Effects of bifemelane hydrochloride on atherosclerosis in aged rats fed low-calcium diets

The preventative effects of bifemelane (4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride) on atherosclerosis in aged rats fed low-calcium diets were investigated. Male 18-month-old Wistar rats were maintained for 90 days on the following: (A) standard diet (n = 7), (B) low calcium, low magnesium, high aluminium diet (n = 8), (C) standard diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6), (D) low calcium and magnesium, high aluminium diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6). All groups were give these diets and water ad lib for 90 days, after which blood samples were taken from the abdominal aorta and samples of aorta were examined for atherosclerotic changes. The serum concentrations of the following were determined: calcium, magnesium, zinc, aluminium, inorganic phosphorus, cholesterol, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, cholinesterase, creatine phosphokinase, blood urea nitrogen and N-terminal parathyroid hormone. The only significant differences between the groups in serum chemistry were reduced concentrations of cholinesterase and magnesium in groups B and D, increased aluminium in group B, and increased N-terminal parathyroid hormone in groups B and D. In groups C and D the atherosclerosis was much improved compared with that in groups A and B. It appears that bifemelane largely prevents atherosclerosis caused by calcium deposition in the arteries of rats fed low-calcium diets, due to its effect in maintaining magnesium and calcium in bones.     

Decreased plasma insulin but normal glucagon in rats fed low protein diets

Plasma glucagon and insulin were determined in rats fed three diets, one control and two low protein (LP 1 & LP 2). In LP 1, the protein omitted was replaced by carbohydrate while in LP 2, fat and alpha-cellulose replaced the omitted protein. Among rats fed LP diets ad libitum, food consumption decreased and body weight loss occurred. In order to separate the effects of reduced food intake and weight loss from the effects of LP diet alone, paired feeding and paired weight experiments were conducted. In another experiment, ingestion of a LP diet for 8 to 10 days was followed by refeeding the control diet for 5 days. The results demonstrate that plasma insulin was reduced in LP rats compared to the full-fed controls and pair-fed controls, the lowest levels being observed in rats fed LP 2 diet. Furthermore, the paired feeding experiment revealed that the diminished food consumption plays no significant role in lowering plasma insulin in LP rats. The refeeding experiment showed that the decline in plasma insulin in LP rats is a transient phenomenon and the plasma insulin promptly reverts to normal upon resumption of feeding the control diet. Plasma glucagon was unaltered throughout these dietary manipulations.     

Protein synthesis in vivo in rats fed on lipid-rich liquid diets

Changes in tissue composition and protein synthesis ratio were studied in the major tissues of the body in young rats fed on lipid-rich, isonitrogenous purified liquid diets, a convenient method for inducing voluntary overfeeding under controlled nutritional conditions. Overfed rats showed faster growth induced by the energy excess. Analysis of tissue composition (protein, DNA and RNA contents) revealed that growth was due mainly to tissue hyperplasia in which protein and DNA contents increased in parallel. Fractional protein synthesis ratio measured in vivo by the flooding-dose method of phenylalanine showed a marked increase in all tissues. This change could be attributed to an increase in the ribosomal activity for protein synthesis in most tissues. Therefore, our results indicate that addition of a supplementary energy source (as lipids) to a well-balanced diet improves growth and protein synthesis in growing rats.     

Craniofacial bone remodeling in growing rats fed a low-calcium and vitamin-D-deficient diet and the influence of masticatory muscle function

