Immunization with Porphyromonas gingivalis cysteine protease: effects on experimental gingivitis and ligature-induced periodontitis in Macaca fascicularis.

Targeting bacterial virulence factors such as proteases for immunization may hold the key to limiting or preventing loss of attachment and alveolar bone in periodontal disease. This study examined the clinical, microbiological, and immununological responses following active immunization with a purified Porphyromonas gingivalis cysteine protease (porphypain-2) in the nonhuman primate (Nhp) Macaca fascicularis. One group of Nhp was immunized with porphypain-2 antigen while control Nhp received placebo injections. All Nhp were subjected to experimental gingivitis followed by ligature-induced periodontitis in a split-mouth design. An enzyme-linked immunosorbent assay demonstrated that immunization elicited a significantly elevated and specific IgG antibody response to both whole cell P. gingivalis (36-fold) and to porphypain-2 (194-fold). Checkerboard hybridization DNA analysis of subgingival plaque from ligated sextants demonstrated that 25% more Gram-negative anaerobic species became significantly elevated from baseline and at earlier timepoints in the control group than in the immununized group. Immunization with this protease did not suppress the emergence of P. gingivalis. Clinical indices showed few changes related to immunization. Alveolar bone density changes demonstrated a highly significant loss in ligated sextants compared to non-ligated sextants within the control group (P < 0.001), and a smaller but significant difference within the immunized group (P = 0.043). Comparison of ligated sextants only demonstrated more bone loss in the control group versus the immunized group (-13.07+/-9.51 versus -9.41+/-6.18; computer-assisted densitometric image analysis units +/- SD); the difference approached, but did not reach, significance. The results suggest that porphypain-2 may contribute to the pathogenic potential of the subgingival plaque microbiota in the Nhp model of ligature-induced periodontitis, and that active immunization with porphypain-2 appeared capable of altering this pathogenic response.

[Biosynthesis of collagen and mode of action of D-penicillamine (author's transl)]. / Zur Kollagen-Biosynthese und zum Wirkungsmechanismus von D-Penicillamin

The biosynthesis and metabolism of collagen are complex processes and are regulated by different enzyme systems. In theory these processes can be influenced at a number of different stages. The therapeutic prevention of excessive collagen and fibril synthesis is a desirable aim, although there is a lack of substances suitable for this purpose. One substance employed is D-penicillamine (D-PA), which blocks aldehyde condensation, inhibits the cross-linking of the peptide chains and the formation of collagen fibrils. Other characteristics of D-PA which are of therapeutic interest are chelate formation with heavy metals and the depolymerizing action on macroglobulins. D-PA may possibly by of some value in the chemotherapy of certain tumours and for sensitizing tumour cells to irradiation. It remains to be investigated whether D-PA or similar substances could be of therapeutic value in arteriosclerosis, in which an increased deposition of collagen in the basal membranes is the fundamental process. The successful therapeutic use of D-PA in rheumatoid arthritis and chronic active cirrhoses of the liver justifies the hope that this substance may favourably influence disorders of collagen metabolism.

[Josamycin in bronchopulmonary and otorhinological diseases in pediatrics]. / Josamycin bei bronchopulmonalen und otorhinologischen Erkrankungen in der Pädiatrie.

Josamycin, one of the more recent macrolide antibiotics, was evaluated in 29 children aged from 2 months to 13 years with bronchopulmonary or otorhinological disease. With a daily dose in the range 30 to 60 mg/kg bodyweight, and an average treatment period of 7.7 days, 24 children were cured and 5 markedly improved. In only 4 children were minor side effects, such as gastrointestinal disturbances, observed, which in no case necessitated interruption of therapy. By virtue of its spectrum of activity josamycin seems to be an ideal antibiotic for the treatment of bacterial respiratory tract infections. In addition, josamycin displays a high degree of activity against mycoplasmas and chlamydiae. Only a very low percentage, reported as 6%, of staphylococcal are primarily resistant to the antibiotic, and the rapid development of resistance to other macrolides, has not been reported for josamycin. No cross resistance exists between josamycin and penicillins, cephalosporins, tetracycline or aminoglycosides. These characteristics represents josamycin for the treatment of respiratory tract infections. The pleasant taste of the preparation used in this study ensured its ready acceptance by the children treated.

Clinical trials with a new influenza subunit vaccine in adults and children.

The reactogenicity and immunogenicity of a new influenza subunit vaccine containing essentially only hemagglutinin and neuraminidase has been studied in man. Studies in primed individuals demonstrated that the subunit vaccine induced antibody levels as high as those induced by a comparable whole virus vaccine, or a commercially available whole virus vaccine or by a split vaccine. The commercial whole virus vaccine caused systemic reactions, including fever and headache in 15% of volunteers. In contrast local and systemic reactions were significantly fewer after application of subunit vaccine. When unprimed individuals were vaccinated serological responses were, however, superior with whole virus vaccines. The subunit vaccine demonstrated good immunogenicity and a very low reactogenicity in children. Three months after vaccination, a number of the children were challenged intranasally with live attenuated influenza virus. All proved, as judged by virus isolation and antibody response to be resistant.

Bioavailability and pharmacokinetics of D-penicillamine.

The absolute and the relative bioavailability of D-penicillamine, available from different dosage forms and products, was studied in 10 healthy volunteers. Plasma levels and urine excretion of D-penicillamine were determined up to 8 h after administration by high performance liquid chromatography after intravenous administration of 250 mg and after oral administration of 250 mg (2 products) and 150 mg (1 product) D-penicillamine. The absolute bioavailability on oral administration was 50-70%. No statistical difference was found between the relative bioavailabilities of the different dosage forms tested.

A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: comparison of a subunit vaccine with a whole-virus vaccine.

In the present vaccination trial, 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m. in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA, using the double-blind procedure. Both vaccines were prepared from the strain A/New Jersey/76 (x 53a-recombinant). The vaccination was followed four weeks later by a booster injection. In tests of local and systemic reactogenicity, it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions. The whole-virus vaccine was marked by a significantly higher rate of adverse reactions, whether of the local or systemic variety. The whole-virus vaccine had, however, a higher immunogenicity than the subunit vaccine, and due to the relatively high rate of adverse reactions it causes, it is not recommended for the vaccination of seronegative children. Because of its low reactogenicity, the subunit vaccine can be given at higher dosage, and it is a matter for consideration whether a better antibody response might not result from two booster injections.