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

---

Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

Epidemiologic studies suggest that daily ingestion of small amounts of alcohol may protect the heart, whereas higher intake may be detrimental. We studied: 1) cardiac performance, bioenergetics, and [Mg2+]i of isolated working rat hearts during perfusion with Krebs-Henseleit medium containing different concentrations of ethanol (EtOH), 2) mechanical responses. Ca2+ metabolism and Mg content of isolated coronary arteries obtained from dogs, sheep, and piglets subjected to varying concentrations of EtOH and [Mg2+]o and 3) intracellular free Ca2+ of isolated rat cardiac myocytes. In intact hearts, EtOH produced a biphasic hemodynamic change, depending upon concentration; 15 mM EtOH (0.07 g/dl) and 45 mM EtOH (0.21 g/dl) were stimulatory: 90 (0.42 g/dl), 135 (0.63 g/dl), and 170 mM (0.79 g/dl) EtOH were depressive. EtOH 15 and 45 mM increased coronary flow up to 150%, cardiac output up to 130%, stroke volume up to 135%, and oxygen consumption (VO2) up to 130%. However, 90 mM and higher EtOH depressed most hemodynamic parameters (except for heart rate) dose dependently. Lactic acid, lactic acid dehydrogenase, and creatine phosphokinase levels in the perfusate tended to be elevated progressively with increasing duration of EtOH perfusion and pH tended to be reduced (p < 0.05). [31P]NMR spectroscopy on hearts revealed that EtOH > or = 90 mM resulted in rises in Pi/ATP concentration ratio with no significant change in PCr/ATP ratio; [Mg2+]i levels fell and cytosolic pH tended to become slightly acidotic [19F]NMR spectroscopy of isolated myocytes revealed that [Ca2+]i rises at high concentrations of EtOH. With respect to coronary vascular muscle (CVM), low concentrations of EtOH resulted in a concentration-dependent reduction in contractions induced by K+, angiotensin II, and 5-HT; concentration-effect curves were shifted rightward to higher concentrations. Low [Mg2+]o potentiated contractions of CVM induced by EtOH. Low EtOH also resulted in reductions in exchangeable and membrane-bound 45Ca in CVM; medium to high concentrations of EtOH reduced Mg content in CVM and increased 45Ca. In the absence of [Ca2+]o, caffeine and EtOH induced similar, transient contractions followed by relaxation in K(+)-depolarized coronary arterial tissues. EtOH-induced contractions were completely abolished by pretreatment of tissues with caffeine. These results on isolated coronary vessels suggest that in addition to a need for [Ca2+]o, an intracellular release of Ca2+ is needed for EtOH to induce contractions. Overall, the data indicate that low concentrations of EtOH (15, 45 mM) are beneficial on cardiac performance, at least in the intact rat heart and coronary arteries: higher concentrations of EtOH (90, 135 mM) are detrimental. High concentrations of EtOH decrease coronary flow, lead to loss of cellular Mg2+, hypoxia, metabolic acidosis of the myocardium, cell membrane damage, and Ca2+ overload, which could result in cardiac failure. Cellular loss of Mg2+ appears to be causative in the detrimental actions of EtOH on the heart.
...
PMID:Beneficial vs. detrimental actions of ethanol on heart and coronary vascular muscle: roles of Mg2+ and Ca2+. 888 48

The cardiovascular effects of the nonselective adenosine receptor agonist 8-butylaminoadenosine (BAA) were quantified in conscious normotensive rats. The potency and intrinsic activity for the A1 and A2a receptor were determined separately. The rats received a short intravenous infusion of 100 mg/kg BAA in combination with a continuous infusion of either the A1-selective antagonist 8-cyclopentyltheophylline (CPT) (8 micrograms/min/kg), the A2a-selective antagonist 8-(3-chlorostyryl)caffeine (CSC) (32 micrograms/min/kg) or the vehicle. Heart rate (HR) and mean arterial pressure (MAP) were recorded continuously as pharmacodynamic indices for adenosine receptor activation. The MAP/HR ratio was derived as an additional cardiovascular parameter. This ratio reflects changes in total peripheral resistance on the assumption that stroke volume remains constant. During the infusion of CSC, the potency and intrinsic activity for the A1 receptor were estimated by relating the negative chronotropic effect to BAA blood concentrations. The sigmoidal curve yielded a potency value based on unbound concentrations (EC50,u) of 1.9 +/- 0.4 micrograms/ml (mean +/- S.E.; n = 5). The maximal reduction (Emax) in HR (-85 +/- 9 beats/min) was significantly smaller than the values reported for full agonists. During A1 blockade, EC50,u values of 5.5 +/- 0.8 and 6.0 +/- 0.8 micrograms/ml were observed for the A2a receptor-mediated reductions in blood pressure and MAP/HR, respectively (mean +/- SE; n = 5). The Emax values for the hypotensive effect and the reduction in MAP/HR (-55 +/- 3 beats/min and -9.7 +/- 0.6 x 10(-2) mm Hg/ beats/min, respectively) were similar to those of a full A2a receptor agonist. This study shows that BAA is a partial agonist for the adenosine A1 receptor and a full agonist for the A2a receptor.
...
PMID:Partial agonism of the nonselective adenosine receptor agonist 8-butylaminoadenosine at the A1 receptor in vivo. 896 69

