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Drug-induced long QT syndrome (DI-LQTS) is fatal and known to have a higher incidence in women rather than in men. Multiple risk factors potentiate the incidence of DI-LQTS, but the actual contribution of obesity remains largely unexplored. Correspondingly, the present study is aimed to evaluate the susceptibility of DI-LQTS in WNIN/Ob rat in comparison with its lean counterpart using 3-lead electrocardiography. Four- and eight-month-old female WNIN/Ob and their lean controls were used for the experimentation. Non-invasive blood pressure measurement and total body electric conductivity (TOBEC) analysis were carried out. After the baseline evaluations, animals were anesthetized with Ketamine (50 mg/kg). Haloperidol (12.5 mg/kg single dose) was administered intraperitoneally and ECG was taken at 0, 10, 20, 30, 60 min, and 24 h time points. Myocardial lystes were used to assess the BNP, protein carbonylation, and hydroxyproline content. Adiposity, as assessed by TOBEC, is higher in obese rats with elevated mean arterial blood pressure. Baseline-corrected QT interval (QTc) is significantly higher in the obese rat with a wider QRS complex. The incidence of PVC and VT are more intense in the obese rat. Haloperidol-induced QT prolongation in obese rats was rapidly induced than in lean, which was observed to remain till 24 h in obese groups while normalized in lean controls. Higher levels of BNP, protein carbonylation, hydroxyproline content, and relative heart weights indicated the presence of cardiac hypertrophy. The study provides preliminary evidence that obesity can be a potential risk factor for DI-LQTS with faster onset and longer subsistence.

The present study was aimed to evaluate the restorative efficacy of asiatic acid (AA), an active constituent in Centella asiatica (L.) in streptozotocin (STZ)-nicotinamide (NAD)-induced diabetic rats. Male Wistar albino rats were made diabetic with STZ-NAD administration and assessed the effect of AA (20, 30, and 40 mg/kg body weight per day, for 45 days) on body weight, glucose, insulin, insulin resistance, lipid metabolic parameters in plasma and tissue (liver and kidney), and histopathology of liver in control and experimental diabetic rats. A significant (p

AIM The human papilloma virus (HPV) type 16 and 18 causes nearly 70% of uterine cervical cancers. Oral administration of live Salmonella typhi Ty21a, expressing major capsid proteins (L1) of HPV 16 and 18 is a potential choice for immunization in adolescent girls under low resource settings. Present study aimed to assess the nonclinical safety of recombinant S. typhi expressing HPV 16 and 18 (rStHPV) proteins. METHODOLOGY The acute toxicity of rStHPV was tested by intranasal single dose administration, of 10 and 50 folds higher than clinical prophylactic dose, in mice and rat followed by monitoring their survival for 14 days. Sub-chronic toxicity was evaluated in rats and rabbits with prophylactic and 5 times (average) to clinical prophylactic dosages on scheduled days (1st, 3rd & 5th day) through oral and intranasal routes. The immune/allergic response of rStHPV was assessed in mice through intranasal and intra-peritoneal routes. Experimental animals were daily monitored for live phase, and clinical chemistry, haematology, immunotoxicology, immunogenic response and histopathological examination of vital organs on 15th, 29th and 93rd days. RESULTS No abnormal changes were noticed in live phase activity, clinical chemistry and haematology profile. The gross necropsy, organ weights and histopathology were found to be normal. No immunotoxicity was recorded as evaluated by tier I tests. Allergic immune response, as evaluated with IgE levels was also negative irrespective of test routes. On the other hand, a significant (P

Hormonal replacement therapy (HRT), as the first-line management of chronic menopausal syndrome (CMS) in women, has limited application due to adverse effects. We aimed to evaluate the therapeutic potential of a herbal alternative (HALT), durva swaras (DS) of Cynodon dactylon L. Pers., in a CMS rat model. Female Sprague-Dawley rats were subjected to Sham and ovariectomy (OVX) surgery. OVX rats received either 0.11 mg/kg oestrogen as a positive treatment control or 1 (DS1), 2 (DS2), and 4 (DS3) g/kg DS for 160 days. Vaginal smear tests indicated the menopausal status. Routine clinical examinations, weekly body weights (BW), serum calcium, proinflammatory cytokines, and reproductive hormones levels were monitored. Clinical chemistry, body composition, bone mineral density (BMD), uterotrophic response, bone morphometry, and histopathology of major organs were evaluated. BW of OVX rats increased by 18–25% compared to Sham. Total fat and fat percentage were significantly elevated in the oestrogen group compared to DS2, DS3, and OVX group. DS treatment groups showed the levels of TNF- α was slightly reduced, while IL-1β and IL-6 levels were significantly reduced (P

