Weanling Rats Research Articles

NUTRITIVE VALUE OF DIFFERENT ANIMAL PROTEIN SOURCES IN WEANLING WISTAR RATS

The main protein sources human diets include the beef, fish and chickens meat. These sources are often consumed indiscriminately without any regard to their relative nutritive value. Hence, the nutritional quality of different animal protein sources in human and animal diets was assessed in this study, using weanling Wistar rats. Rats (n=25) weighing 30g-40g were randomly allotted to five dietary treatments: T1= Caesin-based diet, T2= Nitrogen-Free diet, T3= Beef-based diet, T4= Catfish-based diet, T5= Chicken breast- based diet in a completely randomised design. The diets were fed to respective weanling rats for four weeks, feed and water were offered ad libitum. Daily urine and faecal samples were weighed, and labelled, then stored at 4oC. Data were analysed using descriptive statistics and ANOVA at α0.05. Rats on T3 had significantly higher (p<0.05) feed intake (FI) (48.25) than T4 (43.41) and T5 (22.27). Protein intake was lower significantly (p>0.05) in rats on T4 (3.80) Also, rats on T3 (41.01) had higher weight gain than in T4 (23.51), and T5 (15.30). Faecal nitrogen in rats on T3 (2.36), T4 (1.79), and T5 (2.29) were similar (p>0.05). The protein efficiency ratio (PER) was significantly higher (p<0.05) in T4 (6.07) than in other treatments. The NPR was significantly higher (p<0.05) for T1 (3.30), T3 (4.08), and T4 (3.87) than T5 (1.59) and T2 (0.00). The BV was significantly higher (p<0.05) for T1 (0.89) than T3 (0.67), T4 (0.58), and T5 (0.68), but significantly lower (p>0.05) for T2 (0.12). The NPU values for T3 (75.34), T4 (70.12), and T5 (77.43) were similar (p>0.05). Thus, rats on chicken-breast based diets performed best relative to standard casein-based diets.

Ratios of Essential-to-Nonessential Amino Acids in Plasma from Rats Fed Different Kinds and Amounts of Proteins and Amino Acids

Weanling rats fed diets containing amounts of proteins and amino acids that were suboptimal for growth showed a reduction in the plasma ratio of essential-to-nonessential amino acids (EN ratio) when this ratio was compared with that of rats fed 18% casein diets. For young adult rats fed 18, 8 and 4% casein, there was a decreased plasma EN ratio in rats fed the low casein diets. Glycine supplements in the diet also decreased the EN ratio in the plasma of both weanling and young adult rats. Glutamic acid supplements fed to young adult rats did not have this effect. The decreased plasma EN ratios were the net result of a decrease in essential amino acids and, in most instances, an increase in nonessential amino acids. The limiting essential amino acid in the diet was reduced in the plasma to the greatest degree, but the levels of other essential amino acids were also affected.

Female rats are less prone to clinical heart failure than male rats in a juvenile rat model of right ventricular pressure load.

Sex is increasingly emerging as determinant of right ventricular (RV) adaptation to abnormal loading conditions. It is unknown, however, whether sex-related differences already occur in childhood. Therefore, this study aimed to assess sex differences in a juvenile model of early RV pressure load by pulmonary artery banding (PAB) during transition from pre to postpuberty. Rat pups (n = 57, 3 wk old, 30-45 g) were subjected to PAB or sham surgery. Animals were euthanized either before or after puberty (4 and 8 wk postsurgery, respectively). Male PAB rats demonstrated failure to thrive already after 4 wk, whereas females did not. After 8 wk, female PAB rats showed less clinical symptoms of RV failure than male PAB rats. RV pressure-volume analysis demonstrated increased end-systolic elastance after 4 wk in females only, and a trend toward preserved end-diastolic elastance in female PAB rats compared with males (P = 0.055). Histology showed significantly less RV myocardial fibrosis in female compared with male PAB rats 8 wk after surgery. Myosin heavy chain 7-to-6 ratio switch and calcineurin signaling were less pronounced in female PAB rats compared with males. In this juvenile rat model of RV pressure load, female rats appeared to be less prone to clinical heart failure compared with males. This was driven by increased RV contractility before puberty, and better preservation of diastolic function with less RV myocardial fibrosis after puberty. These findings show that RV adaptation to increased loading differs between sexes already before the introduction of pubertal hormones.NEW & NOTEWORTHY In this study, we describe sex differences in our unique weanling rat model of increased RV pressure load by pulmonary artery banding. We are the first to assess temporal sex-related differences in RV adaptation during pubertal development. Female rats show superior RV function and less diastolic dysfunction and fibrosis compared with male rats. These differences are already present before puberty, indicating that the differences in RV adaptation are not only determined by sex hormones.

