Anti-hyperglycemic compound (GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds, its purification and effect in diabetes mellitus

An anti-hyperglycemic compound named GII was purified from the water extract of the seeds of fenugreek (T. foenum-graecum) and shown to be different from trigonelline and nicotinic acid isolated earlier from the same plant. GII (50 mg/kg body weight, po) reduced blood glucose in glucose tolerance test (GTT) in the sub-diabetic and moderately diabetic rabbits and significantly reduced the area under the curve (AUC) of GTT. Treatment for 7 days of the sub-diabetic rabbits with GII (50 mg/kg body weight, po) improved glucose tolerance without reducing fasting blood glucose (FBG) which was nearly normal. The results suggest that there is no risk of hypoglycemia in near normal animals (may be humans also) with abnormal GTT. Treatment of the moderately diabetic rabbits with GII (100 mg/kg body weight for 3 weeks) reduced FBG to nearly normal value and improved GTT. GII was more effective than the standard drug tolbutamide. Intermittent therapy given on days 1-5, 11-15, 26-30 and 56-60 to moderately diabetic rabbits leaving in between days without treatment brought down FBG to normal and AUC during GTT was normal. After 15 days treatment with GII (100 mg/kg body weight for 3 weeks) glycosylated hemoglobin came down and insulin increased to normal values in the sub-diabetic, moderately diabetic and severely diabetic rabbits. GII treatment (100 mg/kg body weight for 15 days) brought down all the altered serum lipids (TC, HDLC, TAG, PLs and FFAs) to normal levels. The results suggest that intermittent therapy, instead of daily therapy is possible and GII has good potential as an oral anti-diabetic drug with intermittent therapy.     

C3 deposition in cholesterol-induced atherosclerosis in rabbits: a possible etiologic role for complement in atherogenesis.

Hypercholesterolemia was induced in rabbits by feeding Purina Chow supplemented with cholesterol (5 g/kg body weight/day). The serum cholesterol levels of these rabbits increased progressively and after 3 to 5 months were 4 to 9-fold greater than those of the control animals. Decrease in total hemolytic complement was not apparent during the feeding regimen. Morphologic examination of aortae of these hypercholesterolemic rabbits showed typical atherosclerotic intimal plaques. Immunofluorescent microscopy with fluorescein (F)-labeled anti-rabbit C3 showed deposition of C3 in the intimal and inner medial layers as early as 3 months on high cholesterol diet. C3 deposits were also observed in the renal glomeruli and in the walls of coronary arteries. However, fluorescent studies failed to demonstrate the presence of IgG, IgM, and C4 at these sites. Tissues from control animals fed normal diets were negative for immunoglobulins, C3, and C4. These results suggest that the complement system may be implicated in the pathogenesis of cholesterol-induced atherosclerosis in rabbits.     

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.     

Differential effect of polyherbal,antiobesity preparation,OB-200G in male and female mice and monosodium glutamate-treated rats

Effect of administration of different doses (0.25, 0.5, 1 and 2 g/kg, twice daily, po) of a polyherbal preparation, OB-200G and fluoxetine (10 mg/kg, ip) for 21 days was studied on food intake and body weight in male and female Laka mice. The study further investigated the effect of administration of 0.5 g/kg dose of OB-200G for 40 days on body weight, fat pad weights, locomotor activity and biochemical parameters in monosodium glutamate (MSG)-treated male and female Wistar rat pups. Administration of OB-200G produced dose dependent decrease in body weight in both male and female mice. On the other hand, fluoxetine decreased body weight only in female mice. The food intake was significantly (P < 0.05) increased in both fasted male and female mice after treatment with the lower dose (0.25 g/kg, po) of OB-200G. However, significant (P < 0.05) decrease in food intake was recorded with the administration of higher doses (0.5, 1 and 2 g/kg, po) of OB-200G and fluoxetine in fasted female mice on day 1, 7, 14 and 21. But in male mice differential effect on food intake was recorded at different doses on day 1, 7, 14 and 21. Further, OB-200G administration significantly (P < 0.05) decreased body weight and fat pad weights, increased serum glucose levels and ambulatory activity in MSG-treated female rats but not in MSG-treated male rats. The results suggest that OB-200G involves gender differences in mediating its antiobesity effect and may supplement the current armamentarium for the treatment of obesity.     