Fifty-two male growing rats were randomly divided into three groups. The first group (n = 18) received a hard deficient diet, and the second (n = 18) a soft deficient diet. The control group (n = 16) was fed the normal hard diet. At the beginning and in the middle of the 28-day experimental period oxytetracycline was injected. Two representative coronal sections of the snout and the corresponding contact microradiographs were analyzed. The bone mass of the premaxillary and nasal bones seemed to be less in the two deficient diet groups than in the normal one, due to an increased endosteal bone resorption and decreased bone formation. No difference in the bone apposition rate and pattern could be seen between the deficient hard and soft diet groups, except in the dorsal part of the premaxilla, where the bone formed in the first half of the experiment was markedly more resorbed in the deficient soft diet group during the remaining period than in the deficient hard diet group. The morphology of the sutures was influenced by the altered function, since the sutural space became narrower, and premature obliterations of the internasal suture were observed in the deficient soft diet group. In conclusion, poor bone quality was observed in the skull of rats fed a low-calcium and vitamin-D-deficient diet, with less bone mass than in normal conditions. Masticatory function was a significant factor influencing bone remodeling and sutural growth even in situations in which a metabolic bone disturbance exists.     

Responses and physiological modifications of intestinal sucrase in rats fed diets containing various carbohydrates

Weaning rats were submitted during 3 months to complet and balanced diets where only glucidic constituent varied. They were sacrified when fed or after 16 h fasting. 1. The value of intestinal sucrose K(M) is higher in rats fed on glucose dietary than in rats fed on sucrose, fructose or glucose + fructose dietary. These modifications are independant of the states of digestion. 2. The V(MAX) is diversely influenced by the states of digestion: hydric diet increases the V(MAX) in animals fed on sucrose diet when intestinal repletion has the same effect in animals receiving glucose diet. Fructose diet decreases it irreversibility in both cases. 3. Growth of animals is sagging respectively in order from sucrose and glucose diets to glucose + fructose and fructose diets, then weight of organes is unaffected. It was noted that perirenal and epididymal fats are more abundant in rats nourished with glucose diet than with fructose diet. 4. The glucoregulation is correctly effectued in either starved or fed animals and shows an available adaptation of organism in energetic utilisation of various studied sugars. Plasmatic, hepatis and intestinal free fatty acids levels are constant and equal in all series of expements in spite of important variations of reverse fat.     

Dietary flavonoids reduce lipid peroxidation in rats fed polyunsaturated or monounsaturated fat diets

We investigated the influence of dietary flavonoids on alpha-tocopherol status and LDL peroxidation in rats fed diets enriched in either polyunsaturated fatty acids (PUFA) or monounsaturated fatty acids (MUFA). Diets equalized for alpha-tocopherol concentrations were or were not supplemented with 8 g/kg diet of flavonoids (quercetin + catechin, 2:1). After 4 wk of feeding, plasma lipid concentrations were lower in rats fed PUFA than in those fed MUFA with a significant correlation between plasma alpha-tocopherol and cholesterol concentrations, r = 0.94, P < 0. 0001). Dietary lipids influenced the fatty acid composition of VLDL + LDL more than that of HDL or microsomes. The resistance of VLDL + LDL to copper-induced oxidation was higher in rats fed MUFA than in those fed PUFA as assessed by the lower production of conjugated dienes and thiobarbituric acid reactive substances (TBARS) and by the >100% longer lag time for dienes production. (P < 0.0001). Dietary flavonoids significantly reduced by 22% the amounts of dienes produced during 12 h of oxidation in rats fed diets rich in PUFA and lengthened lag time 43% in those fed MUFA. Microsomes of rats fed MUFA produced approximately 50% less TBARS than those of rats fed PUFA (P < 0.0001) and they contained more alpha-tocopherol in rats fed MUFA than in those fed PUFA with higher values (P < 0. 0001) in both groups supplemented with flavonoids (P < 0.0001). Our findings suggest that the intake of dietary flavonoids is beneficial not only when diets are rich in PUFA but also when they are rich in MUFA. It seems likely that these substances contribute to the antioxidant defense and reduce the consumption of alpha-tocopherol in both lipoproteins and membranes.     

