Body Weight Gain (body + weight_gain)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Comparison of insulin detemir and insulin glargine in subjects with Type 1 diabetes using intensive insulin therapy

DIABETIC MEDICINE, Issue 6 2007
T. R. Pieber
Abstract Aims To compare glycaemic control and risk of hypoglycaemia of twice-daily insulin detemir with once-daily insulin glargine in subjects with Type 1 diabetes. Methods In this 26-week, multicentre, open-label, parallel-group trial, 320 subjects with Type 1 diabetes received either insulin detemir twice daily or insulin glargine once daily. each in combination with premeal insulin aspart. Results After 26 weeks, HbA1c had decreased from 8.8 to 8.2% in the insulin detemir group and from 8.7 to 8.2% in the insulin glargine group. Home-measured fasting plasma glucose (PG) was lower with insulin glargine than with insulin detemir (7.0 vs. 7.7 mmol/l, P < 0.001). The overall shape of the home-measured nine-point PG profiles was comparable between treatments (P = 0.125). Overall, there was no significant difference in within-subject variation in PG (P = 0.437). Within-subject variation in predinner PG was lower with insulin detemir than with insulin glargine (P < 0.05). The overall risk of hypoglycaemia was similar with no differences in confirmed hypoglycaemia. However, the risk of severe and nocturnal hypoglycaemia was 72% and 32%, respectively, lower with insulin detemir than with insulin glargine (P < 0.05). Body weight gain was not significantly different comparing insulin detemir and insulin glargine (0.52 kg vs. 0.96 kg, P = 0.193). Conclusions Treatment with twice-daily insulin detemir or once-daily insulin glargine, each in combination with insulin aspart, resulted in similar glycaemic control. The overall risk of hypoglycaemia was comparable, whereas the risks of both severe and nocturnal hypoglycaemia were significantly lower with insulin detemir. [source]


Less frequent body weight gain in elderly type 2 diabetic patients treated with glimepiride

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2003
Kaori Inoue
Background: The purpose of the present paper was to study the effect of a new sulfonylurea, glimepiride, which has an extra-pancreatic action that improves insulin resistance, on glycemic control and body weight gain in elderly patients with type 2 diabetes mellitus (DM). Methods: Thirty-seven type 2 diabetic patients being treated with either gliclazide or glibenclamide were switched to glimepiride for 6 months and clinical parameters were compared between elderly (, 65 years old, n = 9) and non-elderly (< 65 years old, n = 28) patients. Results: There was no significant difference between the two groups in baseline characteristics, or in changes in fasting plasma glucose (FPG) and HbA1c. For body weight change, however, none of the elderly patients (0/9) exhibited an increase, but 9 of 28 (32%) non-elderly subjects showed body weight gain (P < 0.05). Conclusions: Body weight gain with glimepiride treatment is less frequent in elderly patients with type 2 DM than in non-elderly patients with the disease. These data together with the recent increase in obese elderly patients with diabetes suggest that glimepiride is recommended for treatment of type 2 diabetes in this age group. [source]


Increasing dietary crude protein does not increase the methionine requirement in kittens,

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2007
M. J. Strieker
Summary The objective of this study was to determine if the methionine (met) requirement of kittens is correlated with the concentration of dietary crude protein (CP). The study used 48 male kittens in two replications of six 4 × 4 Latin squares, each representing one concentration of met (1.5, 2.5, 3.5, 4.5, 6.0 or 9.0 g/kg diet) with four CP concentrations (150, 200, 300 and 500 g/kg diet) in 2-week periods. Cystine was present in the lowest CP diet at 5.3 g/kg diet and increased as dietary CP increased. Body weight gain, food intake, nitrogen balance and plasma amino acids, glucose, insulin, cortisol, somatomedin C, T3 and T4 concentrations on day 12 were measured. From breakpoint analysis of the nitrogen retention curves, the met requirement of kittens was found to be 3.1, 3.8, 3.1 and 2.4 g met/kg for the 150, 200, 300 and 500 g CP/kg diets, respectively. When met was limiting (1.5 or 2.5 g/kg diet), increasing dietary CP did not decrease, but rather increased food intake, body weight gain and nitrogen retention. Plasma met concentrations increased as dietary met increased and at 2.5,3.5 g met/kg diet were not different among kittens fed the various CP diets. Total plasma T3 and T4 increased significantly as dietary CP increased in kittens given the 2.5 and 4.5 g met/kg diets. Results indicate that food intake and possibly altered hormonal secretion play a role in this growth response. In conclusion, the met requirement of growing kittens, unlike omnivores and herbivores studied, was not positively correlated with the concentration of dietary CP. [source]


Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 7 2010
Jeong-Eun Park
Abstract BACKGROUND: Stevia (Stevia rebaudiana Bertoni) is a non-caloric natural-source alternative to artificially produced sugar substitutes. This study investigated the effect of stevia extract on lipid profiles in C57BL/6J mice. Forty mice were divided into four groups: N-C (normal diet and distilled water), H-C (high-fat diet and distilled water), H-SC (high fat diet and sucrose, 1 mL kg,1 per day), and H-SV (high-fat diet and stevia extract, 1 mL kg,1 per day). RESULTS: Body weight gain was significantly higher in the H-SC group than in the H-SV group. Triglyceride concentrations in serum and liver were lower in the H-SV group than in the H-SC group. Serum total cholesterol concentrations were lower in the H-SV and H-C groups compared to the H-SC group. The concentrations of acid-insoluble acylcarnitine (AIAC) in serum were higher in the H-SV group than in the H-C and H-SC groups and the acyl/free carnitine level in liver was significantly higher in the H-SV group than in the N-C group. These results were supported by mRNA expression of enzymes related to lipid metabolism (ACO, PPAR,, ACS, CPT-I, ACC) assessed by real-time polymerase chain reaction. CONCLUSION: These results suggest that the supplementation of stevia extract might have an anti-obesity effect on high-fat diet induced obese mice. Copyright © 2010 Society of Chemical Industry [source]


A study on feeding hazelnut kernel oil meal as a protein source for broiler chickens

