Showing papers in "Indian Journal of Pharmacology in 2000"

Pharmacology of medicinal plants and natural products

Abstract: time, probably by stimulation of the hepatic microsomal enzyme system3. Similar properties were exhibited by its roots. However, the petroleum ether extract (PEE) of the roots enhanced pentobarbitone sleeping time, probably due to CNS depression4. The PEE of the seed of Pongomia pinnata was further tested for nootropic activity in an experimental model of Alzheimer’s disease (created by ibotenic acid induced lesioning of nuclear basalis magnocellularis). It reversed both, the cognitive deficits and the reduction in cholinergic markers after 2 weeks of treatment. Reversal of perturbed cholinergic function appears to be the possible mechanism5.

Analgesic and antipyretic activities of Dalbergia sissoo leaves

Abstract: Objective: To evaluate the analgesic and antipyretic activities of alcoholic extract of Dalbergia sissoo leaves. Methods: The peripheral analgesic activity of Dalbergia sissoo leaves (SLE; 100, 300 and 1000 mg/kg) was studied using acetic acid induced writhing in mice and by Randall-Selitto assay. The central analgesic activity of SLE was studied using hot-plate method and tail clip test in mice. The antipyretic activity of SLE was studied in Brewer's yeast-induced pyrexia in rats. Results: SLE significantly decreased the writhing movements in mice in acetic acid-induced writhing test. SLE (1000 mg/kg) significantly increased the pain threshold capacity in rats in Randall-Selitto assay and the reaction time in hot-plate test but not in tail-clip test. It also showed significant antipyretic activity in Brewer's yeast-induced pyrexia in rats throughout the observation period of 6 h. Conclusion: SLE may have analgesic and antipyretic activities.

Identification and quantification of some potentially antimicrobial anionic components in miswak extract.

Abstract: Objective: To identify and quantify some potential antimicrobial anionic components in Salvadora persica root and stem aqueous extracts. Methods: Extraction of powdered root and stem samples was performed by soaking the powder in sterile deionised distilled water for 24 h at 4o C. Each 100mg of the freeze-dried extract was reconstituted with 10 ml deionised distilled water and filtered through a 0.45 (m cellulose acetate filter. The anionic components of the filtered extracts were identified and quantified by capillary electrophoresis. Results: The root and stem extracts contained chloride, sulphate, thiocyanate and nitrate in the following concentrations (w/w %) in stem and root extracts, respectively: 6.84% and 4.64%, 20.1% and 19.85%, 0.38 and 0.28%, and 0.05% and 0.05%. Only the differences in chloride were statistically significant (p< 0.05). Conclusion: S. persica contains potential antimicrobial anionic components and that capillary electrophoresis is a convenient method for their identification and quantification.

Assessment of the anti-inflammatory effects of Swertia chirata in acute and chronic experimental models in male albino rats

Abstract: Objectives: To study the anti-inflammatory effect of xanthone derivative (1,5-dihydroxy-3,8-dimethoxy xanthone) of Swertia chirata (SC-I) in acute, sub-acute and chronic experimental models in male albino rats. Methods: Aerial parts of Swertia chirata were extracted with organic solvent and purified by chromatographic procedure. SC-I was studied in carrageenin-induced hind paw oedema in rats and the paw volume was measured plethysmometrically at 0 and 3 h after injection. The compound was subjected to turpentine oil-induced granuloma pouch in rats. The pouch was opened on day 7 under anaesthesia and the exudate collected by a syringe was measured. The drug was also investigated in formalin-induced oedema models in rats. Degree of inflammation was measured plethysmometrically on day 1 and 7 and compared with control and standard drug, diclofenac. All the drugs were administered orally. Results: The higher dose of SC-I significantly reduced carrageenin-induced pedal oedema (57%) and formalin-induced pedal oedema in rats (58%). SC-I also decreased exudate volume (35%) in turpentine oil-induced granuloma formation in comparison to control. Conclusion: 1,5-dihydroxy-3,8-dimethoxy xanthone of Swertia chirata showed significant anti-inflammatory action in acute, sub-acute and chronic experimental models in rats.