Urinary indices in llamas fed different diets

Indices of renal function and damage were measured in 12 healthy male adult llamas fed a diet of mixed alfalfa/grass hay (mixed hay) and water ad libitum. Using a collection bag fitted over the preputial area, urine samples were collected at 6, 12, and 24 hours. Serum samples were obtained concurrently to determine endogenous creatinine clearance (CL), total (TE) and fractional excretion (FE) of electrolytes (Na, K, Cl, P), electrolyte CL, urine and serum osmolality, urine enzyme activities (gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase), and urine protein concentration. Urine production was quantified. Three months later, 10 of the 12 llamas were fed a grass hay diet and water ad libitum. Similar samples were obtained, and similar measurements were made. Urine production was higher when the llamas were fed the mixed hay diet. Total urine volume for llamas fed mixed hay ranged from 628 to 1,760 ml/24 h, with a median of 1,307.5 ml/24h, compared with a range of 620 to 1,380 ml/24 h and a median of 927.50 ml/24h for llamas fed grass hay. Median urine osmolality was higher in llamas fed mixed hay (1,906 mOsm/kg of body weight, with a range of 1,237 to 2,529 mOsm/kg), compared with llamas fed grass hay (1,666 mOsm/kg with a range of 1,163 to 2,044 mOsm/kg). Creatinine CL did not vary significantly over time for either diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Offspring of normal and diabetic rats fed saturated fat in pregnancy demonstrate vascular dysfunction

BACKGROUND: Disturbances of the in utero environment may "program" for disease in later life. In this study, we determined whether dietary fat supplementation and/or diabetes in pregnancy can adversely affect vascular function in the offspring. METHODS AND RESULTS: Female Sprague-Dawley rats were fed a breeding diet or a diet high in saturated fat (30% wt/wt) for 10 days before mating, throughout pregnancy, and postpartum. Endothelium-dependent relaxation to acetylcholine was blunted in isolated femoral arteries of 15-day-old weanling pups from dams fed the 30%-fat diet. Endothelial dysfunction and enhanced constrictor responses to norepinephrine were also observed in an additional study of 60-day-old offspring of dams fed 20% saturated fat. Rats with streptozotocin-induced diabetes were also fed saturated fat during pregnancy. Femoral arteries from their 15-day-old offspring showed impairment of endothelium-dependent dilation and enhanced constrictor responses to norepinephrine and the thromboxane mimetic U46619 compared with young offspring of high-fat-fed normal dams. The 30%-fat diet was also deleterious to vascular function in the maternal diabetic animals when assessed in mesenteric arteries 16 days postpartum. CONCLUSIONS: A high-fat diet in pregnancy led to vascular dysfunction in rat weanlings and young adult offspring. Vascular function further deteriorated in weanlings if the maternal rat was diabetic.     

Elevated expression and altered pattern of activity of DNA methyltransferase in liver tumors of rats fed methyl-deficient diets

DNA methyltransferase (MTase) activity in nuclear extracts from neoplastic and preneoplastic livers of rats fed a methyl-deficient diet (MDD) is elevated compared with that seen in the livers of control rats. Nuclear proteins were prepared in the presence of protease inhibitors including trans-epoxy succinyl-L-leucylamido-(4-guanido)butane and were fractionated by isoelectric focusing. In normal, control liver, two distinct MTase fractions were observed. In MDD-induced malignant liver, a third fraction, in addition to the previous two, was also seen. Both the DNA substrate and the cytosine site specificities of the third MTase fraction differ from those of the other two fractions. The distinct MTase activity in liver tumor has significantly more de novo MTase activity than do the MTase fractions of normal, control liver. Thus, normal and neoplastic rat livers differ in DNA MTase fractionation patterns and site specificities. The altered DNA MTase activity observed in rat liver tumors caused by MDDs may be one of the critical factors contributing to cancer formation through abnormal DNA methylation.     

Cognitive impairment in rats fed high-fat diets: A specific effect of saturated fatty-acid intake.

