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   1997| July-August  | Volume 29 | Issue 4  
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Assessment of nootropic and amnestic activity of centrally acting agents
DS Reddy
July-August 1997, 29(4):208-221
Cognitive deficits have long been recognized as severe and consistent neurological disorders associated with numerous psychiatric and neurodegenerative states such as Alzheimer's disease. Many experimental models are currently available for the evaluation of agents that affect learning and memory processes. Mazes are the traditional tool in assessing cognitive performance in animals. Apart from passive-avoidance task for short-term memory and Morris water maze task for spatial learning, other paradigms such as radial arm maze and Y-maze consistently measure the working/reference memory and agents that affect these processes. The transfer latency on elevated plus-maze is another simple paradigm to reveal the nootropic and amnestic activity of centrally acting agents. The complex-mazes such as Stone T-maze are built by combining several simple maze segments to assess mixed spatial, working/reference and taxon learning skills in animals. The active-avoidance behaviour induced by a sequence of conditioned and unconditional stimuli is a classic model for the assessment of cognitive performance after brain lesions or pharmacological disruption of cognition. Drug-induced acquisition/re-tention deficits, brain lesion-induced task specific cognitive dysfunction and electroshock-induced general amnesia may provide a consistent battery of screening models for the development of agents that ameliorates the memory deficits in rodents. Several human psychometric and verbal learning skill tests are also available for the clinical assessment and confirmation of nootropic activity. These rapid developments in the field of animal models of learning and memory processes may hopefully lead to an improved understanding of the pathophysiology of cognitive disorders, and finally permit a rational designing of novel therapeutic strategies. for distinct cognitive dysfunctions.
[ABSTRACT]   Full text not available  [PDF]
  3,054 804 -
Action of garlic on the hyperlipidemia of experimental induced immune complex disease in rabbits
RC Jain, Khubnani Harish, Khubnani Asha
July-August 1997, 29(4):255-257
Objective: To study the effect of garlic on hyperlipidemia in immune complex disease in rabbits. Methods: Experimental induced immune complex disease was produced in 22 albino male rabbits (1.0-l .5 kg) by injecting horse serum proteins at a dose of 175 mg/kg body weight, every 72 hours i.v., and divided into two groups. Twelve rabbits were treated with 75 mg/kg body weight garlic oil orally daily and served as test group. Ten rabbits without supplementation of garlic oil served as control group. The observation period was 4 weeks. Results: Serum complement titre was significantly decreased in test group as compared to control group (19.50(1.5 vs 2.O(0.5; P<0.001) at the end of 4th week. The total lipids, total cholesterol and beta lipoprotein cholesterol were significantly lower in test group, when compared to control groups, However, levels of triglycerides and phospholipids in test group were not significant when compared to control. Conclusion: It is observed that garlic possesses anticomplementary and hypolipidemic activity in hyperlipidemia due to induced Immune complex disease.
[ABSTRACT]   Full text not available  [PDF]
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In-vitro and in-vivo evaluation of novel injectable contraceptive preparations of centchroman
Shenoy B Dinesh, N Udupa, UV Singh, Kumari Nagaraj
July-August 1997, 29(4):233-237
Objectives: Thein vitro release profile, stability and anti-fertility efficacy of some injectable, biodegradable formulations of Centchroman was investigated. Methods: The formulations included an in situ gelling preparation namely Poly(Lactide-co-Glycolide) (PLGA)-in-Triacetin prepared by solution method and Niosomes prepared by lipid layer hydration method. These were evaluated for physicochemical characteristics like size distribution, percentage entrapment, in vitro drug release profiles in phosphate buffered saline (pH 7.4) and stability at different conditions of storage viz; 4° C room temperature and 37° C. In vivo anti-fertility activity was evaluated in female albino rats showing normal oestrous cycle by giving a single dose of the formulation (5mg/kg body weight) and then checking for number of implantations on 20th day of pregnancy. Also histopathological sections of the uterus and ovary were studied for further evaluation. Results: The formulations showed controlled drug release and enhanced stability whereas in vivo studies showed promising anti-fertility activity for PLGA-in-Triacetin. Conclusions: It was evident from this study, that, PLGA-in-Triacetin was a better candidate for development of a biodegradable, bio-erodable, long acting, injectable contraceptive formulation.