ANIMAL SCIENCE JOURNAL, Issue 3 2009
Guray ERENER
ABSTRACT An experiment was conducted to evaluate the effect of substituting different levels of hazelnut kernel oil meal (HKM) for soybean meal (SBM) in diets for broiler. A total of 450 one-day-old female Ross 308 broiler chicks were allocated randomly to three treatment groups of 150 birds each in a randomized design. Each treatment group consisted of five replicates each of 30 chicks. All diets (in mash form) were formulated to meet nutrient concentrations recommended for broilers. The experiment lasted for six weeks. In the experiment, an SBM control (SBM) diet was compared to two HKM diets, replacing 50 (50HKM) and 100% (HKM) of SBM protein, respectively. Body weight gain, feed intake and feed conversion ratio of broilers were adversely affected (P < 0.05) by the HKM diets at 42 days of age. Broilers fed 50HKM and HKM had growth performances similar (P > 0.05). The carcass yield and abdominal fat pads of birds fed diets with SBM were higher (P < 0.05) than those of chicks fed the 50HKM and HKM diets. The edible inner organ weight of chicks fed diets with HKM was the heaviest (P < 0.05). It is concluded that SBM cannot be replaced even up to 50% with HKM in commercial broiler diet. [source]


Evaluation of supplementary stevia (Stevia rebaudiana, bertoni) leaves and stevioside in broiler diets: effects on feed intake, nutrient metabolism, blood parameters and growth performance

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 6 2008
J. O. Atteh
Summary A perennial schrub, stevia, and its extracts are used as a natural sweetener and have been shown to possess antimicrobial properties. Stevia contains high levels of sweetening glycosides including stevioside which is thought to possess antimicrobial and antifungal properties. Little is known about the nutritional value of the schrub in livestock. This study determined the potential use of the shrub as a prebiotic animal feed supplement in light of the recent ban on the use of antibiotics in animal feed and the role of its constituent stevioside in the effects of the shrub. Male Cobb broiler chicks were fed a basal broiler diet without antibiotic but with performance enhancing enzyme mix (positive control), a basal diet without antibiotic and enzymes (negative control), or diets in which 2% of the negative control diet was replaced with either dried ground stevia leaves or 130 ppm pure stevioside during 2 week starter and 2 week grower periods. Body weight gains, feed conversion, abdominal fat deposition, plasma hormone and metabolites and caecal short chain fatty acids (SCFA) were measured in the broilers at 2 and 4 weeks of age. There was no significant effect of the treatments on feed intake during the starter period but birds fed diet supplemented with stevia leaves and stevioside consumed more feed (p < 0.05) than those fed the positive control diet during the grower period. Weight gain by birds fed the positive control and stevioside diets was higher (p < 0.05) than those fed other diets only during the starter period. Feed/gain ratio of birds fed the positive control and stevioside diets was superior (p < 0.05) to others. There was no effect of the treatments on nutrient retention and water content of the excreta. Dietary stevia leave and stevioside decreased total concentration of SCFA and changed their profile in the ceca. There was no effect of the treatments on pancreas weight. Dietary stevia reduced blood levels of glucose, triglycerides and triiodothyronine (T3) but had no effect on non-esterified fatty acids. In contrast, stevioside only decreased T3. Both the stevia leaves and stevioside diets significantly increased abdominal fat content. It is concluded that dietary enzyme growth promoters are beneficial to the broilers only during the starter stage and that inclusion of stevia leaves or stevioside has no beneficial effect on the performance of broilers. [source]


LIPID-LOWERING EFFECTS OF ARONIA MELANOCARPA FRUIT JUICE IN RATS FED CHOLESTEROL-CONTAINING DIETS

JOURNAL OF FOOD BIOCHEMISTRY, Issue 5 2007
S. VALCHEVA-KUZMANOVA
ABSTRACT Aronia melanocarpa fruit juice (AMFJ) is very rich in phenolic antioxidants, mainly flavonoids from the subclass anthocyanins. The aim of this study was to assess the influence of AMFJ on body and liver mass, plasma lipids and lipoprotein profiles, and the histopathology of liver and aorta in rats fed with cholesterol diets. AMFJ was applied orally for 30 days at doses of 5, 10 and 20 mL/kg. In rats fed the cholesterol-containing diets, AMFJ significantly hindered an increase in plasma lipids (total cholesterol, low-density lipoprotein cholesterol and triglycerides) because of cholesterol feeding. Body weight gains, liver weights, and liver and aorta histopathology were not influenced either by high-cholesterol diets or by AMFJ treatment. In conclusion, AMFJ showed lipid-lowering effects in rats with experimentally induced hyperlipidemia, and could be valuable in reducing lipidemia as a factor of cardiovascular risk. PRACTICAL APPLICATIONS Hyperlipidemia characterized by an increase in low-density lipoprotein (LDL) cholesterol and a decrease in high-density lipoprotein cholesterol is one of the major risk factors for atherosclerosis and cardiovascular disease. Plant foods with high contents of phenolic phytochemicals are reported to be inversely correlated with plasma total cholesterol (TC) and LDL cholesterol. Aronia melanocarpa fruits are remarkably rich in phenolic substances. They are used for human consumption as juice, syrup, jam and wine. Our research demonstrated that A. melanocarpa fruit juice hindered the dietary-induced elevation of plasma TC, LDL cholesterol and triglycerides in rats. In view of the results from our experiment, we can suppose that the juice may be further tested for reducing hyperlipidemia in humans and possibly approved a valuable dietary supplement. [source]


Dietary exposure to low doses of bisphenol A: Effects on reproduction and development in two generations of C57BL/6J mice

CONGENITAL ANOMALIES, Issue 3 2010
Kenichi Kobayashi
Abstract The present study was conducted to examine the effects of low-dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F0) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F1 and F2) from each F0 and F1 dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment-related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F0 dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F1 pups. No treatment-related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F1 and F2 adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F1 males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment-related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F1 or F2 males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice. [source]


Ascorbic acid oral treatment modifies lipolytic response and behavioural activity but not glucocorticoid metabolism in cafeteria diet-fed rats

