The medicinal value of venoms has been known from ancient times. The active principles in venoms have been extensively investigated for their target specificity. Affinity for the primary sites responsible for lethality and efficacy at extremely low concentrations made these agents valuable tools or surrogates for basic biomedical research. The therapeutic effects of these agents are usually achieved by mechanisms that are different from that of conventional therapeutic agents. In the present paper, nonherbal natural therapeutic alternatives approved by the FDA, those that have undergone extensive clinical evaluation and shown promise in preclinical evaluation, or those that are isolated in pure form or subjected for the treatment to venoms are reviewed. These agents are suggested for the treatment of various diseases, including inflammatory, hematological, autoimmune, infectious, cardiovascular, malignant, neuromuscular, and psychotic diseases.

Objectives: The present study was planned to explore the genotoxicity of morphine, buprenorphine, pentazocine, and noscapine. Materials and Methods: Bone marrow micronucleus assay and single cell gel electrophoresis assay were employed after 24 h (single dose) and 72 h (three doses) of treatment with clinically equivalent doses of opioids in albino mice. Percentage of micronucleated polychromatic erythrocytes and comet tail length were determined and the results were analyzed by one-way ANOVA and Student's 't' test. Results: Only morphine and noscapine showed significant (P < 0.01) increase in both the number of micronucleated polychromatic erythrocytes and comet tail lengths in acute (24-h) as well as subacute (72-h) studies. Conclusions: These results clearly indicate the genotoxic potential of morphine and noscapine at the clinically equivalent doses.

Objective: Aging is a continuous and intrinsic process of systems deterioration with time. Although the mean prevalence of tardive dyskinesia (TD), a neurological disorder associated with chronic haloperidol administration, is 20-25%, the cumulative rate of this disorder increases significantly in patients aged 55 years or more. The present study investigated the effect of aging on spontaneous development of orofacial dyskinesia and tried to find out the interactive substrate which is activated by chronic neuroleptic treatment and results in premature emergence of TD in adult animals. Materials and Methods: Various behavioral (orofacial dyskinetic movements, stereotypy, locomotor activity, and percent retention); biochemical (lipid peroxidation, reduced glutathione levels, and antioxidant enzyme levels: SOD and catalase); and neurochemical (neurotransmitter levels) parameters were assessed in young (60-80 gm), matured adult (180-200 gm), and aged (380-400 gm) rats. Results: Aging resulted in significant increase in hyperkinetic motor activities, vacuous chewing movements (VCMs), tongue protrusions, facial jerking, and development of dopamine supersensitivity (increased locomotor activity and stereotypy); there was also associated oxidative damage in all regions of the brain. The extracellular dopamine levels were also significantly decreased (45%) in the forebrain of aged animals. Chronic administration of haloperidol to aged animals further significantly increased all the parameters as compared to age-matched control animals. Chronic administration of haloperidol to matured adult animals showed similar changes, especially hyperkinetic movements, and oxidative damage in different parts of the brain. There was no significant change in young animals on chronic administration of haloperidol. Conclusion: The findings of the present study suggest that free radical generation and development of dopamine supersensitivity are the prime interactive substrates that are activated by chronic neuroleptic treatment in matured animals and are responsible for the development of TD, whereas these paradigms are increased with aging and result in spontaneous orofacial hyperkinetic movements.

Background: Different factors are involved in the induction and progress of atherosclerosis. One of these factors is endothelin-1. Since, in atherosclerotic vessels, there are certain obvious changes, with abnormality in the transfer of calcium ions, some researchers have suggested that calcium channel blockers can slow down the process of atherosclerosis. In this study, we evaluated the effects of amlodipine and/or a high cholesterol diet on the blood and aortic concentration of endothelin in rabbits. Materials and Methods: Thirty-six male New Zealand white rabbits were divided into four groups: the normal control group, normal diet plus amlodipine group, high-cholesterol diet group, and high-cholesterol diet plus amlodipine group. After 8 weeks all animals were anesthetized and blood or tissue samples were collected. Results and Conclusions: Eight weeks of amlodipine treatment significantly reduced total cholesterol, low density lipoproteins (LDL), and triglycerides (TG) in the hypercholesterolemic diet group. Although amlodipine treatment tended to enhance HDL/LDL and HDL/cholesterol ratios in the mentioned group, these effects were not statistically significant. The observed significant increase in plasma high density lipoprotein cholesterol (HDL-C) and decrease in TG is considered to be the main effect of amlodipine treatment on the serum lipid profile in the control group. The plasma level of endothelin-1 in the atherosclerotic model group was significantly increased as compared to the control group ( P < 0.01). After treatment with amlodipine, the ET-1 level reduced significantly in the control and high-cholesterol diet rabbits ( P < 0.01). A high-cholesterol diet induced atherosclerotic lesions and thickening of the intima in the thoracic aorta. Amlodipine consumption reduced atherotic injuries in high-cholesterol diet rabbits. There were no lesions in the normal diet groups or the normal diet with amlodipine group. High cholesterol causes increase in plasma and tissue endothelin. Amlodipine treatment reduced the levels of total cholesterol, LDL, and TG and, in a high lipid intake situation reduced endothelin levels in plasma and aortic tissue. Our data shows that amlodipine treatment may be considered as one of the important interventions for prevention and regression of atherosclerosis.