[ABSTRACT]   Full text not available  [PDF]
  1,847 266 -
Effect of 1-chloroacetophenone (CN) and dibenz (b,f)-1,4 oxazepine (CR) vapour inhalation on some cardiovascular and respiratory variables in anaesthetised rats
Kumar Pravin, D Kumar, R Vijayaraghavan, Gupta S Das
July-August 1997, 29(4):238-243
Objectives: The study was aimed at investigating the effects of inhalation of pyrotechnically generated vapours of two riot controlling agents on some selected physiological variables in rats. Methods: Known quantity of the individual compounds were heated by Bunsen flame and generated vapour was purged into specially designed and fabricated exposure chamber. The animals were allowed to inhale the vapour (for 5 minutes; 1 LC50 or 3 LC50) through tracheal cannula. The effects thus induced in anaesthetized and tracheostomised male rats on blood pressure, heart rate, electrocardiogram, respiratory rate, tidal volume and neuromuscular junction were recorded and analysed. Results: A significant dose dependent fall in mean arterial pressure (MAP) and bradycardia were observed following CN exposure. Pretreatment of atropine sulphate or prior bilateral vagotomy, significantly prevented these changes while atropine methylnitrate was found to be ineffective. CR at equitoxic concentration, induced dose dependent fall in MAP and bradycardia but of low magnitude, and the changes were blocked by pretreatment of atropine sulphate or atropine methylnitrate. The other physiological variables viz. electrocardiogram, respiratory rate, tidal volume and transmission of impulses across the neuromuscular junction remained unaltered. Conclusion: It may be concluded that CN induced hypotension is mediated through central muscarinic cholinergic receptors, while in case of CR the effects are of low magnitude at equitoxic dose level, and are through primarily peripheral muscarinic receptors.
[ABSTRACT]   Full text not available  [PDF]
  1,764 131 -
Role of benzodiazepine-GABA receptor complex in stress - induced modulation of leucocyte migration inhibition factor
PK Mediratta, KK Sharma
July-August 1997, 29(4):228-232
Objectives: To investigate the role of benzodiazepine-GABA receptor mechanisms in stress-induced modulation of leucocyte migration inhibition factor (LMIF), a lymphokine released from sensitized lymphocytes. Methods: Groups of male Wistar rats (n = 6 in each group) were subjected to restraint stress (RS) for 24 h at room temperature on day -1 (one day before), +1 or +13 (one or 13 days after) of sensitization with 0.5 ml of egg albumin (25 mg/ml) and 0.5 ml of complete Freund's adjuvant. Drugs/vehicle were injected i.p. just before submitting the animals to RS and LMIF activity was measured on day +14 by leucocyte migration inhibition (LMI) test. Results: RS per se increased % LMI when given on day -1 but reduced it when administered on day +l and +13. Diazepam (5 mg/kg), muscimol (1 mg/kg) and baclofen (5 mg/kg) significantly attenuated the effect of RS on % LMI. The effect of diazepam was blocked by both flumazenil (10 mg/kg) and bicuculline (2 mg/kg); the latter also antagonised the effect of muscimol. Conclusion: GABA-ergic mechanisms, mediated at both GABAA and GABAB receptors appear to play a role in the regulation of RS-induced changes in release activity of LMF.
