Formation of mitochondrial phospholipid adducts by nephrotoxic cysteine conjugate metabolites.

Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine.     

LUMBOVERTEBRAL SYNDROME AFTER EXTRADURAL BLOOD PATCH

We describe a patient who developed an immobilizing lumbovertebralsyndrome after an extradural blood patch and who was hospitalizedwith a. suspected extradural abscess. An infectious aetiologyof the persistent backache could be excluded and the patientrecovered with analgesics and physiotherapy. The probable aetiologyis discussed.     

Distal Penile Gangrene in a Patient with Chronic Renal Failure

To date, only 10 cases of distal penile gangrene in patients with chronic renal failure have been reported. This rare condition is believed to result from progressive vascular calcification due to secondary hyperparathyroidism in patients with chronic renal failure. We report an additional case of distal penile gangrene in a 41-year-old man who presented with chronic renal disease and pulmonary tuberculosis. Since some authors have emphasized that aggressive surgical treatment in such cases has a significant mortality rate, we took a more conservative approach to treatment.     

Occupational exposure to hazardous substances and risk of cancer in the area of the mouth cavity, oropharynx, hypopharynx and larynx. A case-control study

A case-control study of squamous cell carcinoma of the upper aerodigestive tract conducted in Heidelberg and Giessen (FRG) provided information on occupational factors in 200 patients and 800 controls (adjusted to sex, age and area of living; 4:1 matched design). The number of subjects exposed to wood dusts, organic chemicals, coal products or to cement was significantly elevated in the tumour group. An increased risk for head and neck cancer was observed after exposition to wood dust (RR = 2,2), organic compounds (RR = 2,4), coal products (RR = 2,7) and especially to cement (RR = 4,4). The cancer risk due to cement exposition showed a positive correlation to the duration of exposition and remained significantly elevated after adjustment for alcohol and tobacco consumption.     

Effects of Sclerocarya birroea Hochst. extract on some metabolic activities in the rat

The decoction of Sclerocarya birroea Hochst. shows hypoglycaemic effects, an increase in plasma IRI in normal rats and an incremented oral-glucose tolerance. The decoction is also active against diet-induced hypercholesterolaemia.