Limited controlled trial of the reactogenic properties of ADTP vaccines containing stab cultures as the pertussis component

The reactogenic properties of adsorbed DPT vaccine containing Bordetella pertussis cultures, grown by submerged cultivation, as the pertussis component were studied. The study revealed that the vaccine was low-reactogenic: no severe postvaccinal reactions were recorded in immunized children. The frequency and intensity of febrile and local reactions in children immunized with adsorbed DPT vaccine under trial and the commercial preparation commonly used in the USSR were identical, but considerably less pronounced than in children immunized with foreign vaccines having similar composition.     

Toxic properties of the cell wall of gram-positive bacteria

The biological activity of Odontomyces viscosus, which has been reported to cause periodontal disease in hamsters, was examined. The microorganism was cultured anaerobically in Brain Heart Infusion broth, and the cells were harvested. The washed cells were injected intradermally into the abdomen of rabbits. After 72 hr, a well-defined, firm, raised nodule (about 1.0 by 1.5 cm) with an erythematous border was seen at the injection site. Suspensions of cell wall and cytoplasmic material were injected intradermally, and the lesions appeared only at the site of cell wall injection. The cell walls, which were then treated with trypsin, pepsin, and ribonuclease, again produced the characteristic lesion. These nodular dermal lesions persisted for a minimal time of 10 days. The enzymatically treated cell walls were then hydrolyzed with 1 n HCl, and such hydrolysis up to 1 hr failed to alter the toxic activity of the cell walls. Similar dermal nodular lesions were obtained by injection of enzymatically treated cell walls of strains of Staphylococcus aureus, Streptococcus groups B, C, E, F, K, Lactobacillus casei, and Actinomyces israelii. Treatment with hot and cold trichloroacetic acid solutions and proteolytic enzymes, or with formamide, yielded insoluble fractions which produced the characteristic nodular lesions. The size of the lesion resulting from injection of these fractions was proportional to the amount of the injected material. The active fraction, which does not appear susceptible to hydrolysis by lysozyme, is thought to be cell wall mucopeptide. Histological studies showed skin abscesses due to the toxic reaction; however, in addition to the acute inflammatory reaction, there was local eosinophilia.     

Evaluation of the reactogenic and immunogenic properties of meningococcal vaccines

The results of the study of the reactogenic and immunogenic properties of meningococcal polysaccharide A + C vaccine in the controlled epidemiological trial, with regard to variations depending on the initial immunological characteristics of vaccinees in terms of the levels of antibodies to the polysaccharides contained in the vaccine, are presented. The study was made on school children: 303 of them were immunized with the meningococcal vaccine under test, and 229 (controls) with adsorbed diphtheria-tetanus toxoid. This study revealed that the reactogenic properties of the preparation were more pronounced in those children whose blood sera had been found to contain no antibodies to polysaccharides A and C prior to immunization. The immunological properties were more pronounced with respect to polysaccharide A. The titer of antibodies to polysaccharide A was found to depend on the previous immunological status of the child, which was indicative of the booster effect produced by the vaccine. The data obtained in the study suggest that the evaluation of the reactogenic and immunogenic properties of newly developed prophylactic preparations should be made with due regard for the previous immunological status of vaccinees in respect to the antigens contained in the meningococcal vaccine under test.     

Isolation and purification of a preparation possessing leukocytosis-stimulating properties from pertussis bacteria]

A homogeneous protein LSF-2 preparation was extracted from the cultural fluid of Bordetella pertussis strains of the 1.0.3 serological type by means of precipitation with ammonium sulphate and electrofocussing; this preparation proved to produce a marked leukocytosis-stimulating and a weak toxic action of delayed type in experiments on animals. Intraperitoneal administration of 5 mug of the LSF-2 preparation caused a rise of leukocytosis in mice to 100,000 cells per 1 mm3, a delay in the gain in weight beginning from the 3rd day of the administration and a late death of the animals in 5% of cases. The LSF-2 preparation protected the mice in infection with a virulent pertussis strain No. 18323 in the amount of from 12 to 91%, depending on the immunizing dose; its ImD50 was equal to 2.0 -2.4 mug of protein. The results of investigations carried out permitted to assess the role of this substance in the formation of specific immunity in pertussis infection.     

MMP inhibitors: experimental and clinical studies

Matrix metalloproteases (MMPs) are a family of structurally related enzymes that are capable of degrading proteins of the extracellular matrix. These enzymes play a role in tissue remodelling associated with both physiological and pathogenic processes. A high expression of MMPs is associated with cancer malignancy: it is related to the tumor's ability to metastasize and to the process of angiogenesis. Treatment with MMP inhibitors alone or in combination with cytotoxic therapy is an interesting novel approach to control tumor progression. The expected mechanism of action of these compounds and the difference in side effects compared to cytotoxic drugs make the definition of endpoints and the assessment of response difficult. Furthermore, it is not yet clear whether tumor vascularization or, more specifically, MMP expression/activation should be a criterion of eligibility for this kind of treatment. This review provides an overview of the characteristics of MMPs and their role in tumor progression, metastasis and angiogenesis. Preclinical and clinical studies with synthetic MMP inhibitors are described. The presence of MMPs in biological fluids of patients and their use in prognostic evaluation and in determining the efficacy of treatment with MMP inhibitors is discussed.     

Testing the properties of an experimental batch of zoster immune gammaglobulin (ZIG).

The methods of indirct haemagglutination (IH) and precipitation in gel (ID) were employed to test the level of varicella-zoster (VZ) antibodies in an experimental batch of zoster gammaglobulin (ZIG). The titre of indirect haemagglutinating antibodies in ZIG was about 64 times higher than in the ordinary batches of normal immunoglobulin and about 8 times higher in comparison with the level of the initial plasma pool. In the reaction of precipitation in gel, ZIG produced 5 to 6 zones. In comparison with the initial pool of convalescent plasma, ZIG also showed an 8-fold concentration of precipitating antibodies. ZIG was administered preventively to 6 children with risk diagnoses. None of the children fell ill with varicella. According to the results of subsequent serological examination in the reactions of indirect haemagglutination and radioimmunologic analysis, only 3 children were definitely susceptible to VZ infection. In two other children (very low antibody titres) the risk could not be excluded. No substantial increase in the levels of IH and RIA antibodies was observed in the 4 children under serological observation in a period of 6 months following the administration of ZIG. ZIG was administered therapeutically to four children with varicella. The effect of ZIG therapy was very suggestive, especially in two newborn infants lacking maternal antibodies, where the dose of ZIG per 1 kg body weigt was unusually high.     

Pharmacological and pharmacokinetic properties of lanthipeptides undergoing clinical studies

The intrinsic qualities of lanthipeptides for their use as therapeutic drugs present several challenges because of their properties, which include stability, solubility and bioavailability, which, under physiological conditions, are very low. Researches have encouraged clinical evaluation of a few compounds, such as mutacin 1140, microbisporicin, actagardine and duramycin, with pharmacokinetic profiles showing rapid distribution and elimination rates, good bioavailability and fecal excretion, as well as high protein binding. Local and parenteral administration are currently suitable to minimize environmental influences on lanthipeptides and ensure efficient activity. Nevertheless, valuable improvements on pharmacodynamic and pharmacokinetic properties may also permit systemic applications via enteral routes. Understanding how rational modifications influence the desired pharmacological and pharmacokinetic properties of these biomolecules would help to answer some specific questions about their susceptibility to environmental changes, mechanism of action and how to engineer other peptides of the same group to improve their clinical relevance.