[ABSTRACT]   Full text not available  [PDF]
  1,673 146 -
Further studies on the antihepatotoxic activity of jigrine
N Karunakar, KK Pillai, SZ Hussain, M Rao, DK Balani, M Imran
July-August 1997, 29(4):222-227
Objectives: To evaluate the anti-hepatotoxic activity of Jigrine (a Unani polypharmaceutical herbal formulation) against alcohol and CCl4 induced hepatotoxicity in rats. Methods: Albino rats (Wistar strain) were given alcohol (40% alcohol, 2.0ml/100g, po for 21 days) and CCl4 (1:1 in groundnut oil, 0.1ml/kg, SC on 20th day) to induce hepatotoxicity. Jigrine at two dose levels (0.5ml and 1.0ml/kg, po) was given for a period of 7 days (i.e. 15th to 21st day) to the rats treated with alcohol and CCl4. Silymarin (25mg/kg, po) was given as a reference drug. Biochemical parameters like serum AST, ALT, tissue (-GTP, triglycerides and lipid peroxides were estimated to assess the liver function. Histopathological studies were also done to confirm the biochemical changes, Results: The mean ˝ SEM serum AST, ALT levels in control animals were 44.4 ˝ 5.7 Units/ml and 55.2 ˝ 7.9 Units/ml, where as in alcohol - CCl4 treated rats the levels rose to 234 ˝ 4.6 Units/ml and 122.4 ˝ 21.9 Units/ml. Jigrine at two dose levels reduced the AST and ALT levels to 190.8 ˝ 7.6 Units/ml; 87.2 ˝ 15.6 Units/ml and 160.4 ˝ 9.9 Units/ml; 68.8 ˝ 6.4 Units/ml. Silymarin reduced AST and ALT levels to 136 ˝ 13.4 Units/ml and 64 ˝ 5.3 Units/ml. The tissue mean ˝ SEM of ( -GTP, triglycerides and TBARS in control animals were 40.9 ˝ 3.2 I.U; 26.5 ˝ 4.5 mg/100ml and 1.44 ˝ 0.2 n.mole MDA/mg protein, where as in alcohol -CCl4 treated rats the levels rose to 122.25 ˝ 5.3 I.U; 174 ˝ 12.6 mg/100ml and 7.65 ˝ 0.7 n.mole MDA/mg protein. Jigrine (0.5ml/kg, po) reduced the ( -GTP to 84.13 ˝ 7.2 I.U; triglycerides to 118.5 ˝ 12.8 mg/100ml and TBARS to 3.69 ˝ 0.6 n.mole MDA/mg protein. Jigrine (1ml/kg, po) reduced the y GTP to 69.07 ˝ 13.1 I.U; triglycerides to 84 ˝ 14.8 mg/100ml and TBARS to 1.81 ˝ 0.17 n.mole MDA/mg protein. Silymarin (25mg/kg, po) reduced the ( -GTP to 64.5 ˝ 12.4 I.U; triglycerides to 60 ˝ 9.1 mg/100ml and TBARS to 2.33 ˝ 0.2 n.mole MDA/mg protein. Conclusion: The study confirms the antihepatotoxic activity of Jigrine which may be attributed to the membrane stabilizing and antioxidant property of this medicine.
[ABSTRACT]   Full text not available  [PDF]
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Enhancement of the cytotoxic effects of echitamine chloride by vitamin A: An in vitro study on Ehrlich ascites carcinoma cell culture
Viswanathan Saraswathi, Ramamurthy Nalini, S Subramanian, V Mathuram, S Govindasamy
July-August 1997, 29(4):244-249
Objectives: A study was conducted to examine the in vitro cytotoxic effects of Echitamine chloride (EC), a plant alkaloid extracted from the bark of Alstonia scholaris. Since vitamin A was found to enhance the anticancer effects of several anticancer drugs, the synergistic effects of these two drugs were also studied. Methods: Echitamine chloride at a concentration of 200'M and Vitamin A at a concentration of 10 'M were added alone as well as in combination to the Ehrlich Ascites Carcinoma (EAC) cell cultures. Cell viability, antioxidant enzyme status, lipid peroxidation and 3H -Thymidine incorporation were studied. Results: The cultures treated with EC and vitamin A combination showed significant cytotoxic effect than the cultures treated with individual drugs. Conclusion: It may be concluded that EC in combination with vitamin A has an enhanced cytotoxic effect on Ehrlich Ascites Carcinoma cell culture.