Obstructive sleep apnea is an outcome of obesity, resulting from abnormal upper airway structures. Our main objective was to assess the fat infiltration into the tongue of calorie-restricted rats and its consequences on upper airway obstruction in comparison with lean and obese rats. A total of 24 adults lean, obese and CR obese rats were included in the study. Body fat and lean body mass were determined by TOBEC, DXA measured fat depositions around the neck region, and radiographs of upper airway structure were analysed by digital X-ray. Ex vivo biochemistry was carried out for leptin, and lipids in blood/tissues, and fat infiltration by ORO staining. The tongue, masseter muscle fat, fibre and taste bud morphology was assessed by SEM. Body composition analysis showed higher body fat and low lean body mass in obese animals; DXA results showed excess fat around the neck region of obese rats. Higher triglyceride and reduced leptin levels were observed in CR obese rats compared to lean and obese rats. ORO and SEM analysis showed varying degree of fat accumulation among the groups. Tongue muscle fibres of obese rats showed rugged abnormal folding with an increase in width in comparison with calorie-restricted obese rats. The distance and width between the taste buds of calorie-restricted obese rats were reduced to the levels of lean rats. The calorie restriction in obese rats reduced the fat deposition around the neck and improves the upper airway structures, the morphology of tongue fibre and increased the stiffness of the tongue, thereby reducing the risk of obstructive sleep apnea.

Dietary restriction (DR) has been shown to increase longevity, delay onset of aging, reduce DNA damage and oxidative stress and prevent age-related decline of neuronal activity. We previously reported the role of altered ubiquitin proteasome system (UPS) in the neuronal cell death in a spontaneous obese rat model (WNIN/Ob rat). In this study, we investigated the effect of DR on obesity-induced neuronal cell death in a rat model. Two groups of 40-day-old WNIN/Ob rats were either fed ad libitum (Ob) or pair-fed with lean. The lean phenotype of WNIN/Ob rats served as ad libitum control. These animals were maintained for 6.5months on their respective diet regime. At the end of the study, cerebral cortex was collected and markers of UPS, endoplasmic reticulum (ER) stress and autophagy were analyzed by quantitative real-time polymerase chain reaction, immunoblotting and immunohistochemistry. Chymotrypsin-like activity of proteasome was assayed by the fluorimetric method. Apoptotic cells were analyzed by TUNEL assay. DR improved metabolic abnormalities in obese rats. Alterations in UPS (up-regulation of UCHL1, down-regulation of UCHL5, declined proteasomal activity), increased ER stress, declined autophagy and increased expression of α-synuclein, p53 and BAX were observed in obese rats and DR alleviated these changes in obese rats. Further, DR decreased TUNEL-positive cells. In conclusion, DR in obese rats could not only restore the metabolic abnormalities but also preserved neuronal health in the cerebral cortex by preventing alterations in the UPS.

Piper nigrum Linn (Piperaceae) (PnL) is used in traditional medicine to treat gastric ailments, dyslipidemia, diabetes, and hypertension.The present study explores the possible protective effects of P. nigrum extracts on high-fat diet-induced obesity in rats.High-fat diet-induced obese rats were treated orally with 200 mg/kg bw of different extracts (hexane, ethylacetate, ethanol, and aqueous extracts) of PnL for 42 d. The effects of PnL extracts on body composition, insulin resistance, biochemical parameters, leptin, adiponectin, lipid profile, liver marker enzymes, and antioxidants were studied.The HFD control group rats showed a substantial raise in body weight (472.8 ± 9.3 g), fat% (20.8 ± 0.6%), and fat-free mass (165.9 ± 2.4 g) when compared with normal control rats whose body weight, fat%, and fat-free mass were 314.3 ± 4.4 g, 6.4 ± 1.4%, and 133.8 ± 2.2 g, respectively. Oral administration of ethyl acetate or aqueous extracts of PnL markedly reduced the body weight, fat%, and fat-free mass of HFD-fed rats. In contrast to the normal control group, a profound increase in plasma glucose, insulin resistance, lipid profile, leptin, thiobarbituric acid reactive substance (TBARS), and the activities of lipase and liver marker enzymes, and a decrease in adiponectin and antioxidant enzymes were noted in HFD control rats. Administration of PnL extracts to HFD-induced obese rats significantly (p 0.05) restored the above profiles.PnL extracts significantly reduced the body weight, fat%, and ameliorated HFD-induced hyperlipidemia and its constituents.

