Relative nephrotoxicity of cephalosporin antibiotics in an animal model

An animal model is described in which mild transitory renal impairment is induced with glycerol and the nephrotoxic effects of cephalosporin antibiotics and furosemide studied. Cephaloridine and cephalothin were found to produce extensive acute tubular necrosis in rats when given in subnephrotoxic doses in combination with furosemide; this damage occurred at serum antibiotic levels not much higher than those obtained in clinical practice. No significant renal damage was found with cephalexin or Cephapirin given in equivalent dosage. It is suggested that the cephalosporin antibiotics should be used with caution in the presence of even minor transient renal impairment and particularly if furosemide is being given concurrently.     

Host-guest chemistry: combinatorial receptors.

A combinatorial approach to receptor design provides an expedient method to discover the most effective host-guest complexes from within a library. Recent advances focus on generation of larger libraries, facile detection, combinatorial catalysis and the formation of dynamic receptor libraries.     

Foraging energetics of arctic cormorants and the evolution of diving birds

Efficient body insulation is assumed to have enabled birds and mammals to colonize polar aquatic ecosystems. We challenge this concept by comparing the bioenergetics of cormorants ( Phalacrocorax carbo ) living in temperate and arctic conditions. We show that although these birds have limited insulation, they maintain high body temperature (42.3 °C) when diving in cold water (1–10 °C). Their energy demand at these times is extremely high (up to 60 W kg⁻¹). Free-living cormorants wintering in Greenland (water temperature −1 °C) profoundly alter their foraging activity, thus minimizing time spent in water and the associated high thermoregulatory costs. They then meet their daily food demand within a single intense dive bout (lasting 9 min on average). Their substantial energy requirements are balanced by the highest predatory efficiency so far recorded for aquatic predators. We postulate that similar behavioural patterns allowed early diving birds (Cretaceous) to colonize cold coastal areas before they evolved efficient insulation.     

Molar growth yields, respiration and cytochrome patterns of Beneckea natriegens when grown at different medium dissolved-oxygen tensions.

The effect of medium dissolved-oxygen tension on the molar growth yield, respiration and cytochrome content of Beneckea natriegens in chemostat culture (D 0-37 H-1) was examined. The molar growth yield (Y), the specific rate of oxygen (qo2) and glucose consumption, and the specific rate of carbon dioxide evolution were independent of the dissolved-oxygen tension above a critical value (greatest than 2 mmHg). However, the potential respiration rate increased with reduction in the dissolved-oxygen tension at values of the dissolved-oxygen tension well above the critical value. Changes in the cytochrome content occurred at dissolved-oxygen tensions well above the critical value. An increase in cytochrome c relative to cytochrome b was observed as the dissolved-oxygen tension was decreased. Reduction of the dissolved-oxygen tension to less than I mmHg caused a switch to fermentative metabolism shown by the apparent rise in YO2 and decrease in the molar growth yield from glucose. At this point the potential respiration rate (qO2) increased to its highest value, while the cytochrome pattern reverted to that observed at dissolved-oxygen tensions above 96 mmHg. There appeared to be no correlation between cytochrome content, potential qO2, in situ qO2, and cyanide sensitivity of the organism at various dissolved-oxygen tensions.     

Metabolite production and growth efficiency

The capacity to sustain the large fluxes of carbon and energy required for rapid metabolite production appears to be inversely related to the growth efficiency of micro-organisms. From an overall energetic point of view three main classes of metabolite may be distinguished. These are not discrete categories, as the energetics of biosynthesis will depend on the precise biochemical pathways used and the nature of the starting feed stock(s). (1) for metabolites like exopolysaccharides both the oxidation state and the specific rate of production appear to be inversely related to the growth efficiency of the producing organism. Maximum rates of production are favored when carbon and energy flux are integrated, and alteration of this balance may negatively effect production rates. (2) The production of metabolites like organic acids and some secondary metabolites results in the net production of reducing equivalents and/or ATP. It is thought that the capacity of the organism to dissipate this product associated energy limits its capacity for rapid production. (3) For metabolites like biosurfactants and certain secondary metabolites that are composed of moieties of significantly different oxidation states production from a single carbon source is unfavorable and considerable improvements in specific production rate and final broth concentration may be achieved if mixed carbon sources are used. By careful selection of production organism and starting feedstock(s) it may be possible to tailor the production, such that the adverse physiological consequences of metabolite overproduction on the production organism are minimized.