Aphrodisiac activity of Vanda tessellata (Roxb.) Hook. ex Don extract in male mice.

Abstract: Objective: To study the effect of V. tessellata on the sexual behaviour of male mice and general toxicity, if any, in mice. Methods: An aqueous suspension (2 g/kg, wet wt.) or extract (water or alcohol, 200 mg/kg) of root, flower or leaf of V. tessellata was administered ( p.o.) to male mice and 1 hr, after administration their mounting behaviour was observed. The most active extract (alcohol extract of flower) was administered (50 or 200 mg/kg, p.o.) to different groups of male mice and their mounting behaviour, mating performance and reproductive performance were determined. The general short term toxicity of the alcohol extract in male mice was also determined. Results: The flower and, to some extent, the root, but not the leaf of V. tessellata was found to stimulate the mounting behaviour of male mice. This activity was found in the alcohol extract of the flower. This extract (50 or 200 mg/kg) also increased mating performance in the mice. The pups fathered by the extract treated mice were found to be normal with an increasing trend in the male/female ratio of these pups. The alcohol extract was devoid of any conspicuous general toxicity. Conclusion: The alcohol extract of V. tessellata flower stimulates the sexual behaviour of male mice.

Probucol protects against gentamicin-induced nephrotoxicity in rats

Abstract: Objective: To investigate the effect of probucol on gentamicin-induced nephrotoxicity in rats Methods: Male Wistar rats were divided into 4 groups; normal saline, gentamicin 80 mg/kg, ip, intraperitoneally for 8 days, probucol 10 mg/kg, po, for 11 days, probucol 3 days and concurrently with gentamicin for 8 days Blood urea, serum creatinine, plasma malondialdehyde (MDA), creatinine clearance, urinary sodium, potassium and microscopic examination of kidney were performed after the treatment Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in blood urea and serum creatinine Blood urea and serum creatinine were increased by 963% and 462% respectively with gentamicin compared to saline-treated animals Co-administration of probucol with gentamicin decreased the rise in blood urea and serum creatinine Creatinine clearance (Ccr) was significantly decreased by 89% with gentamicin compared to control Treatment with probucol improved Ccr by 24% compared to gentamicin treated group There was a 177% rise in lipid peroxidation products (MDA) with gentamicin than control, which was significantly reduced by 44% with probucol Study of renal morphology by light microscope showed epithelial loss with intense granular degeneration involving >50% renal cortex in gentamicin treated rats, whereas in probucol plus gentamicin treated rat revealed insignificant changes in tubular epithelium Conclusion: Our data suggest that supplementation of probucol may be useful in reducing gentamicin nephrotoxicity in rats

Antiinflammatory activity of Curcuma amada Roxb. in albino rats

Abstract: Objectives: To study the antiinflammatory activity of Curcuma amada rhizome extract in albino rats. Methods: Rhizomes of Curcuma amada were extracted and subjected to spectroscopic studies. The extract was screened for antiinflammatory activity in albino rats using acute carrageenan paw oedema and chronic granuloma pouch model. Results: The extract showed presence of chemical compounds with hydroxyl, ester, carbonyl and olefin funtionalities and exhibited dose dependant antiinflammatory activity in acute and chronic models. Conclusions: The extract of Curcuma amada rhizomes showed antiinflammatory activity in acute and chronic administration in albino rats. Curcuma amada albino rats antiinflammatory activity SUMMARY

Hepatoprotective and toxicological evaluation of Andrographis paniculata on severe liver damage

Abstract: Objectives: To study the hepatoprotective effect of aqueous extract of Andrographis paniculata (AP) on hexachlorocyclohexane (BHC) induced severe liver damage in Swiss male mice. Methods: The aqueous extract of Andrographis paniculata was given orally to the animals with liver damage induced by hexachlorocyclohexane (BHC). The hepatoprotective activity was monitored by estimating serum ALT & AST and other parameters like alkaline phosphatase, (-Glutamyl transpeptidase, glutathione and lipid peroxidase. Results: Aqueous extract of Andrographis paniculata inhibited BHC induced liver toxicity in Swiss male mice as assessed by the biochemical values. Conclusions: Aqueous extract of Andrographis paniculata has significant hepatoprotective activity.