Dolly Mushahary,1,2 Ragamouni Sravanthi,2 Yuncang Li,2 Mahesh J Kumar,1 Nemani Harishankar,4 Peter D Hodgson,1 Cuie Wen,3 Gopal Pande2 1Institute for Frontier Materials, Deakin University, Geelong, Australia; 2CSIR- Centre for Cellular and Molecular Biology, Hyderabad, India; 3Faculty of Engineering and Industrial Sciences, Swinburne University of Technology, Hawthorn, Australia; 4National Institute of Nutrition (ICMR), Tarnaka, Hyderabad, India Abstract: Development of new biodegradable implants and devices is necessary to meet the increasing needs of regenerative orthopedic procedures. An important consideration while formulating new implant materials is that they should physicochemically and biologically mimic bone-like properties. In earlier studies, we have developed and characterized magnesium based biodegradable alloys, in particular magnesium-zirconium (Mg-Zr) alloys. Here we have reported the biological properties of four Mg-Zr alloys containing different quantities of strontium or calcium. The alloys were implanted in small cavities made in femur bones of New Zealand White rabbits, and the quantitative and qualitative assessments of newly induced bone tissue were carried out. A total of 30 experimental animals, three for each implant type, were studied, and bone induction was assessed by histological, immunohistochemical and radiological methods; cavities in the femurs with no implants and observed for the same period of time were kept as controls. Our results showed that Mg-Zr alloys containing appropriate quantities of strontium were more efficient in inducing good quality mineralized bone than other alloys. Our results have been discussed in the context of physicochemical and biological properties of the alloys, and they could be very useful in determining the nature of future generations of biodegradable orthopedic implants. Keywords: osteoblasts, bone mineralization, corrosion, osseointegration, surface energy, peri-implant

Focal recruitment of monocytes and lymphocytes is one of the earliest detectable cellular responses in atherosclerotic lesion formation. Endothelium may regulate leukocyte recruitment by expressing specific adhesion molecules. Interleukin-18 is a proinflammatory cytokine that plays an important role in vascular pathologies. The present study highlights the modulation of adhesion molecules and PPAR-γ by IL-18 and proposes a novel feedback mechanism by which PPAR-γ may regulate IL-18 expression. Three groups of normal chow diet-fed, male Apo E−/− mice, aged 12 weeks (n = 6/group) were employed: Gp I, phosphate-buffered saline (PBS) (2 mo): Gp II, recombinant IL-18 (rIL-18) (1 mo) followed by PBS (1 mo); Gp III, rIL-18 (1 mo) followed by pyrrolidine dithiocarbamate (PDTC) (1 mo). Significantly augmented mRNA expression of ICAM-1 (~5.7-fold), VCAM-1 (~3.6-fold), and NF-κB (~7-fold) was observed in Gp II mice as compared to Gp I, whereas PPAR-γ expression was not altered. PDTC treatment caused a significant downregulation of ICAM-1 (~4.2-fold), VCAM-1(~2-fold), and NF-κB (~4.5-fold) and upregulation of PPAR-γ expression (~5-fold) in Gp III mice. A similar trend was observed in protein expression. In vivo imaging results demonstrated a marked increase in probe (CF750 dye conjugated to VCAM-1 antibody) fluorescence intensity for VCAM-1 expression in Gp II mice, whereas it was moderately decreased in Gp III. PPAR-γ was found to significantly downregulate both IL-18 levels and IL-18-induced adhesion molecules. The underlying mechanism was found to be via inhibition of NF-κB activity by PDTC, thereby leading to decreased adherence of monocytes to the activated endothelial cells and a step to halt the progression and development of atherosclerotic lesions.

