Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was made of the occurrence of glucose-6-phosphate dehydrogenase (G-6-PDH) deficiency among patients with lung tuberculosis including those suffering from mental diseases (alcoholism or schizophrenia). In Azerbaijani patients, the rate of G-6-PDH demonstration was higher as compared to that among the healthy population. On combined lung tuberculosis and alcoholism the rate of that abnormality demonstration increased whereas on associated lung tuberculosis and schizophrenia, it slightly decreased. Among patients with hereditary G-6-PDH deficiency, the portion of chronic destructive forms of pulmonary tuberculosis is high, the tuberculous process is accompanied more often by isolation of M. tuberculosis. The etiological role of G-6-PDH as a genetic marker is evaluated as 14%; in associated lung tuberculosis and alcoholism, it grows to 18%.
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PMID:[Pulmonary tuberculosis in patients with hereditary glucose-6-phosphate dehydrogenase deficiency]. 253 43

Heavy maternal alcohol intake is a major perinatal risk but, unfortunately, is difficult for obstetricians and gynecologists to detect. To develop a brief questionnaire appropriate for office detection of "risk-drinking," that is, alcohol intake potentially sufficient to damage the fetus, defined here as greater than or equal to 1 ounce of absolute alcohol per day, we obtained a quantitative drinking history at the first prenatal visit from 971 consecutive gravid women who admitted ever having drunk alcohol. In addition, we administered the 25-question Michigan Alcoholism Screening Test and the four CAGE questions (C = cut down, A = annoyed, G = guilt, E = eye opener), a screening test previously unstudied in pregnancy, and sought evidence of tolerance to the inebriating effect of alcohol, a question which does not appear to trigger psychologic denial. The patient was considered tolerant if it took greater than 2 drinks to make her feel "high." Among 42 (4.3%) risk-drinkers and 929 women who did not report drinking at risk levels, four questions were found to contribute to reliably differentiating risk-drinkers from non-risk-drinkers (R2 = 14.6%, p less than 0.0001). The probability of risk-drinking increased from 1.5% for those responding negatively to 62.7% for those responding positively to all four questions (T = tolerance, A = annoyed, C = cut down, E = eye-opener; odds ratio = 109X). A simple scoring scheme (2 points for T and 1 each for A, C, or E, with a total score of greater than or equal to 2 considered positive) correctly identified 69% of the risk-drinkers (sensitivity) with a positive predictive value of 23%). The T-ACE questions take about 1 minute to ask and represent the first validated sensitive screen for risk-drinking appropriate for routine use in obstetric-gynecologic practice. If validated in further samples, broad application might contribute to better risk identification, secondary prevention efforts, and improved pregnancy outcomes for offspring at risk from heavy prenatal alcohol exposure.
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PMID:The T-ACE questions: practical prenatal detection of risk-drinking. 224 68

Hypertension is the commonest cardiovascular disease in Africans occurring in more than 15% of the adult population in some studies. It occurs in the lower as much as in the higher socio-economic groups. Recent studies have confirmed earlier findings that essential hypertension in Africans is characterised by volume loading, low plasma renin activity, high salt taste threshold, high urinary sodium and low potassium excretion and high plasma aldosterone. The commonest complication of hypertension in Africans is congestive cardiac failure followed by cerebrovascular accidents. Coronary heart disease is rare. Even in the absence of overt heart failure and compounding factors like obesity, alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of abnormal left ventricular morphology and function is often present in newly diagnosed patients with moderate or severe hypertension. Response to monotherapy with beta-blockers or ACE inhibitors is usually poor but is good with thiazide diuretics or calcium channel blockers. The diuretics are an essential component of a two or three drug regime containing other classes of antihypertensive drugs. Cost of drugs is the most important determinant of compliance with drug treatment and consequently the likelihood of progression of the diseases to more severe forms in long term follow-up.
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PMID:Hypertension in Africa and effectiveness of its management with various classes of antihypertensive drugs and in different socio-economic and cultural environments. 826 3

