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October-December 1995 Volume 27 | Issue 4
Page Nos. 204-270
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REVIEW ARTICLE |
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Methods for teratogenicity testing-existing and future models |
p. 204 |
Kotwani Anita, VL Mehta, U Gupta, S Prabhu, JS Bapna
Government agencies require that drugs and food additives be evaluated for their teratologic potential before these are released in the market. The presently available methods are (a) studies in rodents and (b) surveillance of human epidemiology. Rat is the species most often used for routine studies and in vivo data obtained from this animal makes up an important part of submission to government agencies with respect to teratogenic potential. However, the routine animal test systems have not proved particularly reliable predictors of hazards to the human fetus. The number of compounds which must be tested for teratogenicity has increased dramatically with the continuous development of therapeutic, cosmetic and food additive chemicals. It is unrealistic to attempt to perform complete in vivo teratogenicity tests on each and every one of these chemicals. Thus cheaper, quicker, more efficient, but nevertheless reliable tests must be developed. In the last few years, a number of other systems have been proposed as possible screening tests for teratogenicity. The available in vitro systems are - mammalian organ culture; vertebrate embryos e.g., chick, fish, and amphibian embryos; invertebrate system like, drosophila, cricket and hydra; organ culture e.g., limb bud and cell culture system. At present no single in vitro system is likely to supersede animal testing, but one can foresee the development of successful battery of tests for identifying compounds for further in vivo testing.
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Neurosteroids: novel regulators of neural functions |
p. 214 |
MR Jain, VS Burade, N Subhedar
Recent studies have demonstrated that some of the enzymes involved in the biosynthesis of steroidal hormones are found in a cell specific and region specific fashion in the brain. The discovery of the biosynthesis of steroids in the brain has generated considerable ex citement. These brain derived steroids (named 'neurosteroids'), in addition to binding to the cytoplasmic/nuclear receptors also interact with the specific binding sites on the GABAA receptor. Several biological functions have been proposed for these neurosteroids for their roles in hypnosis, anxiety, analgesia, convulsion, neural development and regulation of endocrine systems, Although in its infancy, the study of the neurosteroids is an emerging line that has shown considerable potential. It is hoped that the work on neurosteroids in addition to throwing new light on the neural processes, may provide a substratum for the development of new drugs for several neural disorders.
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RESEARCH PAPER |
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Disposition kinetics of sulphamethoxypyridazine during endotoxin induced fever and its modification by sodium salicylate in goats |
p. 222 |
S Juliet, A Barman, S Majumder, TK Mandal, AK Chakraborty
Disposition kinetics of sulphamethoxypyridazine (25 mg/kg, i.v.) in absence and in presence of sodium salicylate (50 mg/kg, i.v.) in both afebrile and endotoxininduced febrile conditions were studied in female black Bengal goats. The disposition kinetics of sul phamethoxypyridazine alone and in presence of sodium salicylate were described by a two compartment and one compartment model respectively. Sulphamethoxypyridazine persisted in afebrile and febrile goats till 36 and 24 h post administration, while in presence of sodium salicylate it persisted till 30 and 24 h in afebrile and febrile goats. Sodium salicylate decreased the plasma protein binding activity of sulphamethoxypyridazine. Besides, sodium salicylate decreased the t1/2(() , Vd(area) (P < 0.01); and increased the AUC value of sulphamethoxy-pyridazine.
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Effects of cuscuta stem extract on various animal tissues |
p. 227 |
HP Kayath, NK Goel
The effects of cuscuta stem extract (CSE) were studied and compared with the effects of acetylcholine (ACh) on isolated piece of rabbit ileum, rectus abdominis muscle of frog and frog heart "in situ". The effects induced by CSE resembled those induced by ACh. These effects on isolated piece of rabbit ileum and frog heart were blocked competitively by atropine. Effect of CSE on isolated rectus abdominis muscle of frog was blocked by pancuronium and potentiated by neostigmine.
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Inhibition of antigen and compound 48/80 induced contractions of Guinea pig trachea by the ethanolic extract of the leaves of Vitex negundo Linn |
p. 230 |
AM Nair, MN Saraf
The ethanolic extract of Vitex negundo was studied for its effect on the sensitised and non-sensitised guinea pig trachea using antigen and compound 48/80 respectively to examine its influence on mediator release and tracheal smooth muscle contraction. Histamine has been shown to contribute only to the initial phase of tracheal contraction while the release of lipoxygenase derived arachidonic acid metabolites have been reported to contribute to the later sustained contraction. The ethanolic extract of V.negundo was found to significantly inhibit both the initial phase of contraction and the later sustained contracture of the trachea. The studies reveal that the ethanolic extract of Knegundo inhibits the release of histamine and products of arachidonic acid metabolism.