Despite significant progress in understanding of the potential of adenosine A1 receptor-based therapies in treatment of cerebral ischemia and stroke, very little is known about the effect of selective stimulation of adenosine A2A receptors on the outcome of a cerebrovascular arrest. In view of a major role played by adenosine A2 receptors in the regulation of cerebral blood flow, we have investigated the effect of both acute and chronic administration of the selective adenosine receptor agonist 2-[(2-aminoethylamino)-carbonylethylphenylethylamino]-5'-N- ethylcarboxoamidoadenosine (APEC) and antagonist 8-(3-chlorostyryl)caffeine (CSC) on the outcome of 10 min ischemia in gerbils. Acute treatment with APEC improved recovery of postischemic blood flow and survival without affecting neuronal preservation in the hippocampus. Acute treatment with CSC had no effect on the cerebral blood flow but resulted in a very significant protection of hippocampal neurons. Significant improvement of survival was present during the initial 10 days postischemia. Due to subsequent deaths of animals treated acutely with CSC, the end-point mortality (14 days postischemia) in this group did not differ statistically from that seen in the controls. It is, however, possible that the late mortality in the acute CSC group was caused by the systemic effects of brain ischemia that are not subject to the treatment with this drug. Chronic treatment with APEC resulted in a statistically significant improvement in all studied measures. Although chronic treatment with CSC improved postischemic blood flow, its effect on neuronal preservation was minimal and statistically insignificant. Mortality remained unaffected. The results indicate that the acute treatment with adenosine A2A receptor antagonists may have a limited value in treatment of global ischemia. However, since administered CSC has no effect on the reestablishment of postischemic blood flow, treatment of stroke with adenosine A2A receptor antagonists may not be advisable. Additional studies are necessary to elucidate whether chronically administered drugs acting at adenosine A2 receptors may be useful in treatment of stroke and other neurodegenerative disorders.
...
PMID:Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. 899 4

The present study examined the effects of caffeine on blood pressure (BP) regulation in hypertensive men during exercise. Twenty unmedicated, mild hypertensives (HT, BP = 140/90 to 160/105 mm Hg) and 12 age-matched, normotensives (NT, BP < 130/80 mm Hg) performed 30 min of extended bicycle exercise following a single dose of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) and placebo in a double-blind, cross-over design. Hemodynamic measurements were made at predrug, 40-min postdrug and during exercise. At predrug baseline, HT had significantly higher HR (67 v 57 beats/min) and BP (141/96 v 118/72 mm Hg) than NT. At postdrug baseline, caffeine increased systolic and diastolic BP, and peripheral vascular resistance (P < .01 in all cases), decreased HR (P < .05) and did not significantly change stroke volume and cardiac output for both groups. During exercise, HR response was greater on caffeine day than placebo day in HT (P < 0.05) only. Systolic BP was consistently elevated on caffeine day compared to placebo day in both groups (P < .001). Diastolic BP was elevated in HT for 30 min of exercise on caffeine day, but this pressor effect disappeared at 15 min of exercise in NT. As a result, rate-pressure products were significantly higher on caffeine days in HT at postdrug and during exercise. On caffeine day, 7 (39%) HT and 1 (8%) NT showed an excessive BP response (> 230 for systolic or > 120 for diastolic) during exercise. In conclusion, caffeine has significant hemodynamic effects on mild hypertensives at rest and during exercise. The increased rate-pressure products following caffeine during exercise place a greater workload on the heart, and abstinence from caffeine, especially before exercise, may be beneficial for persons with hypertension.
...
PMID:Caffeine elevates blood pressure response to exercise in mild hypertensive men. 899 52

