Using mixed silages of sweet sorghum and alfalfa in total mixed rations to improve growth performance, nutrient digestibility, carcass traits and meat quality of sheep.

Combining sweet sorghum (SS) with alfalfa for ensiling has the potential to make a high-quality silage with relatively a better nutrient balance. However, the existing data are insufficient about how changes in ratios of SS to alfalfa in different silage mixtures affect animal performance and meat quality. Therefore, the objective of this study was to determine the effect of feeding total mixed rations containing mixed silages of SS and alfalfa on growth performance, nutrient digestibility, carcass traits and meat quality of Karakul sheep. Five total mixed rations were formulated with different SS proportions at 100%, 80%, 60%, 40%, and 20% on a fresh weight basis. Thirty 4-month old male Karakul sheep with 25.5 ± 1.4 kg BW were randomly allocated into five treatment groups, each with six lambs for this experiment. The results indicated that the Karakul sheep consuming total mixed rations containing SS-Alfalfa (SS-AF) silage mixtures with a lower proportion of SS tended to increase nutrient digestibility, growth performance, carcass traits, and meat quality. Feeding diets with SS at 40% and 20% inclusion rate showed a significant linear increase in the apparent digestibility of DM, CP and NDF, as well as subcutaneous fat thickness and water holding capacity (P < 0.5). Moreover, reduction in SS inclusion rate in these diets caused significant (P < 0.05) linear and quadratic increases in DM intake, final BW, average daily gain, carcass weight, and the amino acid contents of meat (P < 0.05). Conversely, feeding diet with lower SS inclusion rate led to decrease in feed conversion ratio and shear force significantly (P < 0.05) for these sheep. It appears that 40% inclusion of SS was the optimal rate in making the SS-AF silage mixture for lambs to achieve a superior production performance and high-quality meat products in Karakul sheep. However, further research is needed to investigate the effect of feeding SS-AF silage mixtures alongside contrasting ingredients on rumen function, ruminal microorganisms and digestive enzyme activity of sheep and other ruminant animals.

Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats.

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia (C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably (p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Comparative efficacy of Prolene and Prolene-Vicryl composite mesh for experimental ventral hernia repair in dogs.

In this study, efficacy of two hernia mesh implants viz. conventional Prolene and a novel Prolene-Vicryl composite mesh was assessed for experimental ventral hernia repair in dogs. Twelve healthy mongrel dogs were selected and randomly divided into three groups, A, Band C (n=4). In all groups, an experimental laparotomy was performed; thereafter, the posterior rectus sheath and peritoneum were sutured together, while, a 5 × 5 cm defect was created in the rectus muscle belly and anterior rectus sheath. For sublay hernioplasty, the hernia mesh (Prolene: group A; Prolene-Vicryl composite mesh: group B), was implanted over the posterior rectus sheath. In group C (control), mesh was not implanted; instead the laparotomy incision was closed after a herniorrhaphy. Post-operative pain, mesh shrinkage and adhesion formation were assessed as short term complications. Post-operatively, pain at surgical site was significantly less (P<0.001) in group B (composite mesh); mesh shrinkage was also significantly less in group B (21.42%, P<0.05) than in group A (Prolene mesh shrinkage: 58.18%). Group B (composite mesh) also depicted less than 25% adhesions (Mean ± SE: 0.75 ± 0.50 scores, P≤0.013) when assessed on the basis of a Quantitative Modified Diamond scale; a Qualitative Adhesion Tenacity scale also depicted either no adhesions (n=2), or, only flimsy adhesions (n=2) in group B (composite mesh), in contrast to group A (Prolene), which manifested greater adhesion formation and presence of dense adhesions requiring blunt dissection. Conclusively, the Prolene-Vicryl composite mesh proved superior to the Prolene mesh regarding lesser mesh contraction, fewer adhesions and no short-term follow-up complications.

Effects of Varying Levels of Fungal (Arachniotus sp.) Treated Wheat Straw as an Ingredient of Total Mixed Ration on Growth Performance and Nutrient Digestibility in Nili Ravi Buffalo Calves.

