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)

G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptors (GPCRs) to effect receptor phosphorylation and to initiate profound impairment of receptor signalling, or desensitization. GPCRs form the largest family of cell surface receptors known and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations. This review focuses on the physiological role of GRKs revealed by genetically modified animals but also develops the involvement of GRKs in human diseases as, Oguchi disease, heart failure, hypertension or rhumatoid arthritis. Furthermore, the regulation of GRK levels in opiate addiction, cancers, psychiatric diseases, cystic fibrosis and cardiac diseases is discussed. Both transgenic mice and human pathologies have demonstrated the importance of GRKs in the signalling pathways of rhodopsin, beta-adrenergic and dopamine-1 receptors. The modulation of GRK activity in animal models of cardiac diseases can be effective to restore cardiac function in heart failure and opens a novel therapeutic strategy in diseases with GPCR dysregulation.
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PMID:Pathophysiological roles of G-protein-coupled receptor kinases. 1589 65

Drugs used to treat psychiatric disorders, although effective, are often restricted by adverse events. The use of partial agonists for treating hypertension was found to limit some of the side-effects in some patients. This led to the investigation of partial agonists as a treatment modality in psychiatric disorders. Partial agonists have a lower intrinsic efficacy than full agonists leading to reduced maximum response. They can act as antagonists by competing for receptor binding with full agonists. The level of activity depends on the level of endogenous receptor activity. Buprenorphine, a partial agonist at the mu-opioid receptor, is used to treat patients with addiction and decreases the symptoms of withdrawal and risks of overdose and intoxication. The anxiolytic buspirone shows partial agonism at 5-HT(1A) receptors, and this seems to provide anxioselective effects, without inducing extrapyramidal side-effects, convulsions, tolerance or withdrawal reactions. In schizophrenia, partial dopamine agonism results in antagonistic effects at sites activated by high concentrations of dopamine and agonistic effects at sites activated by low concentrations of dopamine. This stabilizes the dopamine system to effect antipsychotic action without inducing adverse motor or hormonal events. Aripiprazole is the first 'dopamine system stabilizer', and the data are promising, with efficacy at least equivalent to that with current atypical antipsychotics but fewer of the troublesome side-effects. Partial agonists seem to provide a way to fine-tune the treatment of psychiatric disorders by maximizing the treatment effect while minimizing undesirable adverse events.
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PMID:The place of partial agonism in psychiatry: recent developments. 1598 97

Intracranial unruptured aneurysm (ICUA) has become a common condition for patient consultation. The mortality rate after fissuration is estimated to be between 52% and 85.7%. The final therapeutic decision results from a balance between the risk of rupture and risks related to the aneurysmal exclusion. Analysis of the risk of rupture risk enables a classification of risk factors. Depending on the circumstances of diagnosis, we considered the ICUA at high risk of rupture for incidental ICUA larger than 7 mm and in the event of associated aneurysms. Classifying by morphologic features, high-risk ICUA were located in the vertebrobasilar system (RR: 4.4; 95%CI: 2.7-6.8), those with a size between 7 and 12 mm (RR: 3.3; 95%CO: 1.3-8.2), larger than 12 mm (RR: 17; 95%CI: 8-36.1), those that were multilobular or a larger size and those ones with a index P/L superior to 3.4 (risk x20). Familial ICUA would expose to a major rupture risk (2 to 7 times sporadic ICUA). Some systemic factors were related to ICUA rupture: arterial hypertension (RR: 1.46; 95%CI: 1.01-2.11) and smoking addiction (RR: 3.04; 95%CI: 1.21-7.66). After microsurgical exclusion, the morbidity and mortality rates were 10% and 2% respectively. Some microsurgical morbidity factors were identified: age (32%>65 years), size (14%>15 mm), vertebrobasilar location and temporary occlusion. The rupture incidence after microsurgical exclusion was estimated 0.26%/year. After endovascular exclusion, the morbidity and mortality rates were 8% and 1% respectively. The complete exclusion rate varied between 47% and 67%. The rupture risk was estimated at 0.9%/year. Treatment recommendations were classified into 3 categories.
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PMID:[Unruptured intracranial aneurysm: possible therapeutic strategies?]. 1632 77