There are several limitations to our knowledge of alcohol abuse and women. First, the efficacy for women of traditional alcohol screening instruments is unclear since most have been tested and normalized on male populations. The T-ACE and the TWEAK have been tested primarily in specialized populations, limiting their generalizability. Second, the efficacy of brief intervention among women who are moderate to heavy drinkers is also unclear. Reasons for this gap in our knowledge include exclusion of women from research studies, inadequate sample sizes of female subjects, limiting generalizability, and conflicting results from the studies focusing on women and brief interventions in the general medical setting. The barriers to early identification of problem drinking in women and subsequent intervention in the primary care setting may have application to psychiatric practice as well. Women with alcohol dependence are more likely to be seen in other mental health facilities than in alcohol treatment centers. Because of the high rate of comorbidity of alcohol use disorders among individuals with other mental disorders, a careful review of alcohol consumption should be part of every psychiatric evaluation. Psychiatrists therefore might play an important role in early identification of women problem drinkers and be able to intervene, educate, and work collaboratively with primary care providers to reduce the morbidity and mortality of alcohol-abusing women.
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PMID:Primary care: detection of women with alcohol use disorders. 938 11

Apolipoprotein E epsilon4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non-alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E epsilon2/2; patients 1.4%, controls 0% p < 0.06; epsilon2/epsilon3; patients 9.3%, controls 6.6% p < 0.29; epsilon2/epsilon4; patients 0%, controls 1% p < 0.31; epsilon3/epsilon3 patients 71.4%, controls 72% p < 0.89; epsilon3/epsilon4; patients 15.7%, controls 19.2%, p < 0.36; epsilon4/epsilon4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, epsilon4/epsilon3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with epsilon2/epsilon3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E epsilon4 allele and reduced cognitive performance in alcoholism.
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PMID:Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients. 1200 18

Naltrexone (NTX) is a potent competitive antagonist with high affinity for the mu-opioid receptor. Therapeutically, NTX is used for the treatment of alcohol dependence and opioid addiction; however, it does not have the ideal physicochemical properties necessary to achieve therapeutic plasma concentrations via the transdermal route. The aim of the present investigation was to evaluate the in vivo transdermal delivery of three 3-O-alkyl ester prodrugs of NTX, including NTX-3-O-acetate (ACE-NTX), NTX-3-O-propionate (PROP-NTX), and NTX-3-O-hexanoate (HEX-NTX) in hairless guinea pigs. The pharmacokinetic parameters for NTX and the 3-O-alkyl ester prodrugs of NTX were determined after intravenous drug administration and topical drug application of transdermal therapeutic systems (TTS) in guinea pigs. The results of the in vivo studies showed mean steady-state plasma concentrations of NTX from NTX, ACE-NTX, PROP-NTX and HEX-NTX at 4.2, 25.2, 16.0, and 8.3 ng/mL, respectively. These NTX plasma concentrations were maintained for 48 h. The results of these in vivo studies demonstrated that ACE-NTX and PROP-NTX prodrugs of NTX were the most promising drug candidates for transdermal delivery.
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PMID:In vivo evaluation of 3-O-alkyl ester transdermal prodrugs of naltrexone in hairless guinea pigs. 1565 67

Essential fatty acids (EFAs): cis-linoleic acid (LA) and alpha-linolenic acid (ALA) are essential for humans and their deficiency is rare in humans due to their easy availability in diet. EFAs are metabolized to their respective long-chain metabolites: dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) from LA; and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA. Some of these long-chain metabolites form precursors to respective prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), lipoxins (LXs) and resolvins. EFAs and their metabolites may function as endogenous angiotensin converting enzyme and HMG-CoA reductase inhibitors, nitric oxide enhancers, anti-hypertensives, and anti-atherosclerotic molecules. EFAs react with nitric oxide (NO) to yield respective nitroalkene derivatives that have cell-signaling actions via ligation and activation of peroxisome proliferator-activated receptors (PPARs). In several diseases such as obesity, hypertension, diabetes mellitus, coronary heart disease, alcoholism, schizophrenia, Alzheimer's disease, atherosclerosis, and cancer the metabolism of EFAs is altered. Thus, EFAs and their derivatives have significant clinical implications.
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PMID:Essential Fatty acids - a review. 1716 64

