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: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ankle-brachial systolic pressure index (ABI), a noninvasive measure of peripheral arterial occlusive disease (PAOD) severity, is considered a marker of atherosclerosis and an independent predictor of mortality. However, it is not known whether factors other than PAOD severity, such as cigarette smoking, have an effect on ABI measurement. Therefore, the authors examined the acute effects of cigarette smoking on ABI and the peripheral circulation in 10 older (63 +/- 10 years) chronic smokers (39 +/- 37 pack-years) with PAOD (ABI=0.64 +/- 0.14). The patients were instructed to refrain from smoking and from consuming caffeine-containing beverages for at least 12 hours before the tests. The patients were randomly assigned to 2 days of testing consisting of a nonsmoking and a smoking day. Resting heart rate, blood pressure, ABI, and calf blood flow by plethysmography were obtained on both testing days. The smoking day consisted of smoking two filter cigarettes over a period of 10 minutes before the measurement of ABI and calf blood flow. The ABI on the smoking day (0.55 +/- 0.11) was lower (p=0.008) than on the nonsmoking day (0.64 +/- 0.14) owing to a lower (p=0.020) ankle systolic blood pressure (81 +/- 28 vs 93 +/- 28 mmHg). Brachial systolic blood pressures, heart rate, and calf blood flow were not altered by smoking (p>0.05). These results demonstrate that the acute effect of cigarette smoking lowers the ABI in chronic smokers with intermittent claudication, thereby yielding evidence of a transient deleterious effect of cigarette smoking on the peripheral circulation in chronic smokers.
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PMID:Acute reduction in ankle/brachial index following smoking in chronic smokers with peripheral arterial occlusive disease. 1034 23

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.
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PMID:Nutrition and dietary supplements. 1051 85

This report describes two cases of acute zolpidem overdose. The decedent in the first case was a 36-year-old female found dead in bed in her secured home. She had a history of psychiatric illness, including paranoid disorder, depression with panic episodes, and post-traumatic stress disorder. She was treated with risperidone and sertraline. Nine months prior to her death, the decedent was also prescribed zolpidem (Ambien). The postmortem examination revealed white foam within the larynx and upper trachea, which is indicative of pulmonary edema. Toxicological analyses of the urine showed the presence of caffeine, risperidone, and zolpidem. Subsequent quantitation of postmortem iliac serum revealed 5.6 microg/L of 9-hydroxyrisperidone and the following zolpidem concentrations: blood (subclavian), 4.5 mg/L; blood (iliac), 7.7 mg/L; vitreous humor, 1.6 mg/L; bile, 8.9 mg/L; urine, 1.2 mg/L; liver, 22.6 mg/kg; and gastric contents, 42 mg. The second case involved a 58-year old female, also found dead in bed, with white foam around her mouth. The decedent had a 25-year history of hypertension and mental illness--manic depression and schizophrenia. She was medicated with carbamazepine, naproxen, risperidone, and zolpidem. The postmortem examination revealed cardiomegaly, pulmonary edema, hepatomegaly, mild coronary atherosclerosis, and no signs of trauma. Toxicological analyses of the urine showed the presence of zolpidem and carbamazepine and metabolite. Zolpidem concentrations were as follows: blood (iliac), 1.6 mg/L; vitreous humor, 0.52 mg/L; bile, 2.6 mg/L; liver, 12 mg/kg; and gastric contents, 0.9 mg. The zolpidem blood concentrations of these cases are consistent with those of the previously published fatalities. The blood/vitreous humor ratios of zolpidem were 2.81 (subclavian) and 4.81 (iliac) in the first case and 3.08 (iliac) in the second case. These ratios, along with the sampling times of blood and vitreous humor for both cases, are not conclusive to indicate a definitive presence or absence of postmortem drug redistribution of zolpidem. The cause of death for both cases was determined to be acute zolpidem overdose, and manner of death was suicide.
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PMID:Acute zolpidem overdose--report of two cases. 1051 69