Vitamin A Status in Neonatal and Weanling Rats Reared by Mothers Consuming Normal and High Fat Diets with or Without Vitamin A Supplementation

Abstract Objectives Although the circulating level of vitamin A (VA) is reported to be significantly lower in obese adults, it is unknown if maternal adiposity would influence the VA status of the offspring. The aim of this study was to investigate the status and distribution of VA in the offspring of rats consuming a normal fat diet (NFD) or a high fat diet (HFD), with or without VA supplementation. Methods Sprague-Dawley rats arrived on their second day of gestation and were randomized to either a NFD (25% fat) or a HFD (50% fat) both with an adequate level of VA at 2.6 mg/kg. Upon the delivery of pups, half of rat mothers from the NFD or HFD cohort were switched to a NFD or a HFD both with supplemented VA at 129 mg/kg (NFD + VA and HFD + VA group), respectively. The other half remained on their diets with adequate VA (NFD and HFD group). At postnatal day 14 (P14) and P25, 4 pups/group were euthanized. At P25, the remaining weanling pups (n = 3/group) were fed diets of their respective mothers until being euthanized at P35. Concentrations of total retinol in serum, liver, visceral white AT (WAT), and brown AT (BAT) were measured by UPLC. Results Through the study, pups in non-supplemented groups showed a normal serum retinol concentration but a marginal liver VA status. At all the time points, serum retinol concentration was significantly (P < 0.05) increased in VA-supplemented groups as compared to non-supplemented ones; no significant difference was noted between the NFD and the HFD group. At P14, serum retinol concentration was significantly lower in the HFD + VA group than in the NFD + VA group. In liver, WAT, and BAT, both the concentration and the mass of total retinol was significantly higher in HFD + VA and NFD + VA group than in their respective control at all the time points, with no significant difference noted between the two control groups. At P25, both the concentration and the mass of total retinol in liver and in WAT was significantly higher in HFD + VA than in NFD + VA group. Conclusions Maternal VA supplementation added to both NFD and HFD raised VA status of the offspring. A lower VA concentration in serum but higher concentration in liver and WAT was observed in the HFD + VA group as compared to the NFD + VA group at given time points, indicating that maternal HFD consumption potentially compromised the availability of functional VA in circulation by increasing its deposition in storage organs. Funding Sources NIH.

Vitamin A Status and Deposition in Neonatal and Weanling Rats Reared by Mothers Consuming Normal and High-Fat Diets with Adequate or Supplemented Vitamin A.

The circulating level of vitamin A (VA; retinol) was reported to be lower in obese adults. It is unknown if maternal obesity influences the VA status of offspring. The objective of the study was to determine the VA status and deposition of neonatal and weanling rats reared by mothers consuming a normal or high-fat diet (NFD or HFD) with or without supplemented VA. Pregnant Sprague-Dawley rats were randomized to an NFD or HFD with 2.6 mg/kg VA. Upon delivery, half of the rat mothers in the NFD or HFD cohort were switched to an NFD or HFD with supplemented VA at 129 mg/kg (NFD+VA and HFD+VA group). The other half remained on their original diet (NFD and HFD group). At postnatal day 14 (P14), P25, and P35, pups (n = 4 or 3/group/time) were euthanized. The total retinol concentration in the serum, liver, visceral white adipose tissue (WAT), and brown adipose tissue (BAT) was measured. At P14, the HFD+VA group showed a significantly lower serum VA than the NFD+VA group. At P25, both the VA concentration and total mass in the liver, WAT, and BAT were significantly higher in the HFD+VA than the NFD+VA group. At P35, the HFD group exhibited a significantly higher VA concentration and mass in the liver and BAT compared with the NFD group. In conclusion, maternal HFD consumption resulted in more VA accumulation in storage organs in neonatal and/or weanling rats, which potentially compromised the availability of VA in circulation, especially under the VA-supplemented condition.

A Working Module for the Neurovascular Unit in the Sexually Dimorphic Nucleus of the Preoptic Area.

