Dose-response relationship of tryptophan with large neutral amino acids, and its impact on physiological responses in the chick model.

Tryptophan (Trp) has been associated with the regulation of several behavioral and physiological processes, through stimulation of serotonergic activity. Tryptophan utilization at the metabolic level is influenced by the competitive carrier system it shares with large neutral amino acids (LNAA). This study was carried out using meat-type chicken as a model, to investigate the dose response effects of Trp/LNAA on fear response (tonic immobility; TI) and hormonal responses, including corticosterone (CORT), serotonin (5-HT), triiodothyronine (T3) and thyroxine (T4). A total of 12 cages (48 birds) were assigned to each of the six experimental groups at 29-42 days of age. Experimental diets were formulated to have incremental levels of Trp/LNAA (0.025, 0.030, 0.035, 0.040, 0.045, and 0.050). The results revealed that, Trp/NAA had no significant effect on growth performance and TI of the birds. However, elevation of Trp/LNAA was concurred with a linear reduction in CORT (P < .0001, r2 = 0.819) and linear increases in 5-HT (P < .0001, r2 = 0.945), T3 (P = .0003, r2 = 0.403) and T4 (P < .0001, r2 = 0.937) levels. In conclusion, the results from the current study demonstrated that, although incremental levels of Trp/LNAA did not affect bird growth performance or fearfulness, it increased 5-HT, T3 and T4, and decreased CORT levels in a linear dose-dependent manner. Manipulation of Trp feeding levels could be applied to manage stressful conditions in birds.

Environmental temperature and stocking density effects on acute phase proteins, heat shock protein 70, circulating corticosterone and performance in broiler chickens.

An experiment was conducted to determine the effect of different stocking densities on serum corticosterone (CORT), ovotransferrin (OVT), α1-acid glycoprotein (AGP) and ceruloplasmin (CP) concentrations, brain heat shock protein (HSP) 70 expression and performance in broiler chickens exposed to unheated and heated conditions. Day-old chicks were stocked at 0.100 m(2)/bird (low density (LD)) or 0.063 m(2)/bird (high density (HD)), in battery cages and housed in environmentally controlled rooms. From 21 to 35 days of age, birds from each stocking density group were exposed to either 24 or 32 °C. Growth performance was recorded during the heat treatment period, and blood and brain samples were collected to determine CORT, OVT, AGP, CP and HSP 70 levels on day 35. Heat treatment but not stocking density was detrimental to growth performance. There were significant temperature × density interactions for CORT, CP and OVT on day 35. Although HD elevated CORT, CP and OVT when compared to LD, the effects of the former were more obvious under heated condition. Both temperature and density had significant effect on AGP and HSP 70. In conclusion, irrespective of temperature, high stocking density was physiologically stressful to broiler chickens, as indicated by CORT, AGP, CP, OVT and HSP 70, but not detrimental to growth performance and survivability. As it was shown in the present study, AGP, CP and OVT could be useful biomarkers to determine the effect of overcrowding and high temperature on the welfare of broiler chickens.

Effect of oligosaccharides extract from palm kernel expeller on growth performance, gut microbiota and immune response in broiler chickens.

This study examined the prebiotic effects of oligosaccharides extract from palm kernel expeller (OligoPKE) on growth performance, cecal microbiota and immune response of broiler chickens. A total of ninety 1-day-old broiler chicks (Cobb-500) were randomly allocated to three treatment groups of six pens (replicates) with five birds per pen. Dietary treatments were: (i) basal diet as control, (ii) basal diet plus 0.5% OligoPKE, and (iii) basal diet plus 1% OligoPKE. Birds growth traits (ADG, ADFI and G:F) were measured during the starter (1-21 day), finisher (22-35 day) and the entire experimental periods. Blood and cecal digesta samples were collected from chickens at 21 and 35 days of age (DOA). Microbial quantification of the digesta samples, white blood cells including heterophil, lymphocyte, monocyte, eosinophil, basophil counts and immunoglobulin (IgA and IgM) were also determined. OligoPKE had no effect on ADG and ADFI throughout the study period, but chickens fed OligoPKE supplemented diet had better (P < 0.05) G:F during finisher and overall rearing periods. Supplementing OligoPKE did not significantly alter the birds' microbiota of the cecal digesta. At 21 DOA, blood IgA concentration increased significantly when birds fed 1% OligoPKE in diet recorded compared to the control treatment. Similar observations were also recorded in birds at 35 DOA. Hematological data showed that heterophil and basophil counts of chickens fed OligoPKE supplement were lower than those in control group at 21 DOA. Our findings suggested that OligoPKE improved immune responses in broiler chickens, especially at younger age when the immune system is not still fully developed.

Omega-3 polyunsaturated fatty acids enrichment alters performance and immune response in infectious bursal disease challenged broilers.