The study was carried out to explore the effects of replacing wheat straw with fungal treated wheat straw as an ingredient of total mixed ration (TMR) on the growth performance and nutrient digestibility in Nili Ravi buffalo male calves. Fungal treated wheat straw was prepared using Arachniotus sp. Four TMRs were formulated where wheat straw was replaced with 0 (TMR1), 33 (TMR2), 67 (TMR3), and 100% (TMR4) fungal treated wheat straw in TMR. All TMRs were iso-caloric and iso-nitrogenous. The experimental TMRs were randomly assigned to four groups of male calves (n = 6) according to completely randomized design and the experiment continued for four months. The calves fed TMR2 exhibited a significant improve in dry matter intake, average daily weight gain, feed conversion ratio and feed economics compared to other groups. The same group also showed higher digestibility of dry matter, crude protein, neutral-, and acid detergent fibers than those fed on other TMRs. It is concluded that TMR with 33% fungal-treated wheat straw replacement has a potential to give an enhanced growth performance and nutrient digestibility in male Nili Ravi buffalo calves.

Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.

Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.58.

Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians.

BACKGROUND & OBJECTIVES: Genetic polymorphism of CYP2C19 is known to occur with a frequency of 12 per cent in north Indian population. But no study correlated CYP2C19 genetic polymorphism with eradication of Helicobacter pylori in north Indian gastritis patients positive for H. pylori and hence this study. METHODS: Ninety one consecutive patients positive for H. pylori fulfilling the study criteria were phenotyped and genotyped for CYP2C19. They were given 20 mg omeprazole (OPZ), 750 mg amoxicillin (AMC) and 500 mg tinidazole (TNZ) (bid) for 7 days followed by 20 mg OPZ (qd) for 21 days. Non eradicated extensive metabolizers (EMs) were retreated with 40 mg OPZ (bid) and 500 mg AMC (qid) for 14 days. RESULTS: EMs and poor metabolizers (PMs) excreted 4.26 +/- 0.34 (95% CI 3.59-4.92) and 0.73 +/- 0.05 (95% CI 0.63-0.82) micromol 5-OH-OPZ in 8 h, respectively. After initial therapy, EMs demonstrated 37 per cent (95% CI: 24.5-49.5) and PMs 92 per cent (95% CI: 77-107) eradication of H. pylori. Non eradicated EMs after retreatment demonstrated 90 per cent (95% CI: 79-101) eradication. INTERPRETATION & CONCLUSIONS: This study demonstrated a direct correlation between CYP2C19 genetic polymorphism and H. pylori eradication in north Indian patients with gastritis. Knowing the CYP2C19 phenotype of a patient may help in prescribing optimum dose of proton pump inhibitor to achieve better therapeutic outcome.

Dietary regulation of ruminal bovine UT-B urea transporter expression and localization.

Facilitative UT-B urea transporters have been located in the gastrointestinal tract of numerous mammalian species. We have previously identified UT-B urea transporters within the epithelial layers of the bovine (b) rumen. The aim of this study was to test the hypothesis that ruminal bUT-B urea transporters are regulated by dietary intake. Six Limousine-cross steers (initial BW = 690 +/- 51 kg) were separated into 2 groups fed a basic silage-based diet (RS) or a concentrate-based diet (RC) for 37 d and compared for ruminal morphology, content, and bUT-B expression. Analysis by reverse transcription-PCR showed that ruminal bUT-B2 mRNA expression was greater in RC-fed than RS-fed animals. Utilizing an anti-bUT-B antibody, we also detected a significant increase in bUT-B2 protein expression in RC-fed rumen (P < 0.05, n = 3). In agreement with these findings, immunolocalization studies of RC-fed ruminal tissue showed strong bUT-B signals throughout all epithelial layers, in contrast to weaker staining in RS-fed rumen that was more localized to the stratum basale. This study therefore confirmed that ruminal bUT-B urea transporter expression and localization were indeed altered by changes in dietary intake. We conclude that UT-B transporters play a significant role in the dietary regulation of bovine nitrogen balance.

Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors.