The neurovascular unit (NVU) can be conceptualized as a functional entity consisting of neurons, astrocytes, pericytes, and endothelial and smooth muscle cells that operate in concert to affect blood flow to a very circumscribed area. Although we are currently in a "golden era" of bioengineering, there are, as yet, no living NVUs-on-a-chip modules available and the development of a neural chip that would mimic NVUs is a seemingly lofty goal. The sexually dimorphic nucleus of the preoptic area (SDN-POA) is a tiny brain structure (between 0.001~0.007mm3 in rats) with an assessable biological function (i.e., male sexual behavior). The present effort was undertaken to determine whether there are identifiable NVUs in the SDN-POA by assessing its vasculature relative to its known neural components. First, a thorough and systematic review of thousands of histologic and immunofluorescent images from 201 weanling and adult rats was undertaken to define the characteristics of the vessels supplying the SDN-POA: its primary supply artery/arteriole and capillaries are physically inseparable from their neural elements. A subsequent immunofluorescent study targeting α-smooth muscle actin confirmed the identity of an artery/arteriole supplying the SDN-POA. In reality, the predominant components of the SDN-POA are calbindin D28k-positive neurons that are comingled with tyrosine hydroxylase-positive projections. Finally, a schematic of an SDN-POA NVU is proposed as a working model of the basic building block of the CNS. Such modules could serve the study of neurovascular mechanisms and potentially inform the development of next generation bioengineered neural transplants, i.e., the construct of an NVU neural chip.

Newly formulated, protein quality-enhanced, extruded sorghum-, cowpea-, corn-, soya-, sugar- and oil-containing fortified-blended foods lead to adequate vitamin A and iron outcomes and improved growth compared with non-extruded CSB+ in rats.

Corn and soyabean micronutrient-fortified-blended foods (FBF) are commonly used for food aid. Sorghum and cowpeas have been suggested as alternative commodities because they are drought tolerant, can be grown in many localities, and are not genetically modified. Change in formulation of blends may improve protein quality, vitamin A and Fe availability of FBF. The primary objective of this study was to compare protein efficiency, Fe and vitamin A availability of newly formulated extruded sorghum-, cowpea-, soya- and corn-based FBF, along with a current, non-extruded United States Agency for International Development (USAID) corn and soya blend FBF (CSB+). A second objective was to compare protein efficiency of whey protein concentrate (WPC) and soya protein isolate (SPI) containing FBF to determine whether WPC inclusion improved outcomes. Eight groups of growing rats (n 10) consumed two white and one red sorghum-cowpea (WSC1 + WPC, WSC2 + WPC, RSC + WPC), white sorghum-soya (WSS + WPC) and corn-soya (CSB14 + WPC) extruded WPC-containing FBF, an extruded white sorghum-cowpea with SPI (WSC1 + SPI), non-extruded CSB+, and American Institute of Nutrition (AIN)-93G, a weanling rat diet, for 4 weeks. There were no significant differences in protein efficiency, Fe or vitamin A outcomes between WPC FBF groups. The CSB+ group consumed significantly less food, gained significantly less weight, and had significantly lower energy efficiency, protein efficiency and length, compared with all other groups. Compared with WSC1 + WPC, the WSC1 + SPI FBF group had significantly lower energy efficiency, protein efficiency and weight gain. These results suggest that a variety of commodities can be used in the formulation of FBF, and that newly formulated extruded FBF are of better nutritional quality than non-extruded CSB+.

Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats

Background: In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value.Objective: The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model.Methods: In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats.Results: Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF.Conclusions: Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012–024.

The protective effect of menhaden oil in the oxidative damage and renal necrosis due to dietary choline deficiency

Weanling rats fed a choline-deficient diet develop kidney oxidative damage, tubular and cortical kidney necrosis, renal failure and animal death. The effect of dietary menhaden oil was assayed on the mentioned sequence correlating oxidative stress with renal structure and function. Rats were fed ad libitum 4 different diets: (a) a choline-deficient diet with corn oil and sunflower hydrogenated oil as a source of fatty acids; (b) the same diet supplemented with choline; (c) a choline-deficient diet with menhaden oil as a source of fatty acids; and (d) the previous diet supplemented with choline. Animals were sacrificed at days 0, 2, 4 and 7. The histopathological study of the kidneys showed that renal necrosis was only observed at day 7 in choline-deficient rats receiving the vegetable oil diet, simultaneously with increased creatinine plasma levels. Homogenate chemiluminescence (BOOH-initiated chemiluminescence) and phospholipid oxidation indicate the development of oxidative stress and damage in choline-deficient rats fed vegetable oils as well as the protective effect of menhaden oil. Rats fed with the fish oil diet showed that oxidative stress and damage develop later, as compared with vegetable oil, with no morphological damage during the experimental period.