ACTA PHYSIOLOGICA, Issue 4 2009
D. F. Garcia-Diaz
Abstract Aim:, To analyse the effects of vitamin C (VC), a potent dietary antioxidant, oral supplementation on body weight gain, behavioural activity, lipolytic response and glucocorticoid metabolism in the early stages of diet-induced overweight in rats. Methods:, Food intake, locomotive activity and faecal corticosterone were assessed during the 14 day trial period. After 2 weeks, the animals were sacrificed and the body composition, biochemical markers and lipolytic response from isolated adipocytes from retroperitoneal white adipose tissue were examined. Results:, The intake of a high-fat diet by rats induced a significant increase in body weight, adiposity and insulin resistance markers as well as a decrease in faecal corticosterone levels compared with standard diet-fed rats. Interestingly, the animals fed on the cafeteria diet showed a significant increase in the isoproterenol-induced lipolytic response in isolated adipocytes. Furthermore, this cafeteria-fed group showed a reduced locomotive behaviour than the control rats. On the other hand, oral VC supplementation in animals receiving the high-fat diet restored the cafeteria diet effect in some of the analysed variables such as final body weight and plasma insulin to control group levels. Remarkably, increases in locomotive behaviour and a significant decrease in the lipolytic response induced by isoproterenol on isolated adipocytes from animals treated with VC were observed. Conclusion:, This work demonstrates that an oral ascorbic acid supplementation has direct effects on behavioural activity and on adipocyte lipolysis in early obesity stages in rats, which could indicate a protective short-term role of this vitamin against adiposity induced by chronic high-fat diet consumption. [source]


Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker rats

DIABETES OBESITY & METABOLISM, Issue 6 2009
D. Laurent
Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source]


Rosiglitazone is more effective than metformin in improving fasting indexes of glucose metabolism in severely obese, non-diabetic patients

DIABETES OBESITY & METABOLISM, Issue 6 2008
A. Brunani
Aim:, In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone. Methods:, From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18,65 years and body mass index 35,50 kg/m2 and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism. Results:, A significant weight loss and reduction of fat mass was demonstrated with metformin (,9.7 ± 1.8 kg and ,6.6 ± 1.1 kg) and also with rosiglitazone (,11.0 ± 1.9 kg and ,7.2 ± 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 ± 0.1 vs. 4.4 ± 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 ± 1.5 vs. 8.0 ± 0.,7 ,U/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 ± 8.8 vs. 109.9 ± 10.3, p < 0.005) with a concomitant decrease in ,-cell function as measured by HOMA of ,-cell function (163.2 ± 16.1 vs. 127.4 ± 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments. Conclusion:, Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction. [source]


Short-term nocturnal hypoglycaemia increases morning food intake in healthy humans

DIABETIC MEDICINE, Issue 2 2008
S. M. Schmid
Abstract Aims Hypoglycaemia during wakefulness increases hunger and food intake. Patients with Type 1 diabetes mellitus are at high risk of recurrent hypoglycaemia and weight gain. Given the background of frequent hypoglycaemic episodes during night-time sleep in diabetic patients, we investigated morning food intake after nocturnal hypoglycaemia. Methods We tested 16 healthy normal-weight subjects (eight women) on three nights. A linear fall in plasma glucose to a nadir of 2.2 mmol/l within 60 min was induced by insulin infusion immediately after sleep onset (,early hypo') or after about 3.5 h of sleep (,late hypo'). On a control night, no hypoglycaemia was induced. Spontaneous food intake at a breakfast buffet was registered on the subsequent morning. Results Compared with the control condition (700 ± 93 kcal), subjects ate more after ,late hypo' (867 ± 108 kcal; P = 0.041), but not after ,early hypo' (852 ± 111 kcal; P = 0.130). Analyses of macronutrient fractions revealed that in comparison with the control condition, subjects ate significantly more carbohydrates after both ,late hypo' (277 ± 25 kcal vs. 206 ± 23 kcal, P < 0.001) and ,early hypo' (245 ± 23 kcal, P = 0.048), with this effect being more pronounced after late than early nocturnal hypoglycaemia (P = 0.026). Conclusions In healthy subjects, nocturnal hypoglycaemia during sleep stimulates spontaneous food intake the following morning, with carbohydrate intake being especially affected. Effects were more pronounced after ,late hypo', suggesting the influence of temporal dynamics. Although healthy non-diabetic subjects were studied, similar mechanisms may contribute to the frequently observed body weight gain in insulin-treated diabetic patients. [source]


Comparison of the effect of a cornstarch thickened formula and strengthened regular formula on regurgitation, gastric emptying and weight gain in infantile regurgitation

DISEASES OF THE ESOPHAGUS, Issue 2 2007
H.-C. Chao
SUMMARY., The purpose of this study was to evaluate the efficacy of a specially selected cornstarch-supplemented formula on clinical symptoms, gastric emptying and weight gain in infants with regurgitation. We performed a prospective randomised trial evaluating the therapeutic efficacy of two different formula feedings (cornstarch-thickened formula, group A; 25% strengthened formula, group B) in 81 young infants with regurgitation/vomiting , 3 times/day. A Tc-99 m milk scintigraphy was performed at inclusion and after 2 months to quantify gastric emptying time; all studied infants underwent a 2-month period of clinical follow-up evaluating regurgitation and body weight gain. At inclusion, group A and B had a similar age and weight. After the 2-month period of intervention, regurgitation and vomiting had both greater decrease (both P < 0.001 at 1 and 2 months) in group A (from a score of 4.19 ± 1.71 to 0.93 ± 0.42) than in group B (from a score of 4.15 ± 1.68 to 2.89 ± 1.16). Non-regurgitation symptoms (irritability, cough, choking, night-waking) decreased (P = 0.045 at 1 month and 0.017 at 2 months) in group A (from a score of 18 at baseline to 3 after 8 weeks) as compared to group B (from a score of 18 at baseline to 11 after 8 weeks). Weight increased more in group A (29.1 ± 3.9 g/day over 8 weeks) versus group B (23.6 ± 3.5 g/day over 8 weeks) (P < 0.01 at 1 and 2 months) Gastric emptying improved significantly in group A as compared with group B (all P < 0.001 for T1/2, and residual volume at 60 and 90 min). Ingested feeding volume was significantly larger in the group receiving cornstarch-thickened formula, both at 4 weeks (109.4 ± 24.5 vs. 98.5 ± 23.6 mL/meal) (P: 0.042) and at 8 weeks (137.6 ± 27.9 vs. 115.7 ± 26.5 mL/meal) (P < 0.001). Cornstarch-thickened formula feeding decreases the frequency of regurgitation/vomiting, provides better body weight gain and has an accelerated gastric emptying in comparison to a 25% strengthened regular formula in infants with regurgitation. [source]


