Effect of subinhibitory concentrations of josamycin on the expression of M protein by group A streptococci.

In an attempt to inhibit the biosynthesis of the type-specific M protein usually expressed on surface fimbriae group A Streptococcus pyogenes delta 2305 was cultivated in Todd-Hewitt broth containing 10% human serum and subinhibitory concentrations of either josamycin, erythromycin or clindamycin. Electron microscopy revealed that the antibiotic-pretreatment had little visible effect on the surface structures of the streptococci. However, josamycin and clindamycin-pretreated bacteria adhered less to hydrophobic gels than erythromycin-pretreated or untreated control cultures. Due to the decrease in surface hydrophobicity, the drug-pretreated bacteria also activated complement more readily and fixed more C3 on their surface. Consequently the killing of josamycin and clindamycin-pretreated bacteria by polymorphonuclear leucocytes was significantly enhanced. Similar findings were obtained when the M protein was removed from the bacteria by digestion with trypsin. These results suggest that josamycin, like clindamycin, reverses the capacity of group A streptococci to resist opsonization by normal human serum and interferes with the adhesion of the organisms to host epithelial cell surfaces.

Protection of mice against lethal endotoxemia by lipid X is mediated through inhibition of neutrophil function.

The effects of lipid X and 3-aza-lipid X on in vitro neutrophil function were related to their ability to inhibit the toxicity of endotoxin in galactosamine-sensitized mice. In vitro, lipid X and 3-aza-lipid X (100 ng/ml) blocked completely endotoxin (100 ng/ml)-enhanced neutrophil aggregation, superoxide anion generation, and release of beta-glucuronidase in response to a chemotactic tripeptide, f-met-leu-phe (10(-7) M). In vivo, lipid X at 250 micrograms/mouse (but not 3-aza-lipid X at a similar dose) protected groups of 10 mice from an otherwise lethal dose of endotoxin in galactosamine-sensitized mice when it was administered IV 4 hr or 2 hr before endotoxin challenge. The minimum effective dose of lipid X that could protect 50% of the challenged mice was calculated to be 715 micrograms/kg. However, lipid X failed to suppress neutrophil infiltration into the lungs. The ability of lipid X to inhibit endotoxin-induced neutrophil responses and to protect against lethal endotoxemia may be due to induction of early phase tolerance to endotoxin by the compound.

[The hypertensive type II diabetic patient treated with captopril in free general practice (Austrian Safety Study). An indications study]. / Der hypertone Typ-II-Diabetiker unter Behandlung mit Captopril in der freien Praxis (Osterreichische Sicherheitsstudie). Eine Anwendungsbeobachtung.

In 826 hypertensive patients including 396 with non-insulin dependent diabetes mellitus safety and efficacy of captopril 50 mg per day was evaluated throughout three months. In all patients blood pressure was significantly reduced. Moreover, in part of the patients with microalbuminuria, these tests turned negative with treatment. In addition, in patients with diabetes fasting and postprandial plasma glucose levels as well as HBA1C levels decreased. Only in 6.8% side effects occurred. In all patients quality of life as evaluated by a 10 item rating scale questionnaire improved. Taken together the results of this observational study confirm improvement of blood pressure levels, kidney function and metabolic derangements in diabetic patients treated with the ACE-inhibitor captopril. Effectiveness of these actions of captopril in respect to longterm prognosis in diabetics, however, remains to be established.