One-month-old rats were fed 1 of 4 high-fat diets (20% fat) or chow (4.5% fat) for 3 months. Dietary saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids varied such that their independent effects on cognitive performance could be tested. Rats were tested on a variable-interval delayed-alternation task. Impairment in both the ability to learn the basic alternation rule and remembering trial-specific information over time was observed in rats fed the experimental diets relative to those fed chow. The degree of impairment was highly associated with the level of SFAs fed and independent of the MUFAs or PUFAs. Dietary fat altered brain phosphatidylcholine fatty-acid profile, but the membrane changes did not correlate with cognitive impairment. The results demonstrate that cognitive impairment is directly associated with SFA intake but suggest that the mechanism is independent of bulk brain membrane compositional changes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficiency of lysine or threonine retention in growing rats fed diets limiting in either lysine or threonine

Over a 21-d experiment, the efficiency of lysine and threonine retention was determined in 80 male Sprague-Dawley rats (65.9 +/- 0.3 g, means +/- SE) fed purified diets containing an amino acid mix limiting in either lysine or threonine. With additional increments of the first limiting amino acid, lysine concentration in total body protein (g/16 g N) increased (P < 0.01) in rats fed lysine-limiting diets but, when fed threonine-limiting diets, lysine concentration in body protein first increased and then decreased (P < 0.01). As increments of the first limiting amino acid were added, the threonine concentration in total body protein increased then decreased when both lysine- (P < 0.01) and threonine- (P < 0.06) limiting diets were fed. Lysine and threonine retention were calculated based on comparative slaughter. Sixteen rats were killed on d 0 to estimate the grams of amino acid in the body. Retention responses were analyzed using a logistic equation in which lysine or threonine intake was used to predict retention. The maximum marginal efficiency (dr/dI, retention/intake) was observed at <40% of maximum retention. For lysine retention, it was 81% when lysine was limiting and 70% when threonine was limiting. For threonine retention, it was 58% when threonine was limiting and 49% when lysine was limiting. The maximum cumulative efficiency (retention adjusted for maintenance relative to cumulative intake) for lysine retention was 62% when lysine was limiting or 58% when threonine was limiting. For threonine retention, it was 51% when threonine was limiting and 35% when lysine was limiting. Thus, amino acid concentration in body protein is not constant, and amino acids are used with higher efficiency when first limiting.     

Estimation of tissue protein synthesis in rats fed diets labeled with (U-14C)tyrosine

The rate of liver and muscle protein synthesis has been measured in 27 rats after feeding L-[U-14C]tyrosine in L-amino acid diets prepared as agar gels. Constant specific activity of the free tyrosine pool, as indicated by constant excretion of 14CO2, was reached within 2 h of feeding and was maintained for the remaining 6 h of the 8-h experiment. Muscle protein synthesis was decreased (P less than 0.05) in rats fed a 0.3% methionine diet compared with rats fed this diet supplemented with 0.51% cystine (fractional rate of synthesis, ks: 0.098 vs. 0.121). No effect (P greater than 0.05) of these diets on liver protein synthesis was observed (ks: 0.603 vs. 0.532). Protein synthetic rate was also determined by the constant-intravenous infusion technique in 17 rats fed unlabeled diets. The two techniques gave similar estimates. Restraint of the rats or the infusion of saline had no measurable effect on the rate of protein synthesis in rats fed labeled diets. This feeding technique is essentially equivalent to the constant-infusion technique and offers an easier, more physiological approach to achieving a steady state.     

