Leukocyte depletion of red cell components prevents exposure of transfusion recipients to neutrophil elastase

BACKGROUND: Polymorphonuclear leukocytes contain a large number of enzymes and bactericidal proteins stored in granules. Neutrophil activation induces degranulation and immediate release of these bioactive substances, including human neutrophil elastase (HNE) also known as elastase-2 (ELA2), which may contaminate whole blood units and blood components. MATERIALS AND METHODS: The HNE concentration was determined in the supernatants of blood components with a commercial enzyme-linked immunosorbent assay (ELISA). The effect of leukocyte depletion and storage was evaluated by testing whole blood, buffy-coat-reduced, and leukocyte-depleted red cell units. Buffy-coat-derived platelets and plasma were also tested. RESULTS: HNE concentrations at day 1 were about 50 microg/l in all types of red cell components with the exception of leukocyte-depleted red cells (<0.26 microg/l). In leukocyte-depleted red cells, platelets and plasma, no significant increase was observed during storage. In whole-blood units and buffy-coat-reduced red cells, the HNE concentrations increased steadily and often exceeded 1,000 microg/l when the units expired. CONCLUSION: Leukocyte depletion may limit the inadvertent infusion of bioactive substances derived from polymorphonuclear leukocytes, of which HNE is but one example. The accumulation of HNE in buffy-coat-reduced red cells may be greater than that of whole blood units. HNE accumulates during storage and its quantity may have pathophysiologic significance. Platelets and plasma derived from buffy coats contain some HNE, but leukocyte-depleted red cells virtually none. However, we consider the accumulation of HNE in these components not to be clinically important. The quantities, kinetics, and occurrence in various blood components of HNE contamination differ from those observed with cytokines.     

Inhibition of growth-factor-activated proliferation by anti-estrogens and effects on early gene expression of mcf-7 cells

Recently, it was reported that the anti-estrogen tamoxifen not only inhibits estradiol-stimulated growth of MCF-7 cells but also significantly reduces the proliferation rate of cells stimulated by growth factors. We have confirmed this finding and also shown that the new anti-estrogen droloxifene inhibits the proliferation of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I)-stimulated MCF-7 cells. The growth-factor-induced proliferation was inhibited in a dose-dependent manner by the anti-estrogens in the complete absence of estrogen and FCS. Of the anti-estrogens, droloxifene was considerably more potent than tamoxifen. Because the exprersion of the proto-oncogenes c-fos and c-myc has been considered a key event in development of the mitogenic response, we examined the effects of anti-estrogens on c-myc and c-fos gene expression. We included in these investigations the steroidal anti-estrogen ICI 164,384 because this compound has no or very little estrogenic activity. The studies revealed that all 3 antiestrogens transiently induced c-myc mRNA expression. However, the anti-estrogens inhibited estradiol-induced c-myc mRNA expression, although with different potencies. Pre-incubation of MCF-7 cells with droloxifene and tamoxifen resulted in elevated levels of growth-factor-induced c-myc mRNA expression. In contrast, the anti-estrogens did not induce c-fos mRNA or affect the expression of c-fos mRNA induced by growth factors. In conclusion, non-steroidal anti-estrogens inhibit growth-factor-stimulated proliferation of MCF-7 cells without inhibitinggrowth-factor-induced c-myc or c-fos mRNA expression.     

Presence of calbindin-d 28k in endocrine pancreatic tumoral cells of the RINm5F Line

Journal of Gastrointestinal Cancer - Calbindin-d 28K expression in insulin-producing tumoral cells of the RINm5F line was assessed by Western-blot and high pressure liquid chromatography. Western...     

Increased level of phosphorylated akt measured by chemiluminescence-linked immunosorbent assay is a predictor of poor prognosis in primary breast cancer overexpressing ErbB-2

Introduction  

Akt1, Akt2 and Akt3 kinases are downstream components of phosphoinositol 3-kinase derived signals from receptor tyrosine kinases, which influence cell growth, proliferation and survival. Akt2 overexpression and amplification have been described in breast, ovarian and pancreatic cancers. The present study was designed to investigate the prognostic significance of activated Akt in primary breast cancer and its association with other tumour biomarkers.     

Do preservation solutions protect rat cremaster microcirculation during ischemia and reperfusion?

