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Diabetes has been reported to cause an increase in offensive and decrease in defensive gastric mucosal factors, the imbalance of which can cause ulceration and delay the ulcer healing. Eugenia jambolana has been documented to have both antidiabetic and antiulcer activities. The present study evaluates the effects of ethanolic extract of E. jambolana on gastric ulcer healing and on rat gastric mucosal defensive factors in gastric ulcer with co-occurring diabetes. E. jambolana extract was administered orally in the dose of 200 mg/kg once daily for 10 days. E. jambolana extract increased mucin secretion, mucosal glycoprotein and glutathione levels and decreased the lipid peroxidation in gastric mucosa of diabetic rats. Its treatment also reversed the decrease in life span of gastric mucosal cells as indicated by decreased cell shedding in the gastric juice but found to have no effect on cell proliferation, indicating enhanced defensive status. E. jambolana extract was effective in reversing the delayed healing of gastric ulcer in diabetic rats near to the normal level. E. jambolana showed better ulcer healing effect than glibenclamide, because of its both antihyperglycemic and mucosal defensive actions. It could thus, be a better choice for treating gastric ulcers co-occurring with diabetes.

Plantain banana (M. sapientum var. paradisiaca, MS) has been shown to possess ulcer healing activity. The present work with plantain banana was undertaken with the premise that the drug promoting ulcer healing could have effect on wound healing also. Wound healing activity of MS was studied in terms of (i) percent wound contraction, epithelization period and scar area; (ii) wound breaking strength and (iii) on granulation tissue antioxidant status [estimation of superoxide dismutase (SOD) and reduced glutathione (GSH), free radical (lipid peroxidation, an indicator of tissue damage) and connective tissue formation and maturation (hexuronic acid, hydroxyproline and hexosamine levels)] in excision, incision and dead space wound models respectively. The rats were given graded doses (50-200 mg/kg/day) of aqueous (MSW) and methanolic (MSE) extracts of MS orally for a period of 10-21 days depending upon the type of study. Both extracts (100 mg/kg) when studied for incision and dead space wounds parameters, increased wound breaking strength and levels of hydroxyproline, hexuronic acid, hexosamine, superoxide dismutase, reduced glutathione in the granulation tissue and decreased percentage of wound area, scar area and lipid peroxidation when compared with the control group. Both the extracts showed good safety profile. Plantain banana thus, favoured wound healing which could be due to its antioxidant effect and on various wound healing biochemical parameters.

Introduction: We aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels., Methods: A total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days). The pregnant mice were euthanized on day 18 of gestation, and foetuses were examined for teratogenic manifestations. Their brains were dissected and examined for gross changes, malformations, histological changes, and quantitative protein estimation., Results: Foetal resorptions were observed in all treated groups with gabapentin administration at early gestation (1-6 days), and mid-gestation (7-12 days). On the other hand, growth retardation along with stunting in size of live foetuses were observed in all the mid-gestation (7-12 days), and late gestation (13-17 days) treated groups. Various gross malformations were observed with all the three doses (113, 226, and 452 mg/kg body weight per day) when gabapentin was administered at mid-gestation (7-12 days). The same trends were confirmed by gross and microscopic examination of brains along with quantitative protein estimation., Conclusion: Gabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned.

Possible effect of an ethanolic root extract of Pongamia pinnata (L) Pierre (P. pinnata) on oxidant-antioxidant status and histopathological changes in acute ischemia-reperfusion injury in the rat forebrain have been investigated. Further, its effect was also assessed on long-term cerebral hypoperfusion-induced changes in anxiety, cognitive and histopathological parameters. Cerebral post-ischemic reperfusion is known to be associated with generation of free radicals. In the present study, bilateral common carotid artery occlusion (BCCAO) for 30 min followed by 45 min reperfusion produced increases in lipid peroxidation, superoxide dismutase (SOD) activity and a fall in the total tissue sulfhydryl (T-SH) levels. The ethanolic extract of roots of P. pinnata (50 mg kg(-1), po for 5 days) attenuated the ischemia-reperfusion-induced increase in lipid peroxidation, SOD activity and a fall in T-SH levels. The extract also ameliorated histopathological changes and inflammatory cell infiltration in the frontoparietal region of the rat brain. The extract (50 mg kg(-1), po for 15 days) was also found to alleviate the long-term hypoperfusion-induced anxiety and listlessness (open field paradigm). There was an improvement of learning and memory deficits (Morris' water maze testing). It also attenuated reactive changes in forebrain histology like gliosis, lymphocytic infiltration, astrocytosis and cellular edema. Results suggest protective role of P. pinnata in ischemia-reperfusion injury and cerebrovascular insufficiency states.

Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).

The acetone extracts of Radix paeoniae (Paeonaceae) root (100 and 200 mg/kg orally) were tested in brewer's yeast-induced pyrexia in rats to assess their antipyretic activity. The pyrexia in rats was reduced significantly (P < 0.05) compared to that of control. These results indicate that the extracts possess antipyretic properties. The root extract showed significant reduction in normal body temperature and yeast-provoked elevated temperature comparable to that of standard antipyretic drug paracetamol. The antipyretic effect was started at 1h and extended for at least 4h after the drug administration.