[ABSTRACT]   Full text not available  [PDF]
  1,604 188 -
Biochemical and physiological alterations following short term exposure to fluvalinate ľA synthetic pyrethroid
SK Garg, Shah MA Ayub, KM Garg, MM Farooqui, M Sabir
July-August 1997, 29(4):250-254
Objectives: To investigate the effect of fluvalinate on certain haematological and blood-biochemical analytes in rats. Methods: Acute toxicity study was done on 4 groups each of 4 male and 4 female rats by administering fluvalinate in doses of 62.5, 125, 250 and 500 mg/kg, orally. Animals were observed for signs of toxicity upto 72 h; rectal temperature recorded and LD50 values determined. For sub-acute toxicity study 4 groups of female rats were used. Group I served as control and the remaining groups received fluvalinate at the dose of 17.5, 35.0 and 70.0 mg/kg/day for 21 days. Blood collected on day 22 and animals sacrificed. The following parameters were studied: (a) Biochemical assays - alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, blood urea nitrogen (BUN), cholesterol, glucose, total proteins and albumin concentrations; (b) Haematological parameters - haemoglobin (Hb), total erythrocyte count (TEC), total leucocyte count (TLC), differential leucocyte count (DLC) and absolute leucocyte count (ALC); and (c) Relative organ weights - relative organ weights of liver, kidneys, spleen and adrenals were calculated. In another set of experiment, 4 groups of female rats were administered fluvalinate (0.0, 17.5, 35, 70 mg/kg/day, orally) for 15 days to study its effect on pentobarbital-induced hypnosis and hepatic proteins. Results: Oral LD50 values of fluvalinate in male and female rats were found to be 293 and 280 mg/kg, respectively. The gross signs of acute intoxication included hyperactivity, incoordination. ataxia. clonic convulsions, profuse sweating, salivation, piloerection and hypothermia. At terminal stage, the animals exhibited dyspnoea and death. In sub-acute studies, fluvalinate @ 17.5-70 mg/kg/day, orally for 21 days did not exert any gross behavioural changes nor significantly alter the haematological profiles. However, it (35 and 70 mg/kg/day) produced marginal to significant (P<0.05-0.01) increase in AST activity, BUN and glucose concentrations, relative liver and adrenal weights, pentobarbital hypnosis and total liver proteins; significant (P<0.05) reduction in estrogen (E2) levels without altering the ALT activity, cholesterol, total proteins and albumin concentrations, progesterone (P4) levels and relative weights of kidneys and spleen. Conclusion: These results reveal fluvalinate to be moderately toxic compound and, seemingly, have the potential to cause chemical injury to liver and kidneys.
[ABSTRACT]   Full text not available  [PDF]
  1,457 141 -
Effect of BR-16A (MentatR) on cognitive deficits in aluminium-treated and aged rats
SS Handu, VK Bhargava
July-August 1997, 29(4):258-261
Objectives: The effect of BR-16A (MentatR) on aluminium-induced cognitive deficits and cognition in aged rats was studied in a one-trial step-through passive avoidance task. Methods: Aluminium chloride (1000 mg/kg/day) was administered to wistar rats for 40 days to produce significant cognitive deficits (P<0.05). Aluminium-treated rats received BR-l 6A (100 mg/kg/day) for 20 days starting day 21. In a second experiment, aged wistar rats (12 months) received BR-16A (100 mg/kg/day) or vehicle for 20 days. Results: BR-16A significantly prolonged the shortened latency of step-through induced by aluminium administration [300 (214.17 - 300) vs 60.5(16 - 213); P<0.05] It also significantly improved retention of learning in aged rats [300(120.8 - 300) vs 37(27.5 - 189.5); P<0.01]. Conclusion: These results suggest that BR-16A improves learning and memory in aluminium-treated and aged rats.