Methionine requirement of channel catfish fed soybean meal-corn-based diets

A soybean meal-corn-based diet was used to determine dietary methionine (Met) required by 14-g channel catfish (Ictalurus punctatus) in a 42-d experiment at 25 degrees C. The basal diet with balanced limiting amino acids relative to the catfish whole-body amino acid profile contained 277 g of CP, 3.6 g of Met, 4.0 g of cystine (Cys), and 10 MJ of DE/kg of DM. DL-Methionine was added to the basal diet from 0 to 12.0 g/kg in 2-g intervals at the expense of L-glutamic acid to produce seven isonitrogenous and isocaloric diets. A reference diet contained 331 g of CP, 8 g of Met, 5 g of Cys, and 10 MJ of DE/kg of DM (included 8% fish meal). Seven graded Met levels resulted in quadratic responses (P < .01) of weight gain, specific growth rate, feed or GE intake, feed or energy efficiency, protein or energy retention, protein efficiency ratio, and apparent net protein or energy utilization. Channel catfish required 9.4 g of Met/kg of DM (34.1 g/kg of CP) with a total 11.3 g/kg of calculated digestible sulfur-containing amino acids based on multiple regression dose-response models or 270 mg of Met/kg of fish per day based on a broken-line response of protein gain to Met intake. At the adequate Met level, catfish with the lowest (P < .05) liver lipids showed feed intake and protein or energy utilization efficiency similar (P > .05) to that of catfish fed the reference diet. Catfish fed all-plant-protein diets require more dietary methionine than previously reported. Catfish fed corn-soybean meal diets fortified adequately with methionine result in performance that approaches that of fish fed a fish meal-based diet.     

Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCl

Cardio-pulmonary function was measured in male broilers reared on diets formulated to contain 1.5% arginine (NORMAL group) or 2.5% arginine (ARGININE group). A snare placed around the right pulmonary artery permitted acute shunting of the entire cardiac output (CO) through the left pulmonary artery, resulting in sustained increases in blood flow (BF) through the left lung in both groups. The unilateral increase in BF was accompanied by sustained increases in pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in the NORMAL group. However, following initial transient increases in PAP and PVR in the ARGININE group, subsequent pulmonary vasodilation gradually reduced PVR, and thus PAP, in spite of the ongoing elevation of BF through the left lung. The capacity of the pulmonary vasculature in the ARGININE group to accommodate an increased BF at a normal PAP accounts for the previously reported lower incidence of pulmonary hypertension syndrome (PHS, ascites) in cold-stressed broilers fed supplemental dietary arginine. Hypoxemia and respiratory acidosis ensued rapidly in both groups after tightening the pulmonary artery snare, in spite of a compensatory increase in the respiratory rate. The gradual return of PVR and PAP to presnare levels in the ARGININE group did not eliminate the concurrent ventilation-perfusion mismatch caused by the increased rate of BF through the left lung. Tightening the pulmonary artery snare caused mean systemic arterial pressure (MAP) to drop from control levels of approximately 98 mm Hg to sustained hypotensive levels of approximately 65 mm Hg in both groups. This systemic hypotension was caused by decreases in CO and total peripheral resistance (TPR). The reduction in CO were caused by reduction in stroke volume (SV) rather than heart rate (HR), suggesting that acutely tightening the pulmonary artery snare increased PVR sufficiently to impede left ventricular filling. Accordingly, the maximum increment in PAP attainable by the right ventricle during acute increases in PVR apparently was inadequate to propel the entire CO through the pulmonary vasculature, setting the stage for the congestive right-sided pooling of blood routinely associated with PHS in broilers.     

Adequacy of amino acids in diets fed to lactating dairy cows

The Cornell Net Carbohydrate and Protein System was used to evaluate absorbable limiting amino acids (AA) for milk yield. The system was utilized to characterize whether diets in five previous experiments met AA requirements for milk protein synthesis. Twenty-nine treatment means for milk yield from 367 cows constituted the database for the evaluation. Using the mechanistic relationships of nutrient metabolism described in the Cornell system, absorbed amounts were predicted of each essential AA from a diet and milk yields allowed by the most limiting AA. Regression of observed milk yield (Y) on predicted milk yield (X) using all treatment means (n = 29) was Y = 2.3 + 0.799X (r2 = 0.72). The linear relationship was stronger using 6 treatment means (n = 18) when protein supplements were fed rather than when ruminally protected AA were fed or when AA were postruminally infused (Y = -1.8 + 0.983X; r2 = 0.93). The Cornell system predicted that, for diets based on corn, Met or Lys was limiting when soybean meal was the protein source, but Lys was limiting when corn gluten meal or brewers grains were the source of protein. By AA limitation, the Cornell system explained differences in milk yield for diets that differed in supplemental protein sources in some of the experiments. As determined from milk protein yields in these studies, requirements for individual essential AA were expressed as a percentage of dietary dry matter or total essential AA, and values were relatively constant among dietary treatments and experiments.     

