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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factors that influence hemoglobin (Hb)A(Ic) synthesis by intact erythrocytes were studied in vitro. After incubation cells were lysed, and hemoglobins were separated by isoelectric focusing on polyacrylamide slab gels and quantitated by microdensitometry. HbA(Ic) increased with time, glucose concentrations (5-500 mM), and incubation temperature (4 degrees -37 degrees C). Low temperatures allowed prolonged incubations with minimal hemolysis. At 4 degrees C HbA(Ic) increased linearly with time for 6 wk; after incubation at the highest glucose concentration, HbA(Ic) comprised 50% of total hemoglobin. Insulin (1 and 0.1 mU/ml) did not affect HbA(Ic) synthesis in vitro. In addition to glucose, galactose and mannose, but not fructose, served as precursors to HbA(Ic). A good substrate for hexokinase (2-deoxyglucose) and a poor hexokinase substrate (3-O-methylglucose), were better precursors for HbA(Ic) synthesis than glucose, suggesting that enzymatic phosphorylation of glucose is not required for HbA(Ic) synthesis. Autoradiography after erythrocyte incubation with (32)P-phosphate showed incorporation of radioactivity into HbA(Ia1) and A(Ia2), but not HbA(Ib), A(Ic), or A. Acetylated HbA, generated during incubation with acetylsalicylate, migrated anodal to HbA(Ic) and clearly separated from it. Erythrocytes from patients with insulinopenic diabetes mellitus synthesized HbA(Ic) at the same rate as controls when incubated with identical glucose concentrations. Likewise, the rate of HbA(Ic) synthesis by erythrocytes from patients with cystic fibrosis and congenital spherocytosis paralleled controls. When erythrocytes from cord blood and from HbC and sickle cell anemia patients were incubated with elevated concentrations of glucose, fetal Hb, HbC, and sickle Hb decreased, whereas hemoglobins focusing at isoelectric points near those expected for the corresponding glycosylated derivatives appeared in proportionately increased amounts.
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PMID:Synthesis of hemoglobin Aic and related minor hemoglobin by erythrocytes. In vitro study of regulation. 3 12

The most important side effects of oral contraceptives (OCs) and their incidence, together with advice and monitoring of the patient at risk, are pointed out. There is a mild increase in blood pressure in longterm contraceptive use caused by increased angiotensinogen production by the liver. It is significant only for women with a history of familial hypertension, diabetes mellitus, or pre-eclampsia. Smoking increases this risk. Urinary tract infections are 25-50% more frequent in pill users. Glucose tolerance is slightly decreased. Contraceptives' diabetogenic effect is higher in women with hereditary tendency for diabetes, latent diabetes, and/or obesity. They are contraindicated in latent diabetes. Findings are contradictory in their effects on cholesterol and triglyceride serum level, but the pill is contraindicated in lipid metabolism disorders. There is an increased incidence in cholecystitis and cholelithiasis in pill-users (70-80 additional cases/100,000 user years). Liver diseases, intrahepatic cholestasis, occur rarely and benign liver tumors have not conclusively been proved to be caused by the pill. A variety of laboratory findings have been related to contraceptive use and drug interactions occur with barbiturates, rifampicin, hydantoin, and phenylbutazone. Blood coagulation is increased, partially by increased production of various blood coagulation factors; but more importantly, by a decreased synthesis of antithrombin III, a natural protective mechanism against intravascular coagulation. This increases thrombosis risk. Risk doubles with simultaneous cigarette smoking. Various epidemiological studies indicate a 5-10 fold increase in thromboembolism and thrombophlebitis, deep vein thrombosis, and pulmonary embolism. There is a correlation between contraceptive use and cerebrovascular disorders and myocardial infarction. This risk increases with age and years of pill use. The pill is contraindicated with symptoms of thrombophlebitis and thromboembolism, sickle cell anemia, proposed surgery, and longterm immobilization. Overall risk factors are not too high. Recommendations for rational pill use related to age are given and further contraindications are mentioned.
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PMID:[Adverse effects of oral contraceptives]. 55 52

Bacterial infections are the most frequent cause of death and an important factor of morbidity in sickle cell disease. A defect in oxidative metabolism of neutrophils from these patients has been reported as a possible cause for these infections. Since normal neutrophil functions are essential in the defense against bacteria, it seemed important to reassess the capacity of neutrophils from patients with sickle cell disease to undergo the metabolic events associated with phagocytic bactericidal activity. Accordingly, neutrophils from patients and controls were compared for their ability to reduce nitroblue tetrazolium dye, to activate the hexose monophosphate shunt, and to generate superoxide anion, hydrogen peroxide, and chemiluminescence. Patients' cells performed normally in each of these assays and, in addition, killed Staphylococcus aureus as well as did cells from controls. Thus, an abnormality of neutrophil oxidative metabolism cannot explain the propensity to bacterial infections in sickle cell disease.
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PMID:Neutrophil oxidative metabolism in sickle cell disease. 95 63