Based on in vitro data suggesting an interaction between methylxanthines and doxorubicin in regulating Ca2+ across muscle sarcoplasmic reticulum, this study was designed to test the hypothesis that a commonly used methylxanthine, caffeine, might influence the cardiac toxicity of doxorubicin. Three days following doxorubicin treatment, in vivo intracardiac pressures, cardiac outputs, in vitro cardiac weights, and cardiac electron microscopy were performed. Guinea pigs were treated with doxorubicin alone, doxorubicin plus caffeine, caffeine alone, and sterile saline as a control measure. Animals treated with doxorubicin had no significant differences in in vivo hemodynamics compared to the control animals. The average histology score was slightly but not statistically greater than the control animals, score (1.19 +/- 0.36 vs 1.60 +/- 0.34, respectively, P = NS). Animals receiving both doxorubicin and caffeine compared to the control animals had important differences in left ventricular systolic pressure (67 +/- 10 vs 92 +/- 7 mmHg; P = .003), cardiac output (154 +/- 35 vs 217 +/- 41 mL/min; P = .0174), stroke volume (.59 +/- 12 vs .79 +/- .07 mL; P = .0045), and histology score (2.36 +/- 0.21 vs 1.19 +/- 0.36; P = .028). There were no differences in left or right heart filling pressures between treatment groups. As an independent confirmation, there was a weak but statistically significant negative correlation between the biopsy score and cardiac output or stroke volume for all four groups of animals (r = .44, P = .031 and r = -.42, P = .040, respectively). These data are consistent with caffeine and doxorubicin having additive or potentiating effects on cardiac toxicity in this animal model.
...
PMID:Caffeine enhances doxorubicin cardiac toxicity in an animal model. 942 Jun 45

Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had decreased Na+/Ca2+ exchange currents (I Na/Ca; 3 Na+ out:1 Ca2+ in) and sarcoplasmic reticulum (SR)-releasable Ca2+ contents. These defects in Ca2+ regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6-8 wk of high-intensity sprint training (HIST) would ameliorate some of the cellular maladaptations observed in post-MI rats with limited exercise activity (Sed). In MI rats, HIST did not affect citrate synthase activities of plantaris muscles but significantly increased the percentage of cardiac alpha-myosin heavy chain (MHC) isoforms (57.2 +/- 1.9 vs. 49.3 +/- 3.5 in MI-HIST vs. MI-Sed, respectively; P < or = 0.05). At the single myocyte level, HIST attenuated cellular hypertrophy observed post-MI, as evidenced by reductions in cell lengths (112 +/- 4 vs. 130 +/- 5 micrograms in MI-HIST vs. MI-Sed, respectively; P < or = 0.005) and cell capacitances (212 +/- 8 vs. 242 +/- 9 pF in MI-HIST vs. MI-Sed, respectively; P < or = 0.015). Reverse I Na/Ca was significantly lower (P < or = 0.0001) in myocytes from MI-Sed rats compared with those from rats that were sham operated and sedentary. HIST significantly increased reverse I Na/Ca (P < or = 0.05) without affecting the amount of Na+/Ca2+ exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca2+ content, as estimated by integrating forward I Na/Ca during caffeine-induced SR Ca2+ release, was also significantly increased (P < or = 0.02) by HIST in MI myocytes. We conclude that the enhanced cardiac output and stroke volume in post-MI rats subjected to HIST are mediated, at least in part, by reversal of cellular maladaptations post-MI.
...
PMID:Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes. 947 64

Low caloric diet is a commonly accepted treatment in obesity. However, owing to moderate results, a pharmacological support has been proposed. As some efficacious drugs activate overall sympathetic activity, they might modify functions of the cardiovascular system. Three groups of subjects were studied: (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg); (3) nine obese women receiving a standard hypocaloric diet and ephedrine (2 x 25 mg) with caffeine (2 x 200 mg) and yohimbine (2 x 5 mg). The cardiovascular state was evaluated by thoracic electrical bioimpedance, automatic sphygmomanometry and continuous ECG recording. In each patient, the haemodynamic study was performed twice: at rest, i.e. before treatment; and after 10 days of treatment. On the same days in each patient, the haemodynamic tests were performed during physical exercises (handgrip stress and cycloergometer exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients. These two drugs led to an increase in ejection fraction during cycloergometer exercise. Addition of yohimbine increased diastolic pressure and heart rate but decreased ejection fraction and stroke index during rest. We also observed that addition of yohimbine decreased ejection fraction during the handgrip and cycloergometer exercise and increased cardiac load during dynamic exercise. Pharmacological supplement of ephedrine and caffeine to a low caloric diet modified the cardiovascular system weakly, but the addition of yohimbine to this regimen attenuated cardiac performance during rest and handgrip and increased cardiac work during dynamic exercise.
...
PMID:Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women. 954 23

