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Pharmacokinetics of pivmecillinam.

1 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam (400 and 600 mg). 2 Similar plasma concentration/time curves of ampicillin and mecillinam in the starved normal subjects followed oral administration of ampicillin (500 mg) and pivmecillinam (600 mg). 3 The plasma concentration/time curve of mecillinam was measured in the same normal subjects after oral administration of pivmecillinam (400 mg) with a reproducible standardized Lundh test meal. 4 There was no statistically significant difference in the plasma concentration/time curve of mecillinam after pivmecillinam/400 mg) and the meal compared with the plasma concentration/time curve after oral pivmecillinam (400 mg) was given to the same subjects when starved. After administration of pivmecillinam (400 mg) with meal, Tasc was significantly delayed beyond the value obtained when the subjects were starved. 5 The pharmacokinetics of pivmecillinam in coeliac disease are normal. This finding contrasts with previous studies on the pharmacokinetics of another pivaloyloxymethylpenicillin ester, pivampicillin, in this condition.

Adolescent↗

The bacteriological ecosystem of the skin of children in an African tropical envirovment (Tanzania).

Using a standardized method for sampling, the aerobic microbial flora of the skin of ninety-five children in Dar es Salaam, Tanzania, was studied qualitatively and quantitatively. The subjects comprised three groups; group A, thirty-seven normal infants (below the age of 1 year); group B, twenty-nine infants with various bacterial skin lesions; and group C, twenty-nine nursery school children between 4-5 and 7 years. The following observations were made: (I) The quantitative results indicated; (a) great variation between individuals, which was more marked among the females; (b) lower bacterial counts in infants than in older children; (c) counts were not affected by the presence of infection or state of cleanliness; (d) there were some differences between females and males and between different ethnic groups. (2) Qualitatively, the types of organisms isolated were similar to those reported elsewhere. There were differences in carrier rates of many organisms but these were most striking with Staphylococcus aureus and Staph. albus. It is concluded that there are great differences in carrier rates between persons in a tropical African environment and those studied elsewhere. These difference may be due to environmental, geographical or ethnic factors. Such observations call for more studies in this area to establish the normal flora.

Aerobiosis↗

Evidence that the recently discovered high-energy nucleotide derivative, oligo(phosphoglyceroyl-ATP) forms the end chains of purinogen, a complex polymeric major storage form of adenine nucleotide and phosphate in heart.

Previous work in our laboratory has shown that free adenine nucleotides in heart, liver and kidney exchange rapidly with a major acid-insoluble species which we have characterised as oligo[3-phospho-glyceroyl-gamma- triphospho(5')adenosine(3')], abbreviated to (PG-ATP)n. This has been found in liver and in heart to be complexed to a specific 3'-phosphodiesterase which releases PG-ATP monomers and is located in mitochondrial inter-membrane space. In [14C]adenosine-perfused hearts, (PG-ATP)n has been shown to reach specific radioactivity equilibrium with free ATP within 30 min. Attempts to estimate the quantities of nucleotide in (PG-ATP)n and free nucleotides in response to a variety of stimuli using previously labelled hearts showed by contrast that the free and sequestered nucleotide pools were not at equilibrium. Re-examination of the rapidly labelled acid-insoluble species led to the recognition of radioactive inhomogeneity and of three additional nucleotide components. Perfusion of hearts with phosphate-free medium increased the proportion of 14C incorporated into the sequestered from by 70% and caused the net transfer of 0.9 mumol.g-1 of purine from free adenine nucleotides to the sequestered form. The findings point to the existence of a more complex polymer whose rapidly exchanging end chains we had previously isolated and characterised as (PG-ATP)n; we suggest the name purinogen for this polymer and show that it can contain between 25% and 55% of the tissue nucleotide pool in rat heart.

Adenine Nucleotides↗

The effect of impairment of renal function and dialysis on the serum and urine levels of clindamycin.

A single 150 mg oral dose of clindamycin was given to three healthy volunteers and 13 patients with varying degrees of renal functional impairment. The mean peak serum levels in the two groups were 2.55 +/- 0.92 mug/ml and 3.39 +/- 0.68 mug/ml respectively. In all patients the levels greatly exceeded the minimum inhibitory concentration for sensitive pathogens. The serum half-life was extremely variable in patients with renal failure and bore no relationship to the glomerular filtration rate. In the normal subjects 11.9% of the administered dose was excreted in the urine but in severe renal failure less than 1% of the bioactivity was detected in the urine in 24 hours. The drug was not removed by haemodialysis. In patients with mild to moderate impairment of renal function no dosage adjustment of clindamycin is necessary. However, in those with severe renal failure some modification to dosage would be prudent and this should be monitored by measuring serum levels of the antibiotic.

Adult↗

Effects of tubulin assembly inhibitors on cell division in prokaryotes in vivo.

The bacterial cell division protein FtsZ is a structural analogue of tubulin. Bacterial mutants in which the ftsZ gene is inactivated are unable to divide. Numerous inhibitors of tubulin assembly are known, some of which are used as fungicides. The strong structural homology between FtsZ and tubulin raises the possibility that some of these inhibitors could affect bacterial cell division. Here we report that the tubulin assembly inhibitors thiabendazole and 2-methylbenzimidazole cause cell elongation in Escherichia coli and cyanobacteria.

Bacterial Proteins↗