Background: Several rodent models are available to study obesity and obesity associated diabetic problems. We developed an obese mutant rat model viz., WNIN/GR-Ob from our existing WNIN (Inbred Wistar) stock of rats, which exhibit hyperglycemia on challenge with oral glucose. Since such impaired glucose tolerance (IGT) is a fore runner to frank diabetes status, we carried out a study to challenge the animals with different purified carbohydrate sources (glucose, sucrose, starch) and see the outcome. Methods: 48 obese rats of both genders and equal number of lean littermates of 35 days of age were taken for the study and were divided in to four groups, A, B, C, and D. A group received purified glucose based diet, B, received purified sucrose, C, received purified starch and the D, served as the control, receiving standard laboratory rat chow developed at our centre, containing roasted bengal gram as the source of carbohydrate. All diets were isocaloric in nature and contained 56 % carbohydrate in principle. Animals were fed for 8 weeks and parameters like food intake, body weights, and plasma glucose and insulin levels were measured in experimental and control rats at initial, 4 weeks and 8 weeks. Results: As expected, food intake, body weight and feed efficiency ratio were significantly higher in obese rats of all groups as compared to their lean littermate controls and also higher in stock diet, compared to purified diets. Both lean and obese animals showed higher values of glucose and insulin on purified diets compared to control diet. But amongst lean and obese animals, the latter showed sexual dimorphism in their response, the situation being worse in starch fed (C) group. Amongst the obese animals, the males seem to suffer more, compared to females, in starch fed group, followed by glucose and sucrose fed in that order. Conclusions: WNIN/ GR-Ob rats thus seem to be a useful animal model, vulnerable to diet manipulations, especially to carbohydrates. This has the potential to be used as a diabetic model, more akin to human systems, where diet is the major trigger for precipitating diabetes.

Maternal undernutrition increases the risk of adult chronic diseases, such as obesity and type 2 diabetes. This study evaluated the effect of maternal zinc restriction in predisposing the offspring to adiposity and altered insulin response in later life. Seventy-day-old female Wistar/NIN rats received a control (ZnC) or zinc-restricted (ZnR) diet for 2 weeks. Following mating with control males, a subgroup of the ZnR dams were rehabilitated with ZnC diet from parturition. Half the offspring born to the remaining ZnR dams were weaned onto the ZnC diet and the other half continued on the ZnR diet throughout their life. Body composition, glucose tolerance, insulin response and plasma lipid profile were assessed in male and female offspring at 3 and 6 months of age. The ZnR offspring weighed less than control offspring at birth and weaning and continued so until 6 months of age. Rehabilitation regimens corrected the body weights of male but not female offspring. Maternal zinc restriction increased the percentage of body fat and decreased lean mass, fat-free mass and fasting plasma insulin levels in both male and female offspring at 6 months of age. Also, glucose-induced insulin secretion was decreased in female but not male offspring. Despite the differences in fasting insulin and the area under the curve for insulin, the fasting glucose and the area under the curve for glucose were in general comparable among offspring of different groups. Rehabilitation from parturition or weaning partly corrected the changes in the percentage of body fat but had no such effect on other parameters. Changes in plasma lipid profile were inconsistent among the offspring of different groups. Thus chronic maternal zinc restriction altered the body composition and impaired the glucose-induced insulin secretion in the offspring.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Epidemiological evidence suggests that some adult diseases like insulin resistance syndrome and diseases associated with it originate in fetal life. The role of maternal macronutrient malnutrition but not of micronutrients in the fetal origin of adult disease is well studied. We hypothesise that chronic maternal vitamin restriction predisposes the offspring to insulin resistance syndrome.Female weanling Wistar/NIN rats received a control diet ( n=6) or a 50% vitamin-restricted diet ( n=14) for 12 weeks and mated with control males. Four dams on the restricted diet were shifted to the control diet from parturition. Pups born to the remaining 10 dams on the restricted diet were weaned on to control diet or continued on the restricted diet. All groups had 8 male pups from weaning onwards.Birthweights of pups were comparable among different groups. Weaning body weights were low in the restricted diet group, but on rehabilitation they caught up with control animals by post-natal day 100. None of the pups had impaired oral glucose tolerance and their insulin resistance status was comparable on days 40, 70, 100 and 180. Compared with offspring on the control diet, offspring on the restricted diet had a significantly higher percentage of body fat and higher plasma triglycerides, as well as lower lean body mass and fat-free mass. They also had increased oxidative stress. Rehabilitation from parturition or weaning prevented the changes in body fat percent, lean body mass, fat-free mass and oxidative stress.Since changes in adiposity and fat metabolism are considered forerunners of insulin resistance syndrome, our observations suggest that maternal dietary vitamin restriction predisposes the offspring to insulin resistance syndrome in later life.