A brain renin angiotensin system (RAS) and its role in cardiovascular control and fluid homeostasis was at first controversial. This was because a circulating kidney-derived renin angiotensin system was so similar and well established. But, the pursuit of brain RAS has proven to be correct. In the course of accepting brain RAS, high standards of proof attracted state of the art techniques in all the new developments of biology. Consequently, brain RAS is a robust concept that has enlightened neuroscience as well as cardiovascular physiology and is a model neuropeptide system. Molecular biology confirmed the components of brain RAS and their location in the brain. Transgenic mice and rats bearing renin and extra copies of angiotensinogen genes revealed the importance of brain RAS. Cre-lox delivery in vectors has enabled pinpoint gene deletion of brain RAS in discrete brain nuclei. The new concept of brain RAS includes ACE-2, Ang1-7, and prorenin and Mas receptors. Angiotensin II (ANG II) generated in the brain by brain renin has many neural effects. It activates behavioral effects by selective activation of ANG II receptor subtypes in different locations. It regulates sympathetic activity and baroreflexes and contributes to neurogenic hypertension. New findings implicate brain RAS in a much wider range of neural effects. We review brain RAS involvement in Alzheimer's disease, stroke memory, and learning alcoholism stress depression. There is growing evidence to consider developing treatment strategies for a variety of neurological disease states based on brain RAS.
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PMID:Brain renin angiotensin in disease. 1838 68

Interleukin-18 (IL-18) is one of the mediators of both pancreas damage and systemic complications like hypotension and multi-organ dysfunction during acute pancreatitis. IL-18 is generated intracellularly from pro-IL-18 by caspase-1 mediated proteolysis. Active caspase-1 itself is generated intracellularly by the action of the inflammasome, autocatalysis and other stimuli. The anti-retroviral drug ritonavir inhibits conversion of inactive pro-caspase-1 to active caspase-1. Since ritonavir is well tolerated in short-term use it may therefore prove useful in treating acute pancreatitis by lowering caspase-1 mediated IL-18 formation and the many inflammatory mediators downstream from that. The alcoholism treatment drug disulfiram has been in continuous use since the 1950s. It likewise has a low risk profile. Disulfiram inhibits several human proteases, among them caspase-1. Given the current morbidity and mortality of pancreatitis, research should be directed to ritonavir and disulfiram as treatment options for illnesses like pancreatitis where excessive IL-18 contributes to pathology. The first clinically used angiotensin converting enzyme inhibitor, captopril, has shown potent caspase-1 inhibiting activity as well and should be investigated in rodent models of human pancreatitis.
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PMID:Ritonavir and disulfiram may be synergistic in lowering active interleukin-18 levels in acute pancreatitis, and thereby hasten recovery. 1846 53

Emergent novel SARS-CoV-2 is responsible for the current pandemic outbreak of severe acute respiratory syndrome with high mortality among the symptomatic population worldwide. Given the absence of a current vaccine or specific antiviral treatment, it is urgent to search for FDA-approved drugs that can potentially inhibit essential viral enzymes. The inhibition of 3CL^pro has potential medical application, due to the fact that it is required for processing of the first translated replicase polyproteins into a series of native proteins, which are essential for viral replication in the host cell. We employed an in silico approach to test if disulfiram, as well as its metabolites, and captopril could be used as potential antiviral drugs against COVID-19. We provide data on the potential covalent interaction of disulfiram and its metabolites with the substrate binding subsite of 3CL^pro and propose a possible mechanism for the irreversible protease inactivation thought the reaction of the aforementioned compounds with the Cys145. Although, captopril is shown to be a potential ligand of 3CL^pro, it is not recommended anti-COVID-19 therapy, due to the fact that it can induce the expression of the viral cellular receptor such as, angiotensin-converting enzyme ACE-2, and thus, making the patient potentially more susceptible to infection. On the other hand, disulfiram, an alcoholism-averting drug, has been previously proposed as an antimicrobial and anti-SARS and MERS agent, safe to use even at higher doses with low side effects, it is recommended to be tested for control of SARS-CoV-2 infection.Communicated by Ramaswamy H. Sarma.
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PMID:FDA-approved thiol-reacting drugs that potentially bind into the SARS-CoV-2 main protease, essential for viral replication. 3236 11


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