Antiendotoxin activity of cationic peptide antimicrobial agents

The endotoxin from gram-negative bacteria consists of a molecule lipopolysaccharide (LPS) which can be shed by bacteria during antimicrobial therapy. A resulting syndrome, endotoxic shock, is a leading cause of death in the developed world. Thus, there is great interest in the development of antimicrobial agents which can reverse rather than promote sepsis, especially given the recent disappointing clinical performance of antiendotoxin therapies. We describe here two small cationic peptides, MBI-27 and MBI-28, which have both antiendotoxic and antibacterial activities in vitro and in vivo in animal models. We had previously demonstrated that these peptides bind to LPS with an affinity equivalent to that of polymyxin B. Consistent with this, the peptides blocked the ability of LPS and intact cells to induce the endotoxic shock mediator, tumor necrosis factor (TNF), upon incubation with the RAW 264.7 murine macrophage cell line. MBI-28 was equivalent to polymyxin B in its ability to block LPS induction of TNF by this cell line, even when added 60 min after the TNF stimulus. Furthermore, MBI-28 offered significant protection in a galactosamine-sensitized mouse model of lethal endotoxic shock. This protection correlated with the ability of MBI-28 to reduce LPS-induced circulating TNF by nearly 90% in this mouse model. Both MBI-27 and MBI-28 demonstrated antibacterial activity against gram-negative bacteria in vitro and in vivo against Pseudomonas aeruginosa infections in neutropenic mice.     

Complications in surgical treatment of varicose veins of the lower limbs and their prevention]

To prevent hemorrhage and hematomas in the bed of subcutaneously removed large saphenous vein after Babcock the authors somewhat modified tactically the order of manipulations during the operative procedure. This method was employed while operating 42 patients with primary and secondary venous varices. It was feasible to prevent hemorrhage and hematomas along the vascular bed in every case. The suggested tactical modification of the removal of venous varices wound improve the postoperative course and shorten the terms of patients' stay at the hospital postoperatively.     

HLA types, blood groups, serum protein and red cell enzyme types among Samoans in New Zealand

101 Samoans living in New Zealand, of whom 77 had no known non-Samoan ancestry, have been typed for nine blood group systems, four serum protein and 23 red cell enzyme systems, for haemoglobin variants and antigens at the HLA A nad B loci. The frequencies of genes in these various systems suggest that Samoans fall partly into an island Melanesian-Micronesian pattern, and partly are unique. Their uniqueness is most distinctive for the HLA system.     

Rice water with and without electrolytes in diarrhea with a high stool output

The objective of the study was to determine the efficacy and safety of two rice-based oral rehydration solutions, with and without added electrolyte in children presenting acute diarrheal dehydration with high stool output (> 10 mL/kg/h) during a two-hour rehydration period. Twenty-two patients of one to 18 months old were recruited and randomly distributed into two groups: group A received the rice-based solution without electrolytes, and group B received the rice-based solution with electrolytes. A stool output diminishing was observed in both groups and rehydration was achieved in 4.0 +/- 0.9 hours in 21 patients from group A and in 4.6 +/- 0.9 hours in 13 patients group group B. There was not a statistically significant difference between the groups regarding the laboratory results. The rice-based oral rehydration solution without added electrolytes was useful for rehydration of children presenting high stool output, after administering the WHO/ORS recommended formula during a two-hour period.     

Identification in the chicken of GRL1 and GRL2: two granule proteins expressed on the surface of activated leukocytes

We report the production of two monoclonal antibodies reacting, respectively, with a 92-kDa protein (GRL1) and a 40- to 65-kDa membrane glycoprotein (GRL2), both present in chicken thrombocyte and myelocyte granules. We examined the expression of GRL1 and GRL2 during the development of the hematopoietic system: GRL1 is restricted to thrombocytes and myelocytes, whereas GRL2 is present in thrombocytes, myelocytes, myeloid progenitors, and a subpopulation of erythroid progenitors. In the lymphoid lineages, neither GRL1 nor GRL2 is expressed during thymus and bursa ontogeny or on resting peripheral blood lymphocytes. However, CD3+ T lymphoblasts obtained by mitogenic stimulation of GRL2-negative quiescent T lymphocytes are stained on their surface by anti-GRL2 Mab. In vitro stimulation of thrombocytes and granulocytes with their specific secretagogues results in the expression of GRL1 and in the overexpression of GRL2 on the cell surface. These observations are consistent with the following two conclusions: the presence on the cell surface of GRL1 epitope is a marker of thrombocyte and myelocyte activation; GRL2 epitope is present on the granule membrane of leukocytes, including T cells. In that respect, GRL2 appears to share certain features with leukocyte activation antigens recently described in human.     

Continuous spinal anaesthesia

CD59 is a cell membrane-bound complement regulatory protein on glomerular cells that inhibits C5b-9 assembly and insertion. This report describes a recently developed model of immune thrombotic microangiopathy (TMA) induced by the renal artery perfusion of anti-glomerular endothelial cell (anti-GEN) antibody. To examine the role of CD59 in protecting the GEN from immune-mediated injury, rats underwent selective renal artery perfusion with F(ab')2 fragments of anti-CD59 monoclonal antibody to block CD59 activity or control mouse IgG followed by anti-GEN antibody or control goat IgG. Neutralization of CD59 in normal rats did not result in any significant functional or histologic changes. Perfusion with anti-CD59 did not change deposition of the pathogenic anti-GEN IgG used to induce the TMA model. However, neutralization of CD59 in the TMA model resulted in more C5b-9 formation in glomeruli, accompanied by increased platelet and fibrin deposition, more severe endothelial injury, and reduced renal function compared with the animals perfused with control F(ab')2 fragments. These results demonstrate directly that CD59 serves a protective role for GEN in this TMA model of rats, and confirm that C5b-9 formation has a critical pathogenic role in the mediation of the disease. CD59 may play an important role in protecting glomerular endothelium from other complement-mediated types of injury.