Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bolesatine is a toxic glycoprotein isolated from Boletus satanas Lenz, which inhibits protein synthesis in vivo and in vitro. The LD50 (24 h) is 1 mg /kg bw (i.p.), in mice and rats. When given i.p. to mice (0.1 - 1.0 mg/kg bw) bolesatine induced thrombi and blood stasis in the liver, 5 - 21 h after injection, and modifications of the number of blood corpuscles in peripheral blood. These effects were efficiently reversed by aspirin, ticlopidin and heparin (as attested by histology and electron microscopy) which however failed to prevent death in animals given lethal doses. Together, these results showed that the death of bolesatine poisoned animals given high doses, was rather due to a combination of thrombosis and other toxic effects. In addition, they suggest that these antithrombotic drugs may overcome cases of human poisoning, with low exposures of this boletus, showing a hypertension probably due to mechanical obstruction which resists normal therapy.
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PMID:Aspirin and heparin prevent hepatic blood stasis and thrombosis induced by the toxic glycoprotein Bolesatine in mice. 986 19

Mibefradil, a tetralol derivative, is a new long-acting calcium antagonist used for the treatment of patients with hypertension and chronic stable angina pectoris. The drug is virtually completely metabolised, with less than 3% of an oral dose excreted unchanged in urine. Its metabolism occurs via parallel pathways, which fall into 2 broad categories: esterase-catalysed hydrolysis (producing the major plasma metabolite) and cytochrome P450 (CYP) 3A4-mediated oxidation. Plasma protein binding is greater than 99.5%, predominantly to alpha 1-acid glycoprotein. Oral multiple dose administration of mibefradil 50 or 100 mg once daily is associated with inhibition of the CYP3A4 pathway of metabolism, increasing the half-life and bioavailability of the parent compound. The intensity of the inhibition of CYP similarly results in numerous clinically relevant drug interactions which ultimately motivated the voluntary withdrawal of mibefradil from the market. With multiple oral doses of 50 to 100 mg once daily, the time to maximum plasma concentration was approximately 2.4 hours, absolute bioavailability was around 80%, clearance was 5.7 to 7.5 L/h, oral terminal exponential volume of distribution was 180 L, and terminal exponential half-life was 22 hours (ranging between 17 and 25 hours). A NONMEM sparse data analysis indicated that apparent clearance is not affected by race, gender, age or bodyweight. Renal function does not affect the pharmacokinetics of mibefradil.
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PMID:Clinical pharmacokinetics of mibefradil. 988 14

-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism at -20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at -20, this sequence binds to the estrogen receptor. We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at -20 is increased on cotransfection of an expression vector containing human estrogen receptor-alpha coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at -20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at -20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at -20. Our data suggest that C/A polymorphism at -20 may modulate the expression of human angiotensinogen gene in a sex-specific manner.
Hypertension 1999 Jan
PMID:Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene. 993 Oct 90

Erythropoietin (EPO) is a glycoprotein hormone and the principal regulator of erythropoiesis in the fetus, newborn, and adult. EPO-alfa is erythropoietin manufactured by recombinant human DNA technology (rhEPO). After counseling, a pregnant woman with anti-Js(b) in her serum was started on rhEPO (600 U/Kg, biweekly) to prevent anemia secondary to serial donations of her blood for fetal transfusions. After a total of 25 rhEPO infusions and autologous donation of 8 units of whole blood, maternal hemoglobin prior to the elective cesarean section at 37 weeks was 11.3 gm/dL. Serum EPO concentration was determined in paired maternal and fetal blood samples, before ultrasound guided intravascular transfusions, in this alloimmunized Js(b)-negative and another Rh(D) alloimmunized pregnancy to determine possible correlations between maternal and fetal serum EPO. rhEPO prevented anemia in a patient who donated 8 units of blood from 18-37 weeks of pregnancy without inducing adverse biological effects such as hypertension or thrombotic complications in the placenta. Data presented in this study suggest that EPO does not cross the human placenta.
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PMID:Use of recombinant human erythropoietin (EPO-alfa) in a mother alloimmunized to the Js(b) antigen. 1033 71

