Isometamidium-dextran complex: Toxicity and activity against Trypanosoma vivax and Trypanosoma congolense in rats and mice

An isometamidium-dextran complex was prepared by adding an equal volume of the same concentration of dextran sulfate solution to isometamidium chloride solution. The optimal amount of dextran that gave good flocculent precipitate was 1 mg/mg isometamidium. In rats treated intradermally with 8 mg of isometamidium alone, there was extensive ulceration and necrosis of the dermis including hair follicles and sebaceous and sweat glands. The same dose of the complex injected intradermally did not cause gross skin changes, but microscopically, diffuse round cell infiltration of the dermis and subcutis, and mild edema of the dermis were observed; these changes were considerably reduced 2 days later. The acute intraperitoneal LD50 of the complex in mice was 307.9 mg/kg body wt, while that of isometamidium alone was 28.5 mg/kg body wt. The intraperitoneal ED50 of isometamidium in mice infected with Trypanosoma vivax was 0.045 mg/kg body wt; that of the complex was 0.124 mg/kg body wt. The therapeutic index of the complex was four times that of isometamidium. Better prophylaxis was obtained in rats against Trypanosoma congolense infection with the complex, possibly because a subcutaneous dose of 120 mg/kg body wt was administered without any serious local or systemic toxicity. The maximum tolerated dose of isometamidium used for prophylaxis was 15.7 mg/kg body wt, given im. The most significant finding is the reduced toxicity due to the complex. It can be injected subcutaneously with the same effectiveness as isometamidium in the therapy and prophylaxis of trypanosomiasis.     

Evolution of aminoacyl-tRNA synthetase quaternary structure and activity: Saccharomyces cerevisiae mitochondrial phenylalanyl-tRNA synthetase

Phenylalanyl-tRNA synthetases [L-phenylalanine:tRNAPhe ligase (AMP-forming), EC 6.1.1.20] from Escherichia coli, yeast cytoplasm, and mammalian cytoplasm have an unusual conserved alpha 2 beta 2 quaternary structure that is shared by only one other aminoacyl-tRNA synthetase. Both subunits are required for activity. We show here that a single mitochondrial polypeptide from Saccharomyces cerevisiae is an active phenylalanyl-tRNA synthetase. This protein (the MSF1 gene product) is active as a monomer. It has all three characteristic sequence motifs of the class II aminoacyl-tRNA synthetases, and its activity may result from the recruitment of additional sequences into an alpha-subunit-like structure.     

Renal transplants from category III non-heart-beating donors with evidence of pre-arrest acute renal failure

Kidneys transplanted from non-heart-beating donors (NHBDs) have been exposed to varying degrees of ischemic damage after death. Category III donors have invariably been managed, treated, and investigated in a hospital setting prior to arrest and death. Some therefore exhibit evidence of renal dysfunction and even acute renal failure (ARF) before death. Many surgeons would regard a NHBD with pre-arrest evidence of ARF as too marginal for renal transplantation. This retrospective study examines five Maastricht category III NHBD donors with evidence of pre-arrest ARF. We compare 3- and 12-month GFR outcome data from the nine resulting transplants with 40 category III NHBD transplants with normal pre-arrest renal function. The mean GFR at 3 months was 45.4 and 43.8 for the ARF and normal group, respectively. At 12 months the GFR was 42.2 and 44.7 in the ARF and normal groups, respectively. Thus evidence of ARF pre-arrest does not preclude successful category III NHBD renal transplantation.     

Dual renal transplantation for kidneys from marginal non-heart-beating donors

Kidneys transplanted from non-heart-beating donors (NHBD) are generally regarded as marginal or extended criteria grafts due to the associated period of warm ischemia. The most prolonged periods occurring in the category II (uncontrolled) donor. This potential for injury can adversely affect the glomular filtration rate (GFR), which in severe cases results in primary nonfunction. Viability testing can identify a group of kidneys that, although unsuitable for solitary transplantation, may be considered for dual transplant. This retrospective study examined a series of 11 dual renal transplants, comparing 3- and 12-month GFR outcome data with 81 single NHBD transplants. The mean GFR at 3 months in the dual group was 47.6 and at 12 months was 48.6. In the single group the GFR at 3 months was 40.6 and at 12 months was 41.9. Thus using viability testing to identify NHBD kidneys suitable for dual transplant appears reliable and predictable.     

Characterization of staphylococci from patients with toxic shock syndrome.

Fifty staphylococcal strains that produced toxic shock syndrome (TSS) toxin 1 and that were isolated from patients with TSS were characterized. One strain had more properties that were characteristic of Staphylococcus hyicus than of Staphylococcus aureus. Forty-four strains had the same properties or differed in only one property. Thirty-five of the 50 strains produced either enterotoxin A or C or both in addition to TSS toxin 1.