Re-examining the ontogeny of the context preexposure facilitation effect in the rat through multiple dependent variables

The capability to acquire context conditioning does not emerge until weaning, at least when the defining features of the context lack explicit and salient olfactory cues. Contextual learning deficits in preweanling rats have been associated with functional immaturity of the dorsal hippocampus. According to recent studies, the so-called context preexposure facilitation effect (CPFE) – a hippocampus-dependent effect – is not observed until postnatal day 23 (PD23). In these studies the footshock intensity employed was higher (1.5mA) than in adult studies, and context conditioning was inferred from a single behavioral measure (percentage of freezing). The present study examined the CPFE on PD17 and PD23 by analyzing multiple dependent variables, including fecal boli and an ethogram covering the complete behavioral repertoire of the rat. A non-shocked control group was included in the design and two footshock intensities were employed (0.5 and 1.5mA). Results showed clear evidence of contextual fear conditioning in preweanling and weanling rats, as well as evidence of conditioned fear in non-preexposed rats from both age groups. In some cases, some dependent variables, such as grooming or vertical exploration, were more sensitive than freezing for detecting evidence of memory. Strong fear responses were detected in weanling (but not preweanling) rats, when rats were evaluated in a different context from the one employed at conditioning. These results indicate that preweanling rats are capable of acquiring contextual conditioning, even in a context lacking explicit odor cues, and highlight the importance of multiple dependent variables for analyzing the ontogeny of memory.

Decreases in Bone Mineral Content by Dietary All-Trans Retinoic Acid Precede Decreases in Bone Mineral Density in a Weanling Rat Model of Cigarette Smoke - Induced Lung Injuries

Research has indicated that excessive vitamin A can have deleterious impacts on bone. Retinoic acid (RA), the most active metabolite of vitamin A, has been tested in clinical trials for treatment of lung cancer and emphysema. These trials are not measuring Bone Mineral Content (BMC) or Bone Mineral Density (BMD). In this study, we used an animal model to determine potential deleterious effects of all-trans RA on bone mass when used as a means to protect against or treat cigarette smoke-induced lung injuries, and also to evaluate BMC as a potential early indicator of osteoporosis risk. Twenty-four male weanling rats were fed either a control diet or a RA-supplemented diet. Half of each group was exposed to 40 cigarettes per day, 5 days per week, for 4 weeks. BMC and BMD were measured at weeks 2 and 4. RA supplementation in all groups significantly decreased (p < 0.05) only BMC at week 2 and both BMC and BMD (both p < 0.05) at week 4. The same results were observed when BMC was expressed relative to body weight. These data suggest that caution should be used when RA is used to treat smoke-related lung injuries.

Trimethoprim-sulfamethoxazole increase micronuclei formation in peripheral blood from weanling well-nourished and malnourished rats

The combination of trimethoprim and sulfamethoxazole (TMP-SMX) is a widely used drug. In spite of this, there are few reports on its genotoxicity, and the results are controversial. Severe malnutrition is a complex condition that increases the susceptibility to infections. Consequently, drugs are extensively used in malnutrition cases. Experimental animal models have been widely used to study the effects of malnutrition. Neonatal rats were experimentally malnourished (UN) during lactation. The UN rats weighed 51.1% less than the well-nourished (WN) controls and had lower concentrations of serum protein and blood lipids. The micronucleus (MN) assay is useful for detecting chromosome damage induced by nutritional deficiencies. In vivo rodent MN assays have been widely used to screen genotoxic agents. In this study, we have evaluated the frequency of spontaneous and TMP-SMX-induced micronuclei in the peripheral blood of weanling (21 days of age) rats using a flow cytometric analysis technique. The spontaneous frequency of micronucleated reticulocytes (MN-RETs) was 2.7 times greater in the UN rats than in the WN rats. In rats that were not treated with TMP-SMX, the percentage of reticulocytes was significantly lower (41.1%) in the UN rats than the WN controls. A therapeutic dose of TMP-SMX (80 mg/kg (TMP), 400 mg/kg (SMX) for 48 hr) increased MN-RETs in the WN and in the UN rats. The data demonstrate the genotoxic effect of this drug. The results indicate that severe protein-calorie restriction and drug treatment enhance DNA damage in rat peripheral blood reticulocytes, potentially increasing the risk of negative effects on health.