Cannabinoid-1 receptor antagonists reduce caloric intake by decreasing palatable diet selection in a novel dessert protocol in female rats

Although many feeding protocols induce obesity, few use multiple foods to analyze diet selection within a single group of animals. To this end, we describe a protocol using time-limited access to a dessert that induces hyperphagia and body weight gain while allowing simple analysis of diet selection. Female retired breeder Sprague-Dawley rats were provided with ad libitum access to standard moist chow (1.67 kcal/g) and daily 8-h nocturnal access to either a sugar gel (SG; 0.31 kcal/g) or sugar fat whip (SFW; 7.35 kcal/g) for 15 days, and food intake and body weight were measured daily. Rats given SFW reduced moist chow intake but not enough to compensate for the large amount of calories consumed from SFW, and thus gained weight. We use this SFW overconsumption protocol to investigate the hypothesis that cannabinoid (CB)1 receptor antagonists reduce caloric intake by selectively decreasing consumption of palatable foods. In two experiments, female retired breeder Sprague-Dawley rats were injected with either Rimonabant (1 mg/kg ip) or vehicle (equal parts polyethylene glycol and saline, 1 ml/kg ip) for 7 days, or one of three doses of AM251 (0.3, 1.0, or 3.0 mg/kg ip), or vehicle for 15 days; food intake and body weight were measured daily. Both Rimonabant and AM251 decreased 24-h caloric intake, but the reduction was specific to a decrease in SFW consumption. This supports the hypothesis that these CB1 receptor antagonists impact feeding by modulating the perception of palatability.     

Ameltolide. I: Developmental toxicology studies of a novel anticonvulsant

Ameltolide, a novel anticonvulsant agent, has been shown in animal models to be effective in controlling seizures. The developmental toxicity of ameltolide was evaluated in two species. Naturally mated rats and rabbits were dosed once daily by gavage on gestation days (GD) 6-17 and 6-18, respectively. Rats were given doses of 0, 10, 25, or 50 mg/kg; rabbits were given 0, 25, 50, or 100 mg/kg. Laparotomy was performed on rats on GD 20 and on rabbits on GD 28. In rats, maternal toxicity was indicated at the 25- and 50-mg/kg dose levels by depressed body weight gain. Fetal body weight was depressed at the 50-mg/kg dose level. Fetal viability and morphology were not affected. The no-observed effect levels (NOEL) for adult and developmental toxicity in the rat were 10 and 25 mg/kg, respectively. In rabbits, maternal toxicity was indicated by a net loss in body weight at the 50- and 100-mg/kg dose levels. Fetal viability and body weight were depressed at the 100 mg/kg dose level. Shortened digits occurred on the right forepaw of one fetus at the 50-mg/kg dose level (in conjunction with severe maternal toxicity) and on the hindpaws of two fetuses from separate litters at the 100-mg/kg dose level. Incomplete ossification of the phalanges occurred on the forepaws of nine fetuses from four litters at the 100-mg/kg dose level. Ameltolide was weakly teratogenic in the rabbit. The NOEL for adult and developmental toxicity in the rabbit was 25 mg/kg.     

The influence of sulphur,molybdenum and cadmium exposure on the growth of goat,cattle and pig

A three factorial designed feeding experiment with common carp (Cyprinus carpio L.) was carried out in an intensive experimental rearing system. Fish (initial body weight 200 g) were fed on two different levels of dietary energy (16 and 18 MJ DE/kg DM), two different levels of protein (320 and 420 g CP/kg DM) and also two different feeding intensities (100% and 75% of the maximum intake). The experiment was terminated when fish reached a mean body weight of 1300 g.

Growth, feed utilization and nutrient composition of the whole body and fillet were observed. The highest growth was obtained when the fish were fed on the diet containing high dietary energy and high dietary protein with satiation feeding. High dietary energy, high dietary protein and restriction of feed intake improved feed conversion ratios. High dietary energy, low dietary protein and restrictive feeding increased energy utilization. Low dietary protein and restrictive feeding resulted in better protein utilization.

Fish fed with high dietary energy contained more fat and less protein in their carcasses. A lower fat content but higher protein and higher ash content in fish carcasses was shown when fish were fed with a diet high in protein and fed restrictively.     

