Comparative toxicity of ethylene dichloride in F344/N, Sprague-Dawley and Osborne-Mendel rats

Studies were conducted to compare the toxicity of ethylene dichloride (EDC) in F344/N rats, Sprague-Dawley rats, and Osborne-Mendel rats. Ten rats/sex/group were exposed to EDC in drinking-water at 0, 500, 1000, 2000, 4000 and 8000 ppm for 13 wk. The highest concentration was limited by the maximum solubility of EDC in water (about 9000 ppm). In addition, F344/N rats (10/sex/group) were administered EDC in corn oil by gavage to compare toxicity resulting from bolus administration with that of continuous exposure in drinking-water. Gavage doses of EDC were within the range of total daily doses (in mg/kg body weight/day) resulting from exposure in drinking-water. EDC administered by gavage resulted in greater toxicity to F344/N rats than did administration of similar doses in drinking-water. All males receiving 240 and 480 mg/kg body weight and 9/10 females receiving 300 mg/kg body weight by gavage died before the end of the study. Necrosis of the cerebellum was observed in the brains of 3 males receiving 240 mg/kg body weight and 3 females receiving 300 mg/kg body weight. Hyperplasia and inflammation of the forestomach mucosa were observed in 8 male and 3 female rats that died or were killed in moribund condition. EDC caused minimal toxicity to F344/N, Sprague-Dawley and Osborne-Mendel rats at the drinking-water concentrations used in these studies; only female F344/N rats had EDC-related renal lesions. Based on mortality and EDC-related lesions, the no-effect levels for EDC administered by gavage to F344/N rats were 120 mg/kg body weight for males and 150 mg/kg body weight for females.     

Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue glycogen content and in vitro release of insulin in streptozotocin induced diabetic rats.

The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats and compared with a known drug, tolbutamide. The oral effective dose (ED) of the extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6% (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous extract of T.chebula (AETC) daily once for two months reduced the elevated blood glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in controlling the elevated blood lipids as well as decreased serum insulin levels in contrast to the untreated diabetic animals. Hepatic and skeletal muscle glycogen content decreased by 75% and 62.9% respectively in diabetic controls, these alterations were partly prevented (34.9% and 21.17%) in AETC treated group when compared to the healthy controls. The in vitro studies with pancreatic islets showed that the insulin release was nearly two times more than that in untreated diabetic animals. The treatment did not have any unfavorable effect on other blood parameters of liver and kidney function tests. LD 50 was found to be above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even at this dose indicating high margin of safety. These findings suggest further investigations for the possible use of the aqueous extract of fruits of T.chebula for the treatment of diabetes.     

Expression and CpG methylation of the insulin-like growth factor II gene in human smooth muscle tumors.

Previously we have shown that expression of the insulin-like growth factor II (IGF-II) gene in 36 normal smooth muscle tissues (myometria) and 26 benign smooth muscle tumors (leiomyomas) was detectable by Northern blot analysis but that the RNA levels were low. In 9 of 20 malignant smooth muscle tumors (leiomyosarcomas) IGF-II gene expression was also low or absent, while in 11 of 20 the IGF-II gene was abundantly expressed. In 32 of these tissues we have now studied the DNA methylation state of the IGF-II gene. For the analysis of overall methylation of the gene the restriction endonucleases HpaII and MspI were used. In normal smooth muscle and in leiomyomas the IGF-II gene appeared to be methylated. In leiomyosarcomas with low IGF-II gene expression the DNA was partly demethylated. In leiomyosarcomas with abundant IGF-II gene expression overall methylation of the DNA tended to be low. In addition, we have studied the methylation state of one particular CpG site in the IGF-II gene with the restriction endonuclease AvaII. The results of the latter analysis confirm the analysis with HpaII and MspI. In conclusion, in malignant smooth muscle tumors the data indicate an inverse correlation between CpG methylation and expression of the IGF-II gene.     

Management of tuberculosis of the spine with neurological complications.

Tuberculosis is still a major cause of spinal compression in the developing countries. In this study 200 patients presenting with neurological lesions secondary to tuberculosis of the spine have been classified according to the Frankel classification and the results evaluated. A combination of surgical decompression and chemotherapy is advocated. The dangers of non-operative treatment are discussed.