Body Weight Of Control Animals Research Articles

ПРИМЕНЕНИЕ БЕЛКОВЫХ ГИДРОЛИЗАТОВ В КРОЛИКОВОДСТВЕ И ИХ ВЛИЯНИЕ НА ПОКАЗАТЕЛИ КАЧЕСТВА И БЕЗОПАСНОСТИ МЯСА

There are presented materials on the use of feed additives based on protein hydrolysates of plant origin (Abiopeptide and Abiotonic) in rabbit breeding, as well as the results of organoleptic studies and determination of safety indicators and biological value of the resulting meat. It was noted that the feed additives Abiopeptide and Abiotonik contributed to an increase in the live-weight of rabbits, which, on average, in animals of the 1st experimental group (Abiopeptide) reached - 3.35 kg, the 2nd (Abiotonic) - 3, 42 kg and in control - 3.08 kg. The analysis of the obtained results showed that the average daily increase in the liveweight of rabbits in the 1st group was 42.6 ± 5.23 g, the 2nd - 44 ± 7.44 g, and in the control - 38.2 ± 5.33 g , which by 11.5% and 15.2%, respectively, exceeded the increase in body weight of control animals. It has been established that in terms of organoleptic characteristics, the meat of rabbits of the experimental and control groups meets the requirements of good-quality meat that meets the requirements of GOST 20235.0-74 “Rabbit meat. Sampling methods. Organoleptic methods of quality assessment”. When examining the toxicity and biological value of meat, its negative effect on the growth and survival of the test culture Tetrachimena pyriformis was not established. Rabbit meat complies with the requirements of SanPiN 2.3.3.1078-01 "Hygienic requirements for the safety and nutritional value of food", p. 1.1.1, 1.1.1.1.

Repurposing Disulfiram as an Anti-Obesity Drug: Treating and Preventing Obesity in High-Fat-Fed Rats.

Background and ObjectivesA drug repurposing strategy is an approach for identifying new therapeutic uses for approved or investigational drugs. Thanks to the moderate cost of repurposing a drug compared to bringing new chemical entity to the market, drug repurposing is rapidly gaining ground. The aim of this work is to study the anti-obesity effect of disulfiram (DSF), an irreversible aldehyde dehydrogenase inhibitor approved by the Food and Drug Administration (FDA) to treat chronic alcoholism since 1951.MethodsThirty male Albino rats were randomly assigned to six groups. G1, the control group, was given a standard diet. G2, the positive control group, was given a high-fat diet (HFD). G3 was given an HFD, and DSF 50 mg/kg/day was administered orally from day one for six weeks. G4 was given an HFD, and DSF 200 mg/kg/day was administered orally from day one for six weeks. G5 was given an HFD for six weeks; then treatment started with 50 mg/kg/day DSF orally. G6 was given an HFD for six weeks; then treatment started with 200 mg/kg/day DSF orally for three weeks. The body weight, food consumption and blood glucose levels were monitored over the given time interval.ResultsBoth doses of DSF significantly limited the body weight gain caused by an HFD for the treated animals. HF-fed rats received 50 and 200 mg/kg/day of DSF had their body weight increased by 51.93 ± 7.89% and 20.88 ± 15.05% respectively, whereas the body weight of control animals increased by 93.1 ± 20.04%. DSF also significantly decreased the body weight of obese animals. At 50 and 200 mg/kg/day of DSF, HF-fed rats lost 16.74 ± 8.61% and 23.9 ± 3.93% respectively, as their untreated counterparts had their body weight increased by 11.85 ± 3.79% after three weeks of treatment, thus restoring a body weight matching those who received a standard diet.ConclusionFDA-approved disulfiram has a strong anti-obesity effect on HFD-fed rats.

Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys

Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR’s effects in primates. Here we show that CR significantly improves age-related and all-cause survival in monkeys on a long-term ~30% restricted diet since young adulthood. These data contrast with observations in the 2012 NIA intramural study report, where a difference in survival was not detected between control-fed and CR monkeys. A comparison of body weight of control animals from both studies with each other, and against data collected in a multi-centred relational database of primate ageing, suggests that the NIA control monkeys were effectively undergoing CR. Our data indicate that the benefits of CR on ageing are conserved in primates.