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RESEARCH PAPER |
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Effects of quinolones on skeletal muscle function |
p. 234 |
N Gopinathan, CN Potkar, AS Barve, NA Kshirsagar
The effect of quinolones on skeletal muscle function was studied using cat tibialis anterior muscle-common peroneal nerve preparation. Screening of four quinolones viz. ciprofloxacin, norfloxacin, nalidixic acid and pefloxacin produced a decrease in nerve stimulation (NS) induced contractions similar to that seen with the positive controls (Gentamicin & streptomycin). Normal saline and penicillin (Negative controls) were devoid of any effect on neuromuscular junction. Periodic stimulation of nerve and muscle ruled out muscle tatigue as a cause of decrease in skeletal muscle function. Characterization of neuromuscular (NM) block by ciprofloxacin was carried out to determine action on postsynaptic site (Close intraarterial injection of ACh, reversal with neostigmine), Presynaptic site (Hemicholinium + high frequency stimulation, reversal with CaCl2) and muscle (continuous pancuronium infusion). Primary action of ciprofloxacin on motor end plate was suggested by no response to close intraarterial ACh and reversal with neostigmine. Action on presynaptic site as well as muscle possibly contributes to the action on NM junction. The results of the study suggest that quinolones probably have a weak curare like effect on NM junction similar to that of aminoglycosides.
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SHORT COMMUNICATION |
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Predominant GABA-B mediated dispersion of the isolated web Melanophores of the Indian bull frog, Rana tigerina(Daud.) |
p. 241 |
SR Chimania, M Ovais
Effect of GABA-ergic agonists on the isolated web melanophores of a frog (Rana tigerina) was examined. Melanophore size index (MSI) was employed as a recording parameter for the responses of the melanophores to drugs. GABA and baclofen both induced strong dispersion in the frog melanophores. Propranolol and 5-aminovaleric acid significantly inhibited the dispersion of frog melanophores induced by GABA and baclofen, while bicuculline failed to inhibit the dispersal responses of the melanophores significantly. It is indicated that the disoersion of the froa melanoohores induced by GABA-ergic agonists is mediated predomi nantly through GABAB receptors.
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Neurobehavioural effects of acute monocrotophos administration in rats and mice |
p. 245 |
SN Mandhane, CT Chopde
A study was conducted on rats and mice to assess the acute behavioral toxicity of oral monocrotophos (MCP). MCP produced hypothermia, reduced locomotor activity and affected the ability of trained mice to ride on rotating rod. Doses as low as 2, 1 and 4 mg/kg were required for these effects respectively. MCP (l-4 mg/kg) caused potentiation of pentobarbitone (40 mg/kg, ip) sedation and haloperidol (1 mg/kg, ip) induced catalepsy. However, pentylenetetrazole (SO mg/kg, SC) induced tonic-clonic convulsions and mortality were not affected. MCP at these doses per se had no hypnotic, cataleptic or convulsant effects. These results suggest that MCP is a potent CNS depressant compound which may cause adverse neurobehavioral effects in mammals.
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The effect of urinary protein from pregnant women on reproductive system of female rats |
p. 250 |
PI Latha, K Narayana, gowda Honne
Urinary protein (UP) was extracted and purified from the pregnant woman urine and the yield was 12 mg per litre of urine. There was a significant (P < 0.05) increase in the uterine weight of immature female rats at doses of 5, 10, 50 and 100 (g per rat given intraperitoneally. There was no change in the weight of ovary, adrenal, kidney, liver and spleen in rats treated with UP thus indicating a specific uterotrophic effect.
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A computer program for calculation of LD50  |
p. 253 |
Shivprakash
A computer program has been described for the calculation of LD50 . This program can be conveniently implemented in BASIC language and can be used in pharmacology and toxicology laboratories for rapid calculation of LD50 which is otherwise a complicated mathematical routine.
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Estrogenic activity in the ethanolic extract of Bupleurum marginatum |
p. 258 |
Jonathan Sheel, Dehadrai Sangeeta, AO Prakash
Ethanolic extract of Bupleurum marginafum (Sipil) having potent antifertility activity in rats has been studied to assess its estrogenic activity in immature rats. It has been observed that administration of extract per se significantly increased the uterine weight and caused opening and cornification of vagina in immature rats. Histological features of uterus were seen to be highly stimulated. Uterotrophic activity of the extract has been compared with diethylstilbestrol, a standard estrogenic agent.
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Antidiarrhoeal evaluation of Nelumbo nucifera rhizome extract |
p. 262 |
Pulok, K Mukherjee, J Das, R Balasubramanian, Saha Kakali, M Pal, BP Saha
A study was undertaken to evaluate the effects of methanolic extract of rhizomes of Nelumbo nucifera Gaertn (FINN) for its antidiarrhoeal potential against several experimental models of diarrhoea in rats. RNN treated animals showed significant inhibitory activity against castor oil induced diarrhoea and inhibited significantly PGE, induced enteropooling in rats. It also showed significant reduction in gastrointestinal motility following charcoal meal in rats. The results obtained establish the efficacy of RNN as an antidiarrhoeal agent.
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Antioxaluric and anticalciuric activity of lupeol derivatives |
p. 265 |
R Anand, GK Patnaik, Roy Kamal, AP Bhaduri
Lupeol and a number of its derivatives were synthesised and evaluated for the possible antiurolithiatic activity in rats against hydroxyproline induced hyperoxaluria and calciuria. Some of the compounds possessed promising antihyperoxaluric and antihypercalciuric activity indicating antiurolithiatic activity.
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LETTER |
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Effect of hyperglycemia on loperamide induced inhibition of gastrointestinal transit in rats |
p. 269 |
BM Patil, Ali MD Taher |
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