Eugenia jambolana (Jamun) fruit has been reported to give soothing effect on human digestive system. Present study includes the effect of ethanolic extract of seeds of E. jambolana (EJE) against gastric ulcers induced by 2 h cold restraint stress (CRS), aspirin (ASP, 200 mg/kg, 4 h), 95% ethanol (EtOH, 1 ml/200 g, 1 h) and 4 h pylorus ligation (PL) in rats. To ascertain the mechanism of action of EJE, its effect was studied on mucosal offensive acid-pepsin secretion, lipid peroxidation (LPO, free radical) and defensive mucin secretion, cell proliferation, glycoprotein and glutathione (GSH, an antioxidant). Acute and subacute toxicity studies were also conducted for the safety profile of Eugenia jambolana. EJE 200 mg/kg, when administered orally for 10 days in rats was found to reduce the ulcer index in all gastric ulcer models. It tended to decrease acid-pepsin secretion, enhanced mucin and mucosal glycoprotein and decreased cell shedding but had no effect on cell proliferation. It showed antioxidant properties indicated by decrease in LPO and increase in GSH levels in the gastric mucosa of rats. Acute toxicity study indicated LD50 to be more than 10 times (>2000 mg/kg) of the effective ulcer protective dose while subactue toxicity study (>1000 mg/kg) indicated no significant change in the general physiological and haematological parameters, liver and renal function tests. The result of the present study indicates that E. jambolana seed has gastro-protective properties mainly through promotion of mucosal defensive factors and antioxidant status and decreasing lipid peroxidation.

Asparagus racemosus (AR) is a herb used as a rasayana in Ayurveda and is considered both general and female reproductive tonic. Methanolic extract of A. racemosus roots (ARM; 100 mg/kg/day for 60 days) showed teratological disorders in terms of increased resorption of fetuses, gross malformations e.g. swelling in legs and intrauterine growth retardation with a small placental size in Charles Foster rats. Pups born to mother exposed to ARM for full duration of gestation showed evidence of higher rate of resorption and therefore smaller litter size. The live pup showed significant decrease in body weight and length and delay of various developmental parameters when compared to respective control groups. AR therefore, should be used in pregnancy cautiously as its exposure during that period may cause damage to the offspring.

Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been reported to show both ulcer protective and ulcer healing effects in normal as well as in diabetic rats. To study the mechanism of its ulcer protective/healing actions, effects of AIE (500 mg/ kg) was studied on various parameters of offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5 microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity and defensive mucin secretion including life span of gastric mucosal cells in rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated rats. Continuous infusion of PENTA significantly increased the acid secretion after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate while, AIE pretreatment significantly decreased them. AIE inhibited the rat gastric mucosal proton pump activity and the effect was comparable with that of omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though it enhanced life span of mucosal cells as evidenced by a decrease in cell shedding in the gastric juice. Thus, our present data suggest that the ulcer protective activity of AIE may be due to its anti-secretary and proton pump inhibitory activity rather than on defensive mucin secretion. Further, acute as well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose of AIE in mice and no significant alterations in body or tissues weight, food and water intake, haematological profile and various liver and kidney function tests in rats when treated for 28 days with 1 g/kg dose of AIE.

Methanolic extract of Musa sapientum var. Paradisiaca (MSE, 100 mg/kg) was studied for its antiulcer and mucosal defensive factors in normal and non-insulin dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by administering streptozotocin (STZ, 70 mg/kg, ip) to 5 days old rat pups. The animals showing blood glucose level >140mg/dL after 12 weeks of STZ administration were considered as NIDDM positive. Effects of MSE were compared with known ulcer protective drug, sucralfate (SFT, 500 mg/kg) and anti-diabetic drug glibenclamide (GLC, 0.6 mg/kg) when administered orally, once daily for 6 days against gastric ulcers (GU) induced by cold-restraint stress (CRS) and ethanol and subsequent changes in gastric mucosal glycoproteins, cell proliferation, free radicals (lipid peroxidation and nitric oxide) and anti-oxidants enzymes (super oxide dismutase and catalase) and glutathione (GSH) levels. MSE showed better ulcer protective effect in NIDDM rats compared with SFT and GLC in CRS-induced GU. NIDDM caused a significant decrease in gastric mucosal glycoprotein level without having any effect on cell proliferation. However, all the test drugs reversed the decrease in glycoprotein level in NIDDM rats, but cell proliferation was enhanced in case of MSE alone. Both CRS or NIDDM as such enhanced gastric mucosal LPO, NO and SOD, but decreased CAT levels while CRS plus NIDDM rats caused further increase in LPO and NO level without causing any further changes in SOD and CAT level. MSE pretreatment showed reversal in the levels of all the above parameters better than GLC. Ethanol caused a decrease in glutathione level which was further reduced in NIDDM-ethanol rats. MSE reversed the above changes significantly in both normal as well as in NIDDM rats, while GLC reversed it only in NIDDM rats. However, SFT was ineffective in reversing the changes induced by CRS or ethanol or when given in NIDDM-CRS or NIDDM-ethanol rats. The results indicated that the ulcer protective effect of MSE could be due to its predominant effect on mucosal glycoprotein, cell proliferation, free radicals and antioxidant systems.

The standardized methanolic extract of leaves of O. sanctum (OSE; eugenol content 5%) given in doses of 50-200 mg/kg, orally, twice daily for five days showed dose-dependent ulcer protective effect against cold restraint stress induced gastric ulcers. Optimal effective dose (100 mg/kg) of OSE showed significant ulcer protection against ethanol and pyloric ligation-induced gastric ulcers, but was ineffective against aspirin-induced ulcers. OSE significantly healed ulcers induced by 50% acetic acid after 5 and 10 days treatment OSE (100 mg/kg) significantly inhibited the offensive acid-pepsin secretion and lipid peroxidation and increased the gastric defensive factors like mucin secretion, cellular mucus, and life span of mucosal cells and had antioxidant effect, but did not induce mucosal cell proliferation. The results indicate that the ulcer protective and healing effects of OSE may be due to its effects both on offensive and defensive mucosal factors.

