF) A1 domain to glycoprotein Ib (GPIb) in vitro. This activation requires the formation of a bitiscetin-VWF A1 complex, suggesting an allosteric mechanism of action. Here, we report the crystal structure of bitiscetin-VWF A1 domain complex solved at 2.85 A. In the complex structure, helix alpha5 of VWF A1 domain lies on a concave depression on bitiscetin, and binding sites are located at both ends of the depression. The binding sites correspond well with those proposed previously based on alanine-scanning mutagenesis (Matsui, T., Hamako, J., Matsushita, T., Nakayama, T., Fujimura, Y., and Titani, K. (2002) Biochemistry 41, 7939-7946). Against our expectations, the structure of the VWF A1 domain bound to bitiscetin does not differ significantly from the structure of the free A1 domain. These results are similar to the case of botrocetin, another snake-derived inducer of platelet aggregation, although the binding modes of botrocetin and bitiscetin are different. The modeled structure of the ternary bitiscetin-VWF A1-GPIb complex suggests that an electropositive surface of bitiscetin may interact with a favorably positioned anionic region of GPIb. These results suggest that snake venom proteins induce VWF A1-GPIbalpha binding by interacting with both proteins, and not by causing conformational changes in VWF A1.
 ...
PMID:Crystal structure of von Willebrand factor A1 domain complexed with snake venom, bitiscetin: insight into glycoprotein Ibalpha binding mechanism induced by snake venom proteins. 1285 90

Serum alphal-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects' AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t49.2 = -3.48, P = .0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r = 0.28, P = .0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients.
 ...
PMID:alpha1-acid glycoprotein in late-life depression: relationship to medical burden and genetics. 1465 33

Extracts of Hypericum perforatum (HP) have been shown to be effective for the treatment of mild to moderate depression. Its mode of action has not been fully elucidated. An increase in plasma and cerebrospinal fluid (CSF) cortisol is frequently observed in depression. Studies have suggested that HP might alter brain cortisol and corticosterone through its effect on multidrug transporter glycoprotein (Pgp). We investigated the effect of sub-chronic treatment with an extract of HP (LI 160) on brain levels of corticosterone and cortisol in the rat. Results show that HP significantly reduced corticosterone and cortisol in brain frontal cortex tissue. These changes are not reflected in serum. These findings may be important with respect to HPs mode of antidepressant action.
 ...
PMID:Sub-chronic treatment with an extract of Hypericum perforatum (St John's wort) significantly reduces cortisol and corticosterone in the rat brain. 1465 82

Preliminary evidence shows that ethyl-eicosapentaenoate (E-EPA) has a marked clinical effect when used as an adjunct in therapy-refractory depression. EPA belongs to the class of polyunsaturated omega-3 fatty acids. The mechanism of its action in depression is not fully understood. There are two related fields where the pathophysiology of refractory depression meets the effect of EPA. First, a general immunosuppressive effect of EPA meets a general immunoactivation in severe depression, especially an increase in CD4/CD8 ratio, neutrophilia, and an increase in interleukins (IL)-6 and IL-12 and of prostaglandin E2 (PGE2). Secondly, a resistance to dexamethasone (Dex) suppression of the HPA axis meets the effects of EPA on multidrug resistance reversing and HPA axis suppression. The effects of EPA on the immune system, the HPA axis, and multidrug resistance are connected through the action of a transport protein called p-glycoprotein (p-gp). Physiological and synthetic steroids such as cortisol and Dex are substrates of p-gp, and so Dex resistance in depression may be related to dysfunction of this protein. In addition, expression of p-gp is induced by PGE2, and EPA inhibits the synthesis of PGE2. The reversal of drug resistance by EPA may be mediated via this immunological mechanism and lead to its antidepressive efficacy. In addition, antidepressants such as amitriptyline, which have special efficacy in severe depression, decrease p-gp function. EPA may, furthermore, enhance the action of antidepressants, like many SSRIs that are p-gp substrates, which are actively transported out of the intracerebral space at the level of the blood-brain barrier.
 ...
PMID:Ethyl-eicosapentaenoate and dexamethasone resistance in therapy-refractory depression. 1500 46

Depression represents an independent risk factor for developing ischemic heart disease, with platelet hyperactivity possibly serving as an important mediator of this association. In this pilot study we analyzed platelet surface activation markers in response to two stimuli, mental stress and physical activity. Using flow cytometry, we quantified the presence of two functional activation-dependent glycoprotein receptors on platelets' surface (P-selectin, GP53). Platelet reactivity was assessed as the difference in markers' fluorescence intensity before and after stimulation. We included 10 depressed psychiatric inpatients and 10 age- and sex-matched healthy subjects in our study. There was a significant rise in platelet activation markers in both groups associated with the stress protocol. When the effect of stressors was analyzed separately, strenuous physical activity was found to lead to a significant rise in platelet activation markers in depressed patients but not in healthy subjects, although values indicated a higher baseline level of activation in healthy subjects. These preliminary results lend partial support to the hypothesis of an exaggerated platelet reactivity after physical activity in depression, thus possibly contributing to an increased cardiovascular risk in this disorder.
 ...
PMID:Effect of mental and physical stress on platelet activation markers in depressed patients and healthy subjects: a pilot study. 1526 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>