The relation between fluoride intake and risk of osteoporotic fractures remains unclear. The lack of individual measures of long-term fluoride intake has limited epidemiologic studies. We used toenail fluoride in this study as a measure of long-term intake to evaluate the relation between fluoride intake and subsequent risk of hip and distal forearm fractures. Between 1982 and 1984, we collected toenail clippings from 62,641 women in the Nurses' Health Study who were free from cancer, heart disease, stroke, and previous hip or forearm fracture. We identified fracture cases (53 proximal femur and 188 distal forearm) through subsequent biennial mailed questionnaires and matched controls to cases on year of birth. The odds ratio of hip fracture among women in the highest quartile of toenail fluoride [ > 5.50 parts per million (ppm)], compared with those in the lowest quartile (> 2.00 ppm), was 0.8 (95% confidence interval = 0.2-4.0), with adjustment for menopausal status, postmenopausal hormone use, caffeine intake, and alcohol consumption. The corresponding adjusted odds ratio for forearm fracture was 1.6 (95% confidence interval = 0.8-3.1). Further adjustment for body mass index, smoking status, and calcium and vitamin D intake did not alter these results.
...
PMID:Use of toenail fluoride levels as an indicator for the risk of hip and forearm fractures in women. 964 5

1. Electrical events and intracellular calcium concentration ([Ca2+]) imaged using fluo-3 and laser scanning confocal microscopy were simultaneously monitored in single smooth muscle cells freshly isolated from guinea-pig vas deferens or urinary bladder. 2. Images obtained every 8 ms, during stepping from -60 to 0 or +10 mV for 50 ms under voltage clamp, showed that a rise in [Ca2+] could be detected within 20 ms of depolarization in five to twenty small (< 2 micrometer diameter) 'hot spots', over 95 % of which were located within 1.5 micrometer of the cell membrane. Depolarization at 30 s intervals activated hot spots at the same places. 3. Cd2+ or verapamil abolished both hot spots and Ca2+-activated K+ current (IK,Ca). Caffeine almost abolished hot spots and markedly reduced IK,Ca. Cyclopiazonic acid, which raised basal global [Ca2+], decreased the rise in hot spot [Ca2+] and IK,Ca amplitude during depolarization. These results suggest that Ca2+ entry caused Ca2+-induced Ca2+ release (CICR). 4. Under voltage clamp, hot spot [Ca2+] closely paralleled the rise in IK,Ca and reached a peak within 20 ms of the start of depolarization, but the rise in global [Ca2+] over the whole cell area was much slower. Step depolarization to potentials positive to -20 mV caused hot spots to grow in size and coalesce, leading to a rise in global [Ca2+] and contraction. Ca2+ hot spots also occurred during the up-stroke of an evoked action potential under current clamp. 5. It is concluded that the entry of Ca2+ in the early stages of an action potential evokes CICR from discrete subplasmalemma Ca2+ storage sites and generates hot spots that spread to initiate a contraction. The activation of Ca2+-dependent K+ channels in the plasmalemma over hot spots initiates IK,Ca and action potential repolarization.
...
PMID:Ca2+ images and K+ current during depolarization in smooth muscle cells of the guinea-pig vas deferens and urinary bladder. 966 Aug 87

1. Despite advances in the art and science of fluid balance, exertional heat illness -- even life-threatening heat stroke -- remains a threat for some athletes today. 2. Risk factors for heat illness include: being unacclimatized, unfit, or hypohydrated; certain illnesses or drugs; not drinking in long events; and a fast finishing pace. 3. Heat cramps typically occur in conditioned athletes who compete for hours in the sun. They can be prevented by increasing dietary salt and staying hydrated. 4. Early diagnosis of heat exhaustion can be vital. Early warning signs include: flushed face, hyperventilation, headache, dizziness, nausea, tingling arms, piloerection, chilliness, incoordination, and confusion. 5. Pitfalls in the diagnosis of heat illness include: confusion preventing self-diagnosis; the lack of trained spotters; rectal temperature not taken promptly; the problem of "seek not, find not;" and the mimicry of heat illness. 6. Heat stroke is a medical emergency. Mainstays of therapy include: emergency on-site cooling; intravenous fluids; treating hypoglycemia as needed; intravenous diazepam for seizures or severe cramping or shivering; and hospitalizing if response is slow or atypical. 7. The best treatment is prevention. Tips to avoiding heat illness include: rely not on thirst; drink on schedule; favor sports drinks; monitor weight; watch urine; shun caffeine and alcohol; key on meals for fluids and salt; stay cool when you can; and know the early warning signs of heat illness.
...
PMID:Treatment of suspected heat illness. 969 24


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

---