Some novel substituted azetidin-2-ones (5-8) were synthesized via [2 + 2] cycloaddition reactions of imines and ketenes and evaluated for their ability to prevent diet and diabetes induced hypercholesterolemia. The test compounds 5a and 7a significantly (p < 0.01) inhibited the rise in serum total cholesterol induced by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%) diet in both acute and chronic models in a dose dependent manner. Compound 5a also raised the high density lipoprotein-cholesterol levels in chronic diet models by peanut oil (5.5%), cholesterol (1.5%) and cholic acid (0.5%). In a diabetes induced model of hypercholesterolemia, the test compounds were evaluated for preventing diabetes-induced hypercholesterolemia (protocol 1) as well as for lowering post diabetic hypercholesterolemia (protocol 2). Test compounds 5a-g and 7a-d significantly (p < 0.05) reduced serum total cholesterol with a greater reduction in protocol 1 as compared with protocol 2. Based on SAR studies, the substituents that favor hypocholesterolemic activity around the azetidin-2-one nucleus are discussed and a possible mechanism of action is proposed on the basis of their differential effects in two protocols of diabetes-induced hypercholesterolemia.

A systematic approach through computer assisted design to identify novel quinazolines having anxiolytic and GABAergic activity has been reported.

Gastric ulcers were induced in normal/NIDDM rats by various physical (2 hr cold restraint stress and 4 hr pylorus ligation) and chemical agents (ethanol, 1 ml/200 g, oral, 1 hr before; aspirin, 200 mg/kg, oral, 4 hr) and duodenal ulcers were induced by cysteamine (40 mg/200 g). Ulcer healing activity was studied in gastric ulcers induced by acetic acid (50%) and HCI (0.6 M). The result indicated that in both, normal and NIDDM rats, B. monniera extract (BME, 20-100 mg/kg) did not show any significant effect on blood glucose level, while A. indica (AIE, 250-1000 mg/kg) significantly decreased it. However, both BME (50 mg/kg) and AIE (500 mg/kg) showed significant anti-ulcer and ulcer-healing activities in normal and NIDDM rats. Further, the present results also indicated that the ulcer protective effects of BME was more pronounced in non-diabetic, while that of AIE was more in NIDDM rats. The anti-ulcer and ulcer-healing activities of BME and AIE may be due to their effects on various mucosal offensive and defensive factors, and correction of blood sugar level by AIE may help to have more ulcer protective effect in NIDDM rats.

Oxidative stress is believed to initiate and aggravate many diseases including peptic ulcers and gastric carcinoma. We observed an increase in rat gastric mucosal lipid peroxidation (LPO) and superoxide dismutase (SOD) and a decrease in catalase (CAT) levels in cold restraint stress-induced gastric ulceration while, in clinical peptic ulceration and gastric carcinoma patients, an increase in serum LPO and a tendency to decrease in SOD and CAT levels were observed. The result thus, indicated a positive correlation between free radical-induced oxidative stress both in gastric and duodenal ulcers and gastric carcinoma.

Asparagus racemosus is an Ayurvedic rasayana, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of methanolic extract of fresh roots of A. racemosus (ARM), 25-100 mg/kg given orally, twice daily for 5 days, was studied on different gastroduodenal ulcer models. ARM 50 mg/kg, twice daily, orally (total saponins 0.9%) showed significant protection against acute gastric ulcers induced by cold restraint stress (CRS), pyloric ligation, aspirin plus pyloric ligation, and duodenal ulcers induced by cysteamine. ARM in the above dose also significantly healed chronic gastric ulcers induced by acetic acid after 10 days treatment. However, ARM was ineffective against aspirin- and ethanol-induced gastric ulcers. Further, gastric juice and mucosal studies showed that ARM significantly increased the mucosal defensive factors like mucus secretion, cellular mucus, life span of cells and also possessed significant anti-oxidant effect, but had little or no effect on offensive factors like acid and pepsin.

Effect of methanolic extract of P. Pinnata roots (PPRM) was studied against various experimental gastric ulcer models and offensive and defensive gastric mucosal factors in rats. An initial dose-response study using 12.5-50 mg/kg P. Pinnata root extract, when given orally in two divided dose for 4 days + 5th full dose on the day of experiment 60 min before the experiment, indicated 25 mg/kg as an optimal regimen and was used for further study. PPRM showed significant protection against aspirin and 4 hr PL, but not against ethanol-induced gastric ulceration. It showed tendency to decrease acetic acid-induced ulcer after 10 days treatment. Ulcer protective effect of PPRM was due to augmentation of mucosal defensive factors like mucin secretion, life span of mucosal cells, mucosal cell glycoproteins, cell proliferation and prevention of lipid per oxidation rather than on the offensive acid-pepsin secretion.

Bacopa monniera is an Indian tratidional medicine widely used to improve intellectual functions. Earlier, we had reported the prophylactic and curative effects of standardized extract of Bacopa monniera (BME) in various gastric ulcer models. The effect was due to augmentation of the defensive mucosal factors like increase in mucin secretion, life span of mucosal cells and gastric antioxidant effect rather than on the offensive acid-pepsin secretion. The present study includes evaluation of standardized BME (bacoside A content--35.5 +/- 0.9) on other contributing factors towards ulcerogenesis. BME in the dose of 1000 microg/ml showed anti-Helicobacter pylori activity in vitrol and in the dose of 10 microg/ml increased in vitro of prostanoids (PGE and PGI2) in human colonic mucosal incubates. It may be concluded that these factors may contribute to antiulcerogenic activity of BME.

Satavari mandur (SM) is a herbo-mineral preparation containing Asparagus racemosus, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of SM, 125-500 mg/kg given orally, twice daily for three, five and seven days, was studied on cold restraint stress-induced gastric ulcer in rats. The effective regimen was found to be 250 mg/kg given for five days and hence was used for further experiments. SM showed significant protection against acute gastric ulcers induced by pyloric ligation but was ineffective against aspirin- and ethanol-induced ulcers. Further, gastric juice studies showed that, SM significantly increased the mucosal defensive factors like mucus secretion, but had little or no effect on offensive factors like acid and pepsin secretion.