Hypothalamic POMC is Overexpressed in Overfed Weanling Rats after Pregnancy Exposure to Swimming

Hypothalamic POMC is Overexpressed in Overfed Weanling Rats after Pregnancy Exposure to Swimming

Effect of Maternal Protein Restriction During Pregnancy and Lactation on the Number of Cardiomyocytes in the Postproliferative Weanling Rat Heart

Maternal protein restriction leads to a reduction in the number of cardiomyocytes in the rat heart at birth. However, in rats, cardiomyocytes continue to proliferate until about 2 weeks after birth. Hence, this study aimed to examine the effect of maternal protein restriction, on the number of cardiomyocytes in the young rat heart at a time point when the cardiomyocytes have ceased proliferating and are terminally differentiated. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low protein diet (LPD; 8.7% casein) during pregnancy and lactation. Offspring (seven males and seven females per group) were perfusion fixed at 4 weeks of age. Heart volume and total cardiomyocyte number were determined using stereological techniques. At 4 weeks of age, body weights in both male and female LPD offspring were significantly reduced compared with NPD controls whereas relative heart volumes were significantly increased in LPD offspring. Total number of cardiomyocytes was not significantly different between groups. In both groups, there was a significant linear correlation between cardiomyocyte number and heart volume. In conclusion, total cardiomyocyte number in the postproliferative rat heart does not appear to be affected by maternal protein restriction per se but is directly related to heart size.

Intestinal Adaptation Following Massive Ileocecal Resection in 20‐day‐old Weanling Rats

Few infant animal models have been used to study infantile short bowel syndrome (SBS). Most SBS models involve removal of the proximal small bowel followed by jejunoileal anastomosis, which has unclear clinical relevance to human infantile SBS that often results from surgical treatment for necrotizing enterocolitis and involves removal of the ileum, ileocecal valve, and part of or the entire colon. Our objective was to develop a more appropriate SBS model in developing rats. Twenty-day-old weanling rats were divided into 2 surgery groups, ileocecal resection (ICR) and sham groups, and a control group that did not undergo surgery. All were fed a liquid diet ad libitum for 7 days after surgery or for 7 days in the controls, and body weight, food intake, and stool changes were recorded daily. The rats were then euthanized and intestinal lengths and weights were recorded. Samples of intestine from the distal jejunum and proximal colon were collected for histology. Mucosal samples from the middle, distal jejunum, and colon were collected for measurements of mucosal weights, DNA, RNA, and protein levels. Maltase activity was determined in the small intestine. Eighty-five percent of rats survived the ICR with subsequent development of diarrhea, hyperphagia, and poor growth. Adaptive responses to ICR, as compared with sham, were evidenced by increased intestinal and mucosal weights, DNA, RNA, and protein levels, increased maltase activity and villous thickness in distal jejunum, and increased mucosal thickness in the colon. This ICR model in weanling rats is appropriate for studying human infantile SBS.

Evaluation of the Antiandrogenic Effects of Flutamide, DDE, and Linuron in the Weanling Rat Assay Using Organ Weight, Histopathological, and Proteomic Approaches

The Organization for Economic Cooperation and Development (OECD) is currently funding the validation of the Hershberger assay as a rapid in vivo means of identifying (anti-) androgens. However, as the assay measures weight changes in the androgen-sensitive tissues of castrated rats, the evaluation of the androgen-stimulated intact weanling as a more ethical model to use in the assay has been requested. As part of the OECD validation exercise two weak antiandrogens, 1,1-dichloro-2,2-bis(4 chlorophenyl)ethane (DDE) and linuron (LIN), were investigated in our laboratory at several dose levels in the testosterone propionate (TP)-stimulated weanling using flutamide (FM) as a positive control. In addition to weight measurements (sex accessory tissues [SATs], epididymides, and testes), histopathological assessment of the seminal vesicles, prostate, and testes was conducted for vehicle control, TP-stimulated, and TP-stimulated animals treated with FM or the top dose level of DDE or LIN. The modulation of a novel prostate protein associated with apoptosis, L-amino acid oxidase (LAO), was evaluated in these same treatment groups. Our gravimetric data (supported by the histopathology data) indicated that the weanling assay can detect SAT and epididymal weight changes induced by the antiandrogens evaluated. Inconsistent and variable data were recorded for the testicular weight and histopathological effects, suggesting that the testis is of little value in the identification of antiandrogens using this model. Three isoforms of LAO were identified, and all were regulated by TP. Modulation of LAO by the antiandrogens indicated that this protein could be a biomarker for endocrine disruption in male rodents.