Apoptosis of arterial smooth muscle cells (ASMCs) could play an important role in the pathogenesis of atherosclerosis and restenosis. Recent studies have demonstrated that extracellular adenosine induces apoptosis in various cell types. Our aim was to delineate the capacity of this nucleoside to induce ASMC apoptosis in arterial diseases. We demonstrate that adenosine dose-dependently triggers apoptosis of cultured human ASMCs. Apoptotic cell death was quantified by analysis of nuclear chromatin morphology and characterized by DNA laddering. The involvement of adenosine receptors was suggested, because neither an adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, nor an inhibitor of cellular nucleoside transport, dipyridamole, was able to inhibit adenosine-induced ASMC apoptosis. In contrast, an A(1)/A(2)-adenosine receptor antagonist, xanthine amine congener, totally inhibited adenosine-induced apoptosis. Furthermore, among more selective inhibitors of P(1) purinoceptor subtypes, only alloxazine, an antagonist of A(1)- and A(2)-adenosine receptors, completely inhibited adenosine-induced ASMC apoptosis, suggesting that adenosine triggers ASMC apoptosis via either 1 or both of these receptors. However, 8-cyclopentyl-1,3-dipropylxanthine, 8-(3-chlorostyryl) caffeine, and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate, which are A(1)-, A(2a)-, and A(3)-adenosine receptor antagonists, did not inhibit adenosine-induced apoptosis, suggesting an involvement of the A(2b)-receptor in this process. Moreover, the cAMP increase followed by cAMP-dependent protein kinase activation appears essential to mediate adenosine-induced ASMC apoptosis, thus confirming the previous hypothesis. These results indicate that adenosine-induced apoptosis of ASMCs is essentially mediated via A(2b)-adenosine receptor and involves a cAMP-dependent pathway.
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PMID:Extracellular adenosine induces apoptosis of human arterial smooth muscle cells via A(2b)-purinoceptor. 1062 8

Green tea contains various antioxidative flavan-3ols (tea catechins), such as (-)-epigallocatechin gallate (EGCg, the major catechin), which exert potent inhibitory effects on LDL oxidation in vitro and ex vivo in humans. In this study, the antiatherogenic effects of tea catechins were examined in atherosclerosis-susceptible C57BL/6J, apoprotein (apo)E-deficient mice. Male apoE-deficient mice (10 wk old) were fed an atherogenic diet for 14 wk; during that time, one group (tea) was supplied drinking water supplemented with green tea extract (0.8 g/L), and another group (control) was offered the vehicle only. The tea extract consisted of the following (g/100 g): EGCg, 58.4; (-)-epigallocatechin (EGC), 11.7; (-)-epicatechin (EC), 6.6; (-)-gallocatechingallate (GCg), 1.6; (-)-epicatechin gallate (ECg), 0.5; and caffeine, 0.4. The estimated actual intake of tea catechin was 1.7 mg/(d. mouse). Tea ingestion did not influence plasma cholesterol or triglyceride concentrations. Plasma lipid peroxides were reduced in the tea group at wk 8, suggesting that the in vivo oxidative state is improved by tea ingestion. Atheromatous areas in the aorta from the arch to the femoral bifurcation and aortic weights were both significantly attenuated by 23% in the tea group compared with the control group. Aortic cholesterol and triglyceride contents were 27 and 50% lower, respectively, in the tea group than in the control group. These results suggest that chronic ingestion of tea extract prevents the development of atherosclerosis without changing the plasma lipid level in apoE-deficient mice, probably through the potent antioxidative activity of the tea.
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PMID:Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. 1120 34

Intracellular Ca(2+) store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca(2+) uptake into intracellular Ca(2+) stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks-- (1) low fat fed (control); (2) hyperlipidemic (F); (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the myoplasmic Ca(2+) (Ca(m)) response measured using single cell fura-2 imaging. The Ca(m) response to caffeine (5 mM to release Ca(2+) from the sarcoplasmic reticulum, SR) and ionomycin (10 microM; to release the total Ca(2+) store) was determined in either the presence of low Na (19Na; inhibits Na(+)-Ca(2+) exchange), thapsigargin (TSG; inhibits the SR Ca(2+) pump), and a 19Na+TSG solution. Low Na induced the uptake of Ca(2+) into both SR and non-SR Ca(2+) stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca(2+) store with TSG, 19Na evoked Ca(2+) uptake into non-SR Ca(2+) stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca(2+) by SR and non-SR Ca(2+) stores in diabetic dyslipidemic pigs.
Atherosclerosis 2001 Nov
PMID:Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet. 1168 13

