Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human red cells, Ca is mainly bound to the inner side of the plasma membrane. A smaller part may be present within intracellular Ca storing vesicles, while only a few percent of total red cell Ca is in ionized form. In some hemolytic anemias (sickle cell anemia, beta-thalassemia), an increased number of endocytotic vesicles storing Ca is probably responsible for the elevation of total red cell Ca content. Red cell Ca inward transport, which is partially susceptible to inhibition by Ca entry blockers, has been reported to be enhanced by physiological shear stress and enrichment in membrane cholesterol, as well as in some hemolytic anemias. Normal intracellular ionized Ca levels have been assessed in several diseases where elevated Ca inward transport rates or decreased Ca efflux through the Ca pump (hemolytic anemias, cystic fibrosis, essential hypertension) had been observed previously. Thus, red cell Ca homeostasis is apparently capable of keeping ionized Ca levels within the physiological range of 20-60 nM under most pathological conditions investigated so far. Conceptually, changes in red cell Ca homeostasis (or also in other red cell membrane parameters) may be of pathophysiological importance in two respects: 1) A disturbance may be directly responsible for some of the symptoms associated with a disease. This is the case in sickle cell anemia, where red cell dehydration is possibly caused by transient elevations of intracellular ionized calcium, which may activate K efflux through the Ca-activated K channel. The presence of dehydrated red cells will, in turn, lead to microvascular occlusion, a pathophysiologically important phenomenon in sickle cell anemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium homeostasis of human erythrocytes and its pathophysiological implications. 164 22

Calpain, a calcium-dependent, neutral cysteine-protease was purified from the erythrocyte cytosol of subjects having essential hypertension (HTN), sickle cell anaemia, (SCA), or kwashiorkor (KWA). Identical electrophoretic mobility on SDS-polyacrylamide gradient gel, sensitivity to micromolar amounts of Ca2+, absolute requirement for a reducing environment and a high susceptibility to inhibition by leupeptin and thiol-group modifying reagents confirm that calpain preparations from these erythrocytes are equivalent to calpain I. Whereas the extent of calpain activation of erythrocyte membrane Ca2(+)-pumping ATPase of normal subjects was almost equal to that due to calmodulin, calpain activation of the HTN and SCA pump was greater than activation by calmodulin. Like in normal membranes, exogenous calmodulin protected the Ca2(+)-pumping ATPase of these erythrocytes against calpainization; the degree of protection by calmodulin is least in SCA and HTN. Electrophoretic separation of erythrocyte membranes and the purified Ca2(+)-pumping ATPase of HTN, SCA and KWA subjects does not indicate the presence of fragments resulting from the proteolytic action of calpain.
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PMID:Comparative action of calpain on erythrocyte Ca2(+)-pumping ATPase in sickle cell anaemia, essential hypertension and kwashiorkor. 214 87

Oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease, ischemic heart attack, or cerebral stroke. Patients requiring long-term anticoagulant treatment can be treated with gonadotropin-releasing hormone analogs to prevent ovulation, because ruptured follicles can cause massive intraperitoneal bleeding. Patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery. Migraine and diabetes mellitus are regarded as relative contraindications, depending on the individual situation. Long-term diseases, such as Crohn's disease, epilepsy, and sickle cell anemia, also require individualized consultation.
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PMID:Oral contraception in disease states. 225 29

Prerequisites for the evaluation of interethnic differences in response to drugs and toxicants are, first, the understanding of population characteristics in social and genetic terms, and second, the development and use of methods suitable for the pharmacological investigation of fair numbers of subjects. The term pharmacoanthropology is proposed to indicate an appreciation of the difficulties in assessing the causes of quantitative differences between populations, and to emphasize the medical and biological (rather than social or economical) nature of the enquiry. A few case histories are sketched to illustrate the scope of the subject. The classical cases of balanced polymorphism include, for instance, acetylation polymorphism, glucose-6-phosphate dehydrogenase deficiency, and sickle cell anemia. Interethnic differences in alcohol response exemplify a consequence of gross but unexplained differences in gene frequencies for two enzymes, i.e., alcohol and aldehyde dehydrogenases. There may be incidental associations of drug response with blood groups, HLA types, or other traits that differ between populations. Interethnic differences in the predominant nature of essential hypertension appear to illustrate an interaction between diet and genetic constitution, and the resulting patterns of pathology may cause differences in drug response. Clarification of scope and nature of interethnic differences will require many future investigations.
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PMID:Pharmacoanthropology: outline, problems, and the nature of case histories. 671 39

Several transport pathways are involved in the regulation of cell volume and ion content in the human erythrocyte. Studies of these pathways have shown that K-Cl contransport and the Ca-gated K channel (Gardos channel) play an important role in the dehydration of sickle erythrocytes. Therapeutic strategies based on the specific blockade of these pathways have been tested in transgenic sickle mice and in patients with sickle cell disease, using oral Mg pidolate to inhibit K-Cl cotransport and oral clotrimazole to inhibit the Gardos channel. Studies on the erythrocyte Na-H (Na-Li) exchanger have uncovered an important role for insulin and blood pressure in mediating the activity of this pathway. These findings explain the reports of abnormal Na-Li exchange in diabetic nephropathy and essential hypertension. Targeted mutagenesis of the anion exchanger protein band 3 in mice has demonstrated that absence of this protein is compatible with life and leads to severe hemolytic anemia, normal assembly of the cytoskeleton, and reduced mechanical stability of the erythrocyte. Identification of the molecular identity of all the major erythrocyte transporters is imminent and will provide the bases for future studies of these proteins in the normal and abnormal erythrocyte.
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PMID:Erythrocyte membrane transport physiology. 910 29