Allyl isothiocyanate sensitizes TRPV1 to heat stimulation

The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca²⁺ imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current–voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca²⁺ imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat.     

UDP-glucuronosyltransferase genetic variation in North African populations: a comparison with African and European data

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases.

Aim: To examine genetic variation in UGT in North African populations.

Subjects and methods: Allele frequencies of SNPs UGT1A4^24Thr, UGT1A4^48Val, UGT2B15^85Tyr, UGT2B15^523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations.

Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A4^48Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations.

Conclusion: North African populations show a high frequency of carriers of UGT2B15^523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17^del, a variant associated with high concentrations of testosterone and oestradiol.     

Failure of daptomycin β-Lactam combination therapy to prevent resistance emergence in Enterococcus faecium

Daptomycin β-Lactam combination therapy offers “protection” against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation.     

Success Rates of Endoscopic-Assisted Probing Compared to Conventional Probing in Children 48 Months or Older

Background: To evaluate the success rates of endoscopic-assisted probing compared to conventional probing in children 48 months or older. Methods: This retrospective study included children 48 months and older with CNLDO who underwent endoscopic-assisted probing or conventional probing between January 2011 to August 2015 at a tertiary eye care hospital in central Saudi Arabia. Probing was considered successful when signals of tearing or discharge disappeared and fluorescein dye disappearance test (FDDT) was normal. Demographic data, clinical features, intraoperative and postoperative variables were correlated to the success rate. Results: One hundred and twelve children with CNLDO undergoing endoscopic-assisted (37 patients) or conventional (75 patients) probing were included. The success rates of endoscopic-assisted and conventional probing were 94.6% [95% confidence interval (CI): 89.5–99.7] and 58.7% [95% (CI): 47.6–69.8], respectively. The success rate was higher with endoscopic probing, especially in older children. Conclusions: Endoscopic-assisted probing can achieve better outcomes to treat CNLDO, even in older children. The significantly higher success rates with endoscopic probing are likely due to the ability to observe and treat associated problems.     

Mode of Childbirth in Low-Risk Pregnancies: Nicaraguan Physicians’ Viewpoints

To explore attitudes of physicians attending births in the public and private sectors and at the managerial level toward cesarean birth in Nicaragua. A qualitative study was conducted consisting of four focus groups with 17 physicians and nine in-depth interviews with decision-makers. Although study participants listed many advantages of vaginal birth and disadvantages of cesarean birth, they perceived that the increase in the cesarean birth rate in Nicaragua has resulted in a reduction in perinatal morbidity and mortality. They ascribed high cesarean birth rates to a web of interrelated provider, patient, and health system factors. They identified five actions that would facilitate a reduction in the number of unnecessary cesarean operations: establishing standards and protocols; preparing women and their families for labor and childbirth; incorporating cesarean birth rate monitoring and audit systems into quality assurance activities at the facility level; strengthening the movement to humanize birth; and promoting community-based interventions to educate women and families about the benefits of vaginal birth. Study participants believe that by performing cesarean operations they are providing the best quality of care feasible within their context. They do not perceive problems with their current practice. The identified causes of unnecessary cesarean operations in Nicaragua are multifactorial, so it appears that a multi-layered strategy is needed to safely reduce cesarean birth rates. The recent Nicaraguan Ministry of Health guidance to promote parto humanizado (“humanization of childbirth”) could serve as the basis for a collaborative effort among health care professionals, government, and consumer advocates to reduce the number of unnecessary cesarean births in Nicaragua.     

In vitro human colonic fermentation of indigestible fraction isolated from lunch menus: impact on the gut metabolites and antioxidant capacity

The indigestible fraction (IF) isolated from three lunch menus: Modified Mexican Lunch (MM-L), Traditional Mexican Lunch (TM-L) and Alternative Mexican Lunch (AM-L), was studied in terms of antioxidant capacity (AOX) and metabolites produced through fermentation by human intestinal microbiota. IFs were isolated after withstanding in vitro gastrointestinal digestion and total soluble polyphenols (TSP), condensed tannins (CT), hydrolysable polyphenols (HP) and AOX (DPPH, FRAP) were evaluated. AOX, pH and bacterial metabolites profile changes were also monitored during in vitro colonic fermentation. Lunch menus showed differences in IF, TSP, CT and FRAP values (p<.05). TM-L had the highest TSP and CT contents (0.84 and 1.89?g/100?g DW, respectively). Changes in pH and AOX during fermentation were time-dependent and substrate-dependent (p<.05). Butyric acid production was not significantly modified by the IFs (p>.05). Fifty-seven microbiota-produced volatile compounds were detected by SPME-GC–MS. This study shows the potential effects of food habits on bacterial metabolite production.