The beverage tea, from the top leaves of the plant Camellia sinensis is one of the most widely used beverages in the world, second only to water. Black and green tea have mostly similar actions. The active components are polyphenols, mainly epigallocatechin gallate in green tea, and the tea leaf polyphenol oxidase mediated oxidation to oolong and black tea, yielding other polyphenols, theaflavin and thearubigins. There is 40-50 mg caffeine in a 160-ml cup of tea. The chemopreventive effects of tea depend on: (1) its action as an antioxidant; (2) the specific induction of detoxifying enzymes; (3) its molecular regulatory functions on cellular growth, development and apoptosis; and (4) a selective improvement in the function of the intestinal bacterial flora. The oxidation of LDL cholesterol, associated with a risk for atherosclerosis and heart disease, is inhibited by tea. Many of cancers are caused by lifestyle elements. One is cigarette and tobacco use, leading to cancer in the oral cavity, esophagus and lung, inhibited by tea. Mice administered a tobacco nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed significantly fewer lung tumors than controls when given green tea or its major polyphenol, epigallocatechin gallate (EGCG). Tea suppressed the formation of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in the lung DNA of mice given NNK. Gastric cancer, caused by a combination of Helicobacter pylori and salted foods, is lower in tea drinkers. Western nutritionally-linked cancers of the breast, colon, prostate and pancreas can be inhibited by tea. The formation of genotoxic carcinogens for these target organs during the cooking of meats, heterocyclic amines, and their effects were decreased by tea. Tea inhibited the formation of reactive oxygen species and radicals and induced cytochromes P450 1A1, 1A2 and 2B1, and glucuronosyl transferase. The higher formation of glucuronides represents an important mechanism in detoxification. The developmental aspects and growth of cancers through promotion are decreased by tea. The regular use of a widely available, tasty, inexpensive beverage, tea, has displayed valuable preventive properties in chronic human diseases.
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PMID:Mechanisms of chronic disease causation by nutritional factors and tobacco products and their prevention by tea polyphenols. 1206 77

Current pharmacological regimens for hypertriglyceridemia and low high-density lipoprotein (HDL) are limited to the peroxisome proliferator-activated receptor (PPAR) alpha activating fibrates, niacin, and statins. This pilot study examined the impact of simultaneous stimulation of cyclic adenosine monophosphate with a beta-adrenergic agonist and PPARgamma with pioglitazone (PIO) on lipoprotein composition in moderately obese, healthy subjects. Subjects were treated with PIO (45 mg) to stimulate PPARgamma or a combination of ephedrine (25 mg TID), a beta-agonist, with caffeine (200 mg TID), a phosphodiesterase inhibitor (ephedrine plus caffeine), or both for 16 weeks. Lipoproteins were separated by gradient ultracentrifugation into very low-density lipoprotein (VLDL), intermediate-density lipoprotein, low-density lipoprotein (LDL), and 3 HDL (L, M, and D) subfractions. Apolipoproteins were measured by high-performance liquid chromatography. PIO alone reduced the core triglyceride (TG) content relative to cholesterol ester (CE) in VLDL (-40%), IDL (-25%), and HDL-M (-38%). Ephedrine plus caffeine alone reduced LDL CE (-13%), phospholipids (-9%), and apolipoprotein (apo) B (-13%); increased HDL-M LpA-I (HDL containing apoA-I without apoA-II, 28%), CE/TG (23%), and CE/apoA-I (8%) while reducing apoA-II (-10%); and increased HDL-L LpA-I (29%). Combination therapy reduced total plasma TG (-28%), LDL cholesterol (LDL-C, -10%), apoB (-16%), apoB/apoA-I ratio (-21%) while increasing HDL cholesterol (HDL-C, 21%), total plasma apoA-I (12%), LpA-I (43%), and apoC-I (26%). It also reduced VLDL total mass (-34%) and apoC-III (-39%), LDL CE (-13%), apoB (-13%), and total mass (-11%). Combination therapy increased HDL-L CE/TG (32%), apoC-I (30%), apoA-I (56%), and LpA-I (70%), as well as HDL-M CE (35%), phospholipids (24%), total mass (19%), apoC-I (25%), apoA-I (18%), and LpA-I (56%). In conclusion, simultaneous beta-adrenergic and PPARgamma activation produced beneficial effects on VLDL, LDL, HDL-L, and HDL-M. Perhaps the most important impact of combination therapy was dramatic increases in LpA-I and apoC-I in HDL-L and HDL-M, which were much greater than the sum of the monotherapies. Because LpA-I appears to be the most efficient mediator of reverse-cholesterol transport and a major negative risk factor for cardiovascular disease, this combination therapy may provide very effective treatment of atherosclerosis.
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PMID:Combining beta-adrenergic and peroxisome proliferator-activated receptor gamma stimulation improves lipoprotein composition in healthy moderately obese subjects. 1632 16