The polymorphisms C807T and G873A of the platelet integrin alpha2beta1 (collagen receptor glycoprotein [GP] Ia-IIa) are linked to the expression density of this receptor. The GPIa T807/A873 allele causes a higher receptor expression, enhancing platelet binding to collagen. This might present a genetic predisposition for the development of thromboembolic complications. In this case-control study, the genotypes of the GPIa C807T polymorphism and presence of conventional risk factors (hypertension, diabetes mellitus, and smoking) were compared in stroke patients and patients without cerebrovascular disease (non-CVD patients) </=50 years of age (n = 45 and 41, respectively) and in stroke patients and non-CVD patients more than 50 years of age (n = 182 and 129, respectively. In patients </=50 years of age, the T807 allele was the only overrepresented variable (P =.023; odds ratio, 3.02; 95% confidence interval, 1.20 to 7.61) and an independent risk factor, whereas the presence of conventional risk factors was similar between stroke patients </=50 years of age and non-CVD patients </=50 years of age. Large epidemiological studies should prove whether the platelet collagen receptor GPIa-IIa T807 allele is an independent risk factor for the development of stroke in younger patients.
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PMID:The alpha2 gene coding sequence T807/A873 of the platelet collagen receptor integrin alpha2beta1 might be a genetic risk factor for the development of stroke in younger patients. 1033 62

Corticosteroids (glucocorticoids), used frequently as potent anti-inflammatory agents, increase the risk of glaucoma by raising the intraocular pressure (IOP) when administered exogenously (topically, periocularly or systemically) and in certain conditions of increased endogenous production (e.g. Cushing's syndrome). Approximately 18 to 36% of the general population are corticosteroid responders. This response is increased to 46 to 92% in patients with primary open-angle glaucoma (POAG). Patients over 40 years of age and with certain systemic diseases (e.g. diabetes mellitus, high myopia) as well as relatives of patients with POAG are more vulnerable to corticosteroid-induced glaucoma. The association of corticosteroid-induced ocular hypertension in other conditions which are considered as risk factors for glaucoma (racial origins, hypertension, migraine, vasospasm) is likely but not fully established. The proposed mechanism of corticosteroid-induced glaucoma includes morphological and functional changes in the trabecular meshwork system and is similar to the pathogenesis of POAG. Trabecular cells exposed to corticosteroids in vitro show endoreplication of nuclei, an increase in cell size and excessive production of an approximately 56kD glycoprotein, identified as myocilin and transcribed by the GLC1A gene. Induction of ocular hypertension after corticosteroid administration depends on the specific drug, the dose, the frequency of administration and the corticosteroid responsiveness of the patient. The risk of corticosteroid-induced glaucoma can be minimised with judicious use of corticosteroids, as well as education of patients and medical practitioners. New treatment modalities include modified steroids and nonsteroidal anti-inflammatory agents that will have less effect on the elevation of IOP.
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PMID:Corticosteroids and glaucoma risk. 1064 55

The 'metabolic syndrome' is a special clinical entity characterized by upper body segment obesity (android obesity), together with one or more of a constellation of metabolic disorders that includes glucose intolerance, which may amount to frank diabetes mellitus, hypertension, cardiovascular lesions, hyperuricemia, and dyslipidemias (hypercholesterolemia, hypertriglyceridemia and reduced serum HDL). Recently, lipoprotein (Lp) (a) proved to be a new member in this syndrome. Lp(a) has the distinctive feature of containing apolipoprotein (a), which is a glycoprotein linked to apo B100, and has a similarity to plasminogen; it is also structurally related to LDL. Lp(a) is a macromolecular complex which is genetically determined, and has been identified as an independent risk factor for premature coronary artery disease (CAD). It is elevated in diabetic and non-diabetic android obese subjects, and aggravates the atherogenic effect of diabetes mellitus. Lp(a) is poorly influenced either by dietary measures or by hypolipidemic drugs. Unfortunately, few pharmacologic agents, such as niacin, nicotinic acid, sex hormones (estrogen and testosterone), alcohol and neomycin, affect Lp(a).
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PMID:Lipoprotein (a) in android obesity and NIDDM: a new member in 'the metabolic syndrome'. 1066 39

