Ex Vivo Electrochemical pH Mapping of the Gastrointestinal Tract in the Absence and Presence of Pharmacological Agents.

Ex vivo pH profiling of the upper gastrointestinal (GI) tract (of a mouse), using an electrochemical pH probe, in both the absence and presence of pharmacological agents aimed at altering acid/bicarbonate production, is reported. Three pH electrodes were first assessed for suitability using a GI tract biological mimic buffer solution containing 0.5% mucin. These include a traditional glass pH probe, an iridium oxide (IrOx)-coated electrode (both operated potentiometrically), and a quinone (Q) surface-integrated boron-doped diamond (BDD-Q) electrode (voltammetric). In mucin, the time scale for both IrOx and glass to provide a representative pH reading was in the ∼100's of s, most likely due to mucin adsorption, in contrast to 6 s with the BDD-Q electrode. Both the glass and IrOx pH electrodes were also compromised on robustness due to fragility and delamination (IrOx) issues; contact with the GI tissue was an experimental requirement. BDD-Q was deemed the most appropriate. Ten measurements were made along the GI tract, esophagus (1), stomach (5), and duodenum (4). Under buffer only conditions, the BDD-Q probe tracked the pH from neutral in the esophagus to acidic in the stomach and rising to more alkaline in the duodenum. In the presence of omeprazole, a proton pump inhibitor, the body regions of the stomach exhibited elevated pH levels. Under melatonin treatment (a bicarbonate agonist and acid inhibitor), both the body of the stomach and the duodenum showed elevated pH levels. This study demonstrates the versatility of the BDD-Q pH electrode for real-time ex vivo biological tissue measurements.

Association of SNP rs7181866 in the nuclear respiratory factor-2 beta subunit encoding GABPB1 gene with obesity and type-2 diabetes mellitus in South Indian population.

GABPB1, known as nuclear respiratory factor 2 (Nrf2), activates mitochondrial genes that are responsible for oxidative phosphorylation. Earlier studies on GABPB1 reported that two single nucleotide polymorphisms (SNPs) such as rs7181866 and rs8031031, to be associated with increased endurance in athletes. In the present study, a cohort of 302 South Indians, including normoglycemic healthy controls, T2DM with and without obesity were genotyped for the two SNPs by PCR-RFLP method and correlated with serum adipokines. The 'G' allele of rs7181866 was found to be associated with obesity whereas rs8031031 didn't show any significant association with obese individuals. The increased levels of adipokines such as Leptin, IL-6 and TNF-α and decreased adiponectin were found among obese-T2DM, when compared to non-obese T2DM subjects. Further, Factor analysis on metabolic components revealed four factors which accounts for 71.5% for non-obese control and 88.3% for obese T2DM of variance. The bias-corrected and accelerated bootstrap analysis revealed GG genotype to have significant positive and negative correlation with both TNF-α and adiponectin. In conclusion, the G allele of (rs7181866 A/G) was found to be significantly associated with risk for obesity among T2DM subjects.

A Coupling Approach for the Generation of α,α-Bis(enolate) Equivalents: Regioselective Synthesis of gem-Difunctionalized Ketones.

Regioselective α,α-difunctionalization adjacent to a ketone is a significant synthetic challenge. Here, we present a solution to this problem through the transition-metal-free coupling of esters with geminal bis(boron) compounds. This forms an α,α-bis(enolate) equivalent which can be trapped with electrophiles including alkyl halides and fluorinating agents. This presents an efficient, convergent synthetic strategy for the synthesis of unsymmetrical blocked ketones.