Combined repeated dose and reproductive/developmental toxicity screening test of the nitrophenolic herbicide dinoseb, 2- sec -butyl-4,6-dinitrophenol, in rats

ENVIRONMENTAL TOXICOLOGY, Issue 2 2008
Mariko Matsumoto
Abstract In a combined repeated dose toxicity study with reproduction/developmental toxicity screening test, Crj:CD(SD)IGS rats were dosed with dinoseb, 2- sec -butyl-4,6-dinitrophenol, by gavage at 0 (vehicle), 0.78, 2.33, or 7.0 mg/kg bw/day. Six males per group were dosed for a total of 42 days beginning 14 days before mating. Twelve females per group were dosed for a total of 44,48 days beginning 14 days before mating to day 6 of lactation throughout the mating and gestation period. Recovery groups of six males per group and nonpregnant six females per group were dosed for 42 days followed by a 14-day recovery period. No deaths were observed in males of any dose group or in females of the recovery groups. At 7.0 mg/kg bw/day, eight females died and two animals were moribund during late pregnancy, and a significant decrease in body weight gain was found in both sexes. Hematocrit was significantly higher at 0.78 mg/kg bw/day and above in the main group males at the end of administration period. Reduction in extramedullary hematopoiesis in the spleen was significant at 2.33 mg/kg bw/day in the main group females. Sperm analysis revealed a decrease in sperm motility and an increase in the rates of abnormal sperm, abnormal tail, and abnormal head at 7.0 mg/kg bw/day. A number of dams delivered their pups and of dams with live pups at delivery was significantly lowered in the 7.0 mg/kg bw/day group. Based on these findings, the LOAEL for males and NOAEL for females were 0.78 mg/kg bw/day, and the NOAEL for reproductive/developmental toxicity was considered to be 2.33 mg/kg bw/day. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source]


Minocycline attenuates hypoxia,ischemia-induced neurological dysfunction and brain injury in the juvenile rat

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006
Lir-Wan Fan
Abstract To investigate whether minocycline provides long-lasting protection against neonatal hypoxia,ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague,Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic,ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic,ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia,ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia,ischemia-induced brain injury and the associated neurological dysfunction. [source]


Influence of Genetically Predisposed Diabetes on Ethanol-Induced Depression of Cardiac Contraction in Adult Rat Ventricular Myocytes

EXPERIMENTAL PHYSIOLOGY, Issue 3 2002
Jun Ren
Diabetes mellitus and alcohol (ethanol) intake are two positively correlated major risk factors for cardiovascular abnormalities. However, the interaction of the two on cardiac function is largely unknown. The purpose of the present study was to examine the impact of genetically predisposed diabetes on acute ethanol exposure-induced cardiac contractile depression at the myocyte level. Ventricular myocytes from spontaneously biobreeding diabetes-prone (BBDP) rats and their diabetes-resistant littermates (BBDR) were stimulated to contract at 0.5 Hz. Contractile properties analysed include: peak shortening amplitude (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (± dL/dt). BBDP rats displayed hyperglycaemia, reduced body weight gain and increased cardiac, hepatic and renal size. Myocytes isolated from BBDP rat hearts exhibited prolonged TPS and TR90 associated with normal PS and ± dL/dt, compared with myocytes from the BBDR group. Acute ethanol exposure (80-640 mg dl,1) caused a concentration-dependent inhibition of PS in both BBDR and BBDP myocytes. However, the degree of inhibition of PS was significantly reduced in BBDP myocytes compared to that of BBDR myocytes. The maximal inhibition was 52.9% and 28.4% in BBDR and BBDP groups, respectively. Ethanol significantly depressed ± dL/dt in both BBDR and BBDP myocytes. In addition, ethanol did not affect TPS or TR90 in either the BBDR or BBDP group. Collectively, these results suggest that the ethanol-induced depression in cardiac myocyte contraction may be ,shadowed' by genetically predisposed diabetes. [source]


Less frequent body weight gain in elderly type 2 diabetic patients treated with glimepiride

GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2003
Kaori Inoue
Background: The purpose of the present paper was to study the effect of a new sulfonylurea, glimepiride, which has an extra-pancreatic action that improves insulin resistance, on glycemic control and body weight gain in elderly patients with type 2 diabetes mellitus (DM). Methods: Thirty-seven type 2 diabetic patients being treated with either gliclazide or glibenclamide were switched to glimepiride for 6 months and clinical parameters were compared between elderly (, 65 years old, n = 9) and non-elderly (< 65 years old, n = 28) patients. Results: There was no significant difference between the two groups in baseline characteristics, or in changes in fasting plasma glucose (FPG) and HbA1c. For body weight change, however, none of the elderly patients (0/9) exhibited an increase, but 9 of 28 (32%) non-elderly subjects showed body weight gain (P < 0.05). Conclusions: Body weight gain with glimepiride treatment is less frequent in elderly patients with type 2 DM than in non-elderly patients with the disease. These data together with the recent increase in obese elderly patients with diabetes suggest that glimepiride is recommended for treatment of type 2 diabetes in this age group. [source]


Contributions of the hippocampus and medial prefrontal cortex to energy and body weight regulation

HIPPOCAMPUS, Issue 3 2009
Terry L. Davidson
Abstract The effects of selective ibotenate lesions of the complete hippocampus (CHip), the hippocampal ventral pole (VP), or the medial prefrontal cortex (mPFC) in male rats were assessed on several measures related to energy regulation (i.e., body weight gain, food intake, body adiposity, metabolic activity, general behavioral activity, conditioned appetitive responding). The testing conditions were designed to minimize the nonspecific debilitating effects of these surgeries on intake and body weight. Rats with CHip and VP lesions exhibited significantly greater weight gain and food intake compared with controls. Furthermore, CHip-lesioned rats, but not rats with VP lesions, showed elevated metabolic activity, general activity in the dark phase of the light-dark cycle, and greater conditioned appetitive behavior, compared with control rats without these brain lesions. In contrast, rats with mPFC lesions were not different from controls on any of these measures. These results indicate that hippocampal damage interferes with energy and body weight regulation, perhaps by disrupting higher-order learning and memory processes that contribute to the control of appetitive and consummatory behavior. © 2008 Wiley-Liss, Inc. [source]