Proton pump inhibitors (PPIs) are extensively metabolized in the liver by CYP2C19, that demonstrates genetic polymorphism with 21 mutant alleles. The subjects can be divided into 2 groups with respect to CYP2C19 phenotypes viz., extensive metabolizers (EMs) and poor metabolizers (PMs) of PPIs. This division results in marked interindividual variations in the pharmacokinetics and pharmacodynamics of PPIs in the population. Intragastric pH values and the plasma concentration of PPIs after oral ingestion were significantly lower in EMs namely normal homozygotes (CYP2C19*1/*1) and heterozygotes (CYP2C19*1/*X) compared to PMs namely mutant homozygotes (CYP2C19*X/*X) where 'X' represents the mutant allele. Hence, association has been found between the genetic polymorphism of CYP2C19 and therapeutic response to PPIs. CYP2C19 polymorphism affected eradication of Helicobacter pylori using diferent PPI based eradication therapies as PM patients demonstrated significantly higher eradication rates compared to EMs. CYP2C19 genetic polymorphism also affects the therapeutic outcome of gastroesophageal reflux disease (GERD), reflux oesophagitis and duodenal ulcers. For optimal therapeutic response with PPIs, CYP2C19 pharmacogenetics should be taken into consideration. This shall help in the prescription of optimal doses of PPIs, thus paving the way for personalized medication.

Comparing two commercial enzymes to estimate in vitro proteolysis of purified or semi-purified proteins.

Two experiments compared the suitability of two commercial enzymes to estimate in vitro proteolysis of different proteins. Experiment 1 compared the proteolytic activity over various incubation times of a microbial enzyme (protease from Streptomyces griseus) with a plant enzyme (papain from Papaya latex) by using either 1.33 (high, H) or 0.4 (low, L) units (U, amount) of each enzyme per mg crude protein (CP) of purified proteins including bovine (BA) or egg albumin (EA). Experiment 2 compared the activity of 0.66 U of each of these enzymes per mg CP of semi-purified proteins including casein, wheat gluten (WG) and maize gluten meal (MG). Each incubation was terminated by adding trichloroacetic acid (TCA) and the TCA soluble supernatant collected to estimate concentration of total amino acids (AA) as the measure of proteolysis of each protein over each time. The data on proteolysis over time were fitted into a non-linear model to derive constants for solubility (a) and rate (c) and extents (a + b) of proteolysis of each food by each amount of each enzyme. All data on proteolysis over time and the derived constants were statistically analysed to study the effect of food, enzyme, amount and their interactions. Significant differences were observed between foods, enzymes, enzyme amount (H vs. L for Experiment 1 only) for the proteolysis at most incubation times in both experiments (p<0.001). The mean proteolysis over all times for BA was 1.6 (SD, 0.52) times greater than EA (p<0.001). While the protease gave about four times (SD, 2.1) more proteolysis than papain (p<0.001), the high amount of enzyme gave only about two times (SD, 0.28) greater proteolysis than that of the low amount (p<0.001). On average, the protease was over three times faster (c) than papain (p<0.001) and high amount was two times faster than the low amount of enzyme (p<0.001). While both purified foods were similar in solubility (p>0.05), they differed in the rate and extent of proteolysis (p<0.001). The BA was degraded about four times faster than EA (p < 0.001). Amongst semi-pure proteins, casein gave the highest but MG the lowest proteolysis at each incubation (p<0.001). However, the magnitude of proteolysis depended upon enzyme, food and hours of incubation. On average, casein was degraded at a much faster rate than WG or MG by both enzymes. It appeared that the protease and not papain can be used to estimate in vitro proteolysis of pure and semi-pure food proteins. However, further studies are needed to standardise the relevant procedures when using protease to estimate proteolysis of ruminant foods.

Modification of methane emission in sheep by cysteine and a microbial preparation.

Modification of methane emission from ruminants by the use of L-cysteine and/or a microbial preparation in wethers fed lucerne hay was assessed in an open circuit respiratory trial according to a 4 x 4 Latin squared design. L-Cysteine (0.1 g kg-1 W0.75, as sulphur equivalent) was drenched daily to wethers as an aqueous solution of hydrochloride. The microbial preparation was a dried mixture of Bacillus subtilis, Bacillus cereus, Bacillus thuringiensis, Pseudomonas fluorescens, Streptomyces cellulosae, Streptomyces albidoflavus and Saccharomyces lypolyticum. The microbial preparation was added at 87 mg kg-1 metabolic weight (W0.75) to the daily diet of a wether sheep offered lucerne chaffed hay at a maintenance level of 54 g DM kg-1 W0.75. L-Cysteine suppressed methane emission from the sheep by 13% whereas the microbial preparation actually increased methane emission by 18%. Oxidation-reduction potential, pH, ammonia and VFA were non-significantly influenced by the applied treatments.