Critical Role for Hypothalamic mTOR Activity in Energy Balance

The mammalian target of rapamycin (mTOR) promotes anabolic cellular processes in response to growth factors and metabolic cues. The TSC1 and TSC2 tumor suppressors are major upstream inhibitory regulators of mTOR signaling. Mice with Rip2/Cre-mediated deletion of Tsc1 (Rip-Tsc1cKO mice) developed hyperphagia and obesity, suggesting that hypothalamic disruption (for which Rip2/Cre is well known) of Tsc1 may dysregulate feeding circuits via mTOR activation. Indeed, Rip-Tsc1cKO mice displayed increased mTOR signaling and enlarged neuron cell size in a number of hypothalamic populations, including Pomc neurons. Furthermore, Tsc1 deletion with Pomc/Cre (Pomc-Tsc1cKO mice) resulted in dysregulation of Pomc neurons and hyperphagic obesity. Treatment with the mTOR inhibitor, rapamycin, ameliorated the hyperphagia, obesity, and the altered Pomc neuronal morphology in developing or adult Pomc-Tsc1cKO mice, and cessation of treatment reinstated these phenotypes. Thus, ongoing mTOR activation in Pomc neurons blocks the catabolic function of these neurons to promote nutrient intake and increased adiposity.

Effects of long-term exogenous bovine somatotropin on water metabolism and milk yield in crossbred Holstein cattle

The present study was conducted to evaluate the effects of long-term administration of recombinant bovine somatotropin (rbST) on the regulation of body fluids, mammary blood flow (MBF) and other variables relevant to milk synthesis, in crossbred dairy cattle (0·875 of Holstein–Friesian (HF) genes and 0·125 Red Shindi (RS) genes. Ten first lactation, non-pregnant, animals were chosen and divided into the control and experimental groups of five animals each. Four consecutive measurements were carried out in each group beginning on days 45 (pre-treatment), 105, 165 and 225 of lactation. Animals that had completed 60 days of lactation were injected subcutaneously every 14 days with 500 mg of rbST (POSILAC, Monsanto, USA) in the experimental group, while animals in the control group were injected subcutaneously every 14 days with 800 mg of sterile sesame oil, without rbST, as a control. All animals were fed with rice straw treated with 50 g urea/l as the source of roughage in combination with a similar concentrate throughout the experiments. During the treatment periods, the daily dry matter intake (DMI) was numerically greater for rbST-treated animals than for control animals, while the relative values of DMI per kg body weight and water intake showed no differences.Animals in both groups gained weight throughout the experiment with no significant differences between the groups. Animals receiving rbST for 45 days increased their peak milk yield from 13·4 kg/day per animal during pre-treatment to 15·9 kg/day per animal (18·7% increase) on day 105 of measurement and this peak yield was higher (19·5%) than those of control animals in the same period. Milk yields on days 225 in late lactation of both groups significantly decreased (P<0·05) in comparison with the early and mid-lactating periods. Over the course of the experiment, milk yield of the rbST-treated animals was significantly higher than those of the control animals (P<0·01). The administration of rbST significantly increased MBF (P<0·05) and mammary plasma flow (MPF) (P<0·01). The ratio of MBF to milk yield slightly increased as lactation advanced in both controls and rbST-treated animals. The administration of rbST significantly increased the absolute values of both plasma volume (P<0·01) and blood volume (P<0·05) when compared with the control animals. The control animals showed no significant changes in values of extracellular water (ECW) throughout the course of treatment periods. The rbST-treated animals increased in both the absolute values and the relative (proportion of body weight) values of ECW throughout the experiment (P<0·05). The estimated values of intracellular water (ICW) in both groups showed no significant changes during the course of treatments. There were no significant changes in the water turnover rate (WTO) and the biological half-life of tritiated water in different periods of lactation in both groups. The absolute values of total body water space (TOH) and total body water (TBW) were significantly greater in rbST-treated than control animals (P<0·05). The relative values of both TOH and TBW as a proportion of body weight of control animals decreased, while no alteration was apparent in rbST-treated animals during the course of treatments. These differences were statistically significant (P<0·05). The absolute values of empty body water (EBW) of the control animals showed no significant changes, while animals treated with rbST tended to increase in absolute values of EBW throughout the course of treatments. The effects of these differences were statistically significant (P<0·05). There were no significant changes in relative values of EBW during the course of treatments in both controls and rbST-treated animals. These data demonstrated that the rbST exerts its galactopoietic action in part through increases in TBW, EBW and ECW in association with an increase in MBF, which partitions the distribution of nutrients to the mammary gland for milk synthesis. During this long-term administration of rbST, the stimulant effect for milk yield was less in late lactation despite a higher MBF. The decline in milk yield during rbST treatment without fall in MBF in late lactation must be attributed to a local change within the mammary gland.

