Gene therapy is a novel method of treating some of the hitherto untreatable diseases. It involves the introduction of a functional gene to replace the activity of a resident defective gene so that biologically active proteins can be synthesized within the cells whose function is to be altered. Introduced as a concept about 2 decades ago it has become a reality today. A variety of DNA delivery systems have been developed involving biological, physical and chemical agents. Gene therapy was initially thought to be a treatment modality for inherited single gene defects however it has also found applications in acquired diseases. It's use is being studied in the treatment of cancer, immunodeficiency diseases, cardiovascular, metabolic and neurological disorders; hormones and blood factors deficiencies. It is also being developed as a "gene" vaccine against influenza and malaria. Recently attempts have been made for its use in treatment of HIV infection. Gene therapy, although still in the infant stages of development offers the possibility for major advances in prevention and treatment of these diseases. Presently the clinical application of gene therapy is limited by the availability of suitable gene transfer methodology. This review describes some of these aspects of this new therapeutic modality.

Urinary excretion profile of total morphine (free and conjugated) was examined in human volunteers after acute administration. Six heroin dependent subjects received single intramuscular injection of 30 mg morphine following their detoxification. Serial urine specimens were collected before and al libitum for 48 h following administration of the drug. Morphine was assayed by thin layer chromatography (TLC) and densitometric methods. Peak concentration was observed within 5 h and the drug was detectable up to 12 h. Total morphine excreted by 12 h was about 61% of total dose. Detection limit of total morphine in our laboratory by the above techniques was 0.5 (glml. The TLC and densitometric techniques are simple, rapid and may be used for detecting morphine in heroin dependent subjects.

The present study was conducted to elucidate the role of a new, anti-diabetic, herbal drug D-400 on the regulation of glucose levels in blood and associated parameters in diabetic rats. Blood glucose levels were evaluated at the intervals of 1, 2 and 4 weeks. Treatment of diabetic rats with D-400 brought the raised glucose levels to within normal limits, Moreover, glycogen levels which were found to be suppressed in diabetic state also became significantly elevated following D-400 treatment. Above all, in vitro 14C- glucose uptake by liver slices which was significantly decreased In diabetic rats was also brought to within normal levels by D-400.

Decontamination of bis (2-chloroethyl) sulphide, commonly known as sulphur mustard (SM), from the skin is recommended as the best protection against its toxicity as there are no specific antidotes for SM. In the present study the decontamination efficacy of N,N'-dichloro-bis [2,4,6-trichlorophenyl] urea known as CC-2, was evaluated against SM, applied dermally. CC-2 was prepared as a formulation either in Fuller's earth (native aluminium silicate) or in white ointment USP in 20:80 ratio (w/w). 20 'l of SM (equivalent to 6 LD50) was applied on the back of mice after closely clipping the hair and then decontaminated with various agents viz., Fuller's earth alone, CC-2 Fuller's earth, ointment alone or CC-2 ointment, by smearing on the applied area and gently wiping it off (200 mg of the agent, twice). The animals were monitored for 14 days after decontamination. The decontamination efficacy was also evaluated with respect to time by decontaminating SM at various time intervals viz., 0.5, 2, 5, 10 or 20 min, after using various agents, following application of SM. The study showed that the decontamination efficacy was maximum with CC-2 Fuller's earth. The order of efficacy was CC-2 Fuller's earth > Fuller's earth alone > CC-2 ointment > ointmentalone = control. The study also showed that the decontamination efficacy is dependent upon the time. The order of efficacy was 0.5 > 2.0 > 5.0 = 10.0 = 20.0. Further CC-2 Fuller's earth and CC-2 ointment were found non-irritant based on rabbit primary skin irritation test.

Ursolic acid isolated from the leaves of Eucalyptus hybrid E. tereticomis showed a dose dependent (5-20 mg/kg) hepatoprotective activity (21-l 00%) in rats against thioacetamide, galactosamine and carbon tetrachloride induced hepatotoxicity in rats. These hepatotoxins decreased the viability of hepatocytes as assessed by trypan blue exclusion and rate of oxygen uptake tests and decreased the volume of bile as well as the level of its contents. Pretreatment with ursolic acid increased the viability of rat hepatocytes significantly. A potent dose dependent antlcholestatic activity was observed in conscious rat by noticing an increase in bile flow and its contents. Ursolic acid had comparable activity to that of silymarin.

