Effects of dietary prebiotics, probiotic and synbiotics on performance, caecal bacterial populations and caecal fermentation concentrations of broiler chickens

Background: In view of a worldwide attempt to restrict or ban the use of antibiotics as growth promoters in animal production, probiotics, prebiotics and combinations of both, as synbiotics, have been suggested as potential alternatives. In this study, the effects of a prebiotic (isomalto-oligosaccharides, IMO), a multi-strain probiotic (consisting of 11 Lactobacillus strains), and a combination of these dietary additives as a synbiotic on the performance, caecal bacterial populations and concentrations of caecal volatile fatty acids and non-volatile fatty acids of broiler chickens were evaluated. Results: Supplementation of 1g kg−1 probiotic (PRO); 5 g kg−1 prebiotic IMO (PRE05); 10 g kg−1 prebiotic IMO (PRE10); synbiotic consisting of 1g kg−1 probiotic + 5 g kg−1 prebiotic IMO (SYN05); or synbiotic consisting of 1g kg−1 probiotic + 10 g kg−1 prebiotic IMO (SYN10) significantly (P < 0.05) improved weight gain of broiler chickens at 22–42 and 1–42 days of age, and feed conversion rate from 1 to 21, 22–42 and 1–42 days of age. The supplementation of probiotic (PRO), prebiotics (PRE05 and PRE10) or synbiotics (SYN05 and SYN10) also significantly (P < 0.05) increased the caecal populations of lactobacilli and bifidobacteria, and decreased the caecal Escherichia coli at 21 days of age, and increased the caecal VFA at 21 and 42 days of age. In all parameters studied, synbiotics did not show a two-fold synergistic effect, when compared to those of probiotic or prebiotic alone. Conclusion: The results of the study indicated that prebiotic IMO (5 g kg−1 or 10 g kg−1), probiotic and their combinations as synbiotics were effective in improving the performance of broiler chickens and in increasing the caecal beneficial bacteria and fatty acids

VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker

Recognizing specific protein changes in response to drug administration in humans has the potential for the development of personalized medicine. Such changes can be identified by pharmacoproteomics approach based on proteomic technologies. It can also be helpful in matching a particular target-based therapy to a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism. Warfarin is a commonly prescribed oral anticoagulant in patients with prosthetic valve disease, venous thromboembolism and stroke.We used a combined pharmacogenetics and iTRAQ-coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles of 53 patients, and identified significantly upregulated level of transthyretin precursor in patients receiving low dose of warfarin but not in those on high dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6 ELISA assay were done for the results validation.This combined pharmacogenomics and pharmacoproteomics approach may be applied for other target-based therapies, in matching a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Characterising the pharmacology of a P-superfamily peptide, pi-conopeptide AMIXA, from the venom of Conus amadis

Peptides from venom of marine cone snails are regarded as promising novel ligands in drug discovery race. They are highly specific, up to subtype level, leading to new therapeutic insights for clinical and neuropharmacological research and applications. In this study, a novel peptide AMIXA, belongs to the P-superfamily, has been characterised pharmacologically and is classed as a π-conopeptide according to its pharmacological function.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Transcriptome profiling of neuronal model cell PC12 from rat pheochromocytoma

GeneChip microarray is a cutting-edge technology being used to study the expression patterns of genes with in a particular cell type. In this study, the Affymetrix RAE230A platform was used to profile stably expressed mRNA transcripts from PC12 cells at passage 5 and 15. The whole-cell PC12 transcriptome revealed that a total of 7,531 stable transcripts (P < 0.05), corresponding to 6,785 genes, were found to be consistently expressed between passage 5 and 15. The data analysis revealed 3,080 functional proteins, belonging to 13 families, which indicate that about 65% of the proteins expressed in PC12 cells are uncharacterized. By using our custom-built rat neuronal reference genome database, we mapped endogenously expressed stable neuronal transcripts from PC12 cells comprising about 765 genes responsible for neuronal function and disease. These neuronal transcripts were further analyzed to provide a genetic blueprint that can be used by neurobiologist to unravel the complex cellular and molecular mechanisms underlying biological functions and their associated signalling networks for diseases affecting the nervous system

Acetic acid production of Lactobacillus strains isolated from chicken gut cultured in the presence of oligosaccharides

Lactobacillus species produce organic acids such as lactic and acetic acids as the end-products in the presence of organic substrates such as glucose and oligosaccharides. The effect of prebiotic fructooligossacharides (FOS) and oligomate 55N on the production of acetic acid by three probiotic Lactobacillus strains isolated from chicken gut was investigated by applying in vitro methodologies. Probiotic Lactobacillus strains (L. reuteri C 16, L. gallinarum I 16, and L. brevis I 218) were cultured separately at 37°C for 0, 3, 6, 9, 12, 15, 18 and 24h in basal MRS broth media containing either 1% prebiotic FOS, oligomate 55N or glucose (control). At the end of each incubation period acetic acid was determined using gas chromatography. The results showed that at the substrate concentration of 1% glucose or 1% oligomate 55N, production of acetic acid by Lactobacillus reuteri C 16 was the highest (maximum concentration of 16.75±1.27 and 17.63±1.19 mM, respectively) and fastest among the three Lactobacillus strains. Lactobacillus brevis I 218 produced the lowest amount of acetic acid compared to the other two Lactobacillus strains. The highest acetic acid yield from L. brevis I 218 was recorded when glucose was used as the substrate (maximum concentration of 6.78±0.43 mM) followed by oligomate 55N and FOS (maximum concentration of 4.06±0.59 and 2.81±1.43 mM, respectively). Probiotic L. gallinarum I 16 produced the highest concentration of acetic acid at 24h in the presence of FOS followed by glucose and oligomate 55N. In conclusion, the study showed that oligosaccharide substrates highly affected the production of acetic acid by the three Lactobacillus strains

Effect of prebiotic oligosaccharides on growth of Lactobacillus strains used as a probiotic for chickens

In the present study, the effect of 10 commercially available oligosaccharides on the growth of 11 Lactobacillus strains, which were isolated from the gastrointestinal tract of chickens and have been used as a multistrain probiotic for chickens, was evaluated in vitro. The utilization of oligosaccharides was highly variable among the 11 Lactobacillusstrains and considerable strains differences (P < 0.05) were observed. Isomaltooligosaccharides (IMO) supported good growth for all the 11 Lactobacillus strains, followed by galactooligosaccharides (GOS), gentiooligosaccharides (GTO) and fructooligosaccharides (FOS). Oligosaccharides such as Raftilose L60, Raftilose P95, Raftiline LS, and mannanoligosaccharides (MOS) were poorly utilized by all theLactobacillus strains. Growth kinetics study also showed variations in the specific growth rates and growth patterns of four representative Lactobacillus species on four selected oligosaccharides. The highest specific growth rate was demonstrated by Lactobacillus salivarius I 24 on FOS. The results showed that the ability of the 11 probiotic Lactobacillusstrains to utilize oligosaccharides could be both strain and substrate specific, which demonstrates the importance of selecting suitable prebiotic oligosaccharides for the preparation of synbiotics