The ulcer protective potential of methanolic extract of Emblica officinalis Gaertn. (EOE) was assessed in different acute gastric ulcer models in rats induced by aspirin, ethanol, cold restraint stress and pyloric ligation and healing effect in chronic gastric ulcers induced by acetic acid in rats. EOE, 10-50 mg/kg administered orally, twice daily for 5 days showed dose-dependent ulcer protective effects in all the above acute ulcer models (36.0-98.3% protection, P < 0.2 to P < 0.001) and significant ulcer healing effect in dose of 20 mg/kg after 5 (control ulcer index: 20.2+/-2.3 mm(2)/rat, % healing 59.6%, P < 0.001) and 10 (control UI: 11.0+/-1.7, % healing 65.5%, P < 0.01) days treatment. Further study on gastric mucosal factors showed that it significantly decreased the offensive factors like acid (acid output-control 118.7+/-12.1 microEq/4 h, EOE% decrease 65.9%, P < 0.01) and pepsin (peptic output-control 738.8 micromol/4 h, EOE% decrease 46.2%, P < 0.001) and increased the defensive factors like mucin secretion (TC:P ratio-control 1.21+/-0.15, EOE% increase 95.0%, P < 0.01), cellular mucus (TC:P ratio-control 1.16+/-0.13, EOE% increase 53.4%, P < 0.05) and life span of mucosal cells (DNA content of gastric juice-control 77.3+/-8.7 microg/m per 100 g body weight, EOE% decrease 42.1%, P < 0.05). EOE showed significant antioxidant effect in stressed animals (control UI 35.8+/-2.5, antioxidant status: LPO 0.58+/-0.03 nmol MDA/mg protein, SOD and CAT 227.8+/-6.3 and 18.4+/-1.2 U/mg protein respectively; EOE% decrease in UI 88.2%, mucosal LPO 69.0%, SOD 53.1% and increase in mucosal CAT 59.8%, P < 0.001 respectively) and did not have any effect on cell proliferation in terms of DNA microg/mg protein or glandular weight. The results showed that EOE had significant ulcer protective and healing effects and this might be due to its effects both on offensive and defensive mucosal factors., (Copyright 2002 Elsevier Science Ireland Ltd.)

Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a commonly used Ayurvedic drug for mental disorders. The standardized extract was reported earlier to have significant anti-oxidant effect, anxiolytic activity and improve memory retention in Alzheimer's disease. Presently, the standardized methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated for potential antidepressant activity in rodent models of depression. The effect was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days was found to have significant antidepressant activity in forced swim and learned helplessness models of depression and was comparable to that of imipramine.

Bacopa monniera Wettst. (BM, syn. Herpestis monniera L; Scrophulariaceae), is an Ayurvedic drug used as a rasayana. Its fresh juice was earlier reported to have significant antiulcerogenic activity. In continuation, methanolic extract of BM (BME) standardized to bacoside-A content (percentage-38.0 +/- 0.9), when given in the dose of 10-50 mg/kg, twice daily for 5 days, showed dose-dependent anti-ulcerogenic on various gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. BME in the dose of 20 mg/kg, given for 10 days, twice daily showed healing effects against 50% acetic acid-induced gastric ulcers. Further work was done to investigate the possible mechanisms of its action by studying its effect on various mucosal offensive acid-pepsin secretion and defensive factors like mucin secretion, mucosal cell shedding, cell proliferation and antioxidant activity in rats. BME 20 mg/kg showed no effect on acid-pepsin secretion, increased mucin secretion, while it decreased cell shedding with no effect on cell proliferation. BME showed significant antioxidant effect per se and in stressed animals. Thus, the gastric prophylactic and curative effects of BME may be due to its predominant effect on mucosal defensive factors.

Studies with plantain banana (Musa sapientum var. paradisiaca) have indicated its ulcer protective and healing activities through its predominant effect on various mucosal defensive factors [Sanyal et.al, Arch Int Pharmacodyn, 149 (1964) 393; 155 (1965) 244]. Oxidative stress and Helicobactorpylori colonization are considered to be important factors in the pathogenesis of gastric ulcers. In the present study methanolic extract of plantain banana pulp (BE) was evaluated for its (i) antiulcer and antioxidant activities in 2 hr cold restraint stress and (ii) anti-H.pylori activity in vitro. The extract (BE, 50 mg/kg, twice daily for 5 days) showed significant antiulcer effect and antioxidant activity in gastric mucosal homogenates, where it reversed the increase in ulcer index, lipid peroxidation and super oxide dismutase values induced by stress. However it did not produce any change in catalase values, which was significantly decreased by stress. Further, in the in vitro study. BE (0.32-1,000 microg/ml) did not show any anti-H.pylori activity. The results suggest absence of anti-H. pyloric activity of methanolic extract of banana in vitro and its antioxidant activity may be involved in its ulcerprotective activity.

Convolvulus pluricaulis is an indigenous plant commonly mentioned in Ayurveda, an ancient system of Indian medicine, as a rasayana which is mainly advocated for use in rejuvenation therapy. The present study was conducted to evaluate the potential anti-ulcerogenic effect of juice of fresh whole plants of C. pluricaulis (CPJ) against various experimental gastric ulcer models induced by ethanol, aspirin, 2 hr cold restraint stress and 4 hr pyloric ligation in rats. The drug was given orally twice daily for five days in the doses of 375 and 750 mg/kg body weight. CPJ showed anti-ulcerogenic effect at both doses in all the experimental gastric ulcer models and was comparable to the reference drug sucralfate (250 mg/kg). Gastric juice secretion and mucosal studies were undertaken to find out the possible mechanism of action of antiulcer effect by studying its effects both on offensive and defensive mucosal factors. The antiulcerogenic effect of CPJ was found to be due to augmentation of mucosal defensive factors like mucin secretion, lifespan of mucosal cells and glycoprotiens rather than on the offensive factors like acid-pepsin.

