Alcohol induced alterations of red cell morphology in carriers of the sickle cell trait.
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Biomedical subjects
Publications and source records attributed to E Roth.
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Nuclear factor (NF)-kappaB and activation protein (AP)-1 transcription factors play an important role in the signal transduction of delayed ischaemic preconditioning (PC) leading to myocardial cytoprotection. Because the exact mechanism of the activation of these factors is still not clear, we aimed to monitor the time fluctuation of NF-kappaB and AP-1 induction in an in vivo animal model. Furthermore, we measured the induction rate of these factors using repeated cycles of PC. Following median thoracotomy, anaesthetized animals (24 New Zealand White rabbits) were subjected to ischaemic PC by occlusion of the left anterior descending coronary artery for 5 min. After 10 and 30 min, and 1, 2, 3 and 4 h of reperfusion, tissue samples were taken from the ischaemic myocardium, and the DNA binding activity of the transcription factors was measured with electrophoretic mobility shift assay. A further 12 animals were subjected to 2 x, 3 x or 4 x 5-min ischaemic PC, and after a 30-min or 1-hour reperfusion period, we investigated the possible modulation of NF-kappaB and AP-1 induction. Our results show significant, biphasically increased NF-kappaB activity with peak levels at 30 min and 3 h of reperfusion in preconditioned myocardium. AP-1 increased monophasically, with the peak level at 1 h of reperfusion. Repeated PC stimuli enhanced the activity of both transcription factors analyzed, but there was no significant correlation between the number of cycles and the rate of activation. Our results show that the activation of NF-kappaB and AP-1 have a specific time curve, and the induction of these factors is only slightly influenced by the number of PC cycles.
OBJECTIVE: Leukocyte activation is thought to be responsible for the adverse effects and postoperative complications following cardiopulmonary bypass (CPB). A novel cell surface molecule, CD97, is a sensitive marker of leukocyte and primary lymphocyte activation. The present study aimed to determine the activation of different leukocyte subsets by comparing the expression of CD97 and adhesion molecules (CD11, CD18) in patients receiving coronary surgery with or without CPB. METHODS: 30 patients were enrolled and scheduled for coronary bypass surgery under CPB (20 patients, group A) and with off-pump (OP) operation (10 patients, group B). Blood samples were taken before and during surgery, and over the following first week. RESULTS: Here, we report an early decrease in CD97 expression of granulocytes (PMN) and monocytes (MC) followed by an intensive increase reaching the maximum on postoperative days 2 and 3 in patients operated with CPB. The rate of active CD97-positive lymphocytes showed a marked, gradual increase until postoperative day 3 and remained elevated up to day 7 after CPB. OP surgery resulted in moderate alteration in the presence of CD97 on PMN, MC and lymphocytes. The expression of adhesion molecules was similar to CD97 in all leukocyte subsets. CONCLUSION: The findings about CD97 expression suggest considerable leukocyte activation following coronary bypass with CPB compared to OP surgery. The collected data show that the lymphocytes are highly activated and involved in leukocyte sequestration after CPB. Moreover, the importance of CD97 in CPB-related inflammatory response can be stated.
This study examined the effects of training in phonological awareness on kindergarten children. Comparisons of children at risk (i.e., children with initially low levels of metalinguistic ability) with initially average and advanced children revealed that training gains were similar for all of these groups. Furthermore, training had comparable long-term effects on reading and spelling in Grades 1 and 2 for each group. In fact, the trained children at risk showed better reading and spelling performance than a randomly selected control group. Although considerable individual differences in training effectiveness were found Within the group of at-risk children, there was clear evidence that the training program substantially reduced the risk of becoming dyslexic in school.
A 21-year-old female patient suffering from fulminant hepatic failure was treated with extracorporeal normothermic baboon's liver perfusion for 60 hours. The amino acids (AA) uptake of the extracorporeal organ and the ratio of plasma and muscle AA at the end of the perfusion were measured. The AA uptake of the extracorporeal liver was 414 millimoles per 60 hours and even greater during hemodialysis treatment. In spite of this AA uptake, the plasma AA pattern was not normalized. At the end of the perfusion, the free AA concentration in muscle tissue was 86.25 millimoles per liter of intracellular water, an increase of 62% compared to healthy volunteers. In the patient, the ratio of glutamine to glutamine in muscle tissue was 20 to 1 compared to 5 to 1 in normals. It is concluded that (1) the extracorporeal baboon liver cannot extract the quantities of AA released by endogenous protein catabolism in hepatic failure, and (2) the muscular ammonia detoxification system gets overloaded as indicated by the increase ratio of glutamine to glutamate.
This study set out to investigate the effect of three different parenterally administered diets on the free amino acid (AA) levels in the plasma, muscle, and liver of scalded rats. Diet I consisted of AA (1.4 g/100 g weight) and a high glucose dose (6 g/100 g weight), diet II consisted of AA and a low glucose dose (1.4 g/100 g weight) and in diet III only a low glucose dose was infused. Parenteral nutrition was started on the 3rd day posttraumatically. Sampling was performed on the 7th day posttraumatically. Nitrogen balances were significantly different in all three groups, being lowest in group III. Scalded rats fed isonitrogenously, but with different amounts of glucose showed only minor changes in AA concentrations. However scalded rats fed with a nitrogen-free diet exhibited significantly reduced total muscle and liver AA levels. These decreased AA levels were due to a drop of glycine in the muscle tissue (74%) and liver (49%). Contrary to the clinical catabolic situation in scalded and starved rats, it was not intracellular glutamine but glycine which was considerably influenced by catabolism and starvation.