Targeting TGF-,1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis

INFLAMMATORY BOWEL DISEASES, Issue 6 2010
Yanbing Ma MSc
Abstract Background: Intestinal fibrosis and stricture formation are major complications of inflammatory bowel disease (IBD), for which there are currently few effective treatments. We sought to investigate whether targeting transforming growth factor-beta1 (TGF-,1), a key profibrotic mediator, with a peptide-based virus-like particle vaccine would be effective in suppressing intestinal fibrosis by using a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis. Methods: The vaccine was prepared by inserting a peptide derived from mouse TGF-,1 into a carrier hepatitis B core antigen using gene recombination methods. Chronic colitis was induced in BALB/c mice by 8 weekly TNBS administrations. Mice were subcutaneously injected with vaccine, carrier, or phosphate-buffered saline (PBS) in 2 separate studies: either before or after acute inflammatory responses commenced. Results: Sera from vaccinated mice exhibited significantly elevated levels of TGF-,1-specific immunoglobulin G (IgG), which inhibited TGF-,1-induced luciferase production in mink lung epithelial cells. In the chronic colitis model, mice receiving vaccine showed improved body weight gain and significantly reduced colonic collagen deposition. Hematoxylin and eosin staining and semiquantitative scoring indicated that vaccination even ameliorated colonic inflammation. Cytokine profile analysis revealed that levels of TGF-,1, interleukin (IL)-17, and IL-23 in vaccinated mouse colon tissues were decreased, and that percentages of IL-17-expressing CD4+ lymphocytes in mesenteric lymph node cells were reduced. Furthermore, Smad3 phosphorylation, a key event in TGF-, signaling, was decreased in colonic tissue in vaccinated mice. Conclusions: This TGF-,1 peptide-based vaccine, which suppressed excessive TGF-,1 bioactivity, may prevent the development of intestinal fibrosis and associated complications, presenting a novel approach in the treatment of IBD. (Inflamm Bowel Dis 2010) [source]


Paliperidone palmitate , review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010
L. Citrome
Summary Objective:, To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. Data sources:, A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term ,paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. Study selection:, All available reports of studies were identified. Product labelling provided additional information. Data extraction:, Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose,response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4,7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Conclusions:, Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use. [source]


ORIGINAL ARTICLE: Effects of dietary supplementation of synbiotics and phytobiotics on performance, caecal coliform population and some oxidant/antioxidant parameters of broilers

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2010
Z. Erdo
Summary The current study was conducted to evaluate the effects of dietary supplementation of synbiotics and phytobiotics on performance, small intestine weight, pH and caecal coliform counts of broilers. The influences of synbiotics and phytobiotics on oxidant/antioxidant status in the blood of broilers were also assessed. A total of 200 broiler chicks were randomly allotted to four dietary treatments, either fed a basal diet or the same diet supplemented with 1 g/kg synbiotic, 1 g/kg phytobiotic or 1 g/kg synbiotic plus 1 g/kg phytobiotic. The diet supplemented with both synbiotic and phytobiotic had no effect on body weight, body weight gain, feed intake and feed efficiency of broilers at the end of the study (p > 0.05). Neither small intestine weight nor pH was affected by any of the treatments. Supplementation of both synbiotic and phytobiotic to diet decreased the caecal coliform count (p < 0.01). Addition of synbiotics and phytobiotics in combination significantly increased plasma malondialdehyde (MDA) levels (p , 0.05), whereasphytobiotic addition alone showed only a slight increase. Similarly, elevated nitric oxide (NO) level was recorded in the synbiotic- and phytobiotic-fed group and in the phytobiotic-fed group (p , 0.001). Superoxide dismutase (SOD) activities did not differ between the groups. In conclusion, dietary supplementation of synbiotic and phytobiotic improved the gut health by decreasing the caecal total coliform count, but growth performance was not affected by the supplementations. Further investigations are needed to determine the effects of phytobiotics on oxidative/antioxidative metabolism as regards their compositional analysis. [source]


Dietary phytate (inositol hexaphosphate) regulates the activity of intestinal mucosa phytase

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 5 2009
E. M. Onyango
Summary The role of dietary phytate (inositol hexaphosphate) in the regulation of intestinal mucosa phytase was investigated in chicks. Seven-day-old chicks were grouped by weight into six blocks of three cages with six birds per cage. Three purified diets [a chemically defined casein diet, a chemically defined casein diet plus sodium phytate (20 g/kg diet) and a chemically defined casein diet plus sodium phytate (20 g/kg diet) and microbial phytase (1000 units/kg diet)] were randomly assigned to cages within each block. Chicks were fed experimental diets from 8 to 22 days of age then killed, and duodenal mucosa and left tibia removed. Phytase activity in duodenal mucosa, growth performance and bone ash content were determined. Addition of phytate to the chemically defined casein diet reduced (p < 0.05) the Vmax of the duodenal brush border phytase, but the Km of the enzyme was not affected. Addition of phytate also reduced (p < 0.05) weight gain, feed intake, feed efficiency and percentage ash. Addition of microbial phytase fully restored the feed efficiency (p < 0.05), but Vmax and body weight gain were only partially restored (p < 0.05). In conclusion, it would seem that dietary phytates non-competitively inhibit intestinal mucosa phytase. [source]