Centella asiatica is commonly mentioned as a Rasayana in Ayurveda, an ancient system of Indian medicine for various ailments including abdominal disorders. Rasayanas have been advocated for use in rejuvenation therapy. The present study was conducted to evaluate the possible anti-ulcerogenic activity of fresh juice of C. asiatica (CAJ) against ethanol-, aspirin-, cold-restraint stress- and pyloric ligation induced gastric ulcers in rats. The drug given orally in doses of 200 and 600 mg/kg twice daily for five days, showed significant protection against all the above experimental ulcer models and the results were comparable with those elicited by sucralfate (SF, 250 mg/kg, p.o., BD x 5 days). CAJ showed little or no effect on offensive acid-pepsin secretion. However, at 600 mg/kg CAJ significantly increased gastric juice mucin secretion and increased the mucosal cell glycoproteins signifying increase in cellular mucus. It also decreased cell shedding indicating fortification of mucosal barrier. Thus, the ulcer protective effect of CAJ may be due to strengthening of the mucosal defensive factors.

The anti-ulcerogenic effect of fresh juice from the whole plant of Bocapa monniera Wettst. (BMJ) commonly known as Brahmi in Hindi was examined using gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. Bocapa monniera juice (BMJ) at doses of 100 and 300 mg/kg and sucralfate at a dose of 250 mg/kg were given orally, twice daily for 5 days. BMJ 100-300 mg/kg produced significant antiulcer activity in all the experimental gastric ulcer models except in case of ethanol-induced ulcers where 100 mg/kg was not found to decrease it significantly. BMJ (100-300 mg/kg) was found to have little or no effect on the offensive acid-pepsin secretion, while cell shedding (microgram DNA/mg of protein) and mucin secretion in terms of total carbohydrates:protein ration (TC:P), the two important parameters of defensive factors were significantly decreased and increased respectively indicating enhancement of protective mucosal factors. Both BMJ (300 mg/kg) and SF showed tendency to increase the mucosal glycoproteins in terms of TC:P, though individual carbohydrates and total carbohydrates were either increased or showed a tendency to increase. Thus, ulcer protective effect of BMJ may be due to its effect on mucosal defensive factors like enhanced mucin secretion, mucosal glycoprotein and decreased cell shedding rather than on offensive factors such as acid and pepsin.

Use of Dipaniya Mahakasaya, a group consisting of 10 herbal drugs, has been suggested in Charaka Samhita to improve digestion. Out of these 10 plants, three, viz. P. longum (water decoction), Z. officianalis (water decoction) and Ferula species (colloidal solution) were studied for their antiulcer and mechanism of antiulcer effects in rats. All the drugs in the dose of 50 mg/kg, p.o., 60 min prior to experiment, showed significant protection against gastric ulcers induced by 2 hr cold restraint stress, aspirin (200 mg/kg, 4 hr) and 4 hr pylorus ligation. The antiulcerogenic effect seemed to be due to the augmentation of mucin secretion and decreased cell shedding rather than offensive acid and pepsin secretion which however, were found to be increased by them.

The effect of hypotonic medium (Distilled water: DW) and hypertonic saline (HS: 5% NaCl) compared to control normal saline (NS) was studied on gastric ulcer induced by aspirin, 6 h cold restraint stress, ethanol, and pylorus ligation in rats. DW did not afford any protection while HS showed significant ulcer protective effects in all gastric ulcer models studied. The cytoprotective effect of HS seemed to be not only due to its effect on gastric acid secretion but also its effect on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding. As determined by radioimmunoassay, DW did not produce any change in the accumulation of PGE and PGI2, while HS increased them significantly in the human gastric mucosal incubates compared to NS. However, in the incubates of human colonic mucosa, both DW and HS showed a significant increase in PGE with a tendency to increase in PGI2 accumulation.

The immunomodulatory effect of the bark of Albizzia lebbeck (Sirisha) was evaluated by studying humoral and cell mediated immune responses. The hot aqueous extract and its butanolic fraction were administered once daily for one week in mice, immunised previously with sheep red blood cells (SRBC). At the dose levels tested (6.25, 12.5 and 25 mg/kg, p.o.), A. lebbeck treated mice developed higher serum antibody titres compared to the vehicle treated group and the effect was comparable to the standard drug muramyl dipeptide (MDP). Delayed type hypersensitivity response was suppressed in SRBC immunised mice treated with A. lebbeck extract. The macrophage migration index remained unaltered in both mice and rats. These results are discussed in the light of possible immunopotentiating effects of A. lebbeck.

Objectives: The purpose of this study was to determine whether identification of contractile reserve with dobutamine would predict recovery of myocardial function during follow-up in patients with recent onset idiopathic dilated cardiomyopathy (IDC)., Background: The prognosis of patients presenting with new onset IDC is variable and difficult to predict., Methods: Twenty-two patients (17 men, 5 women, 46 +/- 14 years) with recently diagnosed IDC (4 +/- 3 months) underwent dobutamine echocardiography. Left ventricular ejection fraction (LVEF) and LV sphericity before and at peak dobutamine infusion (30 +/- 11 microg/kg/min) were determined. A follow-up echocardiographic assessment was done at 6 +/- 4 months., Results: The LVEF on dobutamine was directly related to baseline LV mass expressed as g/ml (Pearson r = 0.65, p = 0.0003). Baseline variables that were significantly predictive of follow-up LVEF were deceleration time (r = 0.69, p = 0.0006), wall motion score index (WMSI) (r = -0.63, p = 0.002), LV mass (r = 0.56, p = 0.008) and LVEF on dobutamine (r = 0.84, p = 0.0001). When either deceleration time or WMSI or LV mass was entered into a regression equation to predict follow-up LVEF, the LVEF on dobutamine added significantly to predictive power. However, if LVEF on dobutamine was entered first, none of the other three variables added significantly to prediction. Baseline LV sphericity at end diastole (ED) (r = 0.13, p = 0.6) did not correlate with follow-up LV sphericity in ED, whereas LV sphericity in ED on dobutamine (ED [r = 0.70, p = 0.0004]) correlated with LV sphericity in ED on follow up., Conclusions: This study demonstrates that dobutamine-induced improvement in baseline LVEF and LV sphericity identifies patients with IDC who exhibit substantial improvement in LV function and geometry over time.