Objectives: The antioxidant potential of gossypin and nevadensin, two flavonoid compounds, were evaluated by in vitro methods. Materials and Methods: Gossypin, nevadensin, and the reference standard, butylated hydroxyl toluene (BHT), were evaluated for DPPH (1, 1-diphenyl-2-picrylhydrazyl), nitric oxide, superoxide, and hydroxyl radical scavenging activity. Results: Gossypin and BHT showed the potential for significant DPPH radical inhibition of up to 88.52 and 91.45% at 100 µg/ml concentration. With a 100 µg/ml concentration of gossypin, the in vitro nitric oxide, superoxide, and hydroxyl radical scavenging activity was found to be 74.00, 74.22, and 67.15%, respectively; and with 100 µg/ml of BHT the corresponding values were 82.24, 81.76, and 73.03% of inhibition, respectively. Conclusion: The study results showed that gossypin has significant antioxidant activity.

Objectives: To investigate the gastrointestinal tract (GIT) permeability of five nucleoside analogue reverse transcriptase inhibitors (NRTIs), viz., zidovudine, stavudine, abacavir sulphate, lamivudine and didanosine, individually and in the presence of rifampicin in rats by ligated-loop technique. Materials and Methods: The permeability studies were carried out on Sprague-Dawley rats in the weight range of 240-260 g. The drug contents were estimated by a validated gradient HPLC method. Degradation and solubility studies were also carried out on the drugs, alone and in combination, to correlate with the results of in situ experiments. Results: The results showed that rifampicin was better absorbed from stomach and duodenum; zidovudine was moderately absorbed throughout GIT; stavudine and lamivudine were absorbed better through the intestine; abacavir was well absorbed through duodenum; and didanosine completely disappeared through stomach and was absorbed moderately from proximal parts of the intestine. In drug combinations, NRTIs did not influence permeability/absorption of rifampicin and vice versa. The disappearance of didanosine through stomach could be ascribed to decomposition of the drug at pH 2. Conclusion: The study reaffirms that rifampicin and NRTIs do not influence gastrointestinal permeability of each other.

Objectives: To investigate the effects of meloxicam and rofecoxib on psychomotor performance in young, healthy volunteers. Materials and Methods: This study was conducted in Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq in 2003. Twelve healthy, young males were allocated randomly from college students and participated in a balanced one-period cross-over investigation, with each period separated by a 7-day washed-out period. Participants were asked to perform psychomotor performance (choice reaction time and critical flicker-fusion threshold tests) before and after 2 h of receiving single oral dose of either meloxicam (7.5 mg) or rofecoxib (25 mg). Results: Meloxicam and rofecoxib were statistically significant, differing from placebo in reducing motor and recognition reaction times, respectively, of the objective test used. Both drugs were not significantly different from placebo in critical flicker-fusion frequency thresholds. Conclusion: These results allow the conclusion that the effects of preferential (meloxicam) and highly selective (rofecoxib) cyclo-oxygenase-2 inhibitors showed central effect by improving psychomotor performance, but in different directions.

Objectives: Cardiovascular disease (CVD) is associated with a generalized atherosclerotic process that begins in the large arteries, representing vascular pathology leading to increased cardiovascular morbidity and mortality. Pulse wave velocity (PWV) is a simple, accurate, reproducible and a good prognostic marker of arterial stiffness. Testing arterial stiffness with non-invasive techniques provides an opportunity to evaluate large patient populations with cardiovascular risk. Therefore, the aim of the present study was to evaluate non-invasively the arterial stiffness (AS) in patients with high cardiovascular risk. Materials and Methods: Totally 3969 subjects [CAD - 845, DM - 973, ESRD - 942, RA - 221 and 988 age-matched healthy controls] were enrolled in the study approved by the IEC, NIMS; and all the subjects gave written informed consent to participate. Pulse wave velocity was determined non-invasively by PeriScope (M/S Genesis Medical Systems, Hyderabad, India). Results: In patients with CAD, DM, ESRD and RA, heart rate (HR), blood pressure (BP) and PP were significantly more than healthy controls. Peripheral and central arteries' PWVs were higher in these patients' group. The mean HR was maximum in RA patient, while systolic blood pressure (SBP) was highest in ESRD patient. There was a good correlation between ba PWV and PP in all patients' group and healthy controls except RA patients. Conclusion: Our study findings emphasize the importance of the PWV in identifying the vascular damage in patients with high CV risk. Increased PWV was found to be a good independent predictor of cardiovascular morbidity.

Objectives: To study the serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone-induced hyperlipidemia and insulin resistance in rats. Materials and Methods: Serum glucose and triglyceride lowering activity of the test compounds and a standard, rosiglitazone, was tested at a dose of 10 mg/kg p.o. against dexamethasone-induced hyperlipidemia and insulin resistance in Sprague-Dawley (SD) rats. On day 11 of treatment, blood was collected for the estimation of serum glucose and triglyceride levels. Results: All the 14 compounds and rosiglitazone significantly ( P < 0.05) decreased dexamethasone-induced elevation of serum glucose when compared to dexamethasone-alone-treated group. Among these compounds, compound 10 showed better antihyperglycemic activity than rosiglitazone. Compounds 7, 8 and 9 have shown significant ( P < 0.05) serum triglyceride lowering activity than did rosiglitazone. Out of the 14 compounds tested, only compounds 7, 8 and 9 have shown both serum glucose and triglyceride lowering activity. Conclusion: The present study indicates that some of the newer glitazones show significant glucose and triglyceride lowering activity. In comparison to rosiglitazone, these glitazones show comparable serum glucose lowering and better triglyceride lowering activity.