Sand intake by laying hens and its effect on egg production parameters

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 4 2008
J. Van Der Meulen
Summary Soil intake may be the most prominent source of environmental contaminants for free range and organic hens, but there are no quantitative data concerning soil intake by domestic hens. Consumption of soil of 14,32 g a day can be estimated from literature, but such a dilution of nutrient intake seems incompatible with high productivity. In this study laying hens were fed pelleted diets with 0%, 10%, 20%, 25% and 30% of sand addition to determine its effect on productivity. Feed intake, feed and nutrient (feed minus sand) conversion ratio, egg production, egg weight and body weight gain were measured over a 4-week period. Acid insoluble ash concentration in the faeces was measured to determine the accuracy of estimating the soil ingestion by the soil-ingestion equation for wildlife as a way to determine soil ingestion of free range and organic hens under practical circumstances. The hens were able to compensate the dilution of the diet with 20%, 25% and 30% of sand by increasing their feed intake. Feed intake increased significantly and feed to egg conversion ratio decreased significantly with increasing sand levels in the diet. The nutrient to egg conversion ratio of the diet without sand tended to be worse than for the diets with sand, presumably due to the total absence of coarse material in the diet. There were no differences in egg production and egg weight between hens fed the different diets but body weight gain was significantly lower for the hens fed the diets with 20%, 25% and 30% of sand. Estimation of sand ingestion was done by the soil-ingestion equation for wildlife. Provided that the actual dry matter digestibility coefficient of the nutrient part of the diet is taken into account, estimating the soil ingestion according to the soil-ingestion equation for wildlife seems an appropriate way to determine soil ingestion for free range and organic hens under practical circumstances. [source]


Increasing dietary crude protein does not increase the methionine requirement in kittens,

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2007
M. J. Strieker
Summary The objective of this study was to determine if the methionine (met) requirement of kittens is correlated with the concentration of dietary crude protein (CP). The study used 48 male kittens in two replications of six 4 × 4 Latin squares, each representing one concentration of met (1.5, 2.5, 3.5, 4.5, 6.0 or 9.0 g/kg diet) with four CP concentrations (150, 200, 300 and 500 g/kg diet) in 2-week periods. Cystine was present in the lowest CP diet at 5.3 g/kg diet and increased as dietary CP increased. Body weight gain, food intake, nitrogen balance and plasma amino acids, glucose, insulin, cortisol, somatomedin C, T3 and T4 concentrations on day 12 were measured. From breakpoint analysis of the nitrogen retention curves, the met requirement of kittens was found to be 3.1, 3.8, 3.1 and 2.4 g met/kg for the 150, 200, 300 and 500 g CP/kg diets, respectively. When met was limiting (1.5 or 2.5 g/kg diet), increasing dietary CP did not decrease, but rather increased food intake, body weight gain and nitrogen retention. Plasma met concentrations increased as dietary met increased and at 2.5,3.5 g met/kg diet were not different among kittens fed the various CP diets. Total plasma T3 and T4 increased significantly as dietary CP increased in kittens given the 2.5 and 4.5 g met/kg diets. Results indicate that food intake and possibly altered hormonal secretion play a role in this growth response. In conclusion, the met requirement of growing kittens, unlike omnivores and herbivores studied, was not positively correlated with the concentration of dietary CP. [source]


Excess dietary cystine intensifies the adverse effect of a methionine deficiency in the cat

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2006
M. J. Strieker
Summary Foot pad dermatitis has been observed in turkeys, puppies and kittens fed diets deficient in methionine. Excess cystine aggravated the lesions and decreased body weight gain in puppies and turkeys. The objective of this study was to determine whether methionine deficiency induced perioral and foot pad lesions in kittens and whether excess cystine exacerbated the lesions. Eighteen kittens were divided into three groups and offered one of three diets: diet 1, low-methionine, low-cystine (LMLC; 1.6 g methionine and 1.6 g cystine/kg diet); diet 2, low-methionine, high-cystine (HMHC; 1.6 methionine and 15 g cystine/kg diet); diet 3, high-methionine, high-cystine (HMHC; 15 g methionine and 15 g cystine/kg diet). Kittens in the LMLC group lost body weight, whereas those in the LMHC group maintained their body weight and those in the HMHC group gained weight. Plasma methionine concentrations were significantly higher (p < 0.001) for the HMHC group than for the LMLC and LMHC groups. Plasma cyst(e)ine (sum of cysteine and cystine) concentrations were different (p < 0.001) among all the three groups. Two kittens given the LMLC diet developed mild perioral lesions. All kittens receiving the LMHC diet developed foot pad lesions and severe perioral lesions. Histopathological changes observed in perioral biopsy specimens were similar to those described in protein deficiency. In conclusion, the results showed that a diet severely deficient in methionine causes perioral lesions in kittens, and that addition of excess cystine to the diet aggravates the perioral lesions and also causes foot pad lesions. [source]


Untersuchungen zur prophylaktischen Wirkung der Verfütterung eines Probiotikums und von erregerspezifischen Kolostrum- und Dotterantikörpern bei neugeborenen Kälbern

JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2000
M. H. Von Erhard
Studies on the prophylactic effect of feeding probiotics, pathogen-specific colostrum antibodies or egg yolk antibodies in newborn calves The prophylactic efficacy of feeding probiotics, specific egg yolk antibodies and specific colostrum antibodies on neonatal diarrhoea was investigated in a field trial with calves, grouped (n = 39/40 per group) according to the following treatments: Group I: feeding no additive; Group II: feeding probiotics (5 g powder/day with Bacillus cereus var. toyoi); Group III: feeding egg powder (10 g/day with specific egg yolk antibodies against rotavirus, coronavirus and Escherichia coli F5); Group IV: feeding colostrum antibodies (10 ml/day containing 1 g bovine immunoglobulins with specific antibodies against rotavirus, coronavirus and E. coli antigens); Group V: feeding egg powder together with probiotics (according to group II and III). The additives were given twice daily with the meal from day 2 to day 14 post-natum. The presence of infectious agents was proved in fecal samples of all calves. Intestinal infections with rotavirus (30.8% of the calves) predominated compared to those with coronavirus (7.1%), E. coli F5 (1.5%) and cryptosporidia (24.2%). In contrast to earlier studies, the manifestation of diarrhoea did not differ significantly between the five groups. Only the growth rate of the calves between day 2 and day 14 of life as a measure of their welfare showed treatmentFspecific differences. The control group (I) showed the lowest body weight gain of about 5.8 kg (SD 5.0), whereas in the treated groups it averaged 6.3 kg (SD 4.1, p = 0,60; group II), 6.8 kg (SD 4.3, p = 0.36; group III), 6.9 kg (SD 4.7, p = 0.61; group IV) and 7.7 kg (SD 4.9, p = 0.08; group V). Considering only the rotavirus-positive calves the body weight gain of the control group (I) was 3.5 kg (SD 4.8) and of the treated groups was 3.8 kg (SD 3.3, p = 0.65; II), 5.0 kg (SD 3.5, p = 0.54; III), 6.6 kg (SD 4.5, p = 0.05; IV) and 6.1 kg (SD 5.0, p = 0.13; V). Obviously, the feeding of antibodies from colostrum or from egg powder does increase the mean body weight gain. The feeding of probiotics alone has nearly no effect. However, in the combination with specific egg antibodies probiotics seem to have a synergistic effect. In serum from the 198 newborn calves the IgG concentration averaged 4.9 mg/ml serum (SD 3.3). From 93 dams of these calves a sample of the first colostrum could be obtained showing a mean IgG concentration of 22.0 mg/ml (SD 11.0). IgG levels in the colostrum and in the serum have been positively correlated (r = 0.37, p < 0.05). Calves with a high intensity of diarrhoea had a significantly (p = 0.01) lower mean IgG serum level (3.7 mg/ml; n = 36; SD 2.5) than calves without diarrhoea (5.6 mg/ml; n = 75; SD 4.0). In Rahmen eines Feldversuches wurde die prophylaktische Wirksamkeit verschiedener Futteradditiva (Probiotikum, spezifische Dotterantikörper, spezifische Kolostrumantikörper) bei der neonatalen Kälberdiarrhoe untersucht. Dazu wurden die Kälber entsprechend der Behandlung in folgende fünf Gruppen (je n = 39/40) eingeteilt: I: Keine Futterzusatzstoffe, II: Verfütterung eines Probiotikums (5 g Pulver/Tag mit Bacillus cereus var. toyoi), III: Verfütterung von Eipulver (10 g/Tag mit spezifischen Dotterantikörpern gegen Rotaviren, Coronaviren und E. coli F5), IV: Verfütterung von Kolostrumantikörpern (10 ml/Tag mit 1 g bovinen Immunglobulin mit spezifischen Antikörpern gegen Rotaviren, Coronaviren und Escherichia coli Antigene), V: Verfütterung von Eipulver zusammen mit einem Probiotikum (analog den Gruppen II und III). Die Prophylaktika wurden zwei Mal täglich vom 2. bis zum 14. Lebenstag mit der Tränke verabreicht. Bei allen Kälbern wurde ein Erregernachweis im Kot geführt. Rotaviren (30,8%) konnten im Vergleich zu Coronaviren (7,1%), E. coli F5 (1,5%) und Kryptosporidien (24,2%) häufiger nachgewiesen werden. Im Gegensatz zu früheren Studien konnten hinsichtlich des Durchfallgeschehens keine signifikanten Unterschiede zwischen den Gruppen festgestellt werden. Nur die Körperge wichtszunahme der Kälber zwischen 2. und 14. Lebenstag zeigte behandlungsspezifische Unterschiede. Die Kontrollgruppe (I) verbuchte mit 5,8 kg (SD 5,0) die niedrigste Körpergewichtszunahme. Verglichen damit lag die Zunahme der behandelten Gruppen bei 6,3 (SD 4,1; p = 0,60; Gruppe II), 6,8 kg (SD 4,3; p = 0,36; Gruppe III), 6,9 kg (SD 4,7, p = 0,61; Gruppe IV) und bei 7,7 kg (SD 4,9, p = 0,08; Gruppe V). Bei Rotavirus-positiven Kälbern war eine Körpergewichtszunahme von 3,5 kg (SD 4,8; Kontrollgruppe), 3,8 kg (SD 3,3, p = 0,65; Gruppe II), 5,0 kg (SD 3,5, p = 0,54; Gruppe III), 6,6 kg (SD 4,5, p = 0,05; Gruppe IV) und von 6,1 kg (SD 5.0, p = 0,13; Gruppe V) zu verzeichnen. Offensichtlich verhindert die prophylaktische Verfütterung von Kolostrum- oder Dotterantikörpern eine infektionsbedingte Verminderung der Körpergewichtszunahme. Die Applikation des Probiotikums alleine zeigte keinen vergleichbaren Effekt. Allerdings ist eine synergistische Wirkung in Kombination mit Antikörpern nicht auszuschließen. In den Seren der 198 neugeborenen Kälber wurde eine mittlere Immunglobulin G (IgG)-Konzentration von 4,9 mg/ml (SD 3,3) gemessen. Von 93 Muttertieren dieser Kälber konnte das Erstgemelk genommen werden, das eine mittlere IgG-Konzentration von 22,0 mg/ml (SD 11,0) aufwies. Die IgG-Gehalte in den Kolostrumproben und den Kälberseren zeigten eine Korrelation von r = 0,37 (p < 0,05). Kälber mit hochgradigem Durchfall hatten mit 3,7 mg/ml Serum (n = 36, SD 2,5) einen signifikant niedrigeren mittleren IgG-Wert als Kälber ohne Durchfall (5,6 mg/ml, n = 75, SD 4,0). [source]


Neurobehavioral toxicity study of dibutyl phthalate on rats following in utero and lactational exposure

JOURNAL OF APPLIED TOXICOLOGY, Issue 7 2009
Yuanfeng Li
Abstract To investigate the neurobehavioral effects of dibutyl phthalate (DBP), an important endocrine disruptor known for reproductive toxicity, on rodent offspring following in utero and lactational exposure, pregnant Wistar rats were treated with DBP (0, 0.037, 0.111, 0.333 and 1% in the diet) from gestation day (GD) 6 to postnatal day (PND) 28, and selected developmental and neurobehavioral parameters of the offspring were measured. There were no significant effects of DBP on body weight gain of the dams during GD 6,20 or on the pups' ages of pinna detachment, incisor eruption or eye opening. Exposure to 1% DBP prolonged gestation period, decreased body weight in both male and female pups, depressed surface righting (PND 7) in male pups, shortened forepaw grip time (PND 10), enhanced spatial learning and reference memory (PND 35) in male pups. Exposure to 0.037% DBP also shortened forepaw grip time (PND 10), but inhibited spatial learning and reference memory in male pups. Sex × treatment effects were found in forepaw grip time (PND 10), spatial learning and reference memory, and the male pups appeared to be more susceptible than the females. However, all levels of DBP exposure did not significantly alter surface righting (PND 4), air righting (PND 16), negative geotaxis (PND 4 or 7), cliff avoidance (PND 7) or open field behavior (PND 28) in either sex. Overall, the dose level of DBP in the present study produced a few adverse effects on the neurobehavioral parameters, and it may alter cognitive abilities of the male rodent. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Differential developmental toxicities of di- n -hexyl phthalate and dicyclohexyl phthalate administered orally to rats

