Extracellular targeting of choline-binding proteins in Streptococcus pneumoniae by a zinc metalloprotease.

A genetic-based search for surface proteins of Streptococcus pneumoniae involved in adhesion identified a putative zinc metalloprotease (ZmpB). ZmpB shared high amino acid sequence similarities with IgA1 proteases of Gram-positive bacteria, but ZmpB had neither IgA1 nor IgA2 protease activity. Analysis of a family of surface-expressed proteins, the choline-binding proteins (Cbp's), in a zmpB-deficient mutant demonstrated a global loss of surface expression of CbpA, CbpE, CbpF and CbpJ. CbpA was detected within the cytoplasm. The zmpB-deficient mutant also failed to lyse with penicillin, a sign of lack of function of the Cbp LytA. Immunodetection studies revealed that the autolysin (LytA), normally located on the cell wall, was trapped in the cytoplasm colocalized with DNA and the transformation protein CinA. Trafficking of CinA and RecA to the cell membrane during genetic competence was also not observed in the zmpB-deficient mutant. These results suggest a protease dependent regulatory mechanism governing the translocation of CinA and the Cbp's LytA and CbpA of S. pneumoniae.

Pharmacokinetics and tolerability of factor XIII concentrates prepared from human placenta or plasma: a crossover randomised study.

The pharmacokinetics and tolerability of factor XIII (FXIII) from plasma were compared with those of FXIII from placenta in a randomised, double-blind, crossover study involving 13 patients with congenital FXIII deficiency. Both FXIII activity and FXIII antigen were monitored. No difference was seen in the mean half-lives of the two preparations (9.3 days and 9.1 days for plasma and placenta FXIII activity, respectively). Response was similar for both preparations, but was slightly greater for FXIII from plasma (1.6 ormula: see text] vs 1.5 [formula: see text]). Similar results were found for recovery (65% vs 60%). The area under the data completed by extrapolation was significantly higher for FXIII from plasma. No differences between preparations in terms of efficacy or tolerability were observed. It can be concluded that treatment with FXIII concentrate from plasma is as efficient as with FXIII concentrate from placenta in terms of recovery and half-life. Both preparations were equivalent in terms of safety during the observation period. With the administration of monthly injections of approximately 30 U/kg serious bleeding events were prevented and no other serious adverse events occurred.

Quality control in haemostasis.

Laboratory investigation of the haemostatic system deserves particular procedures in the quality control of analytical variables as well as preanalytical variables. This paper reviews the precautions that have to be taken in the blood prelevement, the transport of the tubes and the performance of the laboratory tests aimed to investigate the haemostatic system in order to obtain reliable results.

[Depot medroxyprogesterone acetate: clinical and metabolic effects (lipids, glucose, hemostasis)]. / Acétate de médroxyprogestérone-dépôt: effets cliniques et métaboliques (lipides, glucose, hémostase).

Medroxyprogesterone acetate (MPA), a potent progestagen, is used as a very efficient contraceptive agent. The method of administration is by a threemonthly or sixmonthly intramuscular injection. The method is particularly convenient when the desired number of children has been reached. Fertility is sometimes reestablished only slowly after stopping the injections. The main side effects are linked to endometrial atrophy (blood loss, amenorrhoea). Other side effects are infrequent and subjective. A controversy has risen over the product, by reference to its effects on beagle dogs. We have reviewed the literature. We also present the characteristics of 313 patients treated during (all together) 8,000 months. These patients belong to a rather poor sample of the population (amongst them many immigrant women), aged about 30, with above average pregnancy and parity rates. We also studied, in 31 patients, serum levels of glucose and lipids, and haemostasis. Side effects and reasons for discontinuing the drug are reported. The Pearl index was 0,75% women-years. There was no average effect on weight, blood tension, glycemia. Triglycerides increased slightly, and there was a discreet activation of coagulation with inhibition of the fibrinolytic activity, but without clinical consequences. We conclude that we can go on prescribing the drug, in view of our study and after reviewing the literature.

Haemostasis disorders in open heart surgery with extracorporeal circulation. Importance of the platelet function and the heparin neutralization.

The main haemostasis changes observed in a screening study performed in 40 patients who underwent an open heart surgery with extracorporeal circulation (ECC) are: a significant drop in platelet count from the onset of the ECC to the third postoperative day, a decrease of platelet retention and aggregation during ECC with an 8-day persistently increased heparin-neutralizing activity in plasma but not in serum, a moderate decrease of plasma factors I, II, VII-X, X and XIII and a more important drop in factor V which disappears 24 h after ECC, a transitory increase of fibrinolysis during ECC and the lack of FDP elevation in the serum. These disorders require a very good neutralization of the heparin used during ECC. The ratio protamine/heparin can be established by a titration clotting time test. Protamine chloride seems to be more efficacious and to act more quickly than protamine sulfate for the neutralization. An overload in protamine can enhance the hemostatic, biological and clinical disorders. The preventive administration of platelet concentrate immediately after the heparin neutralization contributes to reduce the bleeding disorders related to the quantitative and qualitative platelet defects.

Comparative effects of proteinase inhibitors, plasminogen antiactivators, heparin and acetylsalicylic acid on the experimental disseminated intravascular coagulation induced by thormbin.

In an experimental study in the rabbit, the modifications of some haemostasis parameters (platelet count, platelet retention and aggregation, platelet factors 3 and 4, platelet and plasma plasmin inhibiting activities, fibrinogen and other plasma factor levels, FDP), and histological findings are compared in both the normal animal and the animal with disseminated intravascular coagulation (DIC) induced by thrombin perfusion after administration of fibrinolytic inhibitors (plasminogen antiactivators and proteinase inhibitors). In the normal animal, the administration of fibrinolytic inhibitors is followed by haemostatic changes similar to those found in thrombophilic states. The modifications are more pronounced with plasminogen antiactivators than with proteinase inhibitors. In the animal with DIC, the administration of fibrinolytic inhibitors enhances the haemostatic and the biological disorders produced by thrombin perfusion. The effect of the plasminogen antiactivators is even more evident. The preventive administration of heparin reduces or abolishes the biological and histological disorders induced by thrombin; its beneficial effect is considerably reduced when thrombin is combined with fibrinolytic inhibitors. The administration of acetylsalicylic acid appears to be ineffective for the prevention of haemostatic and histological changes induced by thrombin perfusion.

Effects of alpha and beta receptor stimulating and blocking agents on experimental disseminated intravascular coagulation.

In this experimental study on rabbits, we compare the haemostatic and histological changes observed in animals with disseminated intravascular coagulation (DIC) induced by thrombin perfusion (100 u/kg/hr during 3 hours) with or without preventive administration of alpha and beta receptor stimulating or blocking agents. Both alpha and beta receptor stimulating agents enhance the disorders induced by thrombin alone, while alpha or beta blocking agents reduce them. This favourable action is still more pronounced with the combination of these two last types of drugs. The modifications observed appear to be related to changes in platelet function.