Leptin increases luteinizing hormone secretion of fasting female rats.

PURPOSE: To investigate whether leptin acts directly on the anterior hypophysis by influencing gonadotropin secretion in vivo. MATERIALS AND METHODS: Cycling female rats were catheterised for frequent blood sampling and were either fasted or allowed free access to food. Stereotactic lesion of the medial preoptic area (MPOA) of the hypothalamus was performed in order to eliminate gonadotropin releasing hormone (GnRH) production. Leptin was administered at a dose of one mg/kg i.v. and blood samples were taken just before leptin administration and then after 30, 60, 90, 120, and 180 minutes. Plasma gonadotropin levels were determined. With completion of sampling, the brains were removed and the localisation of the lesions was verified histologically. RESULTS: Leptin at one mg/kg induced an increase in luteinizing hormone (LH) secretion in fasting rats, both in those with a lesion and those with intact medial preoptic area with a peak occurring 90 minutes after infusion. The augmenting effect was more prominent when the hypothalamus was intact. There was no effect in fed animals with or without lesion. Similarly, no effect was observed on follicle stimulating hormone (FSH) levels in any of the experimental groups. CONCLUSIONS: Leptin acts directly on the hypophysis enhancing LH but not FSH secretion. Nutritional state influences leptin's effect on the hypothalamus and the hypophysis.

Activity of cefpirome (HR810) against Pseudomonas aeruginosa strains with characterised resistance mechanisms to beta-lactam antibiotics.

The activities of cefpirome, cefotaxime, ceftazidime and ceftriaxone were compared against laboratory and clinical strains of Pseudomonas aeruginosa. Isolates with well characterised resistance mechanisms were included. Against carbenicillin-susceptible isolates cefpirome was more active than cefotaxime and ceftriaxone, but less active than ceftazidime. The activity of all four cephalosporins was impaired against isolates that had increased intrinsic (i.e. non-beta-lactamase-mediated) carbenicillin resistance. However, cefpirome and ceftazidime, unlike the other compounds, remained active at less than 16 mg/l against such strains, whereas cefotaxime and ceftriaxone largely failed to do so. Cefpirome maintained full activity against most isolates with plasmid-mediated beta-lactamases, as did the other cephalosporins. Transconjugant studies indicated that only LCR-1 and PSE-2 enzymes could protect P. aeruginosa against cefpirome. Isolates with partial or total chromosomal beta-lactamase derepression were highly resistant to cefotaxime and ceftriaxone (MIC greater than 128 mg/l) but only those with total derepression were resistant (MIC 16-32 mg/l) to cefpirome and ceftazidime, while those with partial derepression were sensitive to 4-8 mg/l of the latter antibiotics. Comparison of cefpirome MICs for totally-derepressed P. aeruginosa and their enzyme-deficient mutants indicated that chromosomal beta-lactamase gave less protection against cefpirome than against other cephalosporins tested. Cefpirome was a weak inducer of class I beta-lactamases. Overall, therefore, cefpirome behaved similarly to ceftazidime against the different P. aeruginosa resistance types.