Hypolipidemic effect of fenugreek: A clinical study

Abstract: Objective: To investigate the hypolipidemic effect of fenugreek in hypercholesterolaemic patients. Methods: Fenugreek ( Trigonella foenum graecum) seeds (FG) were powdered and extracted with hexane to remove its lipid content and alcohol to remove the saponins. This powder was used for the study. The patients were divided into 3 groups of 6 each as follows: Group I received placebo 50 gm (rice powder and Bengal gram powder in equal measures); Group II -placebo 25 gm + FG 25 gm and Group III -FG 50 gm. Patients were directed to take each 50 gm pack orally before lunch and dinner every day for 20 days. Blood samples were collected after overnight fasting on 0, 10th and 20th days during test period and estimated for lipid profile. Results: There were no significant changes in lipid profile of group I patients. In groups II and III serum cholesterol, triglycerides and VLDL levels were significantly decreased when compared to group I. Conclusion: FG powder given orally before food at 25 and 50 gm twice a day may have hypolipidemic effect in hypercholesterolaemic patients.

Protective Effect of Abana, a Poly-herbal Formulation, on Isoproterenol- induced Myocardial Infarction in Rats

Abstract: SUMMARY Objective: To find out the possible role of lipid peroxidation and glutathione in the pathogenesis of myocardial infarction and the protective role of Abana, a polyherbal drug. Methods: The effect of Abana pretreatment (75 mg/100 g) for a period of 60 days on isoproterenol (20 mg/100 g s.c. twice at an interval of 24 hrs) induced lipid peroxidation was studied in rats. Marker enzymes levels such as creatinine kinase, lactate dehydrogenase, alanine transaminase and aspartate transaminase were assessed in serum and heart homogenate. Glutathione content and lipid peroxide levels were also estimated. Results: In isoproterenol administered rats, a significant decrease was observed in the levels of marker enzymes in the heart with a corresponding increase in their levels in serum. Lipid peroxide level measured in terms of “TBA reactants” increased significantly in serum and heart. In rats pretreated with Abana, the alterations observed in the marker enzymes and lipid peroxide level were minimum on isoproterenol administration, and the levels were retained at near normal values. Conclusion: Abana pretreatment may offer protection in experimental myocardial infarction induced by isoproterenol.

Anti-inflammatory activity of Heliotropium indicum Linn and Leucas aspera spreng. in albino rats

Abstract: Objective: To study the anti-inflammatory effect of Heliotropium indicum, and Leucas aspera on carrageenin induced hind paw oedema and cotton pellet granuloma in rats. Methods: Hind paw oedema was produced by subplantar injection of carrageenin and paw volume was measured plethysmometrically at '0' and '3' hours intervals after injection. Cotton pellet granuloma was produced by implantation of 50 ( 1 mg sterile cotton in each axilla under ether anaesthesia. The animals were treated with H. indicum and L. aspera and the standard drugs viz., acetylsalicylic acid and phenylbutazone. Results: H. indicum and L. aspera produced significant anti-inflammatory effect in both acute and subacute models of inflammation. In acute inflammation, L. aspera was more effective than acetylsalicylic acid. However in subacute inflammation, these two drugs were found to be less effective than phenylbutazone. Conclusion: H. indicum and L. aspera possess anti-inflammatory effects in both acute and subacute inflammation.