Cells within the lateral hypothalamic area (LHA) are important in eating control. Glutamate or its analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), elicit intense eating when microinjected there, and, conversely, LHA-administered NMDA receptor antagonists suppress deprivation- and NMDA-elicited eating. The subunit composition of LHA NMDA receptors (NMDA-Rs) mediating feeding, however, has not yet been determined. Identifying this is important, because distinct second messengers/modulators may be activated by NMDA-Rs with differing compositions. To begin to address this, we detected LHA NR2A and NR2B subunits by immunoblotting and NR2B subunits by immunohistochemistry using subunit-specific antibodies. To help determine whether NMDA-Rs mediating feeding might contain these subunits, we conducted behavioral studies using LHA-administered ifenprodil, an antagonist selective for NR2A- and/or NR2B-containing NMDA-Rs at the doses we used (0.001-100 nmol). Ifenprodil maximally suppressed NMDA- and deprivation-elicited feeding by 63 and 39%, respectively, but failed to suppress KA-elicited eating, suggesting its actions were behaviorally specific. Collectively, these results suggest that LHA NMDA-Rs, some of which contribute to feeding control, are composed of NR2A and/or NR2B subunits, and implicate NR2A- and/or NR2B-linked signal transduction in feeding behavior.

Petroleum ether (PE), benzene (BE), chloroform (CE), acetone (AE) and ethanolic (EE) extracts (50-200 or 200 mg/kg, i.p. or 200 mg/kg, p.o.) of dried Abies pindrow leaves, given 30-45 min before showed significant anti-inflammatory (both against acute and sub-acute models), analgesic, barbiturate hypnosis potentiation and anti-ulcerogenic acitivities in rats. All the extracts except EE decreased swim stress immobility in mice indicating some degree of anti-depressant activity. Only PE exhibited hypotension in dogs blocked by atropine. Chemically, extracts showed the presence of glycosides, steroids, terpenoids and flavonoids. They had no anti-bacterial effect. However, toxicity studies indicated that the extracts had an extended safety index. The investigations are consonant with some of the uses of this plant in Ayurveda.

GABA and baclofen (BAC), a GABA-mimetic agent, were investigated for antiulcerogenic activity. Orally administered GABA (100 mg/kg) and BAC (10 mg/kg) showed significant ulcer protection when given either alone for one day or for 4 days, or when given together with aspirin (ASP; 200 mg/kg x 3 days) in their 4 days treatment time in pylorus-ligated rats. Both the drugs showed a tendency to increase acid and decrease peptic output, and increased gastric mucus secretion in terms of total carbohydrate to protein ratio (TC:P) in both the above treatment groups. ASP tended to decrease acid and increase peptic output and significantly decreased TC:P ratio. Both GABA and BAC tended to reverse aspirin-induced effects, though they had little per se effect on TC:P ratio of gastric mucosal glycoproteins except an increase in sialic acid content both after one day or four days treatment. No, per se, effect on cell shedding (DNA and protein content of gastric juice) or cell proliferation (DNA/mg protein) was noted with GABA or BAC but the enhanced cell shedding induced by ASP was attenuated by them. ASP was found to enhance cell proliferation. However, neither of drug showed any effect on cell proliferation when given either alone or in combination with ASP. The antiulcerogenic effect of GABA and BAC may be due to their predominant effects on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding or mucosal damage.

Oral administration of bergenin and norbergenin, two isocoumarins, isolated from the leaves and roots of Flueggea microcarpa and luvangetin, a pyranocoumarin isolated from the seeds of Aegle marmelos Correa, showed significant protection against pylorus-ligated and aspirin-induced gastric ulcers in rats and cold restraint stress-induced gastric ulcers in rats and guinea pigs. The study on prostaglandins release by human colonic mucosal incubates, indicated a concentration-dependent (1-10 micrograms/ml) stimulatory effect of bergenin and norbergenin, while luvangetin (1-10 micrograms/ml) did not produce any effect. The results suggest that gastroprotective effects of bergenin and norbergenin could be due to increased prostaglandin production while, some other mucosal defensive factors may be involved for luvangetin.

Four Sitavirya plants viz. Satavari (fresh root juice, 1250 mg/kg), Yastimadhu (water decoction of root, 600 mg/kg), Kutaja and Aswattha (water decoctions of bark; 400 and 500 mg/kg respectively) were studied for their effects on different models of gastroduodenal ulcers in rats, when given orally for 3 days. All of them were found to protect the animals against 2 hr cold restraint stress and pylorus ligation-induced gastric and cysteamine-induced duodenal ulcers. However, they were ineffective against acute aspirin-induced gastric ulcers. The antiulcerogenic effect could be due to their inhibitory effect on offensive acid-pepsin secretion and augmentation of mucosal defensive factors in terms of enhanced mucin secretion and decreased cell shedding.

Pongamia pinnata root has been advocated in Ayurveda for treatment of various inflammatory and infective conditions including ulcers. Sequential petroleum ether, benzene, chloroform, acetone and ethanolic extracts of P. pinnata roots when administered in the dose of 50 mg/kg, i.p. in rats was found to have anti-inflammatory, analgesic activity while pentobarbitone-induced 'sleep time' was reduced by all the extracts except petroleum ether which, however, enhanced it. They were also found to possess antiulcer effects when administered either by i.p. (45 min before) or oral route (45 min before or for 4 days) against restraint-stress or pylorus-ligated gastric ulcers in rats, the maximum protection being afforded by petroleum ether and ethanol extracts. The mechanism of antiulcer effect could either be due to decrease in acid-pepsin secretion and augmentation of mucin secretion as observed with ethanol extract, while petroleum ether extract might be producing the effect by virtue of its anti-stress activity.