Effects of feed restriction during organogenesis on embryo-fetal development in rabbit

BACKGROUND: Appropriate maternal nutrition and body weight gain during pregnancy is well established as a major factor in healthy prenatal development in humans. Given the role of nutrition and body weight gain in normal development, pharmaceuticals intended to reduce appetite and promote weight loss will generate developmental toxicity data that may be challenging to interpret. To aid with this, the effects of feed restriction, and subsequent reduction in maternal body weight gain, on embryo-fetal development was investigated in the rabbit. METHODS: Groups of 15 pregnant New Zealand White rabbits were offered 150 (control), 110, 75, 55, 35, and 15 g feed/day from gestation day (GD) 7-19. Cesarean sections were carried out on GD 29 and fetuses were examined for external, visceral, and skeletal development. RESULTS: Maternal body weights at the end of the feed restriction period (GD 20) were 0.97, 0.98, 0.93, 0.94, and 0.86 x control for the 110, 75, 55, 35, and 15 g feed/day groups, respectively. Only at 15 g feed/day was there a net maternal body weight loss (the GD 20 body weight was 0.93 x the GD 6 body weight) at the end of the feed restriction period. Six does aborted in the 15 g feed/day group; there were no other abortions associated with feed restriction. Fetal body weight was significantly reduced at 75, 55, 35, and 15 g feed/day (0.95, 0.90, 0.86, and 0.84 x control, respectively). There were no external or visceral malformations or variations, and no skeletal malformations associated with feed restriction. The incidence of fetuses with sternebrae 5 or 6 unossified was increased at feed levels < or = 75 g/day. At a feed level of 35 g/day there was an increase in unossified metatarsals and metacarpals, and an increase in the number of fetuses with a reduced number of caudal vertebrae ossified. Although these findings were not increased at a feed level of 15 g/day, the lack of dose response was likely due to increased abortion and subsequent decrease in fetuses available for evaluation at 15 g feed/day. CONCLUSION: These data demonstrate that feed restriction to feed levels that produce substantial reductions in maternal body weight gain can result in developmental toxicity expressed by abortion, reduced fetal weight, and alterations in ossification. Abortion only occurred when feed was restricted to an amount that produced maternal body weight loss (15 g feed/day) whereas reduced fetal weight and increased incidence of fetuses with unossified sternebrae, metatarsals, metacarpals, or caudal vertebrae were noted at feed levels of < or = 75 g/day. There were no fetal malformations associated with feed restriction.     

The effect of experimental, long-term exposure to low-dose zearalenone mycotoxicosis on the histological condition of ovaries in sexually immature gilts

Farm animals are at risk of exposure to zearalenone (ZEA) in feedstuffs, which may lead to aberrations in their reproductive development, thereby adversely affecting production outcomes. The objective of this study was to determine the effect of long-term (48 days), per os administration of low ZEA doses (50% [20 μg ZEA/kg body weight (bw)] and 100% [40 μg ZEA/kg bw] NOAEL values) on anatomopathological changes in the ovaries of sexually immature gilts. The experiment involved 12 clinically healthy gilts aged 2 months with an initial body weight of about 40 kg and a determined immune status. The animals were randomly divided into two experimental groups (E1, E2) and a control group (C; all n = 4). Group E1 received per os 20 μg ZEA/kg bw for 48 days; group E2 received per os 40 μg ZEA/kg bw for 48 days; and group C received per os placebo for 48 days. Analytical samples of the mycotoxin were administered daily per os in gelatine capsules before morning feeding. Animals were sacrificed at the end of the experiment. The results of anatomopathological examinations of the ovaries in immature gilts subjected to long-term, low-dose ZEA exposure showed that ZEA-induced experimental hyperoestrogenism lowered the proliferative ability of granulosa cells of the ovarian follicle walls and of the connective tissue of the ovarian stroma, in particular at the lower ZEA dose.     

The effect of calf nutrition on the performance of dairy herd replacements

Sixty-five Holstein-Friesian calves were randomly allocated to one of eight nutritional treatments at 4 days of age. In this factorial design study, the treatments comprised of four levels of milk replacer (MR) mixed in 6 l of water (500, 750, 1000 and 1250 g/day) × two crude protein (CP) concentrations (230 and 270 g CP/kg dry matter (DM)). MR was fed via automatic teat feeders and concentrates were offered via automated dispensers during the pre-wean period. MR and calf starter concentrate intake were recorded until weaning with live weight and body measurements recorded throughout the rearing period until heifers entered the dairy herd at a targeted 24 months of age. There was no effect of MR protein concentration on concentrate or MR intake, and no effect on body size or live weight at any stage of development. During the pre-weaning period, for every 100 g increase in MR allowance, concentrate consumption was reduced by 39 g/day. While, for every 100 g increase in the amount of MR offered, live weight at days 28 and 270 increased by 0.76 and 2.61 kg, respectively (P < 0.05). Increasing MR feed levels increased (P < 0.05) heart girth and body condition score at recordings during the first year of life, but these effects disappeared thereafter. Increasing MR feeding level tended to reduce both age at first observed oestrus and age at first service but no significant effect on age at first calving was observed. Neither MR feeding level nor MR CP content affected post-calving live weight or subsequent milk production. Balance measurements conducted using 44 male calves during the pre-weaning period showed that increasing milk allowance increased energy and nitrogen (N) intake, diet DM digestibility, true N digestibility and the biological value of the dietary protein. Increasing the MR protein content had no significant effect on the apparent digestibility of N or DM.     