Anti-cataleptic, anti-anxiety and anti-depressant activity of gold preparations used in Indian systems of medicine

Abstract: Objectives: To study traditional gold preparations for anti-cataleptic, anti-anxiety and anti-depressant effects. Methods: Swarna Bhasma used in Ayurveda, Kushta Tila Kalan used in Unani-Tibb and Auranofin used in modern medicine were subjected to videopath analyzer, vogel conflict/anxiometer, elevated plus maze, and social behavioural deficit tests for anxiolytic activity, behavioural despair and learned helplessness tests for antidepressant activity, haloperidol-induced catalepsy tests for neuroleptic activity, and maximum tolerated dose, gross behavioural observations and hematological parameters for safety evaluation in rats and mice. Results: The test drugs caused significant increase in punished drinking episodes in anxiometer and open arm entries and time in elevated plus maze and decrease in behavioural deficit. A decrease in immobility time in forced swimming test, normalization of shock induced escape failures in learned helplessness test, and reduction of haloperidol-induced catalepsy scores were also noted in treated animals. The maximum tolerated doses were found to be more than 80 times the effective doses and no weight loss or untoward effects were observed on gross behaviour and hematological parameters. Conclusions: Traditional gold preparations used in Ayurveda and Unani-Tibb exhibited anxiolytic, antidepressant and anticataleptic actions with wide margin of safety.

Antidotes to cyanide poisoning: present status

Abstract: Cyanide is ubiquitously present in the environment. It is considered as a potent suicidal, homicidal, genocidal and chemical warfare agent. Cyanide toxicity is mediated through inhibition of cellular respiration, but its other complex toxic manifestations are also well documented. There are a number of antidotes available for cyanide poisoning ( e.g. sodium nitrite, 4-dimethyl aminophenol, sodium thiosulphate, etc.), however, there is still uncertainty about their safety, efficacy and correct indication for use. This review provides a comprehensive account of toxicology of cyanide and the present status of various antidotes employed clinically or pursued experimentally.

Antiobesity effect of a polyherbal formulation, OB-200G in female rats fed on cafeteria and atherogenic diets.

Abstract: Objective: To study the antiobesity effect of OB-200G, a polyherbal formulation in female Wistar rats fed on cafeteria and atherogenic diets. Methods: Female rats were fed cafeteria diet (highly palatable, energy rich animal diet that includes a variety of human snack foods) and atherogenic diet for 40 days. OB-200G was administered in a dose of 400 mg/kg, p.o., twice a day to the drug treatment groups. The effect of OB-200G on following parameters was recorded - body weight, rectal temperature, locomotor activity and various biochemical parameters like serum glucose, total cholesterol and triglyceride levels. Results: There was a significant (p < 0.05) reduction in body weight, increase in body temperature, locomotor activity and serum glucose levels after treatment with OB-200G in cafeteria diet and atherogenic diet fed rats. Treatment with OB-200G also significantly (p < 0.05) decreased total cholesterol in rats fed with atherogenic diet. Conclusion: OB-200G, a polyherbal formulation exhibited antiobesity effect in cafeteria and atherogenic diet fed rats.

Antiulcer effect of shankha bhasma in rats: a preliminary study

Abstract: Objective: To investigate the anti-peptic ulcer effect of Shankha bhasma (conch shell ash) in rats. Methods: Gastric ulcers were induced in rats by indomethacin and cold restraint stress, and the effect of two different doses of Shankha bhasma was studied. The response of the bhasma on ulcer index, lipid peroxidation (thiobarbituric acid reacting substances TBARS) in gastric tissue and serum calcium was determined. Results: Shankha bhasma caused significant reduction in ulcer index (P<0.001) in both the indomethacin and cold restraint models. TBARS of stomach in indomethacin treated rat was also reduced (P<0.001) by Shankha bhasma but serum calcium level was not altered. Conclusion: Shankha bhasma induced dose dependent protection against experimental gastric ulcers.

Effects of gingko biloba extract on ethanol-induced gastric mucosal lesions in rats

Abstract: Objective: To investigate the effect of Gingko biloba extract (Gbe) on ethanol induced gastric mucosal lesions in rats. Methods: Male Wistar rats used in the study were divided into 3 groups and fasted for 24 hours; Group one received oral normal saline and served as control; group two received 1.0ml of 80% ethanol orally and group three received Gbe (300 mg/kg) orally 1 hour before ethanol (80%, 1.0 ml) administration. Results: Ethanol treated rats showed marked gross mucosal lesions in the stomach and these were characterized by multiple red bands (patches). Histologically, ethanol treated rats showed ulcerated mucosa with marked mucosal haemorrhage and destruction of glandular elements. Pretreatment with Gbe showed protection against ethanol-induced gastric mucosal damage. Conclusion: Our data suggests that supplementation of Gbe may be useful in preventing the ethanol-induced gastric ulcers.