To study the effect of hypercholesterolemia on vascular smooth muscle cell (VSMC) function, atherosclerosis-prone but plaque-free endothelium-denuded aortic rings (width 2mm) from C57Bl6 Wild Type (WT) and apolipoprotein E-deficient (apoE(-/-)) mice (age 4 months) were mounted in a myograph and loaded with Fura-2 AM to simultaneously measure free Ca(2+) ([Ca(2+)](i)) and force development. In comparison with WT, apoE(-/-) mice displayed higher basal [Ca(2+)](i). Moreover, the time constant of the second phase of the biphasic high K(+)-induced [Ca(2+)](i) response was significantly increased in apoE(-/-) compared to WT mice. This phase was abolished by treatment with cyclopiazonic acid (CPA), depleting sarcoplasmic reticulum (SR). Further investigation of SR dependent [Ca(2+)](i) handling with CPA and caffeine revealed no alteration of maximal SERCA or ryanodine receptor function. Inositol (1,4,5)-triphosphate receptor (IP(3)R)-mediated [Ca(2+)](i) release was, however, significantly increased in apoE(-/-) mice compared to WT mice as established with phenylephrine and ATP. In Ca(2+)-free conditions the ATP-induced [Ca(2+)](i) was not altered. The ATP-induced store-operated Ca(2+) entry was, however, significantly increased in apoE(-/-) compared to WT mice. The results demonstrate that basal [Ca(2+)](i) levels and IP(3)R-mediated store-operated [Ca(2+)](i) release over the plasma membrane were elevated in hypercholesterolemic but plaque-free apoE(-/-) mice.
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PMID:Altered Ca2+ handling of smooth muscle cells in aorta of apolipoprotein E-deficient mice before development of atherosclerotic lesions. 1699 97

Approximately 6 million cardiac stress tests are performed annually in the United States, of which 2.4 million are pharmacologic stress tests using agents such as adenosine. Adenosine induces differential coronary hyperemia in normal coronary arteries versus coronary arteries with atherosclerosis, allowing single photon emission computed tomography (SPECT) imaging to identify reduced coronary flow in segments subtended by diseased coronary arteries. The potential attenuation of pharmacologic effects of adenosine in the presence of caffeine is why patients are routinely instructed to abstain from caffeine for 12 to 24 hours prior to administration of an adenosine stress test. Failure to abstain from caffeine results in cancellation or delaying of cardiac stress testing, resulting in procedural delays and its impact on patient throughput. Recent studies have evaluated such interaction and suggested a lack of clinically significant effect of caffeine on adenosine-induced hyperemia during myocardial SPECT imaging. This article reviews the clinical pharmacology of caffeine, adenosine, and dipyridamole and effect of caffeine on myocardial stress testing using adenosine and dipyridamole in clinical cardiovascular medicine. The limited published data are conflicting, but some recent publications suggest that myocardial perfusion SPECT imaging using adenosine may not be clinically significantly altered by routine consumption of caffeine, such as a cup of coffee. Although prospective randomized studies would be required to obtain a definitive answer to this question, it appears on the basis of some of the studies reviewed in this article that caffeine consumption prior to myocardial perfusion imaging may not necessitate cancellation or rescheduling of adenosine stress testing.
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PMID:Effect of caffeine on myocardial perfusion imaging using single photon emission computed tomography during adenosine pharmacologic stress. 1880 18


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