Withafastuosin E (WE), a withanolide of Datura fastuosa, has been reported to possess anti-stress activity and augment prostaglandins. The present investigation has been undertaken to evaluate the anti-ulcer activity and its mechanism in various models of experimentally induced ulcers in rats. WE (20 mg/kg, po) reduced the incidence of ulcer and ulcer index significantly in rats. The drug also decreased volume of gastric secretion, acid and peptic output, though it did not affect mucin secretion or mucosal glycoprotein content in terms of total carbohydrate:protein ratio or gastric cell shedding (in terms of gastric juice DNA content) or cell replication (in terms of microgram DNA/mg of protein). The results suggest significant anti-ulcer activity of WE which may be due to its effect on decreasing the offensive acid-pepsin factors.

Direct ethanolic and sequential petroleum ether, chloroform, acetone and ethanolic extracts (50-100 mg/kg, i.p.) of P. pinnata seeds given 30-60 min before revealed anti-inflammatory, analgesic and anti-ulcerogenic activities in rats. The activities were present maximum in petroleum ether and chloroform extracts. However, the extracts also showed shortening of pentobarbitone induced 'sleep time' in rats.

Continuous infusion of gamma- aminobutyric acid (GABA) and baclofen (BAC) on gastric acid and pepsin secretion in perfused rat stomach showed that GABA (25-100 mg/kg/hr, i.v.) and BAC (1 mg/kg/hr, i.v.) increased the acid output which was blocked by bicuculline (Bicc, 1 mg/kg, i.v.) when given 30 min before their infusion. However, lower dose of GABA (5 mg/kg/hr) and hig her doses of BAC (5 or 10 mg/kg/hr) did not show any significant effect on acid secretion. GABA (5 and 25 mg/kg/hr) inhibited peptic output and again Bicc in the above dose inhibited the inhibitory effect of 25 mg/kg/hr of GABA on peptic output. The result indicate dichotomy on the effects of GABA on acid and pepsin secretion. As both the effects were blocked by Bicc, involvement of GABAA receptor may be a possibility. The antiulcer effect of GABA and BAC could not be due to their effect on gastric acid secretion, but may be due to inhibition of pepsin secretion by GABA or effects of GABA or BAC on mucosal defensive factors.

To elucidate the involvement of peripheral gamma- aminobutyric acid (GABA) and some GABA-mimetic agents in different models of gastric and duodenal ulcerations in rats and guinea pigs, effects of GABA, baclofen (GABAB agonist), diazepam, gamma-butyrolactone (GABA receptor agonist), sodium valproate, isoniazid (GABA-T inhibitor) and glycine (an inhibitory neurotransmitter), given po or ip were studied. All the drugs significantly reduced the ulcer index, incidence and number of ulcer in various models of gastric ulcers except glycine which failed to protect in reserpine-induced ulcers in rats. None of the drugs, except diazepam, had any protective effect on histamine-induced gastric ulcers in guinea pigs. Similarly, no protection was observed by any drug against cysteamine-induced duodenal ulcers in rats, while sodium valproate, isoniazid and glycine significantly decreased number of ulcers against histamine-induced duodenal ulcer in guinea pigs. The results suggest that GABA and GABA-mimetic agents, and glycine, an inhibitory neurotransmitter, afforded protection against some experimental models of peptic ulcer in rats. The effects appear to be due to their inhibitory effect on mucosal defensive factors.

Effect of UL-409, a multiconstituent herbal preparation was evaluated on different models of gastric ulcers in rats. In doses 25, 50 and 100 mg/kg. p.o. it significantly reduced the gastric secretory volume and ulcer index in pylorus ligated rats, and showed significant mucoprotective effect at 100 mg/kg dose on both acute and chronic treatment. UL-409(50 and 100 mg/kg doses) prevented immobilization induced gastric ulceration and showed significant mucosal protection. In forced swimming induced ulcers, UL-4093(50 and 100 mg/kg) completely abolished the ulcerogenesis and strengthened the mucosal barrier. It also protected the indomethacin-induced gastric ulcers and significantly increased the mucosal content. Cimetidine (10 mg/kg) and diazepam (20 mg/kg) were used for comparison. The results indicate that UL-409 has anti-ulcerogenic effects due to its mucoprotective effect. The preparation can be used alone or in combination with other ulcer healing agents.

Neurochemical effects of different fusarial toxins elaborated from F. moniliforme (FM) and F. oxysporum (FO) were investigated. FM showed significant nonspecific and irreversible monoamine oxidase (MAO) inhibition which was qualitatively comparable to that induced by nialamide, a nonselective MAO inhibitor. FO did not exhibit any significant MAO inhibitory effect. FM produced a dose related increase in monoamine concentrations (dopamine, noradrenaline and 5-hydroxytryptamine) in different rat brain areas namely, diencephalon-midbrain, caudate nucleus and pons-medulla. FO, on the contrary, produced marked increase in dopamine concentration in the caudate nucleus with concomitant reduction in noradrenaline levels in diencephalon-midbrain and pons-medulla with little effect on 5-HT concentration. The neurochemical effects of FM and FO are consonant with the earlier reports on the neuropharmacological profile of these toxins. Thus, FM was reported to have nialamide like activity, whereas FO actions were dopaminergic in nature.