Butyrate has a dramatic effect on transformed cells in culture. This effect disappears as soon as butyrate is removed from the medium. The other short chain fatty acids are much less effective. Butyrate produces an arrest of cell proliferation at the early G1 phase of the cell cycle. The effect is very general and may be used for cell growth synchronization. This compound increases the expression of the c-fos oncogene and inhibits the expression of c-myc in all phases of the cell cycle. Butyrate modulates the expression of several genes. In general it induces the expression of markers of cell differentiation. Many studies have been devoted to hemoglobin synthesis which is induced in erythroleukemia cells. In general it induces the synthesis of embryonic and of fetal hemoglobin, and delays and even suppresses the switch to adult hemoglobin, which could be useful for the treatment of sickle cell anemia and beta thalassemia. This effect of butyrate seems to require specific DNA regulatory sequences. Butyrate induces the synthesis of alkaline phosphatase, placental and intestinal isozymes, especially in cells where these syntheses are ectopic. It has the same effect on peptidic hormone syntheses and also on receptors of thyroid hormone and insulin. It stimulates their synthesis in cells which are poor in receptor and inhibits the synthesis in cells which have high amounts of these receptors. The use of antibiotics and of the run on method strongly suggest that butyrate acts at the transcriptional level. Butyrate inhibits the induction of proteins, including enzymes, by steroid hormones as has been shown for the induction of tyrosine aminotransferase by glucocorticoids, of ovalbumin and transferrin by estradiol in chick oviduct. Butyrate strongly alters cell morphology, usually it produces an enlargement of the cells with formation of protrusions. In HTC cells alteration of nucleoli and of the nuclear shape are observed. All these alterations are reversible and the cells recover the normal morphology upon removal of butyrate. These alterations result at least partly from modifications of the cytoskeleton: induction of vimentin and cytokeratin, formation of microfilaments, of microtubules and of actin fibers. The external matrix is also modified, as are the cell surface glycoproteins, and gangliosides. Most of these alterations are consistent with the loss of transformation characteristics of the cell. The mechanism of action of butyrate has been studied by many authors. It has been well established that butyrate induces an hyperacetylation of histones by inhibiting histone deacetylases, which is consistent with its stimulatory effect on gene expression.4+ and would require transacting proteins. The use of butyrate in therapeutics would require the synthesis of new molecules including butyrate but more active and metabolized at a slower rate. Several such molecules have been synthesized: monobutyrate 3 (or 6) monoacetate glucose, pivalyloxymethyl-butyrate. The use of such molecules in human therapeutics has been suggested, especially in hematology (sickle cell anemia, beta thalassemia) and in cancerology.
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PMID:[Molecular and cellular action of butyrate]. 145 Sep 86

Diabetic and sickle retinopathy have features in common--for example, venous dilatation, microaneurysms, and capillary closure preceding neovascularisation. Bearing in mind that haemoglobin in poorly controlled diabetes is abnormal and that extremely low oxygen tensions (known to cause sickling) exist in the healthy cat retina, we wished to explore the possibility that diabetic blood, like that of sickle cell disease, may become more viscous when deoxygenated. To do this we measured whole blood viscosity, under oxygenated and deoxygenated conditions, of 23 normal persons, 23 diabetic patients without retinopathy, and 34 diabetic patients with retinopathy. The shear rate used was 230 s-1, which is similar to that thought to prevail in the major retinal veins. The viscosity of blood from normal persons, corrected for packed cell volume, did not change significantly on deoxygenation: mean 4.54 (SD 0.38) cps, versus, 4.57 (0.39) paired t test, p = 0.66. Similarly the blood from diabetics without retinopathy showed no change: 4.42 (0.45) versus 4.42 (0.30), p = 0.98; whereas the blood from patients with retinopathy changed from 4.82 (0.48) to 4.95 (0.63), p = 0.027. The hypoxic viscosity ratio (deoxygenated divided by oxygenated viscosity) correlated with total serum cholesterol (r = 0.44, p = 0.018) but not with HbA1, serum glucose, triglycerides, or age. A disproportionate increase in venous viscosity relative to arterial viscosity would lead to increased intraluminal and transmural pressure and therefore exacerbate leakage across capillary walls.
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PMID:Hypoxic viscosity and diabetic retinopathy. 237 52

Intravenous glucose tolerance tests (IVGTT) were performed on 9 adults with sickle cell anemia and 15 normal controls. Blood samples were collected before and 1, 3, 5, 10, 20, 30, 40, 50, and 60 min after intravenous glucose infusion and used for glucose and C-peptide assays. The mean C-peptide concentration after glucose infusion was significantly (p less than 0.05) lower for the SCA patients as compared to the controls. No significant differences were observed in the glucose concentration of IVGTT between the two groups. These results suggest an inadequate insulin secretion by the endocrine pancreas in sickle cell anemia or an independent genetic abnormality in linkage disequilibrium with the beta s gene.
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PMID:Decreased C-peptide secretion in sickle cell anemia. 250 99

