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Decreased systemic formation of prostaglandin E and prostacyclin, and unchanged thromboxane formation, in alcoholics during withdrawal as estimated from metabolites in urine.

1. The rates of secretion into the circulation of prostaglandin E, prostacyclin, and thromboxane A2 were estimated in male alcoholics on the third day of withdrawal and in control subjects by measuring appropriate metabolites in urine. 2. Urinary levels of tetranor-5,11-diketo-7 alpha-hydroxyprostane-1,16-dioic acid (the major urinary metabolite of prostaglandins E1 and E2), of 2,3-dinor-6-keto-prostaglandin F1 alpha (the major urinary metabolite of prostacyclin) and of 6-keto-prostaglandin F1 alpha (the stable hydrolysis product of prostacyclin) were significantly different from the normal subjects in the alcoholic group. In contrast, 2,3-dinor-thromboxane B2 (the major urinary metabolite of thromboxane A2) and thromboxane B2 (the stable hydrolysis product of thromboxane A2) were not significantly different between the groups. 3. These data suggest that the ratio of the vasodilator prostanoids prostaglandin E and prostacyclin and the vasoconstrictor prostanoid thromboxane A2 is lower than in normal subjects, in alcoholics during withdrawal. This may be one causal factor for the higher incidence of hypertension observed in withdrawing alcoholics compared with control subjects.

6-Ketoprostaglandin F1 alpha↗

Free radical formation and erythrocyte membrane alterations during MetHb formation induced by the BHA metabolite, tert-butylhydroquinone.

Erythrocyte membranes are altered as a consequence of oxidative stress following the incubation of intact erythrocytes with one of the major metabolites of the antioxidant butylated hydroxyanisole (BHA), tertbutylhydroquinone(tBHQ). Arather persistent semiquinone radical was observed by electron spin resonance (ESR) spectroscopy when tBHQ was incubated with either homogeneous oxyhemoglobin solutions or suspensions of intact erythrocytes. Erythrocyte ghosts prepared from fresh control erythrocytes and ghosts from erythrocytes preincubated with BHA and its metabolite, tBHQ, were subjected to polyacrylamide gel electrophoresis (SDS-PAGE). Only minor changes of the electrophoresis pattern relative to the control was observed in the BHA incubations whereas tBHQ significantly increased the amount of high molecular weight degradation products of erythrocyte membrane constituents. These changes were only observed when incubations were performed in the presence of oxygen. In control experiments where heme oxygen was replaced by carbon monoxide, no membrane degradation products appeared. These observations can be interpreted in terms of metabolic activation of the antioxidant BHAvia tBHQ to the tert-butylsemiquinone free radical and finally to the corresponding quinone, thereby leading to harmful effects on erythrocyte membrane structures. Moreover, deleterious effects on other biological membranes are also likely to occur.

Animals↗

Cytoplasmic granule formation in myelocytes. An electron microscope radioautographic study on the mechanism of formation of cytoplasmic granules in rabbit heterophilic myelocytes.

The intracellular flow of tritiated lysine as revealed by electron microscope radioautography was studied in heterophilic myelocytes of rabbit marrow. Label over the Golgi complex rose to a maximum of 37% of total cytoplasmic grains 30 min after initial exposure to the tracer and fell to 11% after 3 to 4 hr of incubation. Coincident with decrease in label over the Golgi complex, grain counts over granules rose to 32% after 3 to 4 hr. The time sequence of incorporation and flow of tritiated lysine and the per cent distribution of label was similar in bone marrow myelocytes under in vivo and in vitro conditions. The results demonstrate a function of the Golgi complex in incorporating or packaging certain basic amino acids or proteins into cytoplasmic granules of heterophilic myelocytes.

Animals↗

Factors influencing hematopoietic spleen colony formation in irradiated mice. I. The normal pattern of endogenous colony formation.

Data pertaining to the endogenous mouse spleen colony system, 10 days postirradiation, are presented. The D(o) for visible colonies is 78 R, while that for 6 hr iron uptake over a range of 600-800 R is 50 R. The D(o) for spleen weight is 196 R and that for IUdR uptake is 193 R. These measurements increase with the age of the mouse. Hypertransfusion decreases spleen iron uptake and colony number. DF-(32)P and sodium sulfate-(35)S are not useful indicators of splenic hematopoiesis in this system. Visible hematopoietic colonies in the spleen are not produced by vinblastine, nitrogen mustard, methotrexate, or cyclophosphamide.

Age Factors↗