Developmental toxicity of soman in rats and rabbits

Soman (GD; phosphonofluoridic acid, methyl-,1,2,2-trimethylpropyl ester) is an organophosphate compound with potent anticholinesterase activity. To determine developmental toxicity, soman was administered orally to CD rats on days 6 through 15 of gestation at dose levels of 0, 37.5, 75, 150, or 165 micrograms/kg/day and to New Zealand White (NZW) rabbits on days 6 through 19 of gestation at dose levels of 0, 2.5, 5, 10, or 15 micrograms/kg/day. At sacrifice, gravid uteri were weighed and examined for number and status of implants. Individual fetal body weights and external, visceral, and skeletal malformations were recorded. Mean maternal weight changes, fetal implantation status/litter, fetal weight, and fetal malformations/litter were compared between dose groups. Monitors for maternal toxicity were net body weight change, treatment weight change, mortality, and clinical signs of toxicity such as lethargy, ataxia, and tremors. Maternal rats and rabbits in the high-dose groups exhibited statistically significant increases in toxicity and mortality when compared to controls. There were no significant dose-related effects among dose groups in the prevalence of postimplantation loss, malformations, or in average body weight of live fetuses per litter. There was no evidence of increased prenatal mortality or fetal toxicity in the CD rat or NZW rabbit following exposure to soman, even at a dose that produced significant maternal toxicity.     

Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits

The developmental toxicity of the potent adenosine deaminase (ADA) inhibitor, pentostatin (2'-deoxycoformycin), was investigated in pregnant rats and rabbits administered daily iv doses during organogenesis. Rats received 0, 0.01, 0.10, or 0.75 mg/kg on gestation days 6-15 and rabbits received 0, 0.005, 0.01, or 0.02 mg/kg on gestation days 6-18 and maternal and fetal parameters were evaluated on gestation day 21 (rats) or 30 (rabbits). Live fetuses were examined for external, visceral, and skeletal malformations and variations. In rats, maternal body weight gain and food consumption were significantly suppressed at doses of 0.10 and 0.75 mg/kg during the treatment period but returned to control levels during posttreatment. Increased postimplantation loss and decreased numbers of live fetuses, litter size, and fetal body weight were observed at 0.75 mg/kg. A statistically significant increase in the incidence of vertebral malformations occurred at 0.75 mg/kg. The incidence of certain skeletal variations (extra presacral vertebrae, extra ribs, hypoplastic vertebrae) was also increased at 0.75 mg/kg. Ossification of cervical centra was reduced at 0.75 mg/kg compared with controls. In rabbits, marked maternal toxicity (death, body weight loss, and decreased food consumption) and reproductive toxicity (abortion and premature delivery) occurred in all pentostatin-treated groups. However, there were no significant effects on number of live fetuses, pre- or postimplantation loss, litter size, or fetal body weights in the animals with live litters. There was also no apparent increase in the incidence of malformations or variations in the live fetuses of pentostatin-treated rabbits. Thus, these studies demonstrate developmental toxicity of pentostatin in rats and rabbits, and teratogenicity in rats, at maternally toxic doses.     

Herbage intake and growth of rabbits under different pasture type,herbage allowance and quality conditions in organic production