A protective role for keratinocyte growth factor in a murine model of chemotherapy and radiotherapy-induced mucositis

To evaluate the activity of palifermin (rHuKGF) in a murine model of mucosal damage induced by a radiotherapy/chemotherapy (RT/CT) regimen mimicking treatment protocols used in head-and-neck cancer patients. A model of mucosal damage induced by RT/CT was established by injecting female BDF1 mice with cisplatin (10 mg/kg) on Day 1; 5-fluorouracil (40 mg/kg/day) on Days 1-4, and irradiation (5 Gy/day) to the head and neck on Days 1-5. Palifermin was administered subcutaneously on Days -2 to 0 (5 mg/kg/day) and on Day 5 (5 mg/kg). Evaluations included body weight, organ weight, keratinocyte growth factor receptor expression, epithelial thickness, and cellular proliferation. Initiation of the radiochemotherapeutic regimen resulted in a reduction in body weight in control animals. Palifermin administration suppressed weight loss and resulted in increased organ weight (salivary glands and small intestine), epithelial thickness (esophagus and tongue), and cellular proliferation (tongue and salivary glands). Administration of palifermin before RT/CT promotes cell proliferation and increases in epithelial thickness in the oral mucosa, salivary glands, and digestive tract. Palifermin administration before and after RT/CT mitigates weight loss and a trophic effect on the intestinal mucosa and salivary glands, suggesting that palifermin use should be investigated further in the RT/CT settings, in which intestinal mucositis and salivary gland dysfunction are predominant side effects of cytotoxic therapy.

Dietary protein reduction in sheep and goats: different effects on L-alanine and L-leucine transport across the brush-border membrane of jejunal enterocytes.

It was the aim of this study to examine the potential regulatory effects of a long-term low dietary protein supply on the transport capacity of the jejunal brush-border membrane for amino acids. For this purpose, we used the neutral amino acids L-alanine (representative for nonessential amino acids) and L-leucine (representative for essential amino acids) as model substances. Ten sheep lambs, 8 weeks of age and 19-27 kg body weight, were allotted to two dietary regimes with either adequate or reduced protein supply which was achieved by 17.9% and 9.7% of crude protein in the concentrated feed, respectively. The feeding periods were 4-6 weeks in length. Similarly, eight goat kids of 5-7 weeks of age and 8-14 kg body weight were allotted to either adequate (crude protein 20.1%, feeding period 9-12 weeks) or reduced protein supply (10.1%, feeding period 17-18 weeks). Dietary protein reduction in lambs caused a significant body weight loss of 0.6 +/- 0.7 kg, whereas the body weight in control animals increased by 1.9 +/- 0.7 kg (P<0.05). Plasma urea concentrations decreased significantly by 60% (low protein 2.3 +/- 0.1 versus control 5.7 +/- 0.2 mmol l(-1), P<0.001). In kids, reduction of dietary protein intake led to significant decreases of the daily weight gain by 48% from 181 +/- 8 g to 94 +/- 3 g (P<0.001) and daily dry matter intake by 27% from 568 +/- 13 g to 417 +/- 6 g (P<0.01). Respective urea concentrations in plasma were reduced by 77% from 5.2 +/- 0.4 to 1.2 +/- 0.2 mmol l(-1) (P<0.01). Kinetic analyses of the initial rates of alanine uptake into isolated jejunal brush-border membrane vesicles from sheep and goats as affected by low dietary protein supply yielded that the apparent Km was neither significantly different between the species nor significantly affected by the feeding regime thus ranging between 0.12 and 0.16 mmol.l(-1). Reduction of dietary protein, however, resulted in significantly decreased Vmax values of the transport system by 25-30%, irrespective of the species. Kinetic analyses of the initial rates of leucine uptake into jejunal brush-border membrane vesicles from sheep and goats yielded that leucine uptake was mediated by Na+-dependent as well as Na+-independent processes. Similar to alanine, apparent Km values of leucine uptake were neither different between the species nor affected due to low dietary protein and ranged between 0.08 and 0.15 mmol l(-1). In contrast to the alanine transport mechanism, dietary protein reduction resulted in increased Vmax values of Na+-dependent leucine transport by 53% in sheep and 230% in goats. Similarly, Na+-independent leucine uptake was stimulated by 85% and 200% in sheep and in goats, respectively. This study shows adaptation of amino acid absorption at the brush-border membrane level of jejunal enterocytes of small ruminants due to dietary protein reduction. Whereas the transport capacity for the nonessential amino acid alanine was reduced due to low dietary protein, the transport capacity for the essential amino acid leucine was markedly stimulated. From this, the involvement of rather different feedback mechanisms in adaptation of intestinal amino acid transport mechanisms has to be discussed.

FDA points-to-consider documents: the need for dietary control for the reduction of experimental variability within animal assays and the use of dietary restriction to achieve dietary control.