Health care practitioners are often faced with the dilemma of whether or not to provide oral contraceptives (OCs) to women who have certain chronic medical conditions. Oral contraceptive use among gestational diabetics who use OCs may be at increased risk for developing insulin- dependent diabetes. It appears that progestins are primarily responsible because they decrease the number of insulin receptors on cell membranes. Norgestrel has a more marked effect on carbohydrate metabolism than norethindrone. Estrogen may also play a role by slowing the uptake of glucose. Findings of available studies show that progestin only OCs, combined, low-dose OCs (35 mcg of ethinyl estradiol), or preparations with norethindrone are relatively safe for gestational diabetics. In mitral valve prolapse (MVP) abnormal hemodynamics at the prolapsed valve may promote formation of thrombi and lead to cerebrovascular accidents (CVAs). Oral contraceptives are also known to increase the incidence of thrombi, especially in the lower extremities. A 1986 study of 11 OC users who had had CVAS found that a specific subject of women with MVP are at risk for CVA, perhaps due to persistent clotting abnormalities, however most could safely use a combined, low-dose pill unless headaches, smoking, and MVP symptoms. Oral contraceptive use has usually been avoided in women with sickle cell disease. The major concern has been the possibility of an additive or synergistic effect of OCs on the blood-clotting mechanism. However sickle cell disease is a relative contraindication. Several studies showed that OC use, even up to 54 months, did not increase sickle cell crises, and only 5 cases of thromboses have been reported. The increase of fetal and maternal mortality, however, is a definite risk, therefore a similar low-dose pill may be safe for women with the sickle cell trait.
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PMID:Oral contraceptive use in women with chronic medical conditions. 267 89

Colorimetric determinations of glycosylated Hb were carried out in a sample (n = 97) of sickle cell anemia patients, and in an age- and sex-matched group of individuals (n = 45) heterozygous for sickle cell anemia, from the Eastern Province of Saudi Arabia. A statistically significant increase in the value of glycosylated Hb was found in sickle cell trait (HbAS) group, when compared with those of sickle cell anemia (HbSS) and normal (HbAA) groups. Since glycosylated Hb is considered a valid indicator of long-term blood glucose, and assuming normal red blood cell survival in HbAS carriers, the increased value of glycosylated Hb may suggest that there exists a higher incidence of undiagnosed diabetes mellitus in individuals with heterozygous inheritance for sickle cell hemoglobin than homozygous sickle cell patients and normal individuals. The mechanism underlying this observation remains to be defined.
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PMID:Prevalence of diabetes mellitus in individuals heterozygous and homozygous for sickle cell anemia. 275 34

Neurologic dysfunction is a significant source of morbidity and mortality in the sickle cell diseases, occurring with a prevalence of 6% to 34%. Because changes in brain glucose metabolism may precede gross functional or morphologic alterations, we recently applied the technique of positron emission tomography with fluorodeoxyglucose F 18 in an exploratory study to compare six patients with sickle cell disease without prior neurologic abnormalities (and with normal cranial computed tomographic scans) with six healthy age-matched controls, with respect to overall and regional cerebral metabolic rates for glucose. We found no significant difference in the global metabolic rates for the two groups. However, we observed an unusual clustering of abnormal regional cerebral metabolic rates for glucose in the frontal lobes of these subjects. These results support previous observations that frontal lobe involvement may be quite prevalent in sickle cell disease, even among individuals with normal computed tomographic scans.
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PMID:Brain glucose metabolism in neurologically normal patients with sickle cell disease. Regional alterations. 325 87

The authors examined the ability of antioxidants to prevent in vitro oxidant damage to the sickle red blood cell (RBC). One millimolar ascorbic acid and alpha-mercaptopropionylglycine significantly (p less than 0.005) protected against RBC Heinz body formation during incubation with acetylphenylhydrazine, while cysteine, cysteamine, and methionine did not. The effect of ascorbic acid was concentration dependent with concentrations as low as 0.1 mM having significant antioxidant effects. Ascorbic acid protected the RBC against hydrogen peroxide induced hemolysis as well (p less than 0.05). Ascorbic acid had a significant stimulatory effect on the rate of glucose oxidation by the pentose phosphate shunt (PPS), especially in the sickle RBC. Ascorbic acid did not protect the RBC from a patient with chronic hemolytic anemia due to G6PDTorrance from Heinz body formation, suggesting that an intact PPS is necessary for ascorbic acid to express its antioxidant properties. These data suggest that clinical trials should be undertaken to examine the efficacy of ascorbic acid in the treatment of SCD.
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PMID:Antioxidants in sickle cell disease: the in vitro effects of ascorbic acid. 352 Dec 79


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