An appraisal of the healing profiles of oral and external (GEL) metronidazole on partial thickness burn wounds

Abstract: Objective: To assess the influence of oral and topical (gel) metronidazole on partial thickness thermal burn wound healing. Methods: Partial thickness burn wounds were produced on dorsum of rats by pouring hot molten wax at 80oC. Oral and two topical gel (MGEL-1and MGEL-2) preparations of metronidazole or their corresponding vehicles were administered to different groups of wound bearing animals. The effects of the treatments were compared by periodically observing wound contraction and epithelization and histological features as indicative of the progress of healing. Results: Healing of burn wounds was significantly promoted by oral metronidazole (p<0.01) and the gel base of MGEL-2. In contrast, the MGEL-1 significantly (p<0.05) depressed the epithelization process while its base was without effect, indicating that topical metronidazole retards healing. The effect of MGEL-2 appeared to be an algebraic sum of pro- and anti-healing effects of the base and drug respectively more in favour of the base (p<0.05). Conclusion: Metronidazole orally promotes but topically depresses healing of burn wounds. The latter effect can be reversed if the base has pro-healing property.

Thermosensitive liposomes and localised hyperthermia - an effective bimodality approach for tumour management

Abstract: Objectives: To entrap methotrexate (MTX) in thermosensitive liposomes, to characterise liposomes for different physicochemical properties and to investigate the potential of liposome entrapped MTX and localised hyperthermia (HT) in management of melanoma B16F1. Methods: Thermosensitive liposomes, made of synthetic lipids (distearoylphosphatidylcholine, DSPC and dipalmitoyl phosphatidyl choline, DPPC) showing gel to liquid phase transition at 41o C, were used for encapsulation of methotrexate. The liposomes were prepared by reverse phase evaporation method. The entrapment efficiency of the drug within the liposomes was determined by gel filtration on Sephadex G-50 column. The in vitro release studies of the vesicles were conducted by incubating the drug encapsulated liposomes in saline at various temperatures for 15 min. The vesicle stability was assessed by storage at room temperature, 37o C and under refrigeration (4o C) for a period of three months. The MTX containing liposomes were administered intravenously to C57BL/6J mice bearing melanoma B16F1 tumour at 12 mg kg-1 dose. Immediately after the drug administration, localised hyperthermia treatment was applied by placing the tumours in water bath at 43o C either for 30 min. or 1 hr. The volume doubling time and growth delay of the tumour were taken as parameters to assess the antitumour efficacy. Results: The thermosensitive liposomes encapsulated about 52% of the MTX. Comparison of the drug release profile at various temperatures revealed that maximum drug release (83%) occurred at 42o C compared to less than 5% release at 37o C. Better stability on storage was also observed with thermosensitive MTX liposomes. The thermosensitive liposomes and localised hyperthermia produced an improved anticancer activity as evident by enhanced volume doubling time and growth delay. Conclusion: These results suggest that localised hyperthermia in combination with temperature sensitive liposome encapsulated MTX may serve as a useful targeted drug delivery system for more effective management of melanoma B16F1.

Anti-fertility activity of the stem bark of Alangium Salviifolium (Linn.F) wang in Wister female rats

Abstract: The family Alangiaceae consists of twenty-two species out of which Alangium salviifolium (Linn.f) Wang is mainly used as medicine in India, China and Phillipines1. Different parts of this plant are reported to possess acrid, astringent, emollient, anthelmintic, diuretic and purgative properties. It is also used externally in acute case of rheumatism, leprosy and inflammation. Applied externally and internally in case of rabid dog bite. Root bark is an antidote for several poisons. Fruits are sweet, cooling and purgative and used as a poultice for treating burning sensation and haemorrhage2. The leaves are used as a poultice in rheumatism. Interviews with villagers in different parts of Tamilnadu revealed that, stem bark of this plant is used both as contraceptive and abortifacient. This plant is said to suppress the sexual desire of male dogs. Hence the present study was carried out to validate scientifically the claimed antifertility activity of stem bark of this plant.