BACKGROUND: Maternal undernutrition is hypothesized to predispose the offspring to disease in adult life. The relevance of maternal macronutrient deficiency has been well studied but not that of micronutrients. OBJECTIVE: To assess the effect of maternal dietary mineral restriction per se on oral glucose tolerance (OGT), insulin resistance (IR) and fat metabolism in offspring. DESIGN: Female weanling Wistar/NIN rats received a control or a 50% mineral-restricted (MR) diet for 12 weeks, by which time MR rats had lower plasma Fe, Zn, Mg and Ca concentrations. Following mating with control males, a third of the MR dams were shifted to the control diet from parturition. Half of the pups born to the remaining MR dams were weaned onto the control diet while the other half continued on the MR diet. RESULTS: Pregnant MR dams had a higher abortion rate, body weights of their pups at birth and weaning were lower and rehabilitation had no beneficial effect. No offspring had impaired OGT, and IR status was comparable among different groups on postnatal days 40, 70, 100 or 180. Compared with controls, total body electrical conductivity measurements indicated significantly higher body fat %, lower lean body mass and fat-free mass in MR offspring besides elevated plasma triacylglycerols. Mineral rehabilitation from parturition or weaning had little effect on these changes, which did not appear to be due to increased oxidative stress. CONCLUSIONS: Maternal MR per se resulted in an increase in body fat and in plasma triacylglycerol concentrations in the offspring. These changes had, however, no discernable effect on insulin sensitivity over the first 180 days of life.

Biodegradable magnesium–zirconia–calcium (Mg–Zr–Ca) alloy implants were coated with Collagen type-I (Coll-I) and assessed for their rate and efficacy of bone mineralization and implant stabilization. The phases, microstructure and mechanical properties of these alloys were analyzed using X-ray diffraction (XRD), optical microscopy and compression test, respectively, and the corrosion behavior was established by their hydrogen production rate in simulated body fluid (SBF). Coll-I extracted from rat tail, and characterized using fourier transform infrared (FT-IR) spectroscopy, was used for dip-coating the Mg-based alloys. The coated alloys were implanted into the femur bones of male New Zealand white rabbits. In vivo bone formation around the implants was quantified by measuring the bone mineral content/density (BMC/BMD) using dual-energy X-ray absorptiometry (DXA). Osseointegration of the implant and new bone mineralization was visualized by histological and immunohistochemical analysis. Upon surface coating with Coll-I, these alloys demonstrated high surface energy showing enhanced performance as an implant material that is suitable for rapid and efficient new bone tissue induction with optimal mineral content and cellular properties. The results demonstrate that Coll-I coated Mg–Zr–Ca alloys have a tendency to form superior trabecular bone structure with better osteoinduction around the implants and higher implant secondary stabilization, through the phenomenon of contact osteogenesis, compared to the control and uncoated ones in shorter periods of implantation. Hence, Coll-I surface coating of Mg–Zr–Ca alloys is a promising method for expediting new bone formation in vivo and enhancing osseointegration in load bearing implant applications.

Novel Mg–Zr–Sr alloys have recently been developed for use as biodegradable implant materials. The Mg–Zr–Sr alloys were prepared by diluting Mg–Zr and Mg–Sr master alloys with pure Mg. The impact of Zr and Sr on the mechanical and biological properties has been thoroughly examined. The microstructures and mechanical properties of the alloys were characterized using optical microscopy, X-ray diffraction and compressive tests. The corrosion resistance was evaluated by electrochemical analysis and hydrogen evolution measurement. The in vitro biocompatibility was assessed using osteoblast-like SaOS2 cells and MTS and haemolysis tests. In vivo bone formation and biodegradability were studied in a rabbit model. The results indicated that both Zr and Sr are excellent candidates for Mg alloying elements in manufacturing biodegradable Mg alloy implants. Zr addition refined the grain size, improved the ductility, smoothed the grain boundaries and enhanced the corrosion resistance of Mg alloys. Sr addition led to an increase in compressive strength, better in vitro biocompatibility, and significantly higher bone formation in vivo. This study demonstrated that Mg–xZr–ySr alloys with x and y ⩽5 wt.% would make excellent biodegradable implant materials for load-bearing applications.

We are maintaining two obese mutant rat strains (WNIN/Ob and WNIN/GR-Ob) in our animal facility since 1997. These rat colonies are perpetuated by crossing heterozygous littermates, since the obese phenotypes of both genders turned out be infertile. The present study revealed the reasons for this infertility. The male obese rats, though appeared normal in terms of sperm count, sperm motility and testis histology, however found wanting in terms of libido. This appeared to be due to low circulating testosterone levels seen in these animals, which should also account for low testis and accessory gland weights seen in them. The females exhibited delayed puberty, in terms of days taken for opening of vagina, irregular oestrus cycles and had small ovaries and short and stumpy uterine horns. The FSH peak observed in control lean animals during oestrus stage of the sexual cycle and also the E2 peak of normal oestrus cycle was conspicuously absent in these animals. They also showed elevated levels of progesterone throughout the sexual cycle. Thus the infertility seen in these mutants could be attributed to their abnormal gonadosteroid levels and the resulting anatomical and physiological defects.

