Apoptosis: future directions in cancer therapy.

Cancer as a multifactorial disease results in gain of immortality due to defective apoptosis. The primary mode of cell death by apoptosis induced by various modes of treatment often fail in vivo. The in vitro environment is less complex while the in vivo environment is influenced by various external regulatory signals besides the existence of multiple, parallel and independent apoptotic pathways. Further, specific preference for an apoptotic pathway in a certain cell type would significantly alter the apoptotic responses. Identification of defects in preferred pathways and choosing alternative and potentially inducible pathways would help in deciding on apoptosis-based treatment protocols. Mechanisms involved in the execution of apoptosis may also not be unique to apoptotic pathways since similar events, possibly with strict control, do occur during mitosis. Further evaluation may yield new dimensions to apoptosis and apoptosis-based therapy.

Effect of leaf extract of Aegle marmelose in diabetic rats.

Alloxan induced animal model was used to evaluate the potential antidiabetic effect of A. marmelose leaf extract. The diabetic animals were given insulin injection and another group A. marmelose leaf extract orally. It maintained the weight of the animals near to the control rats but a significant decrease in weight was noted in diabetic animals without any treatment. The blood glucose level in treated animals were near to that of control ones. Also a significantly increased glucose tolerance was observed in animals orally given the leaf extract prior to the experiment. A significant decrease in liver glycogen (1.24 +/- .07 g/100 g of wet tissue) was observed in diabetic rats which was brought to almost the normal level (1.84 +/- .14 g/100 g) with leaf extract treatment. Blood urea and serum cholesterol increased (62.66 +/- 3.50 and 192.67 +/- 13.64 mg/dl) significantly in alloxan diabetic rats. The leaf extract treatment decreased the blood urea and serum cholesterol (37.83 +/- 3.97 and 99.20 +/- 8.43 mg/dl) to that of control ones. A similar effect was seen with insulin treatment. The results indicate that the active principle in A. marmelose leaf extract has similar hypoglycaemic activity to insulin treatment.

Intermediary metabolic changes in rabbits administered linamarin or potassium cyanide.

Since cassava (Manihot esculenta Crantz) is a staple food item of several million people in the tropics, its toxicity cannot be underestimated. Therefore an attempt has been made to understand the metabolic changes caused by the chronic administration of sublethal doses linamarin, the principal cyanoglucoside of cassava, to rabbits. A significant rise in lactic acid and total cholesterol in liver and brain and a highly significant depletion of phospholipids of brain tissue was observed. There were also significant variations in the lactate dehydrogenase isoenzyme pattern of treated animals as compared with the control rabbits. The findings suggest that some of the biological effects of linamarin are similar to those of free cyanide.

Pattern of enzyme changes in rabbits administered linamarin or potassium cyanide.

Diseases like tropical ataxic neuropathy and endemic goitre have been reported to have definite correlation with a chronic ingestion of cassava (Manihot esculenta Crantz). The toxicity of cassava has been attributed to its two cyanogenic glycosides, linamarin and lotaustralin. In this study, an attempt has been made to understand the pattern of changes in certain clinically significant enzymes brought about by the chronic administration of sublethal doses of linamarin to rabbits. The profound elevation in rhodanese activity observed in the linamarin and cyanide treated rabbits indicated the attempt of the tissues to detoxify cyanide. That intact linamarin could be hydrolysed in vivo was a significant finding from the study. The mode of toxicity of linamarin was similar to that of cyanide by producing a gradual shift from aerobic to anaerobic metabolism.