In only recent history, illicit use of methamphetamine, once isolated to urban areas on the West Coast, has spread into rural areas of the Midwest and southern United States. Although past and current methamphetamine legislation has increased penalties for methamphetamine manufacturers and tightened restrictions on sales of known precursors, the problem still persists. In fact, a 2004 survey indicates that an alarming 6.2% of high school seniors have tried methamphetamine. A number of biological, genetic, and environmental factors influence children's and adolescents' paths to substance abuse. Nurses should recognize the symptoms of methamphetamine abuse, which include agitation; aggressive behavior; rapid mood swings; hypertension; tachycardia; and eventually lesion-marked skin, clinical depression, and paranoid psychosis. Treatment for methamphetamine addiction includes behavioral therapy. Research on pharmacologic therapy is lacking. Educating youth on methamphetamine prevention appears to be the best approach to curb the spreading use of this addictive and deadly drug.
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PMID:Methamphetamine: putting the brakes on speed. 1656 27

Among adults, chronic alcohol dependence is associated with cardiovascular disease (CVD). While it is unlikely that adolescents with alcohol use disorders (AUDs) would exhibit CVD, they might show elevated CVD risk factors. The purpose of this study was to compare CVD risk factors in adolescents with AUDs and an adolescent reference group. Adolescents with AUDs were recruited from treatment sources and reference adolescents were recruited from the community. Information about smoking behavior, exercise, and diet were gathered from interview and self-report measures. Body mass index and blood pressure were determined by physical exam and a blood sample was drawn to measure serum cholesterol and triglycerides. Compared with the reference group, adolescents with AUDs reported significantly more smoking, were less likely to report exercising regularly, and were less likely to report eating a balanced diet. Adolescents with AUDs were not more likely to be overweight or to exhibit hypertension, and lipid levels were also not significantly elevated. These results indicated that adolescents with AUDs endorsed problematic health behaviors while not yet exhibiting the consequences of these behaviors. Interventions focusing on health behaviors in conjunction with addiction treatment might help improve long-term health outcomes in adolescents with AUDs.
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PMID:Cardiovascular risk factors in adolescents with alcohol use disorders. 1663 69

Under the headline "drug addiction" the medical world has exclusively been interested in psychoactive drugs. For diagnosis of substance dependence (addiction), DSM-IV-TR has determined seven criteria, and fulfilling at least tree of them signifies addiction. When studied salt intake according to these criteria it is seen that most of them are fulfilled, showing that sodium chloride, which is not classified under the psychoactive drugs, is capable of producing addiction. Namely: at the beginning of salt abstinence, anorexia and slight nausea during meal time (withdrawal symptoms); about 1000-fold difference of per capita salt consumption between several human societies, and life-long continuation of discretional salt intake behaviour (high dose and very long duration of use); difficulty of restriction of salt intake (unsuccessful efforts to cut down or control); lack of success of salt restriction campaigns in hypertensive patients (substance use despite health problem). Additionally, the decrease of salt preferences of individuals whose salt intake are restricted for some time, and vice versa, signifies tolerance. On the other hand, it is evident that as the main culprit of developing systemic hypertension and as producing or promoting some other important health problems, salt intake causes millions of deaths in the world yearly. The recognition of addicting property of salt will facilitate combating these health problems.
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PMID:Salt addiction: a different kind of drug addiction. 1679 Mar 20

Smoking is related to 30% of cancer deaths. It is a risk factor for respiratory tract, esophagus, stomach, pancreas, uterine cervix, kidney and bladder carcinomas. Nicotine induces tolerance and addiction by acting on the central dopaminergic pathways, thus leading to pleasure and reward sensations within the limbic system. It stimulates the central nervous system (CNS), enhances alertness and reduces the appetite. A 50% reduction of nicotine consumption may trigger withdrawal symptoms in addicted individuals: anxiety, anger, sleep disorders, hunger, cognitive dysfunction and cigarette craving. Medical advice is the cornerstone of smoking cessation. Pharmacotherapy of nicotine addiction comprises first-line (bupropion and nicotine replacement therapy) and second-line (clonidine and nortriptyline) drugs. Bupropion is a non-tricyclic antidepressant that inhibits dopamine uptake, whose contraindications are: epilepsy, eating disorders, uncontrolled hypertension, recent alcohol abstinence and current therapy with MAO inhibitors. Nicotine replacement therapy can be done with patches or gums. Counseling groups and behavioral interventions are efficacious. The effects of acupuncture on smoking cessation are not fully elucidated. Prompt smoking cessation or gradual reduction strategies have similar success rates.
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PMID:Methods for smoking cessation and treatment of nicotine dependence. 1687 54