Modulatory effects of nifedipine and nimodipine in experimental convulsions

Abstract: Objectives : To investigate the effect of nifedipine and nimodipine on acute [maximal electroshock and pentylenetetrazol (PTZ) induced convulsions in rats] and chronic (pentylenetetrazol induced kindling in rats and mice) models of epilepsy. Methods: The maximal seizure pattern was induced in animals by giving an alternating current of 150 mA for 0.2 secs, while tonic clonic seizures were seen with 50 mg/kg i.p. dose of PTZ. Test drugs were administered 30 min before electrical or chemical induction. The ability of test drug to abolish/reduce tonic hind limb extensor component in MES group and jerky movements and clonic seizures in PTZ group was selected as antiepileptic criteria. Kindling was established in mice with PTZ in subconvulsive dose (30 mg/kg i.p.) thrice a week for nine weeks and effect observed for 15 min using 4 point scoring system. Rechallenge with same dose on 3rd and 10th day showed that kindling was established. Calcium channel blockers were then administered prior to convulsions and effects observed. Results : In acute studies, both nifedipine and nimodipine decreased the duration of tonic hind limb extensor phase in maximal electroshock seizures while in PTZ (50 mg/kg) treated animals, both drugs significantly decreased the duration of clonic convulsions, only nifedipine increased the latent period while nimodipine did not affect the latent period. The protective effect with nifedipine was significant (p<0.05) at 10 mg/kg while with nimodipine at 5 mg/kg dose. In chronic studies, nifedipine (2 mg/kg) given prophylactically in PTZ (30 mg/kg thrice weekly for 9 weeks) kindled rats and mice significantly (p<0.05) reduced the convulsive score in both the animals, however, the pattern of response was different. No significant effect on kindling was observed with nimodipine. Conclusions :The results with acute studies suggest that both nifedipine and nimodipine, the calcium channel blockers, possess anticonvulsant activity. Chronic studies showed anticonvulsant profile only with nifedipine and better response observed in mice as compared to rats.

Antibacterial activity of Holarrhena Antidysenterica [Kurchi] against the enteric pathogens

Abstract: The present study was undertaken to find the antibacterial activity of the crude aqueous and alcoholic extracts of stem bark of Holarrhena antidysenterica against the known enteric pathogens. Holarrhena is a genus of trees or shrubs distributed throughout the tropical and subtropical regions of the world. It is a small deciduous tree with white flowers and found throughout the dry forests of India even as far as as Travancore1. The different parts of the plant were used since antiquity in the indegenous system of medicine. As far as our knowledge goes, antibacterial activity of H. antidysenterica against the enteric pathogens has not been reported from India .

Effect of fish oil on cigarette smoking induced dyslipidemia in rats

Abstract: Objective: To evaluate the effect of fish oil, on experimental animals exposed to cigarette smoke. Methods: Fish oil was administered orally to male albino rats at a dosage of 0.5 ml/kg b.wt/day to study the effect of fish oil in cigarette smoke exposed animals. During the experimental period ( i.e. 30 or 90 days) the animals were exposed to cigarette smoke for a period of 2 hr/day. At the end of 30 or 90 days the animals were sacrificed, serum was separated and tissues (heart and lungs) were used for the lipid extraction to analyse the biochemical parameters such as total cholesterol, triglycerides, free fatty acids, phospholipids and MDA levels. Results: Animals exposed to cigarette smoke for 30 or 90 days, resulted in the elevated levels of cholesterol and triglycerides in serum and tissues. No significant change was observed in the levels of free fatty acids in both 30 or 90 days of all four groups. The levels of phospholipid was found to be significantly decreased in serum and tissues of the experimental rats after smoke exposure. The above changes were prevented with simultaneous supplementation of fish oil in 30 or 90 days co-treatment. Conclusion: Administration of fish oil may prevent the cigarette smoke induced dyslipidemia in rats.