Ketorolac and nefopam are two newly introduced non-steroidal non-narcotic analgesics. Their comparative analgesic efficacy is not known. Therefore this prospective double blind randomized clinical trial was conducted in 161 patients after single intravenous (I.V.) bolus dose of these two drugs for relieving acute post-operative pain following upper abdominal surgery. 100 patients received 30 mg ketorolac (group A) while 61 patients received 20 mg nefopam (group B). Both the groups were comparable in terms of age and sex. Pain assessment was done at frequent intervals upto 6 hrs using a 10 point visual analogue scale VAS). Simultaneously pulse and blood pressure were recorded. Pain intensity difference (PID) and total pain relief (TOTPAR) were calculated using standard formulae. PID curves suggested that group B patients had better analgesia for first 4 hrs but it worsened in the last 4 hrs. On the other hand, group A patients had progressive analgesia till 7 h which slightly decreased during last hour of the study. TOTPAR for the entire study period was significantly (p=0.002) greater in group B than group A. TOTPAR during first 4 hrs of study was also significantly (p=0.0001) greater in group B than group A. However, TOTPAR during last 4 hrs of study was significantly (p=0.001) greater in group A as compared to group B. Further, significantly (p=0.006) lesser number of patients in group A demanded second dose of analgesia at night as compared to group B. No drug related complications were seen, and pulse rate and mean arterial pressure remained within the normal limits in both groups. To conclude, 30 mg ketorolac provides progressively increasing and lasting pain relief compared to 20 mg nefopam when used as single I.V. bolus dose in immediate post-operative period following upper abdominal surgery. However, the reported side effects of ketorolac need caution during multi-dose therapy which itself may reveal a different picture of the analgesia achieved.

The short and long term effects of aluminium toxicity on brain catecholamine level was investigated. Rats were injected daily with varying amounts of aluminium and the contents of catecholamine in cerebellum, mid-brain and brain cortex was determined. The short term administration of aluminium (740 'mole/kg) did not have significant effect on catecholamine levels of cerebellum, mid-brain and brain cortex. Catecholamine levels of cerebellum, mid-brain and brain cortex were reduced by 5, 8 and 4 percent in intact male rats given daily dose of 74 'mole/kg of aluminium daily for 15 days. Administration of 74 'mole/kg aluminium for 30 and/or 60 days reduced catecholamine levels of cerebellum 11 to 19%, mid-brain 20 to 38% and brain - cortex 13 to 24% respectively. Examination of rats given higher dose of 185 'mole/kg aluminium daily for 15 and 30 days showed that catecholamine level of cerebellum decreased by 9 to 18%, mid-brain by 13 to 33% and brain cortex by 11 to 22% respectively. It might be concluded that brain disturbances in aluminium intoxified rat occurred through the reduction in the catecholamine levels.

A study to investigate the use of different extracts of the herb Centella asiaficain promoting wound healing on experimentally induced open wounds in albino rats was conducted. The extracts were applied externally daily on the excised areas on the back of the albino rats for 24 days and compared with control on the other side of the same animal. Aqueous, alcoholic, petroleum ether, chloroform, propylene glycol and glycosidal extract and aqueous extract with zinc oxide were tried. Only aqueous extract suspension in 5% propylene glycol favoured wound healing and the rest did not have any significant effect. The collagen content and the thickness of the epithelium are more in aqueous extract treated animals.

The present study describes the effect of methyl isocyanate (MIC) on the hepatic glycerol 3-phosphate shuttle. Addition of MIC to the isolated rat liver mitochondria in vitro resulted in a dose-dependent inhibition of glycerol 3-phosphate dehydrogenase. Subcutaneous ad-ministration of MIC at lethal dose to rats caused a significant effect on hepatic glycerol 3- phosphate shuttle. There was a significant inhibition of both mitochondrial and cytosolic glycerol 3-phosphate dehydrogenase indicating the impairment of translocation of the reducing equivalents, NADH into the mitochondria.

Effect of malathion, an organophosphate compound on plasma concentration of luteinizing hormone (LH) and testosterone (T4) was studied in adult male rats. A single s.c administration of malathion (23 mg/kg, 1/5Oth LD50 dose) significantly (P( 0.05) reduced plasmaconcentration of both LH and T4 at 24,36 and 48 h post-treatment. Prior administration of human chorionic gonadotrophins (hcG, 50 IU) for two days at 24 h interval protected the malathion induced hormonal changes. These results suggest that malathion induced inhibition of testicular steroidogenesis may be due to its cholinergic activity influencing central mechanisms involved in LH secretion and/or release.

The effects of isolation-rearing on the sensitivity of cholinergic receptors and passive avoidance behavior were studied to examine the activity of the central cholinergic system. Rat pups were weaned from mother on 15th day postpartum and thereafter isolated to adulthood. At three months of age the thermic response to three different doses of oxotremorine were measured. One day following oxotremorine challenge study, the animals were subjected to passive avoidance training and retention was measured 24-hr later. Isolated animals exhibited an enhanced cholinomimetic-induced hypothermia and an increased latency in passive avoidance test which may reflect an altered sensitivity of central cholinegic system in isolated animals. The possible involvement of an interaction between cholinergic and monoaminergic system in isolated animals are discussed.

An aqueous suspension of a herbal drug formulation (UL-409) was tested in male Wistar rats for antiulcerogenic activity. The drug formulation displayed cytoprotective action against experimentally induced peptic ulcer. A daily dose of 600 mg/kg body weight of the formulation orally for 30 days decreased the number of ulcerative lesions, prevented the increased lipid peroxidation and enhanced the activities of antioxidant enzymes namely, superoxide dismutase, catalase and glutathione peroxidase along with the reduction in the consumption of glutathione. Since UL-409 reduced the damage caused by HCl/ethanol and increased the activities of scavenging enzymes, it is concluded that its antiulcerogenic activity is mediated through antioxidant defense mechanism.