Peculiarities of clinical pharmacology of new generation loop diuretic torasemide and its possible place in the treatment of arterial hypertension, chronic heart failure (CHF) and liver cirrhosis are considered. Main advantage of torasemide over loop diuretics of furosemide and bumetamide type is that in addiction to powerful diuretic and natriuretic actions it produces potassium sparing effect that is explainded by ability its of to tosasimide to block aldosterone receptors in renal tubules. Moreover torasemide exerts longer action than furosemide and bumetamide what allows to take it once a day. In low doses torasemide produces pronounced antihypertensive effect without augmentation of excretion of potassium and water with urine. Because of this it can be used as antihypertensive drug for monotherapy or in combination with other drugs. Contrary to thiazide and loop diuretics prescription of subdiuretic doses of torasemide usually does not require control of potassium content in the blood or addition of potassium preparations. In higher doses (10 mg/day or more) torasemide acts as typical loop diuretic and can be used in the treatment of CHF and liver cirrhosis with ascites. Due to potassium sparing action it more rarely than furosemide and bumetamide causes hypokalemia. Comparative studies have shown than in CHF torasemide exerts more favorable effect on clinical signs of disease and functional status of patients than furosemide. Total mortality, cardiovascular mortality and requirements in hospitalization of patients receiving torasemide is substantially less than of patients receiving furosemide.
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PMID:[Torasemide--new generation loop diuretic: clinical pharmacology and therapeutic application]. 1715 56

An endogenous natriuretic and vasoconstrictor Na/K-ATPase inhibitor, marinobufagenin (MBG), is implicated in NaCl-induced hypertension and in ethanol addiction. In rats, MBG suppresses voluntary alcohol intake, while immunization against MBG induces alcohol-seeking behavior. Since alcohol withdrawal is associated with elevation of blood pressure (BP) and renal sodium retention, we hypothesized that MBG mediates pressor response to ethanol withdrawal. In male Sprague-Dawley rats, forced ethanol intake (20% v/v, 2.8+/-0.2 g/day for 7 days) did not affect BP and MBG excretion. Ethanol withdrawal was associated with a 21 mm Hg increase in BP, a 10% decrease in hematocrit, and a three-fold increase in renal MBG excretion. In vivo administration of anti-MBG antibody to rats prevented withdrawal-induced BP elevation. Therefore, MBG mediates pressor response to ethanol withdrawal, and may link mechanisms of ethanol dependence and hypertension.
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PMID:Endogenous bufadienolide mediates pressor response to ethanol withdrawal in rats. 1768 16

There is a close association between social circumstances and health. In India, there is a significant burden of both communicable and non communicable diseases. Risk factors responsible for these conditions are underweight, unsafe sex, unsafe water, poor sanitation and hygiene, indoor smoke pollution, zinc, iron and vitamin A deficiency, tobacco use, high blood pressure, and high cholesterol. All these risk factors are influenced by social factors and in India the more important factors are poverty and illiteracy. Changing lifestyles as a result of rising incomes are significant risk factors for non communicable diseases. The social evils that influence poverty and health are macrolevel national and regional issues such as physical geography, governance patterns and failures, geopolitics, economic policy, natural resources decline, population growth, the demographic trap and the fiscal trap. Household and microlevel factors include the poverty trap, cultural barriers, lack of innovation and saving, absence of trade or business, unemployment, technological reversal, adverse productivity shock, social issues related to females, and adolescent social issues. Social determinants important for non communicable diseases, defined by the World Health Organization include the social gradient, stress, early life events, social exclusion, improper work conditions, unemployment, lack of social support, addiction, food scarcity or excess and uneven distribution, lack of proper transport, and illiteracy or low educational status. There are multiple pathways through which social factors influence health, and pathophysiological mechanisms involve homeostatic and allostatic changes in response to stress, neuroendocrine changes and altered autonomic functions, and abnormal inflammatory and immune responses. A concerted action to eradicate these social evils shall have to focus on reducing poverty, improving educational status and providing equitable and accessible healthcare to all.
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PMID:Social evils, poverty & health. 1803 3


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