Investigation into the pharmacological basis for some of the folkloric uses of Bonny light crude oil in Nigeria

Abstract: Objective: The effects of Bonny light crude oil on the smooth and skeletal muscles contraction and pain were investigated. Methods: Analgesic effect of Bonny light crude oil was tested in mice using acetic acid (0.75%)- induced writhing model. Its effects on histamine-, and Ach-induced smooth muscle contraction were studied in guinea pig ileum. The effects of crude oil on Ach-induced contraction of rat duodenum and frog rectus abdominis muscle were also studied. Results: The crude oil caused complete inhibition of histamine - induced smooth muscle contraction, while producing only a partial inhibition of the acetylcholine - induced contraction. It had no effects on the acetylcholine-induced skeletal muscle contraction, but showed good analgesic effect comparable to aspirin. Conclusion: The Bonny light crude oil possesses inhibitory action on smooth muscle contraction induced by histamine, and analgesic property.

Effect of Trichopus zeylanicus Gaertn (active fraction) on phagocytosis by peritoneal macrophages and humoral immune response in mice.

Abstract: Objectives: To evaluate whether Trichopus zeylanicus (active fraction) influences (1) phagocytosis by mice peritoneal macrophages (2) antibody dependent complement mediated cytotoxicity to Ehrlichs ascitic carcinoma (EAC) cells and (3) humoral antibody response in mice. Methods: Phagocytosis of opsonized sheep RBC by peritoneal macrophages obtained from control or T. zeylanicus (active fraction) treated (10-40 mg/kg, daily, p.o., 5 days) mice was determined. The in vitro effect of the drug on macrophage phagocytosis was also studied. The effect of the drug on antibody dependent and complement mediated toxicity (ACC) to EAC cells was carried out using antiserum obtained from drug treated ( p.o., daily for 5 days) mice which were challenged with or without EAC cells. The effect of the drug on humoral immune response in mice was studied by measuring haemagglutination antibody titre and Jerne's plaque forming assay using sheep RBC as antigens. Results: The drug treatment to mice resulted in stimulation of phagocytosis by peritoneal macrophages; but in vitro treatment to macrophages did not influence their phagocytic efficacy. The drug treatment enhanced ACC, haemagglutinating antibody titre and the number of antibody producing spleen cells in mice. Conclusion: The drug stimulates macrophage phagocytosis in mice; but not under in vitro conditions. The drug also enhances ACC mediated cancer cell killing and humoral antibody response in mice.

Antinociceptive activity of Azadirachta Indica (neem) in rats

Abstract: Objective: To study the antinociceptive effect of Aindica in rats Methods: Analgesia was evaluated using tail flick reaction time to thermal stimulus and glacial acetic acid (GAA) induced writhing A indica leaf extract (500mg/kg) and A indica seed oil (2ml/kg) were given orally by an intragastric tube Naloxone was given to study the mechanism of antinociceptive effect Results: Tail flick reaction time was significantly increased in rats with both leaf extract and seed oil Naloxone pretreatment partially reversed the antinociceptive effect of leaf extract and seed oil GAA induced writhing was reduced with both leaf extract and seed oil Pretreatment with naloxone partially reversed the inhibitory effect of leaf extract and seed oil on GAA induced writhing Leaf extract was more potent than seed oil Conclusion: The results indicate that both the preparations of A indica (leaf extract and seed oil) possess antinociceptive activity in rats, leaf extract being more potent

Pharmacodynamic evaluation of transdermal drug delivery system of glibenclamide in rats

