Physiology and function of platelets from patients with Alzheimer's disease.

The discovery that intact Alzheimer amyloid precursor protein is present in platelet granules, has created a great interest in the biochemistry, physiology and function of platelets of patients with Alzheimer disease (AD). In this study we monitored various biochemical and physiological parameters, such as serotonin and adenine nucleotide levels, membrane fluidity, agonist-mediated release of arachidonic acid, thromboxane formation, calcium mobilization, as well as irreversible aggregation and secretion of granule contents. Platelets of patients with AD responded poorly when stirred with weak or potent agonists on a platelet aggregometer. Although capable of agonist-mediated calcium mobilization and synthesis of thromboxanes, the aggregation response of platelets of patients with AD to thrombin and archidonate was considerably compromised. In view of the normal biochemistry and signal transduction capabilities, the compromised response of these cells to potent agonists like thrombin suggested an extrinsic defect. The present study has shown that a plasmatic factor is at least in part responsible for the functional abnormalities of AD platelets.

Coronary artery disease: an overview of risk factors.

Coronary artery disease (CAD) is an important cause of morbidity and mortality in most industrialized nations, and is gaining in importance as a major disease in developing countries as well. Several risk factors, such as cholesterol, smoking, hypertension, obesity, diabetes, stress and physical activity, have been identified as contributors to the pathogenesis of this disease. Studies done in many countries on South Asian immigrants clearly demonstrate the increased risk for coronary heart disease in this population compared to that of local ethnic groups. Higher prevalence of diabetes, blood pressure, glucose intolerance, insulin resistance, low levels of HDL-cholesterol, high levels of LDL-cholesterol, increased plasma triglycerides and obesity are some of the risk factors identified as contributing to CAD in South Asians. The present report will review briefly the available data on CAD and its pathogenesis with particular emphasis on the problems unique to South Asians.

Aspirin in ischemic heart disease--an overview.

Aspirin is one of the oldest and most commonly used nonprescription drugs in the world. Although commonly it is used for relief from common headache and muscular pain, its use in the prevention and treatment of platelet related complications in cardiovascular diseases (CVD) and cerebrovascular disease (CBVD) is quite controversial. A brief review of the major aspirin trials indicated that a full strength aspirin taken daily had no significant beneficial effect in reducing mortality of patients with CVD/CBVD. However, two major trials (ISIS-2, PHS) in which either low dose aspirin (160 mg) or one aspirin administered every other day, have demonstrated significant reduction in fatal and nonfatal cardiovascular events. Even a dose as low as 1 mg aspirin per day significantly lowers platelet thromboxane synthesis. As a result of these studies, low dose aspirin should be the choice of prophylactic therapy aimed at the inhibition of platelet cyclooxygenase activity. Controlled-release low dose aspirin may favorably reduce platelet thromboxane production and spare vascular prostacyclin synthesis. At least 100 mgs of aspirin per day are essential to completely inhibit steady state thromboxane formation. Low dose aspirin (160 mgs) has been shown to be as effective as the full strength aspirin (325 mgs) in reducing clinical complications related to platelet activation. The antithrombotic effect of aspirin is well established and improved formulations, well thought out therapeutic protocols, customized dosage, appropriate timing of delivery, a better understanding of platelet function and pathophysiology of CUD/CBUD will facilitate maximization of the beneficial effects of aspirin.

Influence of low dose enteric-coated aspirin on platelet function.

Little is known about the effect of low dose, enteric-coated aspirin on human blood platelet function. This study was conducted to evaluate the acute effects of a single daily dose of commercially available enteric-coated aspirin on platelet biochemistry, physiology and function. Blood for these studies was obtained from drug-free volunteer donors prior to ingestion of aspirin or following ingestion, either before breakfast or following lunch. Response of platelets to the action of weak agonists was evaluated. In addition, ability of platelets to convert radiolabeled arachidonic acid to thromboxane was monitored. Results of our studies show that a single daily dose of 50 mg of aspirin taken either before breakfast or after lunch effectively prevented the secondary wave aggregation response, as well as secretion of dense body contents when stimulated by agonists such as epinephrine and ADP. Aspirin ingestion caused a dose-dependent inhibition of platelet cyclooxygenase activity as evidenced by the extent of arachidonic acid converted to thromboxane by platelets exposed to aspirin for different time periods. Based on these observations, it is suggested that low dose aspirin may be very useful and desirable to restrain platelet activity in clinical situations in which increased thromboxane formation may initiate vascular hypertension and platelet hyperactivity.