A lack of knowledge about rabbit herbage intake during grazing limits the development of organic rabbit production. This study describes rabbit herbage intake under a wide range of grazing conditions and characterises the factors that decrease rabbit herbage intake and daily weight gain. It was conducted with growing rabbits reared in moving cages with 0.4 m² of grazing area per rabbit. Rabbits grazed on pastures dominated by legumes (LEG) or grass and forbs (GRF) and received 60 g/day per rabbit of a complete pelleted feed. Three trials were performed in winter, summer and spring. Mean herbage allowance was 27% higher in LEG (62.3 g dry matter (DM)/kg metabolic weight (MW), equal to kg^0.75) than in GRF (49.2 g DM/kg MW). Herbage intake varied greatly (36.3±18.0 g DM/kg MW) among trials and was higher in LEG than in GRF (39.5v.34.1 g DM/kg MW). For both pasture types, herbage intake was logarithmically related to herbage allowance and plateaued around 75 g DM/kg MW. Crude protein and digestible energy (DE) intake differed by pasture type and season. Mean CP intake was 40% higher in LEG (15.0 g/kg MW) than in GRF (10.7 g/kg MW). In summer, mean DE intake was 27% higher in LEG than in GRF but no significant differences in DE intake were found between LEG and GRF in winter and spring. Maximum DE intake plateaued near 1000 kJ/kg MW. Daily weight gain was always higher for rabbits grazing LEG (mean=22.6 g) than GRF (mean=16.0 g). Weight gain was significantly related to CP intake, whereas DE intake had no significant effect. Meeting the objective of mean daily weight gain of 20 g requires herbage intake of 32 and 50 g DM/kg MW in LEG and GRF, respectively. Therefore, according to the herbage use efficiency observed in our experiments, herbage allowance must reach 42 and 78 g DM/kg MW in LEG and GRF, respectively. When herbage allowance is lower, rabbits cannot meet the CP intake (13 g/kg MW) required for this weight gain objective.     

Evaluation of the developmental toxicity of lenalidomide in rabbits

BACKGROUND: Lenalidomide, a thalidomide analog, is indicated for treatment of patients with deletion-5q myelodysplastic syndromes or multiple myeloma. NZW rabbits were used because of sensitivity to thalidomide's teratogenicity. METHODS: Range-finding and pulse-dosing studies preceded a full developmental toxicity study in New Zealand white (NZW) rabbits (25/group) given lenalidomide (0, 3, 10, or 20 mg/kg/day) or thalidomide (180 mg/kg/day) by stomach tube on gestation days (GD) 7-19. Clinical signs, body weights, and feed consumption were recorded daily from GD 7. On GD 29, standard maternal necropsy, uterine content, and fetal evaluations were carried out. RESULTS: In all studies, thalidomide was selectively toxic to development. In the pulse-dosing study, lenalidomide did not affect development at 100 mg/kg/day. Increases in C(max) and AUC(0-24 hr) values for lenalidomide were slightly less than dose-proportional; lenalidomide occurred in the fetuses. At 10 and 20 mg/kg/day, lenalidomide was maternally toxic (reduced body weight gain and feed consumption; at 20 mg/kg/day, weight loss and one abortion). Developmental toxicity at 10 and 20 mg/kg/day included reduced fetal body weights and increased postimplantation losses and fetal variations (morbidity/purple-discolored skin, undeveloped intermediate lung lobe, irregular nasal-frontal suture, and delayed metacarpal ossification). Thalidomide selectively reduced fetal body weight, increased postimplantation loss and caused characteristic limb and other dysmorphology. CONCLUSIONS: The maternal and developmental NOAELs for lenalidomide are 3 mg/kg/day. Unlike thalidomide, lenalidomide affected embryo-fetal development only at maternally toxic dosages, confirming that structure-activity relationships may not predict maternal or developmental effects. No fetal malformations were attributable to lenalidomide.     

The relationship between protein retention and energy requirements in rats of different ages

Male Wistar rats aged 30, 75 and 150 days were fed for 14 days ad libitum on diets with an optimum protein content (15% for 30-day-old, 12.5% for 75-day-old and 10% for 150-day-old animals) and a mounting fat content (from 5 to 40%), supplemented by saccharides (from 76 to 41%). Net protein utilization was determined for each of the diets from the body nitrogen and protein intake values. Protein retention values were determined from protein intake on the basis of net protein utilization (NPU). Energy intake was computed from fat and saccharide intake, using energy coefficients. The optimum fat content of the diet, evaluated from the maximum protein retention value per day and the minimum amount of energy needed for the retention of 1 g protein, is 30% at 30 days, 15% at 75 days and 10% at 150 days. Protein retention per kg body weight falls with advancing age--mildly at 75 days compared with 30 days, but markedly at 150 days. From their smaller weight increments and NPU values and also from their lower protein retention, 150-day-old animals are characterized by slower growth and higher protein requirements for maintenance of their organism likewise demonstrated by the growth parameter net protein ratio (NPR). Energy requirements for total protein retention/day per kg body weight diminish with age. In old age a small amount of energy is needed only for the maintenance of body functions. This study contributes to the expression of the interrelationship of energy requirements and protein retention.     