Lysine deficiency in postweaned calves fed corn and corn gluten meal diets

Holstein bull calves (n = 36) weaned at 6 wk of age were used in six trials to examine the response of N balance to postruminal administration of lysine with or without methionine in postweaned calves receiving diets based on corn and corn gluten meal. Calves were younger than 3 mo of age in Trials 1 and 2 but older than 3 mo in Trials 4 to 6. L-Lysine monohydrochloride was supplemented with or without DL-methionine twice daily through the reticular groove, except in Trial 4, in which N supplements were infused through duodenal cannulas. L-Glutamine was used as a nonspecific N source in every trial, and casein was a positive control in Trials 4 and 5. When daily CP intake from the diet was 3.9 g/kg BW, lysine was limiting for calves less than 11 wk of age (Trials 1 and 2) but not limiting for calves greater than 12 wk of age (Trial 3). No amino acid seemed to be limiting for calves greater than 20 wk of age (Trial 4) when daily CP intake was 4.1 g/kg BW, but lysine was limiting when CP intake was restricted to 3.0 g/kg BW when calves were more than 17 wk of age (Trial 5). However, lysine was not limiting above 18 wk of age (Trial 6) when CP intake was increased to 3.8 g/kg BW by adding urea to the diet. Results suggest that lysine may be limiting for corn and corn gluten meal diets only when ruminal microbial protein synthesis is restricted.     

Black tea and mammary gland carcinogenesis by 7,12-dimethylbenz[a]anthracene in rats fed control or high fat diets

Epidemiological studies suggest that tea may reduce cancer risk, and in laboratory rodents, chemopreventive effects of tea or purified extracts of tea have been demonstrated in lung, gastrointestinal tract and skin. There is some evidence of chemoprevention by tea in the mammary gland, but the data are not conclusive. In order to evaluate more fully the possible influence of black tea on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland tumors in the female S-D (Sprague-Dawley) rat, three large studies were performed: experiment 1, tumorigenesis in rats fed AIN-76A diet and given 25 mg/kg DMBA and 1.25 or 2.5% whole tea extract or water to drink; experiment 2, tumorigenesis in rats given 15 mg/kg DMBA and the same diet and fluids as in experiment 1; experiment 3, tumorigenesis in rats fed control or HF (high fat, corn oil) diet and given 15 mg/kg DMBA and 2% tea or water to drink. Tea was given throughout the experiment; DMBA was given by gastric gavage at 8 weeks of age. There was no consistent effect of tea on tumorigenesis in rats fed AIN-76A diet; there was, however, evidence in experiment 3 of a reduction of tumorigenesis by tea in rats fed the HF diet. In experiment 3, rats fed the HF diet and given water showed the expected increase in tumor burden (number and weight) compared with rats fed control diet. However, rats fed the HF diet and given 2% tea showed no increase in tumor burden; their tumor burden was significantly lower than in rats fed the HF diet and given water (P < 0.01) and was not different from rats fed control diet and given water or tea. In addition, in experiment 3, the number of malignant tumors per tumor-bearing rat was increased by the HF diet in water-drinking rats (P < 0.01) but not in tea-drinking rats. Therefore, it appears that tea partially blocked the promotion of DMBA-induced mammary tumorigenesis by the HF diet.