OBJECTIVE We demonstrated previously that chronic maternal micronutrient restriction altered the body composition in rat offspring and may predispose offspring to adult-onset diseases. Chromium (Cr) regulates glucose and fat metabolism. The objective of this study is to determine the long-term effects of maternal Cr restriction on adipose tissue development and function in a rat model. RESEARCH DESIGN AND METHODS Female weanling WNIN rats received, ad libitum, a control diet or the same with 65% restriction of Cr (CrR) for 3 months and mated with control males. Some pregnant CrR mothers were rehabilitated from conception or parturition and their pups weaned to control diet. Whereas some CrR offspring were weaned to control diet, others continued on CrR diet. Various parameters were monitored in the offspring at three monthly intervals up to 15–18 months of age. RESULTS Maternal Cr restriction significantly increased body weight and fat percentage, especially the central adiposity in both male and female offspring. Further, the expression of leptin and 11 β-hydroxysteroid dehydrogenase 1 genes were significantly increased in CrR offspring of both the sexes. Adipocytokine levels were altered in plasma and adipose tissue; circulating triglyceride and FFA levels were increased, albeit in female offspring only. Rehabilitation regimes did not correct body adiposity but restored the circulating levels of lipids and adipocytokines. CONCLUSIONS Chronic maternal Cr restriction increased body adiposity probably due to increased stress and altered lipid metabolism in WNIN rat offspring, which may predispose them to obesity and associated diseases in later life.

Maternal undernutrition increases the risk of adult chronic diseases, such as obesity and type 2 diabetes. This study evaluated the effect of maternal zinc restriction in predisposing the offspring to adiposity and altered insulin response in later life. Seventy-day-old female Wistar/NIN rats received a control (ZnC) or zinc-restricted (ZnR) diet for 2 weeks. Following mating with control males, a subgroup of the ZnR dams were rehabilitated with ZnC diet from parturition. Half the offspring born to the remaining ZnR dams were weaned onto the ZnC diet and the other half continued on the ZnR diet throughout their life. Body composition, glucose tolerance, insulin response and plasma lipid profile were assessed in male and female offspring at 3 and 6 months of age. The ZnR offspring weighed less than control offspring at birth and weaning and continued so until 6 months of age. Rehabilitation regimens corrected the body weights of male but not female offspring. Maternal zinc restriction increased the percentage of body fat and decreased lean mass, fat-free mass and fasting plasma insulin levels in both male and female offspring at 6 months of age. Also, glucose-induced insulin secretion was decreased in female but not male offspring. Despite the differences in fasting insulin and the area under the curve for insulin, the fasting glucose and the area under the curve for glucose were in general comparable among offspring of different groups. Rehabilitation from parturition or weaning partly corrected the changes in the percentage of body fat but had no such effect on other parameters. Changes in plasma lipid profile were inconsistent among the offspring of different groups. Thus chronic maternal zinc restriction altered the body composition and impaired the glucose-induced insulin secretion in the offspring.

Azadirachta indica, popularly known as 'Neem' in India, is widely grown all over the tropics. The seed contains 45% oil and is a minor oil of considerable potential. Neem oil is bitter and inedible. Recently, a method has been developed to completely remove the bitter and odoriferous principles and leave a bitterless, odourless and colourless oil. The nutritional and chemical evaluation of debitterized neem oil (NO) was reported earlier (C. Rukmini, Food Chemistry 1987, 26, 119). We report here a three-generation study, carried out according to WHO/FDA protocol in groups of 15 male and 15 female rats fed a diet containing 10% NO or groundnut oil (GNO). Reproductive toxicology was monitored for three generations. The results obtained in both the matings in all the three generations did not show any adverse effects on the reproductive parameters studied in rats fed NO and were similar to those observed in rats fed GNO. The mean organ weights and the histopathological evaluation of all the organs were similar to those of the control (GNO-fed) rats. A mutagenicity test of NO was also found to be negative in Ames test as reported earlier (K. Polasa and C. Rukmini, Food and Chemical Toxicology 1987, 25, 763). These studies indicate that NO devoid of all the bitter and odoriferous principles, may be recommended as safe for consumption by humans.