Antidiabetic, antihypercholesterolaemic and antioxidant effect of Ocimum sanctum (Linn) seed oil

Antihyperlipidaemic and antioxidant effect of Ocimum sanctum Linn. seed oil (OSSO) was investigated in rabbits. Administration of OSSO (0.8 g/kg body weight/day) for four weeks, in cholesterol (100 mg/kg body weight/day) fed rabbits significantly decreased serum cholesterol, triacylglycerol and LDL-+VLDL-cholesterol as compared to untreated cholesterol fed group. There was significant fall in atherogenic index in OSSO treated group. In addition, treatment with OSSO decreased lipid peroxidation and increased reduced glutathione content in blood. Antidiabetic effect of O. sanctum seed oil was evaluated in alloxan diabetic rabbits. Two weeks treatment of diabetic rabbits with OSSO (0.8 gm/kg/day) showed no significant hypoglycaemic effect. Results of the present study show that OSSO has hypocholesterolaemic and antioxidant effects but it does not have antidiabetic effect.     

Developmental Toxicity Studies with Atrazine and its Major Metabolites in Rats and Rabbits

Atrazine (ATR), hydroxyatrazine (OH‐ATR), and the three chloro metabolites of ATR (deethylatrazine [DEA], deisopropylatrazine [DIA], diaminochlorotriazine [DACT]) were evaluated for developmental effects in rats and rabbits. Three developmental toxicity studies were conducted on ATR in rats (two studies) and rabbits and a developmental toxicity study was conducted in rats for each of the four ATR metabolites DEA, DIA, DACT, and OH‐ATZ. ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit) did not statistically significantly alter the incidence of developmental abnormalities or malformations at dose levels up to 100 (rat) or 75 (rabbit) mg/kg bw/day. There were no effects on developmental toxicity parameters for DEA, DIA, DACT, or OH‐ATR at oral dose levels up to 100, 100, 150, or 125 mg/kg bw/day, respectively, with the exception of reductions in fetal body weight by DACT and OH‐ATR in the presence of decreased maternal body weight gain. ATR did not adversely affect developmental end points in a two‐generation study conducted in rats exposed to dose levels up to 500 ppm (38.7 mg/kg/day) in the diet. The 500‐ppm dose level resulted in significantly reduced maternal body weight gain. Overall, data show that neither ATR nor its metabolites statistically significantly affected rat or rabbit embryo‐fetal development even at dose levels producing maternal toxicity.     

Effect of lupeol isolated from Crataeva nurvala Buch.-Ham. stem bark extract against free radical induced nephrotoxicity in rats

Lupeol, isolated from Crataeva nurvala stem bark in doses 40 and 80 mg/kg body weight, po, for 10 days, decreased the concentration of blood urea nitrogen, creatinine and lipid peroxidation and increased glutathione and catalase activities in cisplatin (5 mg/kg body weight, ip) induced nephrotoxicity in rats. The increased glutathione and catalase activities are indicative of antioxidant properties of lupeol.     

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.     

Effects of feeding level and protein content of milk replacer on the performance of dairy herd replacements

It has been suggested that United Kingdom recommendations for feeding the neonatal calf (500 g milk replacer (MR)/day; 200-230 g CP/kg milk powder) are inadequate to sustain optimal growth rates in early life. The current study was undertaken with 153 high genetic merit, male and female Holstein-Friesian calves (PIN2000 = ￡48) born between September and March, with heifers reared and bred to calve at 24 months of age. Calves were allocated to one of four pre-weaning dietary treatments arranged in a 2 MR feeding level (5 v. 10 l/day) × 2 MR protein content (210 v. 270 g CP/kg dry matter (DM)) factorial design. MR was reconstituted at a rate of 120 g/l of water, throughout, and was offered via computerised automated milk feeders. Calves were introduced to pre-weaning diets at 5 days of age and weaned at day 56. During the first 56 days of life, calves offered 10 l MR/day had significantly higher liveweight gains (P < 0.001) than calves fed 5 l MR/day. No significant differences in liveweight gain were found between calves fed 210 g CP/kg DM MR and those fed 270 g CP/kg DM MR from birth to day 56. Differences in live weight and body size due to feeding level disappeared by day 90. Neither MR feeding level nor MR CP content affected age at first service or age at successful service, and with no milk production effects, the results indicate no post-weaning benefits of increased nutrition during the milk-feeding period in dairy heifers.