Multichannel intraluminal impedance to study gastroesophageal reflux in mechanically ventilated children in the first 48 h after PICU admission

ObjectiveThe aim of this study was to determine the incidence, characteristics, related factors, and clinical implications of gastroesophageal reflux (GER) in critically ill children using esophageal pH monitoring and multichannel intraluminal impedance.MethodsA prospective observational clinical study was performed including 36 non-enterally fed critically ill children with mechanical ventilation, aged 1 mo to 7 y, in the first 48 h after admission in the pediatric intensive care unit (PICU). Esophageal pH monitoring and multichannel intraluminal impedance were used.ResultsMultichannel intraluminal impedance detected 352 episodes of GER (20.1% acid, 53.8% weak acid, 26% alkaline), whereas pH monitoring detected 171 episodes (100% acid). There were no differences in the type of reflux according to age and no differences in the number or type of reflux according to the administration of inotropic or sedatives drugs or the duration of mechanical ventilation. Patients treated with vecuronium had fewer episodes of GER than those without muscle relaxant drugs.ConclusionsThe incidence of GER in non-enterally fed critically ill children with mechanical ventilation is high in the first 48 h after admission to the PICU. Multichannel intraluminal impedance is more sensitive than pH monitoring for establishing the diagnosis of GER because the refluxate is alkaline or weak acid in the majority of episodes. Patients who received muscle relaxants had a lower frequency of GER.     

The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating,Food-Seeking Behavior,and Compulsive Eating: Role of the Nucleus Accumbens Shell

Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic N-methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive NMDA receptor antagonist memantine on palatable food-induced behavioral adaptations using a rat model, which mimics the characteristic symptomatology observed in binge-eating disorder. For this purpose, we allowed male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed-ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding, we tested the effects of memantine on the Chow and Palatable food groups'' intake. Then, we tested the effects of memantine on food-seeking behavior, under a second-order schedule of reinforcement. Furthermore, we investigated the effects of memantine on the intake of food when it was offered in an aversive, bright compartment of a light/dark conflict test. Finally, we evaluated the effects of memantine on FR1 responding for food, when microinfused into the nucleus accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like eating and fully blocked food-seeking behavior and compulsive eating, selectively in the Palatable food group. The drug treatment did not affect performance of the control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion of memantine decreased binge-like eating. Together, these findings substantiate a role of memantine as a potential pharmacological treatment for binge-eating disorder.     

The inhibitory effect of diphenyltin on gap junctional intercellular communication in HEK-293 cells is reduced by thioredoxin reductase 1

Organotins display high biological activity and are toxic to animals and humans. Besides carcinogenic effects, they have been shown to have highly immunotoxic and/or neurotoxic activity; however, the molecular mechanism of their toxicity is not fully understood. The ability of chemicals to inhibit communication via gap junctions has been associated with their toxicological properties. The aim of this study was to determine whether diphenyltin (DPhT) affects the gap junctional intercellular communication (GJIC) and whether thioredoxin reductase (TrxR1) is involved in the regulation of this process. We found that DPhT inhibits GJIC in HEK-293 cells. The inhibition of GJIC depends on the activation of PKC delta and is associated with the induction of Cx43 phosphorylation at Ser262. Moreover, we found that GJIC inhibited by DPhT in HEK-293 cells is fully re-established as a result of TrxR1 overexpression.     

The consequences of 3,4-methylenedioxymethamphetamine induced CYP2D6 inhibition in humans

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused substituted amphetamine. MDMA is predominantly O-demethylenated in humans by cytochrome P450 isoforms 2D6 and 1A2 (CYP2D6 and CYP CYP1A2, respectively). MDMA is also a mechanism-based inhibitor of CYP2D6. A controlled clinical trial was conducted in 15 healthy male subjects whereby a probe drug, dextromethorphan (DEX), was administered after an oral dose of 1.5 mg/kg MDMA. The pharmacokinetics of DEX and its metabolites were used to evaluate changes in CYP2D6 activity. The urinary metabolic ratio of DEX and dextrorphan was used to calculate a recovery half-life of CYP2D6. After MDMA, DEX Cmax and area under the curve increased approximately 10-fold with corresponding decreases in dextrorphan pharmacokinetic parameters. The metabolic ratio increased almost 100-fold from 0.0061 +/- 0.0056 to 0.4322 +/- 0.2848 after MDMA administration, with 67% of the subjects having a value greater than the antimode of 0.3 for assigning the poor metabolizer phenotype. CYP2D6 activity recovered after 10 days with a recovery half-life of 46.6 hours. In addition to the possible long-term serotonergic effects of MDMA, users must be warned of the consequences of such an inhibition.     

AphaMax®, an Aphanizomenon Flos-Aquae Aqueous Extract,Exerts Intestinal Protective Effects in Experimental Colitis in Rats

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a “superfood” for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax^®, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax^® (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-κB, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax^® treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax^® reduced the histological colonic damage and decreased MPO activity, NF-κB activation, as well as iNOS and COX-2 expression. AphaMax^® treatment improved the altered immune response associated with colonic inflammation reducing IL-1β, IL-6 expression. Lastly, AphaMax^® reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax^® attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax^® could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.     

Quality of life in women with endometriosis: a cross-sectional survey

Quality of Life Research - The aim of the study was to assess QoL and identify and analyse its determinants in women with endometriosis. The study was performed in 2019 in health centres in Lublin...     

Does attainment status for the PM10 National Air Ambient Quality Standard change the trend in ambient levels of particulate matter?

Despite increasingly stringent and cost-demanding national, state, and local air quality regulations, adverse health effects associated with ambient exposure to air pollution persist. Accountability research, aimed at evaluating the effects of air quality regulation on health outcome, is increasingly viewed as an essential component of responsible government intervention. In this paper, we focused on assessing the impact of air quality regulations on ambient levels of air pollution. We considered two groups of counties: the first group (A) includes counties that in 1991 were designated as in attainment or unclassifiable with respect to the 1987 National Ambient Air Quality Standards (NAAQS) and maintained their status through 2006; the second group (Ā), includes counties that in 1991 were designated as nonattainment and were subsequently redesignated as in attainment. We hypothesized that if air pollution control programs adopted to meet the NAAQS are effective in reducing air pollution levels, counties in group Ā will experience a sharper decrease in PM₁₀ levels than counties in group A. To provide evidence to support this hypothesis, Bayesian hierarchical models were developed for estimating 1) the yearly percentage change in ambient PM₁₀ levels for 100 counties and the entire USA during the period 1987–2007 and 2) the change in PM₁₀ ambient levels in counties in group Ā compared with counties in group A. We found statistically significant evidence of variability across counties in trends of PM₁₀ concentrations. We also found strong evidence that counties transitioning from nonattainment to attainment status during the period 1987–2007 experienced a sharper decline in PM₁₀ when compared with counties that were always in attainment.