Abstract: Objective: To develop acrylate based transdermal drug delivery system (TDDS) for glibenclamide and evaluate it for its pharmacodynamic performance in male Wistar rats. Methods: The drug embedded in a polymeric matrix of polymethyl methacrylate and ethylcellulose was evaluated for its hypoglycemic activity in normal and streptozotocin induced diabetic rats in comparison with its oral therapy. A glucose tolerance test (GTT) was conducted in oral, TDDS and control group. Results: TDDS significantly sustained the hypoglycemic activity for 24 hrs in normal rats when compared to oral administration where the effect declined after 8 hrs. In diabetic rats, normoglycemic levels were maintained for a period of 24 hrs after transdermal delivery, an effect comparable to that of oral glibenclamide. The GTT curve was inhibited in both the groups. However, the reduction was slow and sustained in case of TDDS when compared to oral administration where significant hypoglycemic response was observed in all the three studies performed. Conclusion: The transdermal system is effective in preventing the frequent hypoglycemic episodes encountered after oral glibenclamide administration.

Efficient source data verification

Abstract: The ICH harmonised tripartite guidelines for good clinical practice, the WHO guidelines for good clinical practice for trials on pharmaceutical products and the FDA's Code of Federal Regulations require that source data verification must be undertaken for all clinical trials in phases I-IV. SDV, which is an evaluation of the conformity of the data presented in case report form with source data, is conducted to ensure that the data collected are reliable and allow reconstruction and evaluation of the study. The responsibilities of the principal investigator, sub-investigator, study coordinator, monitor, quality assurance auditor and the clinical trial manager in SDV must be made clear at the outset of the clinical trial and adequate training should be provided to the personnel involved. Special emphasis should be placed on direct access to data and confidentiality, so that there are no misunderstandings and errors when SDV is undertaken. Meticulous recording of what was done and found, including an evaluation of the findings, must be made to arrive at an indication whether the errors are random or systematic errors and are arising due to carelessness or deliberate actions. All personnel involved must realize that SDV adds to the scientific and ethical integrity of the clinical trial. This review highlights the various aspects governing the conduct, extent, difficulties and stream lining of the process of SDV and gives some suggestions for fast and effective SDV avoiding the common pitfalls observed by the clinical trial monitors.

Antiviral drugs against herpes infections

Abstract: Several new and promising antiviral drugs have been approved which allow better options to control infections caused by herpes virus. Vidarabine has been the earliest available drug against herpes simplex (HSV) and varicella zoster (VZV), but is an agent that is rarely used at present. Acyclovir has replaced vidarabine in treating herpes infections in immunocompetent and immuno compromised patients. The low oral bioavailability of acyclovir, as well as emergence of drug resistant strains have stimulated efforts towards development of newer compounds for treatment of herpes infection. These include penciclovir and its oral prodrug famciclovir and the oral prodrug form of acyclovir, valacyclovir. These drugs are dependent on virus encoded thymidine kinase (TK) for their intracellular activation (phosphorylation) and, upon conversion to their triphosphate form which act as inhibitors/alternative substrate of viral DNA polymerase. Therefore resistance of these drugs may occur for virus mutants that are TK-deificient. Newer drugs as Sorivudine which is a nucleoside analogue has been pursued in treating herpes infections. Foscarnet, which does not require any previous metabolism to interact with viral DNA polymerase is useful in clinical settings when TK deficient mutant strains emerge. Cidofovir, an acyclic nucleoside phosphonate is yet another available drug to which TK deficient strains are sensitive. This review describes these currently available antiviral drugs against herpes virus, some approved and others under clinical evaluation for approval.

Effect of locomotor activity on the passive avoidance test for the evaluation of cognitive function

Abstract: Objective: To probe whether locomotor activity (LA) affects passive avoidance response (PAR) in mice Methods: PAR and LA were studied in mice treated with known amnesic (scopolamine, diazepam) and nootropic (piracetam, Bacopa monniera extract) drugs. For PAR, the step-down latency (SDL), step-down errors (SDE) and time spent in shock zone (TSZ) were measured. A videopath analyzer was used for recording LA. Results: An increase in LA augmented SDE scores and vice-versa, indicating a direct correlation. No such correlation was seen between LA and the other two parameters viz SDL and TSZ. The latter increased with amnesic agents and decreased in nootropic treated animals. Conclusion: LA affects parameters for evaluation of cognitive function by the PAR test. TSZ appears to be the best indicator for nootropic/amnesic activity.