[ABSTRACT]   Full text not available  [PDF]
  1,440 155 -
An interaction study of verapamil with the neuromuscular blocker gallamine
BG Patel, NP Chotai, NN Shah
July-August 1997, 29(4):266-268
Objectives: To study the interaction of verapamil with the neuromuscular blocking gallamine. Methods: The interaction study was carried out in rats and rabbits using inclined screen and rabbit head drop methods respectively. Results: A non-paralysing dose of gallamine (25 'g/kg) caused a quicker onset and longer duration of hind limb paralysis in rats pretreated with verapamil (5, 10 mg/kg, i.p.). A similar result was also obtained with rabbit head drop method. Twelve hours after the administration of verapamil (10 mg/kg, i.p.) the amount of gallamine required to elicit head drop in the rabbit was significantly less than that required 4 days earlier in the same rabbit without verapamil. When 5 mgkg of verapamil was used, significantly less quantities of gallamine were required at 0.5 h and 6 h intervals after verapamil injection to elicit head drop. Conclusion: It is suggested that the enhancement of action of gallamine by verapamil may be of clinical importance in patients, especially if verapamil has been taken shortly before.
[ABSTRACT]   Full text not available  [PDF]
  1,410 135 -
The internet: Basics and relevance to pharmacologists
C Adithan
July-August 1997, 29(4):269-277
The new information super highway is the Internet. The basic facilities of the Internet, at present, available in India are Electronic mail, World Wide Web, File Transfer Protocol, Telnet and Internet Relay Chat. The Internet can be used for electronic conferencing, subscribing to mail servers, browsing many journals, free Medline search, obtaining teaching materials / computer software and seeking for jobs and fellowships. An outline of the procedure for Medline search on the Internet is given. Some of the interesting Website addressess of pharmacology journals and associations are provided. Finally, the minimum requirement of hard- ware and the procedure for obtaining Internet connection in India is explained.
[ABSTRACT]   Full text not available  [PDF]
  1,156 172 -
Effect of dietary fat on tissue disposition of clofazimine in mice receiving the drug orally as suspension in oils
A Mathur, K Venkatesan, Sreevatsa, KB Kannan, KV Desikan
July-August 1997, 29(4):262-265
Objective: To evaluate the effect of dietary fats on the tissue disposition of clofazimine in mice receiving the drug orally as suspension in oil(s). Methods: Forty-five Balb/C mice were fed with either laboratory made fat-restricted diet or this diet supplemented to a fat content of 10% (w/w) with mustard oil-groundnut oil/vegetable ghee and administered clofazimine suspension in mustard oil/groundnut oil/lard oil orally at a daily dose of 50 'g for seven consecutive days. Four hours after the last daily dose the mice were sacrificed, tissues collected and clofazimine content estimated by spectrophotometric methods. Results: The drug was found accumulated in greater amounts in mesentric lymph nodes, mesentric fat, lungs, spleen, liver, kidney and small intestine and to a lesser extent in heart, muscle and tail. Most tissues from mice fed with fat-supplemented diet presented significantly more levels of clofazimine (P<0.05). The mean ˝ SD cumulative tissue clofazimine content in mice fed with fat supplemented diet ranged from 41.2 ˝ 6.38 to 43.4 ˝ 2.10 'g/g while it ranged from 34.6 ˝ 3.16 to 37.7 ˝ 2.97 'g/g in mice fed with fat restricted diet. However, the variety of oil/fat used either in the diet or drug suspensions failed to make any significant difference in drug availability in tissues. Conclusion: An extrapolation of these findings to human beings suggest that clofazimine may be administered to the patients along with or after any fatty meal for better absorption and tissue deposition.
[ABSTRACT]   Full text not available  [PDF]
  1,211 102 -
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