BACKGROUND: Infectious bursal disease (IBD) results in economic loss due to mortality, reduction in production efficiency and increasing the usage of antibiotics. This study was carried out to investigate the modulatory roles of dietary n-3 polyunsaturated fatty acids (PUFA) enrichment in immune response and performance of IBD challenged broiler chickens. METHODS: A total of 300 day old male broiler chicks were assigned to four dietary n-3 PUFA ascending levels as the treatment groups (T1: 0.5; T2: 8.0; T3: 11.5; T4: 16.5) using combinations of tuna oil and sunflower oil. All diets were isocaloric and isonitrogenous. On day 28, all birds were challenged with IBD virus. Antibody titer, cytokine production, bursa lesion pre and post-challenge and lymphoid organ weight were recorded. RESULTS: On d 42 the highest body weight was observed in the T2 and T3 and the lowest in T4 chickens. Feed conversion ratio of the T2 broilers was significantly better than the other groups. Although productive parameters were not responded to the dietary n-3 PUFA in a dose-dependent manner, spleen weight, IBD and Newcastle disease antibody titers and IL-2 and IFN-γ concentrations were constantly elevated by n-3 PUFA enrichment. CONCLUSIONS: Dietary n-3 PUFA enrichment may improve the immune response and IBD resistance, but the optimum performance does not coincide with the optimum immune response. It seems that dietary n-3 PUFA modulates the broiler chicken performance and immune response in a dose-dependent manner. Thus, a moderate level of dietary n-3 PUFA enrichment may help to put together the efficiency of performance and relative immune response enhancement in broiler chickens.

Impact of Feeding Fermented Palm Kernel Cake and High Dietary Fat on Nutrient Digestibility, Enzyme Activity, Intestinal Morphology and Intestinal Nutrient Transporters mRNA Expression in Broiler Chickens under Hot and Humid Conditions.

The study aimed at determining the ileal nutrient digestibility, digestive enzyme activity, intestinal morphology, and nutrient transporters mRNA expressions in broiler chickens fed with fermented PKC (LPKC) based diets with different levels of fat supplementation under hot and humid conditions. From day 22 to 35, broiler chickens were randomly fed with either (1) 20% LPKC-based diet with 5% palm oil, (2) 20% LPKC based diet with 9.5% palm oil, (3) 20% PKC-based diet with 5% palm oil or (4) 20% PKC-based diet with 9.5% palm oil. Feeding LPKC and PKC diets at the finisher phase have not affected the nutrient's digestibility, but a higher level of oil supplementation does. This was seconded by changes in the digestive enzyme activity, villus height, and mRNA expression of nutrient transporters in the higher level of oil-supplemented diets fed chickens. In conclusion, the inclusion of oil at 9.5% in a 20% LPKC/PKC-based diet is necessary to ensure better nutrient digestibility in chickens via improved digestive function, especially in hot and humid tropical regions.

Involvement of NF-κB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens.

BACKGROUND: Cratoxylum arborescens has been used traditionally in Malaysia for the treatment of various ailments. METHODS: α-Mangostin (AM) was isolated from C. arborescens and its cell death mechanism was investigated. AM-induced cytotoxicity was observed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Acridine orange/propidium iodide staining and annexin V were used to detect cells in early phases of apoptosis. High-content screening was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release. The role of caspases-3/7, -8, and -9, reactive oxygen species, Bcl-2 and Bax expression, and cell cycle arrest were also investigated. To determine the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-κB) was also analyzed. RESULTS: Apoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P<0.05) concomitant with an increase in reactive oxygen species. The protein array and Western blotting demonstrated the expression of HSP70. Moreover, AM significantly blocked the induced translocation of NF-κB from cytoplasm to nucleus. CONCLUSION: Together, the results demonstrate that the AM isolated from C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell cycle arrest and programmed cell death, which was suggested to occur through both the extrinsic and intrinsic apoptosis pathways with involvement of the NF-κB and HSP70 signaling pathways.

Preparation and characterization of a gastric floating dosage form of capecitabine.

Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.

Diet high in alpha-linolenic acid up-regulate PPAR-gamma gene expression in the liver of goats

Background There is little information on the effects of diets containing high α-linolenic acid (C18:3n-3) on liver lipid composition and lipogenic gene expressions. In this study fourteen goats (Capra aegagrus hircus) were fed either a flaxseed oil (FSO) supplemented diet containing high α-linolenic acid or a control diet without added flaxseed oil (CON) for 100-d to evaluate the effects on liver lipid composition and the gene expression of peroxisome proliferator-activated receptors (PPAR-α) and stearoyl-CoA-desaturase (SCD) in the liver. Results An increase in the levels of C18:3n-3 and C20:5n-3, C22:5n-3, C22:6n-3 was observed in the liver of FSO-treated goats. There was a significant (P < 0.05) up-regulation of PPAR-α gene expression and downregulation of SCD gene in the liver of goats fed the high α-linolenic acid diet. Conclusions In conclusion, genes associated with the control of fatty acid (FA) conversion (SCD and PPAR) were affected by the α-linolenic acid supplementation in the goat diet. It is suggested that PPAR-α is the key messenger responsible for the translation of nutritional stimuli into changes in hepatic gene expression.