[Nanofiltration in production of Beriplex P/N: increasing the capacity of virus elimination while maintaining product quality].

For the manufacture of the PCC Beriplex P/N, nanofiltration was introduced into the production process of Beriplex HS providing an additional means to heat treatment for the clearance/inactivation of viruses. By nanofiltration, large enveloped viruses (HSV-1, HIV-1) were completely eliminated by a factor of more than 7 log10. While medium-sized enveloped viruses (HBV, BVDV) were cleared by a factor of approximately 4 log10, small non-enveloped viruses (poliovirus) were not removed.

Investigation of activated prothrombin complex concentrate as potential hirudin antidote in animal models.

The specific thrombin inhibitor r-hirudin (HBW 023) has been demonstrated to be effective in preventing thrombosis in preclinical models. Up to now, no bleeding complications have been observed using therapeutically effective doses in animals studies. However, in case of inadvertent overdosing the occurrence of undesired impairment of coagulation cannot be excluded.

Functionally inactive S. aureus alpha-toxin containing a single amino acid substitution: potential usefulness as a vaccine.

Substitution of His-35 with arginine in staphylococcal alpha-toxin leads to loss of its membrane perturbating properties in vitro. In this study, we report that the inactive mutant toxin is also devoid of toxic properties when injected intravenously into rabbits. Whereas a single application of native toxin at a dose of 20 micrograms/kg proved uniformly lethal within 3 hours (n = 3), all animals receiving 20, 100 or 200 micrograms/kg mutant toxin (n = 3 for each group) remained in unaltered, healthy states over a 15 day period of observation.

Activity of coagulation and fibrinolysis parameters in animals.

Using diagnostics for the determination of clotting factors and fibrinolytic parameters in human plasma, samples from rat, guinea pig, rabbit, cat, dog, sheep, cattle, horse, pig, and monkey were analysed. The human system was employed even for standard curves and controls. Results obtained in this way are relative values in relation to pooled fresh human plasma of healthy donors which is defined to contain 100% of the norm or 1 unit of each factor per 1 ml.

In vivo effects of intravascularly applied Escherichia coli hemolysin: dissociation between induction of granulocytopenia and lethality in monkeys.

The effects of intravascular application of endotoxin-depleted Escherichia coli hemolysin (HlyA) was studied in rabbits and monkeys. In rabbits, bolus application of HlyA calculated to effect final blood levels of approximately 2-3 HU/ml (200-300 ng/ml) caused an acute fall of polymorphonuclear blood leukocytes to less than 20% of starting levels within 5 min. Additionally, platelet counts dropped to approximately 30% of starting levels, whereas lymphocyte counts varied considerably and seldom fell to less than 50%.

[In vitro and in vivo efficacy of a toxin-neutralizing human staphylococcal immunoglobulin].

The pathogenic relevance of alpha-hemolysin of Staph. aureus in human infections is up to the present in discussion. Numerous therapeutic human trials to modify the outcome of a Staph.

Toxicological testing of monoclonal antibodies.

Toxicity studies with monoclonal antibodies for in vivo diagnostic or therapeutic administration must be designed case by case to take into account the intended use in humans and the type of structure (nude or coupled to immunotoxins or radionuclides). The design of experiments is influenced by the origin of the clone (murine or human with different problems of antigenicity) and the type of culture (ascites or fermentation with various kinds of possible contaminations). Therefore, routine animal tests must be supplemented by analytical procedures and assays of pharmacological quality control (pyrogenicity, abnormal toxicity).

Human hyperimmune globulin protects against the cytotoxic action of staphylococcal alpha-toxin in vitro and in vivo.

Alpha-toxin, the major cytolysin of Staphylococcus aureus, preferentially attacks human platelets and cultured monocytes, thereby promoting coagulation and the release of interleukin-1 and tumor necrosis factor. Titers of naturally occurring antibodies in human blood are not high enough to substantially inhibit these pathological reactions. In the present study, F(ab')2 fragment preparations from hyperimmune globulin obtained from immunized volunteers were tested for their capacity to inhibit the cytotoxic action of alpha-toxin in vitro and in vivo.

