Synovial fluid urate concentration in normouricemic and hyperuricemic subjects without joint diseases.
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Biomedical subjects
Publications and source records attributed to G Agam.
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The hemin effect on protein synthesis of human granulocytes, lymphocytes and platelets was examined. Hemin added to culture media without serum caused a dose-dependent inhibition of protein synthesis in all three cell types. A cell-specific enhancement of protein-synthesizing capability was observed in 24-hour cultures in the presence of hemin and serum. A marked increase of protein synthesis was found in granulocytes, unchanged in lymphocytes and decreased in platelets. Lymphocytes from patients with chronic lymphatic leukemia (CLL) were moderately inhibited by hemin when incubated in media containing serum, the effect being more pronounced in the presence of freshly disolved doses of hemin. Addition of protoporphyrin IX to cells cultures resulted in a marked suppression of protein synthesis by the three cell types, in all experiments. These results confirm the importance of serum proteins in preventing the inhibitory effects of free hemin and protoporphyrin IX on blood cell protein synthesis. On the other hand, they show a cell-specific enhancement of the protein-synthesizing capacity mediated by hemin.
Erythropoietin (Ep), insulin, and prostaglandins E1 and A1 (PGE1, PGA1) enhanced heme synthesis by mitochondria isolated from embryonic and adult mouse liver cells. The combination of Ep with PGE1 had an antagonistic effect, while that of Ep with PGA1 gave an additive result. The capability of isolated human platelet mitochondria to synthesize heme was also shown. This activity was stimulated by Ep.
This study presents evidence on the occurrence of an inverse relationship between activation of glycogen synthetase and inactivation of phosphorylase in a platelet preparation in vitro. The activities of glycogen synthetase and phosphorylase and the pattern of changes in these activities in platelets from controls and multiple myeloma patients were compared. Platelets obtained from multiple myeloma patients were shown to have an increased glycogen content, accompanied by an elevated level of glycogen synthetase a and a decreased activity of phosphorylase a. The pattern of changes in these enzyme activities during incubation was also different in platelets of controls and multiple myeloma patients. Extracts from patients' platelets prevented glycogen synthetase activation and phosphorylase inactivation of control platelets. Preincubation of platelets from multiple myeloma patients in control plasma resulted in an increased rate of glycogen synthetase activation, and abolished activation of phosphorylase which was found after preincubation in autologous plasma.
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Human platelet mitochondrial protein synthesis, assayed by "in vitro" 3H-leucine incorporation into the protein moiety of isolated mitochondria, was shown to be inhibited by a therapeutic concentration of chloramphenicol (CAP). This finding is in accordance with the ultrastructural damage caused to these organelles by the antibiotic, and with the inhibition of mitochondrial protein synthesis found in other kinds of mammalian cells.
A three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased. Vincristine (20 mug/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.
In vitro incorporation of [Me-3H] thymidine and [5-3H] uridine into human platelets was demonstrated. Thymidine incorporation was inhibited by three specific inhibitors of DNA synthesis: hydroxyurea, cytosine arabinoside and daunomycin. The effect was dose-dependent. Uridine uptake by platelets was found to be inhibited by specific inhibitors of RNA synthesis such as actinomycin D, rifampicin and vincristine, the effect of actinomycin D being dose dependent. The drug also led to a time-dependent inhibition of protein synthesis when preincubated with platelets. The platelet RNA profile on polyacrylamide gel was demonstrated to be similar to that of embryonic mouse erythroblast RNA. Synthesis of all three fractions, 28 S, 18 S and 4 S, was inhibited by actinomycin D. These findings show that human platelets are capable of DNA and RNA synthesis, and that these activities play a role in controlling protein synthesis in these cells. Detectable amounts of DNA have been found in whole human platelets, and in isolated mitochondria derived from these cells. Isolated platelet mitochondria incorporated [3H] thymidine and [3H] uridine into their macromolecules. These activities were inhibited by daunomycin and by both rifampicin and actinomycin D, respectively. These results support the assumption that DNA and RNA synthesis found in intact cell preparations takes place most probably in platelet mitochondria.
Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose- and time-dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria. Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5-4.0 h after its administration, when minimal leucine incorporation values of 9-40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment.
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Lithium (Li) has often been compared to ECT in therapeutic spectrum and mechanism. Inhibition of inositol monophosphatase and reduction of brain inositol are major mechanisms of Li action. Many Li effects in animals and humans are reversible by inositol. We therefore studied interactions of ECS and inositol. ECS in rats did not reduce brain inositol monophosphatase activity or brain inositol levels. Intracerebroventricular injection of 10 mg inositol, a dose that reverses Li effects, had no effect on seizure length or post-ictal length.
Many anti-panic drugs, administered chronically, can block pharmacologically-induced "panic attacks"; acutely they often exacerbate panic disorder. Theories of action need to account for this biphasic effect. Chronic inositol had previously shown efficacy against panic disorder. The authors investigated the effect of a single dose of 20 g inositol on an m-CPP challenge in a double-blind placebo-controlled crossover trial in panic-disorder patients. Seven patients had robust psychological, physiological and endocrine responses to 0.08 mg m-CPP i.v.; inositol had virtually no effect on these responses, although it had some acute effects during the evening before the challenge. A similar trial involving chronic inositol would be of interest.
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