Bone marrow and renal injury associated with haloalkene cysteine conjugates in calves

Almost 40 years ago, it was reported that cattle-feed which had been extracted with hot trichloroethylene and then fed to calves produced renal injury and a fatal aplastic anaemia. The toxic factor was subsequently identified as S-(1,2-dichlorovinyl)-L-cysteine (DCVC). These original findings have been confirmed, a single intravenous dose of DCVC at 4 mg/kg, or 0.4 mg/kg intravenously per day administered for 10 days to calves produced aplastic anaemia, and renal injury after a single dose of 4 mg/kg. The toxicity to calves of a number of other haloalkene cysteine conjugates has been examined to ascertain whether, like DCVC, they produce bone marrow and renal injury. Intravenous administration of the N-acetyl cysteine conjugate of DCVC produced renal but not bone marrow injury at a molar equivalent dose to DCVC, indicating that the calf can deacetylate the mercapturic acid and further that sufficient chemical had reached the kidney to be a substrate for the enzyme cysteine conjugate beta-lyase. However, intravenous administration of the alpha-methyl analogue of DCVC, which cannot undergo metabolism via the enzyme cysteine conjugate beta-lyase, was without toxicity at doses about five-fold higher than DCVC. These latter findings provide strong evidence that metabolism of DCVC via the enzyme beta-lyase is necessary for bone marrow and renal injury to occur. The cysteine conjugates of perchloroethylene and hexachloro-1,3-butadiene(HCBD) when given intravenously to calves at molar equivalent doses to DCVC, or above, did not produce either bone marrow or renal injury. In contrast, intravenous administration of the cysteine conjugate of tetrafluoroethylene (TFEC) produced severe renal tubular injury in calves without affecting the bone marrow. In vitro studies with these haloalkene cysteine conjugates showed, like DCVC, that they were good substrates for calf renal cysteine conjugate beta-lyase and toxic to renal cells as judged by their ability to reduce organic anion and cation transport by slices of calf renal cortex and inhibit the renal enzyme glutathione reductase. Calves were also dosed either orally or intravenously with HCBD to assess its toxicity. HCBD at higher molar equivalent doses than DCVC produced mid-zonal necrosis in the liver, renal tubular necrosis but no bone marrow injury in calves. The key findings emerging from these studies are (1) that none of the other cysteine conjugates, at molar equivalent doses to DCVC and above, produce bone marrow injury in calves, (2) TFEC produced only renal injury, suggesting that sufficient of the other conjugates had not reached the kidney for metabolism by beta-lyase to produce cytotoxicity and (3) that HCBD itself is more toxic than its cysteine or mercapturic acid conjugate, suggesting that pharmaco-kinetics and disposition are important factors in determining the toxicity of these conjugates to calves. Further studies are needed to understand the basis for the selective toxicity of DCVC to the bone marrow of calves.     

Identification of a cyclase-associated protein (CAP) homologue in Dictyostelium discoideum and characterization of its interaction with actin

In search for novel actin binding proteins in Dictyostelium discoideum we have isolated a cDNA clone coding for a protein of approximately 50 kDa that is highly homologous to the class of adenylyl cyclase-associated proteins (CAP). In Saccharomyces cerevisiae the amino-terminal part of CAP is involved in the regulation of the adenylyl cyclase whereas the loss of the carboxyl-terminal domain results in morphological and nutritional defects. To study the interaction of Dictyostelium CAP with actin, the complete protein and its amino-terminal and carboxyl-terminal domains were expressed in Escherichia coli and used in actin binding assays. CAP sequestered actin in a Ca2+ independent way. This activity was localized to the carboxyl-terminal domain. CAP and its carboxyl-terminal domain led to a fluorescence enhancement of pyrene-labeled G-actin up to 50% indicating a direct interaction, whereas the amino-terminal domain did not enhance. In polymerization as well as in viscometric assays the ability of the carboxyl-terminal domain to sequester actin and to prevent F-actin formation was approximately two times higher than that of intact CAP. The sequestering activity of full length CAP could be inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2), whereas the activity of the carboxyl-terminal domain alone was not influenced, suggesting that the amino-terminal half of the protein is required for the PIP2 modulation of the CAP function. In profilin-minus cells the CAP concentration is increased by approximately 73%, indicating that CAP may compensate some profilin functions in vivo. In migrating D. discoideum cells CAP was enriched at anterior and posterior plasma membrane regions. Only a weak staining of the cytoplasm was observed. In chemotactically stimulated cells the protein was very prominent in leading fronts. The data suggest an involvement of D. discoideum CAP in microfilament reorganization near the plasma membrane in a PIP2-regulated manner.     

Compulsory notification of cysticercosis in Ribeir?o Preto-SP, Brazil

Cysticercosis is a severe public health problem in several regions of Asia, Africa and Latin America. Epidemiologic studies based on the frequency of cases observed in specialized neurology, neurosurgery and computed tomography services, at autopsy and in seroepidemiologic studies do not permit the determination of the true prevalence of the disease in the population. The objective of the present study was to investigate the prevalence of cysticercosis by compulsory notification. The coefficient of prevalence was 54 cases/100,000 inhabitants in the municipality of Ribeir?o Preto. The results also indicated that cysticercosis is not under control in our region since 21% of cases presented the active form of the disease. Compulsory notification proved to be a valuable resource for the epidemiologic study of cysticercosis, also permitting the mapping of more affected areas for a better direction of prevention strategies.     

Gestational choriocarcinoma metastatic to the brain treated successfully by stereotactic radiosurgery and chemotherapy

This report analyzes the intracorporal lengths of 236 consecutive organically impotent men who underwent insertion of a penile prosthesis. The average right or left intracorporal length in this series was 20.9 cm, with a standard deviation of 2.2 cm. Intracorporal length ranged from 14-27 cm. This data may be used as reference ranges for penile prosthesis manufacturers, and for Urologists who implant prostheses or perform penile lengthening procedures.     

News: Lung damage linked to combined fine-particle, ozone exposure in new toxicology study

Science.     

Leiomyoma of the stomach as a cause of hemorrhage from the upper segment of the gastrointestinal tract

Two cases of female patients operated fo the tumors of the stomach are presented. Result of histologic examination was rather surprising in both cases--leiomyoma.     

Effect of electric skin stimulation on the level of succinate dehydrogenase activation and changes in the parameters of glutamatergic synaptic transmission in response ro sensory stimulation

Livedo racemosa with cerebrovascular lesions has been described as Ehrmann-Sneddon syndrome. The etiopathogenetic factors provoking the vascular lesions, however, are of high diversity reaching from mechanical to autoimmune causes. We present a male patient with typical livedo racemosa, muscle pain and feeling of coldness of the forearms. By dermatohistopathology and magnetic resonance tomography of the brain, Ehrmann-Sneddon syndrome could be confirmed. At this time a chronic streptococcal infection could be diagnosed. Antibiotics, anticoagulants and vascularity-supplying therapy improved the clinical and subjective symptoms. Six months later, the patient developed dizziness, vision disorder, hypesthesia of the right forehead, malaise and weight loss. A further diagnostic workup including echocardiography revealed a myxoma of the left atrium. This report illustrates the association of Ehrmann-Sneddon syndrome with cardiac myxoma and points out that cardiac diagnostic examination should be included when dealing with small-vessel involvement of the brain.