Antibodies to beta(2)-glycoprotein (beta(2)-GPI) have been associated with recurrent thrombotic events in patients with systemic lupus erythematosus. The present study investigated the prevalence of antibodies to beta(2)-GPI in an unselected group of patients with ischemic stroke. One hundred and twenty-one sera from patients with ischemic stroke and 174 control sera from patients with nonischemic neurological disorders (n = 43) and healthy subjects (n = 131) were tested for antibodies to beta(2)-GPI by a solid-phase ELISA. Twenty-nine stroke patients (24%) had antibodies to beta(2)-GPI. Of the 43 patients in the neurological control group, 2 were positive. For comparison between the groups, Fisher's exact test was used for categorical variables and ANOVA for antibody titers. Antibody levels and frequencies of positivity were significantly different between the study groups. None of the sera from the healthy control group had abnormal antibody levels. When risk factors and associated diseases were taken into account, a marginal association was found between the presence of antibodies to beta(2)-GPI and hypertension (p = 0.036). This study demonstrates a significant prevalence of antibodies to beta(2)-GPI in an unselected stroke population.
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PMID:Antibodies to beta(2)-glycoprotein I in ischemic stroke. 1087 35

Fifty patients with stable slight and moderate uncomplicated essential hypertension, treated by ramipril, atenolol, or isradipine, were examined. Total protein and urinary excretion of individual proteins were studied before and after treatment. Urinary concentrations of apolipoproteins A1 and B1, alpha 1-acid glycoprotein, alpha 1-antitrypsin, prealbumin, albumin, beta 2-microglobulin, transferrin, haptoglobin, IgG and IgA, and C3 and C4 complement components were measured. Index of proteinuria selectiveness was calculated for each portion of urine. All three drugs exerted a nephroprotective effect, atenolol being the most active of them. Apolipoproteins, IgG, and complement components were the most valuable for diagnosis. Their excretion correlated with the severity of arterial hypertension and efficiency of treatment. Use of protein markers helps reliably assess the renal function and monitor the treatment efficiency.
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PMID:[Protein markers in evaluation of nephroprotective effects of antihypertensive drugs in patients with arterial hypertension]. 1098 85

Thrombomodulin is an endothelial glycoprotein that decreases thrombin activity and activates protein C. A recent study has shown that G-33A promoter mutation of the thrombomodulin gene occurs particularly in Asians. In this study, we analyzed the distribution of G-33A mutation in the promoter region of the thrombomodulin gene in the Chinese population and determined whether the mutation might be a risk for coronary artery disease (CAD). In addition, the influence of this mutation on plasma soluble thrombomodulin levels in patients with CAD was also examined. We studied 320 consecutive patients (mean age 63 years; 73% men) with CAD and 200 age- and sex-matched control subjects. Screening for thrombomodulin G-33A promoter mutation was conducted using polymerase chain reaction, single-strand conformation polymorphism, and direct deoxyribonucleic acid sequencing. The frequency of the G-33A mutation (GA+AA genotypes) was significantly higher in the CAD group (23.8% vs 15.5%, odds ratio [OR] 1.70, p = 0.031). Multiple logistic regression analysis showed that the mutation was an independent risk factor (OR 1.81, p = 0.016) for CAD, as was hypertension (OR 1.44, p = 0.040), diabetes mellitus (OR 2.50, p <0.001), and smoking (OR 2.15, p <0.001). In CAD patients with GG genotype, the soluble thrombomodulin level increased with the extent of CAD (36 +/- 15 vs 47 +/- 18 vs 55 +/- 36 ng/ml in 1-, 2-, or 3-vessel CAD, p <0.001). However, in CAD patients with G-33A mutation, there was no difference between the levels of soluble thrombomodulin (39 +/- 17 vs 37 +/- 15 vs 42 +/- 18 ng/ml, p = NS) in 1-, 2-, or 3-vessel CAD. Our observations suggest that there is a significant association of the G-33A mutation in thrombomodulin gene with CAD, and this mutation may influence the soluble thrombomodulin levels in patients with CAD.
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PMID:G-33A mutation in the promoter region of thrombomodulin gene and its association with coronary artery disease and plasma soluble thrombomodulin levels. 1107 28


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