Standard protocols for conducting chronic toxicity and carcinogenicity studies have been refined over the years to carefully control for many variables. Nevertheless, over the last 2 decades, there has been a steady increase in variability, a decrease in survival, an increase in tumor incidence rates, and an increase in the average body weight of control animals among the various rodent species and strains used for toxicity testing. These observations have prompted an evaluation of chronic study designs to determine what factor(s) may be responsible for such confounding changes. Ad libitum feeding and the selection of successful breeders with rapid offspring growth is believed to be at least partially responsible for the heavier, obese rodents with which many laboratories are coping today. As a result of these changes, some studies used for the evaluation of safety have been deemed inconclusive or inadequate for regulatory purposes and either additional supportive studies have been requested and/or studies per se have been repeated. Research on the molecular mechanisms of caloric restriction and agent-induced toxicity at the Food and Drug Administration (FDA) National Center for Toxicological Research stimulated the first international conference on the biological effects of dietary restriction in 1989; this was followed in 1993 by an FDA workshop exploring the utility of dietary restriction in controlling reduced survival in chronic tests and an international conference in 1994 exploring the implications for the regulatory community of using dietary restriction in toxicity and carcinogenicity studies used in support of a sponsor's submission or in risk assessments. The outcome of that conference was the FDA's commitment to develop Points-to-Consider documents that address the issue of dietary control in chronic toxicity and carcinogenicity studies.

The Effect of Body Weight on Tumor Incidence and Carcinogenicity Testing in B6C3F1 Mice and F344 Rats

The Effect of Body Weight on Tumor Incidence and Carcinogenicity Testing in B6C3F1 Mice and F344 Rats. Seilkop, S. K. (1995). Fundam. Appl. Toxicol. 24, 247-259.Associations between animal body weights and tumor incidence were examined using individual control animal data from 55 mouse and 53 rat studies conducted by the National Toxicology Program. Several statistically significant associations were found, the strongest of which were positive relationships between body weight and risk of liver tumors in both sexes of mice, pituitary gland tumors in both sexes of rats, and mammary gland tumors in female rats. The most compelling evidence that these relationships were causal in nature was the replication of the correlations across individual experiments. In addition, significant correlations between tumor occurrence and body weights occurred in animals as young as 9 weeks of age. Logistic regression models relating 12-month body weight to tumor risk were developed for the strongest relationships, and utilized in the reanalysis of tumor data from two National Toxicology Program studies with treatment-related decreases in body weight. A simulation study based on the logistic regression models indicated that statistical power to detect a treatment-related increase in tumor incidence can be seriously diminished when mean body weight in treated animals is depressed by as little as 10%. Conversely, when mean body weight in control animals is 10% lower than that of treated animals, false positive rates can increase to 20-30%. The severity of the effects of such commonly observed treatment-related disparities in body weight suggests that alternative data analysis methods or experimental designs should be considered to address this potential problem in carcinogenicity testing.

Fetal intestinal transplantation: A new therapeutic approach in short-bowel syndrome

Intraperitoneally transplanted fetal rat intestine can be anastomosed to the intestine of the host after 4 weeks of maturation. In syngeneic transplant combinations morphological findings as well as functional parameters suggest that the intestinal transplant might provide a substitute for normal intestinal tissue. Four weeks after fetal intestinal transplantation in adult Lewis rats we resected the total small bowel of the host and interposed the matured transplant. Resection of total small bowel without transplant interposition led to a decline of body weight in control animals but was prevented in the transplanted group. After total small bowel resection and cecectomy (a lethal resection in the control group) we found a 40% ( 4 10 ) survival in the group in which the transplant had been anastomosed to the remaining bowel.

Hemodynamic and pathological results from experimentally induced left ventricular hypertrophy in the rabbit.

Many studies of ventricular structure and function of the hypertrophied cardiac muscle have been performed using a model of right ventricular hypertrophy because a reliable experimental model for the chronically hypertrophied left ventricle was not available. Adult rabbits underwent thoractomy with placement of an ameroid band on the proximal aorta. The ameroid band closed to a maximal extent at 9 days. Systolic gradients were measured at 3 weeks. 37 animals (group I) were sacrificed at an average of 7 weeks, and 5 (group II) at 18 weeks. Specific cardiac chambers were weighed. The average left ventricular weight expressed as a percentage of body weight of control animals was 0.13 +/- 0.01 compared to group I 0.17 +/- 0.04 (P = 0.001) and group II 0.23 +/- 0.04. Hemodynamic data revealed significant aortic outflow obstruction with systolic gradients averaging at least 50 mm Hg. Left ventricular end-diastolic pressures were elevated in 13 of 29 animals compatible with left ventricular failure. These results indicate that this technique affords a reliable experimental model for inducing biventricular hypertrophy which can be evaluated hemodynamically.