Gut Microbial Signatures of Distinct Trimethylamine N-Oxide Response to Raspberry Consumption

The aim of this exploratory study was to evaluate the gut microbial signatures of distinct trimethylamine N-oxide (TMAO) responses following raspberry consumption. Investigations were carried out in 24 subjects at risk of developing metabolic syndrome who received 280 g/day of frozen raspberries for 8 weeks. Blood and stool samples were collected at weeks 0 and 8. Inter-individual variability in plasma TMAO levels was analyzed, 7 subjects were excluded due to noninformative signals and 17 subjects were kept for analysis and further stratified according to their TMAO response. Whole-metagenome shotgun sequencing analysis was used to determine the impact of raspberry consumption on gut microbial composition. Before the intervention, the relative abundance of Actinobacteriota was significantly higher in participants whose TMAO levels increased after the intervention (p = 0.03). The delta TMAO (absolute differences of baseline and week 8 levels) was positively associated with the abundance of gut bacteria such as Bilophila wadsworthia (p = 0.02; r² = 0.37), from the genus Granulicatella (p = 0.03; r² = 0.48) or the Erysipelotrichia class (p = 0.03; r² = 0.45). Changes in the gut microbial ecology induced by raspberry consumption over an 8-week period presumably impacted quaternary amines-utilizing activity and thus plasma TMAO levels.     

Evaluation of a training and communication-network nephrology program for community pharmacists

Objectives To assess the feasibility and impact of implementing ProFiL program to optimize community-pharmacist management of drug-related problems among chronic kidney disease patients followed in a predialysis clinic. The program comprises a training workshop, communication-network program and consultation service. Setting Forty-two community pharmacies, 101 pharmacists, and 90 chronic kidney disease patients attending a predialysis clinic in Laval (Canada). Patients were followed-up for 6 months. Method In a six-month, pilot, open, cluster-randomized controlled trial, community pharmacies were assigned to ProFiL or the usual care. Chronic kidney disease patients of these pharmacies attending a predialysis clinic were recruited. ProFiL pharmacists attended a workshop, received patient information (diagnoses, medications, and laboratory-test results) and had access to a consultation service. Their knowledge and satisfaction were measured before and after the workshop. The mean numbers of pharmacists’ written recommendations to physicians (pharmaceutical opinions) and refusals to dispense a medication were computed. Results Of the ProFiL pharmacists, 84% attended the workshop; their knowledge increased from 52% to 88% (95% CI: 29–40%). Most ProFiL pharmacists rated workshop (95%), communication program (82%) and consultation service (59%) as “excellent” or “very good”; 82% said the program improved the quality of their follow-up. The consultation service received 21 requests. ProFiL and usual care pharmacists issued a mean of 0.50 and 0.02 opinion/patient, respectively, (95% CI of the adjusted difference: 0.28–1.01 opinion/patient). Conclusion The results of this pilot study suggest that ProFiL can be implemented and may help community pharmacists intervene more frequently to manage drug-related problems. However, a larger-scale study with longer follow-up is necessary to evaluate the impact of the program on management of drug-related problems and its clinical relevance. Institution where the study was conducted: Centre ambulatoire, Centre de santé et de services sociaux de Laval. Information about presentation of the work as an abstract or poster: Abstracts of this study have been published in the proceedings of the 3rd Canadian Joint Therapeutics Congress of the Canadian Society for Clinical Pharmacology—Canadian Association for Population Therapeutics—Canadian College of Clinical Pharmacy (Toronto, Canada, May 2006), the Colloque 2006 of the Réseau québécois de recherche sur l’usage des médicaments (Quebec, Canada, June 2006), the 22nd International Conference of the International Society of Pharmacoepidemiology (Lisbon, Portugal, August 2006), and the North American Primary Care Research Group (NAPCRG) annual meeting (Vancouver, Canada, October 2007).     

Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro

The role of reactive oxygen metabolites in the toxic effectsof asbestos on pleural mesothelial cells is not well defined.We exposed rat pleural mesothelial cells (RPMC) to chrysotileand crocidolite fibers (0–40 µg/cm²) in the presenceor absence of catalase and superoxide dismutase (SOD). Cellinjury was measured using the colorimetric 3–4 (5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and DNA damage was evaluated in terms of unscheduledDNA synthesis (UDS). Catalase (100 U/ml) and SOD (250 U/ml)protected RPMC against asbestos-induced cytotoxicity and DNAdamage. However, the inactivated enzymes and bovine serum albuminalso showed some protection, suggesting that the effect of antioxidantenzymes may be partly related to their protein nature. Theseresults suggest that oxygen derivatives are partly involvedin the toxic effects of asbestos on cultures of RPMC. The presenceof extracellular proteins may also decrease asbestos-producedtoxicity by reducing the degree of RPMC–fiber interaction.     

Effects of human sera and human serum albumin on mouse embryo culture

Human proteins normally used to supplement human in vitro fertilization—embryo transfer (IVF-ET) culture media were tested for their effects on mouse embryo development from the zygote stage. These proteins included follicular and luteal-phase maternal sera, fetal cord sera, and both human and bovine serum albumin. Our results revealed that both maternal and fetal cord sera did not permit mouse blastocyst formation. Furthermore, predialysis of the human maternal sera and removal of IgG by protein A column chromatography did not improve their support of mouse embryonic development to the blastocyst stage. Similar detrimental effects were observed with maternal sera from term-pregnant IVF-ET patients. Interestingly, these serum samples had supported the in vitro growth of the human zygotes which resulted in these patients' pregnancies. Only some batches of human serum albumin supported mouse blastocyst formation, whereas all sources of bovine serum albumin were effective in this regard. These results raise the question of the suitability of the mouse embryo culture system as a quality control for the testing of protein supplements for human IVF-ET.     

Pulse protein feeding pattern restores stimulation of muscle protein synthesis during the feeding period in old rats

Muscle loss during aging could be related to a lower sensitivity of muscle protein synthesis to feeding. To overcome this decrease without increasing protein intake, we proposed to modulate the daily protein feeding pattern. We showed that consuming 80% of dietary proteins at noon (pulse pattern) improved nitrogen balance in elderly women. The present study was undertaken in rats to determine which tissues are the targets of the pulse pattern and what mechanisms are involved. Male Sprague-Dawley 11- and 23-mo-old rats (n = 32 per age) were fed 4 isoproteic (18% protein) meals/d for 10 d. Then half of the rats at each age were switched to a 11/66/11/11% repartition of daily proteins (pulse pattern) for 21 d. On d 21, rats were injected with a flooding dose of L-(13)C-valine (50 atom% excess, 150 micromol/100 g body) and protein synthesis rates were measured in liver, small intestine and gastrocnemius muscle in either the postabsorptive or the fed state. Epitrochlearis muscle degradation rates and plasma amino acid concentrations were measured at the same times. The pulse pattern had the following effects: 1) it significantly increased liver protein synthesis response to feeding and postprandial plasma amino acid concentrations at both ages; 2) it restored a significant response to feeding of gastrocnemius muscle protein synthesis in old rats; and 3) it had no effect in small intestine or on muscle breakdown. Thus, using a pulse pattern could be useful in preventing the age-related loss of muscle by increasing feeding-induced stimulation of muscle protein synthesis.