BACKGROUND: Our aim was to investigate the potential of the preservation solution Celsior to protect rat cremaster muscle microcirculation during ischemia and reperfusion, and to compare its effects with those of HTK (histidine-tryptophan-ketoglutarate-Bretschneider solution). Because of its anti-oxidant contents, we expected Celsior to be more protective than HTK. MATERIALS AND METHODS: Capillary perfusion and leukocyte-endothelium interactions were examined in rat cremaster muscle using intravital microscopy. After perfusion with Celsior or HTK (4 degrees C), the cremaster was subjected to 4 or 6 h of warm (33-34 degrees C) ischemia and 2 h of reperfusion. Measurements were performed prior to perfusion and/or ischemia, and 0, 1, and 2 h after restoration of flow. RESULTS: Without Celsior or HTK, capillary perfusion transiently decreased to 50% of baseline after 4 h of ischemia; it remained low (45%) after 6 h of ischemia. Whereas HTK had no significant influence, Celsior deteriorated capillary perfusion: it remained low after 4 h of ischemia (39-48%) and decreased even further after 6 h of ischemia (18-8%). Both preservation solutions similarly reduced the increase in leukocyte-endothelium interactions after ischemia. CONCLUSIONS: Preischemic tissue perfusion with Celsior had an adverse effect on capillary perfusion in rat cremaster muscle after 4 and 6 h of ischemia, whereas HTK did not significantly influence this parameter. Both preservation solutions similarly prevented the increase in leukocyte-endothelium interactions after ischemia. These data suggest that HTK is more suited as a preservation solution for muscular tissue than Celsior, especially when the known protective effects of HTK on muscle function are taken into account.     

Trial of zinc supplements in relation to pregnancy outcomes, hematologic indicators, and T cell counts among HIV-1-infected women in Tanzania

BACKGROUND: In observational studies, the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes. Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women. OBJECTIVE: We examined the effects of zinc supplements on birth outcomes, hematologic indicators, and counts of T lymphocyte subsets among 400 HIV-infected pregnant women. DESIGN: Eligible women between 12 and 27 wk of gestation were randomly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery. All women received iron, folic acid, and multivitamin supplements irrespective of the experimental assignment. RESULTS: We observed no significant differences in birth weight, duration of gestation, or fetal and neonatal mortality between women in the zinc and placebo groups. Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups. However, the rise in hemoglobin over this period was significantly lower (P = 0.03) in the zinc group (x +/- SD: 11.5 +/- 17.9 g/L) than in the placebo group (15.2 +/- 18.6 g/L). Similarly, the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group (P < 0.01 and P = 0.01, respectively). Zinc had no effect on CD4(+), CD8(+), or CD3(+) cell counts during the follow-up period. CONCLUSION: Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations, no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women.     

Ein neues retrogrades Femurmarknagelsystem mit durchleuchtungsfreier proximaler Verriegelung

INTRODUCTION: Conventional retrograde nailing of the femur causes two important disadvantages: the proximal locking of the nail is difficult because of the anatomic conditions and a chondral defect was left into the knee. MATERIAL AND METHODS: After the retrograde implantation the new nail was lead through the greater trochanter. An additional proximal aiming device for proximal interlocking can be fixed. The entrance portal will be sealed by an osteochondral cylinder. 50 cases of femur fractures were selected for the prospective study. We recorded all intraoperative complications and technical difficulties. The cases were followed up for 52 weeks, both clinical and radiology examinations were performed. RESULTS: The mean follow up was 15.5+/-5 months. All fractures were healed. Knee movement was 125+/-14 degrees. The Leung Score was 84+/-12.6 points; HSS Score was 90+/-9 points. In two cases wound infections were developed. Mal-union was observed in three cases, in two cases nail brake down. CONCLUSIONS: The new retrograde interlocking nail could be used to manage femur fractures successfully. Two aiming devices enable a easy interlocking. Replacement of the osteochondral cylinder into the entry portal reduces cartilage damage.     

Glutaconyl-CoA is the main toxic agent in glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)

Despite early diagnosis and treatment, 35% of the patients with glutaric aciduria type I (GA I) develop severe neurologic damage. Glutaric acid and 3-hydroxyglutaric acid have been suspected to cause neurodegeneration. Lately, this has been questioned, however. We postulate that glutaconyl Coenzyme A (glutaconyl-CoA) is responsible for brain damage. Chemically, glutaconyl-CoA is an analogue of acrylyl-CoA, the parent substance of the extremely reactive class of acrylates. It is expected to react spontaneously with sulfhydryl groups, thus modifying membranes, disturbing enzyme functions and trapping glutathione. Enhanced production of glutaconyl-CoA together with lack of glutathione precipitates brain damage. Such a mechanism is supported by three findings. (1) The addition product of glutaconyl-CoA to cysteine is present in small amounts in normal human urine. (2) Reaction of methacrylyl-CoA with free sulfhydryl groups has been reported previously in a patient with 3-hydroxyisobutyryl CoA deacylase deficiency. (3) Glutathione has been found to be decreased in homozygous glutaryl-CoA dehydrogenase-deficient knock-out mice.