Discovery of a Dihydropyrimidine Series of Molecules that Selectively Mimic the Biological Actions of Calcitonin.

Abstract The use of a multiplex mimetic assay led us to identify 1,4-dihydropyrimidines with potent and selective calcitonin receptor mimetic activity. Subsequent modification of the dihydropyrimidine scaffold led to a series of molecules that were efficacious in a neonatal mouse calvaria in vitro model. Dihydropyrimidine 5h, in particular, was identified as a calcitonin mimetic (EC50=6 μM), active in-vivo in the Weanling rat model when administered subcutaneously.

Regulation of pancreatic lipase by dietary medium chain triglycerides in the weanling rat.

Pancreatic lipase (PL) and its related protein 1 (PLRP1) are regulated by the amount of dietary fat through an apparent transcriptional mechanism. Regulation of PL and PLRP1 by type of fat (chain length and degree of saturation) is less well understood. The aim of this study was to determine whether medium-chain triglycerides regulate PL and PLRP1. For 7 d, weanling (21-d-old) Sprague Dawley male rats were fed diets low (11% of energy), moderate (40% of energy), or high (67% of energy) in trioctanoate/tridecanoate (MCT) or safflower (low fat only) oils. Food consumption decreased as dietary MCT increased, and the consumption of MCT diets was lower than that of the low-safflower (control) diet. Final body weight was similar among rats fed the low- or moderate-MCT or control diets, but was significantly reduced (17%) in those fed the high-MCT diets. PL activity was significantly elevated 53-60% (p < 0.002) in rats fed low and moderate MCT diets, respectively, compared with that of rats fed high-MCT or control diets. PL and PLRP1 mRNA levels were not significantly different among diets, suggesting that chain length regulates PL and PLRP1 translationally or posttranslationally. The beta-hydroxybutyrate plasma concentration was significantly (p < 0.02) higher (85%) in rats consuming low-MCT diet compared with those of rats fed the control diet. MCT at low levels, but not high levels, increase PL activity without changing its mRNA levels.

Discovery of a dihydropyrimidine series of molecules that selectively mimic the biological actions of calcitonin

The use of a multiplex mimetic assay led us to identify 1,4-dihydropyrimidines with potent and selective calcitonin receptor mimetic activity. Subsequent modification of the dihydropyrimidine scaffold led to a series of molecules that were efficacious in a neonatal mouse calvaria in vitro model. Dihydropyrimidine 5h, in particular, was identified as a calcitonin mimetic (EC50=6 μM), active in-vivo in the Weanling rat model when administered subcutaneously.

Quantity as well as quality of dietary protein affects serine dehydratase gene expression in rat liver.

Weanling rats were fed respective diets diverse in protein source and content for a full week, and hepatic serine dehydratase (SDH) was examined for its gene expression and activity induction attendant on high protein intake. The protein sources used were three kinds of milk casein, codfish meat, and wheat gluten. The body weight gain (% augmentation/wk) increased with increasing protein intake and reached a plateau in both milk casein- and codfish meat-fed rats by protein intake above 2.5 g/100 g BW/d; however, the body weight gain continued to increase albeit at a slower rate in wheat gluten-fed rats. Quite similar tendencies were also seen in nitrogen balance. The ascent of SDH activity induction and its causal gene expression were characterized as codfish meat>milk casein>>wheat gluten in order of response to protein intake near or more than 4 g/100 g BW/d. The difference in SDH gene expression among these dietary proteins was substantiated by a confirmation experiment in which six rats of each group were fed 25% or 50% protein diets under the same conditions as above. Hence, the quantity as well as quality of dietary protein turned out to have an influence on SDH gene expression.