The neuropharmacological activity profile of total fungal extract of F. oxysporum (FO) was investigated. FO enhanced spontaneous locomotor activity, exploratory behaviour and reduced pentobarbitone hypnosis. It had per se anticonvulsant action against maximal electroshock seizure (MES) and potentiated phenobarbitone and phenytoin in MES and also potentiated pentylenetetrazol (PTZ) convulsion. It antagonised morphine, tetrabenazine and haloperidol catalepsy. FO did not show per se analgesia or potentiation of morphine antinociception in mice, while both effects were present in rats. The effect of FO on body temperature was complex. It produced per se reduction in rectal temperature and potentiated the hypothermic responses of reserpine, apomorphine, PEA and I-dopa, and also the hyperthermic response of 5-HTP. The hyperthermic response of haloperidol was reversed by FO. It potentiated amphetamine and morphine lethality, amphetamine, PEA and apomorphine stereotypy, 5-HTP headtwitch response and post-swim grooming response. On swim-stress immobility, while the time of onset of immobility was reduced, FO did not modify the duration of immobility. On foot-shock induced aggression in paired rats, FO produced a decrease in the latency to onset of fighting behaviour and increased the total contact period and the cumulative aggressive score. FO potentiated clonidine automutilation. It has, thus, facilitated aggressive behaviour. The effects are likely to be due to the presence of fusaric acid in FO, which inhibits dopamine beta-hydroxylase and is known to have dopaminergic effects. This investigation has practical implications. since F. oxysporum is a common food contaminant.

The neuropharmacological profile of the total fungal extract of F. moniliforme (FM) has been investigated. FM produced dose related decrease in spontaneous motor activity (SMA) and exploratory activity, potentiated pentobarbitone hypnosis and the anticonvulsant actions of phenobarbitone and phenytoin against MES seizures, potentiated PTZ and tryptamine seizures, antagonised reserpine induced syndrome, attenuated tetrabenazine and morphine induced catalepsy and potentiated haloperidol catalepsy. FM showed per se antinociceptive activity and potentiated morphine analgesia. It increased rectal temperature, antagonised reserpine and apomorphine hypothermia and potentiated the hyperthermic response of haloperidol and 5-hydroxytryptophan (5-HTP) and hypothermic response of betaphenylethylamine (PEA) and L-dopa. FM had no per se effect on amphetamine lethality, but enhanced the lethality induced by morphine in aggregated animals. Stereotypy by amphetamine was potentiated while that of apomorphine was not affected. The behavioural response of 5-HTP and L-dopa was potentiated. FM had no effect on swim induced behavioural despair. The effect on aggressive behavior was complex, and while the cumulative aggressive score was reduced, the onset of fighting behaviour and contact period was increased. It also inhibited clonidine induced auto mutilation. Since earlier investigation had shown that FM, like nialamide, induced non-selective inhibition of monoamine oxidase (MAO), the results were compared with those induced by nialamide. A comparative profile of action reveals that the neuropharmacological action of FM are qualitatively similar to those induced by nialamide, and likely to be due to inhibition of MAO. The investigation has practical implications because F. moniliforme is a common contaminant of cereals and fruits.

The effect of continuous infusion (iv) of graded doses of methysergide (0.1-50 microgram(s)/kg/hr) was studied on basal and pentagastrin (5 microgram(s)/kg/hr) stimulated gastric acid secretion in anaesthetised rats by the slow, continuous stomach perfusion method. Both basal and pentagastrin stimulated acid secretion indicated a biphasic response. Methysergide induced stimulation at a lower dose of 1 microgram(s)/kg/hr and inhibition at higher doses of 20-50 microgram(s)/kg/hr. The stimulatory effect may be due to postsynaptic receptor blockade while the inhibitory effect at higher dose may be due to blockade of presynaptic 5-HT autoreceptors, or due to a direct inhibitory effect of unknown basis.

Twenty-three opponensplasties for ulnar median paralysis in 20 leprosy patients were performed by two different procedures i.e. extensor indicis proprius and flexor digitorum superficialis transfers using standard techniques. The results were evaluated using various objective and subjective, anatomical and functional parameters. Two tendon transfers appeared to be superior to single tendon two insertion transfers. It was concluded that if situation permits, two tendon transfers should be performed for combined ulnar median paralysis.

The current EPI methodology for identifying immunization coverage is simple and easy to carry out under field conditions and gives a good idea about immunization coverage. However, it is not useful for local managers. It does not identify small health units with poor performance. Information on performance at the local level is vital to enhance overall immunization coverage. Estimation of coverage on a small area basis can be made by Lot Quality Assurance Sampling (LQAS). LQAS was used in nine sub-centres of district Saharanpur. The methodology was found to be feasible and identified seven sub-centres with poor current performance. Although LQAS may not be a good substitute for current EPI methodology to evaluate immunization coverage in a large administrative area, it is suggested that LQAS is a useful additional method for routine monitoring and evaluation of health programmes on a small area basis, especially as the overall coverage increases.

Tamrabhasma (TMB), an Indian indigenous preparation of copper, was studied for its effects on factors related to rat gastric mucosal resistance. Rats of either sex treated with TMB (2.5 mg/kg po, twice daily for 3 days) showed (i) increased mucosal sialomucin and fucose contents; (ii) decreased gastric juice DNA and protein; and (iii) no change in DNA and the incorporation of [3H]-thymidine in to mucosal cell DNA. aspirin treatment decreased both the sialomucin and fucose contents, and increased DNA and incorporation of [3H]-thymidine in to mucosal cell DNA. However, aspirin increased gastric juice DNA and protein contents. Since gastric juice DNA and the incorporation of [3H]-thymidine into mucosal cell DNA indicate the rate of mucosal shedding and cell proliferation, the results indicate ways in which TMB may increase gastric mucosal resistance to damage.

The gastric antiulcer and ulcer healing effect of the ethanolic and aqueous extracts of the dried leaves of Wedelia calendulacea. Less was found to be significant. The effect of the aqueous extract was observed to be more pronounced in comparison with that of the ethanolic extract.