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September-October 2000 Volume 32 | Issue 5
Page Nos. 256-328
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REVIEW ARTICLE |
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Cancer chemotherapy and radiation induced emesis (CRIE): current and future therapeutic approaches |
p. 256 |
A Abraham, N Sridhar, A Veeranjaneyulu
Nausea and vomiting caused by radiation and chemotherapy in cancer patients often tends to be more traumatic than the disease itself. Classical anti-emetic agents have offered very little protection against cancer chemotherapy and radiation induced emesis (CRIE). Newer agents that have immense potential and efficacy to treat this type of emesis are the 5-HT3 antagonists and NK1 antagonists. The high cost of 5-HT3 antagonists calls for the use of prudent combination regimens so as to have cost-effective management of emesis in cancer patients. Delayed emesis, a problem often witnessed in CRIE cannot be managed by the administration of serotonergic antagonists alone. Hence a cost-effective combination regimen which includes classical anti-emetic drugs may perhaps find an important place in future therapeutic approaches. This review highlights the various aspects associated with CRIE, including its physiology and newer therapeutic agents available to treat CRIE.
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REVIEW ARTICLE |
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Pilosebaceous unit: anatomical considerations and drug delivery opportunities |
p. 269 |
P Singh, V Sihorkar, V Jaitely, P Kanaujia, SP Vyas
Pilosebaceous unit is composed of hair follicle, hair shaft and sebaceous gland. This three-dimensional complex structure present on the surface of mammalian skin has been considered as an important pathway for percutaneous absorption of topically applied drugs and delivery systems. This pathway could be exploited for localized drug delivery for diseases associated with pilosebaceous gland vis-…-vis systemic absorption of drugs. A comprehensive overview of pilosebaceous anatomy and surrounding environment is needed for rationale designing of drug delivery systems targeted toward hair follicle. The present communication presents a review of hair follicle anatomy with physiological environment, rationale, opportunities, means and modes for drug targeting to pilosebaceous compartment.
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RESEARCH PAPER |
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An appraisal of the healing profiles of oral and external (GEL) metronidazole on partial thickness burn wounds  |
p. 282 |
CM Rao, KM George, KL Bairy, SN Somayaji
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.
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Hepatoprotective and toxicological evaluation of Andrographis paniculata on severe liver damage |
p. 288 |
Trivedi Neha, UM Rawal
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.
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Antiobesity effect a polyherbal formulation, OB-200G in female rats fed on cafeteria and atherogenic diets |
p. 294 |
Kaur Gurpreet, SK Kulkarni
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.
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Aphrodisiac activity of Vanda tessellata (Roxb.) Hook.Ex Don extract in male mice |
p. 300 |
Kumar PK Suresh, A Subramoniam, P Pushpangadan
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.
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Pharmacokinetics of enrofloxacin in febrile cross-bred bovine calves |
p. 305 |
AH Ahangar, AK Srivastava
Objective: To determine the pharmacokinetics, urinary excretion and dosage regimen of enrofloxacin in febrile cross-bred bovine calves.
Methods: Fever was induced with iv injection of E. coli endotoxin (1(g/kg). Following single iv administration of enrofloxacin (5mg/kg) in febrile calves, the blood and urine samples were collected at different predetermined time intervals. The level of drug in plasma and urine was measured by microbiological assay using Staphylococcus aureus (ATCC 6538P) as test organism. The minimum detection level of enrofloxacin was 0.02 (g/ml. The data on plasma drug concentration-time profile were analysed by nonlinear least-square regression technique.
Results: The peak plasma level of enrofloxacin at 1 min was 36.7 ( 1.15 (g/ml. The minimum therapeutic concentration was maintained up to 4 h. The t 1/2( , t 1/2(, V d(area) and ClB were 0.05 ( 0.004 h, 1.02 ( 0.05 h, 0.44 ( 0.02 L.kg and 0.30 ( 0.01 L/kg/h, respectively. Approximately 10% of total administered dose was excreted in urine within 24 h.
Conclusion: The most appropriate intravenous dosage regimen of enrofloxacin in febrile cross bred bovine calves would be 7 mg/kg repeated at 6 h intervals.
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Pharmacodynamic evaluation of transdermal drug delivery system of glibenclamide in rats |
p. 309 |
S Sridevi, MG Chary, DR Krishna, PV Diwan
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.
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RESEARCH PAPER |
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Protective effect of Gingko biloba extract on ethanol-induced gastric mucosal lesions in rats |
p. 313 |
R Shetty, KV Kumar, MUR Naidu, KS Ratnakar
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.
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SHORT COMMUNICATION |
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Role of nitric oxide in central regulation of humoral immune response in rats |
p. 318 |
Roy Sunita, Roy Goutam, SC Mishra, V Raviprakash
Objective: To investigate the role of nitric oxide (NO) in central regulation of immune response in rats.
Methods: The investigation was carried out using sheep red blood cells (SRBC)-immunized rats. The animals were administered NO modulators intracerebroventricularly ( icv), both prior to, and following immunization. Blood collected postimmunization was analyzed for humoral immune response by haemagglutination test.
Results: Centrally administered NO stimulators (L-arginine and SIN-1) were found to have immunopotentiating effect whereas, L- NAME (NOS inhibitor) and methylene blue (guanylyl cyclase inhibitor) did not produce any change in humoral immune response.
Conclusion: L- arginine (NO precursor) and SIN-1 (NO donor) when administered icv produced an increase in the anti-SRBC antibody titre, while L-NAME and methylene blue (NO inhibitors) did not alter this humoral immune response.
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Effect of physostigmine and cisapride on morphine-induced delayed gastric transit in mice |
p. 321 |
CS Patil, SK Kulkarni |
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Effect of fish oil on isoproterenol induced myocardial necrosis |
p. 324 |
Padma V Vijaya, Devi CS Shyamala
Objective: To study the effect of fish oil treatment on isoproterenol induced myocardial necrosis in rats.
Methods: Four groups of rats each comprising of 6 animals were selected for this study. Group I served as control and Group II animals were given isoproterenol hydrochloride (60 mg/kg, s.c.). Group III animals were orally administered fish oil for a period of 45 days. Group IV animals received both fish oil (45 days) and isoproterenol (at the end of the fish oil treatment). The transaminases (AST and ALT), lactate dehydrogenase (LDH) and creatine phosphokinase (CK), in both serum and heart tissue and serum uric acid levels were estimated.
Results: Isoproterenol significantly increased the activities of CK, LDH and transaminases in serum with concomitant decrease of these enzymes in tissue. Fish oil pretreatment maintained these enzyme activities at near normal. Serum uric acid level was increased on isoproterenol administration. Pretreatment with fish oil registered near normal values.
Conclusion: The study confirms the protective effect of fish oil on isoproterenol induced biochemical alterations in rats.
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Long term facilitation of bicuculline convulsion by kainic acid in mice |
p. 327 |
KK Sharma, PK Mediratta, SP Dubey |
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