Identification of immunotoxic effects of chemicals and assessment of their relevance to man.

Immunotoxicity is defined as the adverse effects of foreign substances (xenobiotics) on the immune system. Two types of effects are possible: immunosuppression (which may result in an increased susceptibility to infection or to the development of tumours) and immunopotentiation (which may manifest as an allergy or as autoimmunity). There is, as yet, little evidence that well controlled occupational exposure to industrial chemicals has led to clinically significant immunosuppression.

Quality criteria for i.v. immunoglobulins: importance of tests and product properties.

Quality criteria for i.v. immunoglobulins (i.

Quality criteria for i.v.-immunoglobulins: importance of tests and product properties.

Quality criteria for i.v.-immunoglobulins (i.

Assay of possible formation of antigenic components in heat-treated plasma protein preparations.

To eliminate the risk of hepatitis infections, human plasma protein preparations can be heated in solution to 60 degrees C for 10 h thus inactivating several viruses. Preclinical safety experiments were performed in order to exclude the possibility of the formation of antigenic components, not present in normal human plasma, through this pasteurization step. Rabbits were immunized with either the heated or the unheated product.

Influence of antithrombin III on carbon tetrachloride intoxication of rabbits.

Intraperitoneal application of carbon tetrachloride into rabbits caused high mortality due to liver damage with increase of serum transaminases, coagulation disorders, and decrease of antithrombin III (AT III) blood levels. Groups of animals were treated i.v.

[Studies of a fibrin adhesive on punch wounds in rats].

The efficacy of fibrin adhesive in routine quality control was examined in experimentally induced skin wounds of rats with fixation of punched-out skin pieces. In this rat model the influence of factor XIII, different fibrinogen concentrations, the stability of the dissolved lyophilized components, variation of adhesion time, and of CIG (cold insoluble globulin) was investigated. The adhesive strength was improved by factor XIII (optimum 60 U/ml).

[Effect of antithrombin III on experimental hepatotoxin poisoning in dogs].

Carbon tetrachloride (CCl4) produces hepatic necrosis and Galactosamine (GALN) causes acute hepatocellular injury in dogs. 8 Beagle dogs were treated orally twice with 0.4 ml/kg CCl4 and 12 Beagle dogs with 200 mg/kg GALN i.

A new inactivated tissue culture rabies vaccine for use in man. Evaluation of PCEC-vaccine by laboratory tests.

A new inactivated rabies vaccine (purified chick embryo cell vaccine) has been developed using the Flury LEP-C 25 strain of rabies virus propagated in primary chick embryo cell cultures. The antigen was purified and concentrated by continuous density gradient centrifugation and inactivated by betapropiolactone. This vaccine was tested for innocuity, tolerability and protective capacity in a series of laboratory tests and compared with human diploid cell strain (HDC)-vaccines of similar antigenicity.

Toxicity studies with human fibroblast interferon.

Acute toxicity studies of interferon derived from human fibroblasts (FHIF) were performed in mice and rats with doses between 6 X 10(4) and 480 X 10(4) IU/kg i.v. and an observation period of 14 days.

Pertussis antigens--screening models on toxicity.

From the same batch of B. pertussis bacteria two types of DPT-vaccines were produced after harvest of the inactivated organisms by centrifugation or acid precipitation. The first vaccine contained whole pertussis bacteria and the second an extracted antigen complex.

Serotype determinant protein of Neisseria Meningitidis. Large scale preparation by direct detergent treatment of the bacterial cells.

Neisseria meningitidis Group B microorganisms, inactivated with phenol and harvested by centrifugation, were subjected to direct treatment with various detergents to solubilize the serotype determinant proteins localized in the outer membrane. Analysis of the data showed that extraction of the cells with detergents provided yields of the serotype protein substantially exceeding those obtained by simple salt extraction of the bacteria. Routinely, more than 2 mg of end product per g of cell mass (wet weight) may be recovered by the present method.

Pharmacokinetics of human interferon-beta in monkeys.

Human fibroblast-derived interferon (HuIFN-beta) was administered to cynomolgus monkeys i.m. (2 x 10(5) iu/kg), i.