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BACKGROUND: In this study we compared the expression of selected monocyte surface antigens with the potential to transmigrate through an endothelial layer before and after surgery from breast cancer patients (CA) and patients with benign disease of the breast (BE). MATERIALS AND METHODS: Transmigration capacity of mononuclear cells was determined after isolation by Ficoll density gradient, layered over human umbilical vein endothelial cells and cultured in a two chamber plate added with fMLP as a chemotactic stimulus. We determined monocyte phenotye (HLA-DR, FcgRI/CD64, CR1/CD11b and LFA-1/CD11a) and the phagocytosis of E. coli by flow cytometry. RESULTS: Before surgery blood monocytes had an equal expression of the measured surface antigens, but were different in regard to their interaction with endothelial cells. Monocytes derived from CA had a higher transmigration potency than those of BE. Moreover, the migration through the endothelial cell layer created different populations of monocytes. Surgical stress modified transmigrated monocytes of BE into the direction of monocytes from CA. Phagocytic capacity of peripheral blood monocytes from CA was significantly diminished and was further reduced after surgery when measured in transmigrated cells. CONCLUSION: Our study shows that monocytes from CA and BE can be discriminated in regard to their interaction with endothelial cells.
BACKGROUND: Reactive oxygen species (ROS) play a crucial role in membrane damage in ischemic-reperfusion syndromes. The aim of our work was to determine whether blood samples taken from a peripheral vein are a reliable indicator to reflect the development of oxidative stress following acute heart ischemia and reperfusion. MATERIAL AND METHODS: In a dog model, the left descending coronary artery (LAD) was occluded for 60 min followed by 60 minutes of reperfusion. The lipid peroxidation marker malondialdehyde (MDA), endogenous antioxidants reduced glutathione (GSH), the activity of superoxide dismutase (SOD) enzyme and the stimulated radical production of isolated neutrophil granulocytes (PMN) were measured simultaneously from the peripheral vein and the coronary sinus before and at the end of the LAD occlusion, and again during reperfusion. RESULTS: MDA and SOD values increased during reperfusion. At the end of 1 hour the reperfusion changes in the coronary sinus were significant (p<0.05). GSH increased in the femoral vein, but decreased in the coronary sinus. The radical-producing capacity of PMNs decreased by the end of LAD occlusion, and a further significant decrease was measured during reperfusion in the coronary sinus (p<0.01). In the peripheral venous blood samples the decrease of PMN radical production became significant only at 30 minutes of reperfusion (p<0.02), and the earlier difference between the coronary sinus and the femoral vein tended to level out following 60 minutes of reperfusion. CONCLUSIONS: During early reperfusion following myocardial ischemia coronary sinus blood sampling gives an earlier indication of myocardial damage. At a later phase, peripheral blood samples may also be informative regarding the altered balance between ROS production and the antioxidant capacity.
In pig coronary artery rings contracted by the thromboxane analogue U 46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F 2 alpha), spiperone induced a relaxation which, at 30 mumol/l, corresponded to a complete reversal of the U 46619-induced contraction. The concentration-response curve for spiperone was bell-shaped. The second phase, i.e. the reduction of the relaxant effect (at concentrations above 30 mumol/l) was due to a contractile effect which was the only response in (1) endothelium-denuded arteries, (2) arteries treated with gossypol or methylene blue, or (3) arteries not precontracted with U 46619. Suramin and reactive blue 2 antagonized the relaxing effect, whereas metitepine, spiroxatrine, propranolol, idazoxan, flupenthixol, atropine and 8-phenyltheophylline did not. The endothelium-independent contraction was not reduced by metitepine. In strips of arteries with intact endothelium, incubated with [3H]adenosine and subsequently superfused with physiological salt solution containing dipyridamole, spiperone evoked an increase in tritium overflow above basal efflux. The present results are compatible with the hypothesis that spiperone releases ATP from the pig coronary artery. ATP, in turn, seems to activate endothelial P2 purinoceptors, leading to the release of endothelium-derived relaxing factor (NO) with a subsequent vascular relaxation.
Due to large individual differences in absorption, utilization and metabolism of the predominantly used drug ciclosporin (CsA) for selective immunosuppression in kidney graft recipients, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the CsA concentrations in blood samples and dosage readjustments. The purpose of the present study was to investigate the usefulness of a high-performance liquid chromatography (HPLC) method for native CsA and a radioimmunoassay (RIA) method for CsA and metabolites measuring simultaneously using both HPLC and RIA and creatinine serum levels (Crea) in whole blood samples from 19 kidney-transplanted children over a 3-year observation period. By comparison of the results of HPLC, RIA and Crea determinations (n = 1,284) we found a highly variable metabolization rate (RIA/HPLC ratio) of 5.25 +/- 2.33 (range 1.37-12.9). No direct correlation was found between changes in RIA/HPLC ratios and kidney function, rejection and infection periods. Dosage/HPLC and dosage/RIA showed no significant correlation. A higher correlation between HPLC, Crea and nephrotoxicity was found than between RIA and Crea. Because of rapid and large variations of CsA metabolization rates in young allograft recipients, we recommend measurements of CsA blood concentrations with any HPLC method specific for unchanged drug, since CsA metabolites detected by RIA, at least those which are most abundant, have less immunosuppressive and toxic effects.
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Immunofluorescent and light-microscopic investigations of the temporal artery were carried out in 36 patients with polymyalgia rheumatica. An arteritis was seen in 21 patients. Depositions of fibrin, immunoglobulins, and complement were found in the wall of the temporal artery and/or the vasa vasorum in 24 patients. 14 control patients showed neither an arteritis nor depositions of complement. Positive results were obtained in 91.6% of the patients with polymyalgia rheumatica when simultaneous light-microscopic and immunofluorescent examinations of the temporal artery were carried out.