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2009
Anne-Marie Saillenfait
Abstract The objective of this study was to evaluate the developmental toxic potential of di- n -hexyl phthalate (DnHP) and dicyclohexyl phthalate (DCHP) in rats. Pregnant Sprague,Dawley rats were exposed to DnHP or DCHP at doses of 0 (olive oil), 250, 500 and 750 mg kg,1 per day, by gavage, on gestational days (GD) 6,20. Maternal food consumption and body weight gain were significantly reduced at 750 mg kg,1 per day of DnHP and at the two high doses of DCHP. Slight changes in liver weight associated with peroxisomal enzyme induction were seen in dams treated with DnHP or DCHP. DnHP caused dose-related developmental toxic effects, including marked embryo mortality at 750 mg kg,1 per day, and presence of malformations (mainly cleft palate, eye defects and axial skeleton abnormalities) and significant decreases in fetal weight at 500 and 750 mg kg,1 per day. Significant delay of ossification and increase in the incidence of skeletal variants (e.g. supernumerary lumbar ribs) also appeared at 250 mg kg,1 per day. DCHP produced fetal growth retardation at 750 mg kg,1 per day, as evidenced by significant reduction of fetal weight. DnHP and DCHP induced a significant and dose-related decrease in the anogenital distance of male fetuses at all doses, and there was a significant increase in the incidence of male fetuses with undescended testis at 500 and 750 mg kg,1 per day of DnHP. In conclusion, DnHP showed clear embryolethality and teratogenicity, but not DCHP. There was evidence that both phthalates could alter the development of the male reproductive system after in utero exposure, DnHP being much more potent than DCHP. Copyright © 2009 John Wiley & Sons, Ltd. [source]


Chronic ethanol intake inhibits in vitro osteogenesis induced by osteoblasts differentiated from stem cells

JOURNAL OF APPLIED TOXICOLOGY, Issue 2 2008
Maria L. Rosa
Abstract The study investigated whether chronic ethanol (ETH) intake and subsequent ETH exposure of cell cultures affects osteoblast differentiation by evaluating key parameters of in vitro osteogenesis. Rats were treated with 5,20% (0.85,3.43 mm) ETH, increasing by 5% per week for a period of 4 weeks (habituation), after which the 20% level was maintained for 15 days (chronic intake). Bone-marrow stem cells from control (CONT) or ETH-treated rats were cultured in osteogenic medium which was either supplemented (ETH) or not supplemented (CONT) with 1.3 mm ethanol. Thus, four groups relating to rat treatment/culture supplementation were evaluated: (1) CONT/CONT, (2) ETH/CONT, (3) CONT/ETH and (4) ETH/ETH. Cell morphology, proliferation and viability, total protein content, alkaline phosphatase (ALP) activity and bone-like nodule formation were evaluated. Chronic ethanol intake significantly reduced both food and liquid consumption and body weight gain. No difference was seen in cell morphology among treatments. Cell number was affected at 7 and 10 days as follows: CONT/CONT = CONT/ETH < ETH/CONT = ETH/ETH. Doubling time between 3 and 10 days was greater in groups of CONT animals: ETH/ETH = ETH/CONT < CONT/ETH = CONT/CONT. Cell viability and ALP activity were not affected by either animal treatment or culture exposure to ethanol. At day 21, the total protein content was affected as follows: ETH/ETH = CONT/ETH < ETH/CONT = CONT/CONT. Bone-like nodule formation was affected as follows: ETH/ETH < CONT/ETH < ETH/CONT < CONT/CONT. These results show that chronic ethanol intake, followed by the exposure of osteoblasts to ethanol, inhibited the differentiation of osteoblasts, as indicated by an increased proliferation rate and reduced bone-like nodule formation. Copyright © 2007 John Wiley & Sons, Ltd. [source]


A Vacuolar ATPase Inhibitor, FR167356, Prevents Bone Resorption in Ovariectomized Rats With High Potency and Specificity: Potential for Clinical Application,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005
Kazuaki Niikura MS
Abstract FR167356, a novel inhibitor of vacuolar ATPase, has high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. FR167356 is the first compound of this nature to be tested. It has the potential to be useful for clinical application. Introduction: It has been suggested that the key issue regarding the therapeutic usefulness of V-ATPase inhibitors is their selectivity. Materials and Methods: In in vitro and in vivo studies, we compared FR167356 with other vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 and SB242784. H+ transport by various membrane vesicles was assayed by measuring uptake of acridine orange. Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from cultured calvariae. In vivo, hypercalcemia was induced by retinoic acid in thyroparathyroidectomized-ovariectomized rats, and the effect on serum Ca2+ level was assessed. Ovariectomized rats were treated with FR167356 or SB242784. One week after surgery, free deoxypyridinoline levels in 24-h urine samples, which were collected from 6 h after administration of FR167356, were measured by ELISA. After 4 weeks of treatment, plasma biochemical parameters were analyzed. BMD of the distal femur metaphysis was measured with pQCT. Histomorphometric analysis of the proximal tibias was performed. Blood gases of rats treated with FR167356 were measured with a blood gas analyzer for estimating the effect of FR167356 on in vivo function of renal V-ATPase. Results: FR167356, which is distinctly different from other V-ATPase inhibitors, has a high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. Similarly, FR167356 inhibited bone resorption in vitro when stimulated by PTH, IL-1, and IL-6. FR167356 reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats in a dose-dependent manner. Moreover, FR167356 was shown to restore BMD of ovariectomized rats caused by the inhibition of bone resorption. Ovariectomized rats treated with FR167356 did not show adverse symptoms, whereas SB242784 caused a decrease in body weight gain and significant changes in two plasma biochemical parameters. Interestingly, FR167356 treatment did not affect blood acid-base balance; however, FR167356 inhibited renal V-ATPase with a similar potency as for osteoclast V-ATPase inhibition. Conclusion: Comparison of FR167356 with SB242784 implies that the characteristics of FR167356 may be more appropriate for clinical application as a V-ATPase inhibitor. [source]