Exposure to Secondhand Smoke and Arrhythmogenic Cardiac Alternans in a Mouse Model.

BackgroundEpidemiological evidence suggests that a majority of deaths attributed to secondhand smoke (SHS) exposure are cardiovascular related. However, to our knowledge, the impact of SHS on cardiac electrophysiology, [Formula: see text] handling, and arrhythmia risk has not been studied.ObjectivesThe purpose of this study was to investigate the impact of an environmentally relevant concentration of SHS on cardiac electrophysiology and indicators of arrhythmia.MethodsMale C57BL/6 mice were exposed to SHS [total suspended particles (THS): [Formula: see text], nicotine: [Formula: see text], carbon monoxide: [Formula: see text], or filtered air (FA) for 4, 8, or 12 wk ([Formula: see text]]. Hearts were excised and Langendorff perfused for dual optical mapping with voltage- and [Formula: see text]-sensitive dyes.ResultsAt slow pacing rates, SHS exposure did not alter baseline electrophysiological parameters. With increasing pacing frequency, action potential duration (APD), and intracellular [Formula: see text] alternans magnitude progressively increased in all groups. At 4 and 8 wk, there were no statistical differences in APD or [Formula: see text] alternans magnitude between SHS and FA groups. At 12 wk, both APD and [Formula: see text] alternans magnitude were significantly increased in the SHS compared to FA group ([Formula: see text]). SHS exposure did not impact the time constant of [Formula: see text] transient decay ([Formula: see text]) at any exposure time point. At 12 wk exposure, the recovery of [Formula: see text] transient amplitude with premature stimuli was slightly (but nonsignificantly) delayed in SHS compared to FA hearts, suggesting that [Formula: see text] release via ryanodine receptors may be impaired.ConclusionsIn male mice, chronic exposure to SHS at levels relevant to social situations in humans increased their susceptibility to cardiac alternans, a known precursor to ventricular arrhythmia. https://doi.org/10.1289/EHP3664

β-adrenergic inhibition prevents action potential and calcium handling changes during regional myocardial ischemia

β-adrenergic receptor (β-AR) blockers may be administered during acute myocardial infarction (MI), as they reduce energy demand through negative chronotropic and inotropic effects and prevent ischemia-induced arrhythmogenesis. However, the direct effects of β-AR blockers on ventricular electrophysiology and intracellular Ca2+ handling during ischemia remain unknown. Using optical mapping of transmembrane potential (with RH237) and sarcoplasmic reticulum (SR) Ca2+ (with the low-affinity indicator Fluo-5N AM), the effects of 15 min of regional ischemia were assessed in isolated rabbit hearts (n = 19). The impact of β-AR inhibition on isolated hearts was assessed by pre-treatment with 100 nM propranolol (Prop) prior to ischemia (n = 7). To control for chronotropy and inotropy, hearts were continuously paced at 3.3 Hz and contraction was inhibited with 20 μM blebbistatin. Untreated ischemic hearts displayed prototypical shortening of action potential duration (APD80) in the ischemic zone (IZ) compared to the non-ischemic zone (NI) at 10 and 15 min ischemia, whereas APD shortening was prevented with Prop. Untreated ischemic hearts also displayed significant changes in SR Ca2+ handling in the IZ, including prolongation of SR Ca2+ reuptake and SR Ca2+ alternans, which were prevented with Prop pre-treatment. At 5 min ischemia, Prop pre-treated hearts also showed larger SR Ca2+ release amplitude in the IZ compared to untreated hearts. These results suggest that even when controlling for chronotropic and inotropic effects, β-AR inhibition has a favorable effect during acute regional ischemia via direct effects on APD and Ca2+ handling

The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Association between body image dissatisfaction and body anthropometric indices among Chinese children and adolescents at different developmental stages

ObjectiveChildren at different developmental stages show different physical development and psychological cognitive characteristics and may pay different attention to body parts. The purpose of this study was to analyze the associations between body image dissatisfaction (BID) and body anthropometric indices (BAIs) among Chinese children and adolescents at different developmental stages.MethodsA total of 609 Chinese primary and secondary school students aged 8–15 years (329 boys and 280 girls) were selected using stratified cluster sampling. The students' body height, sitting height (SH), weight, chest circumference (CC), hip circumference (HC), waist circumference (WC), scapular skinfold thickness (SST), triceps skinfold thickness (TST), and abdominal skinfold thickness (AST) were measured. Boys' testicular volumes and first spermatorrhea and girls' breast measures and menarche were assessed using the Tanner stage standard. A body shape questionnaire (BSQ) was used to survey the subject's BID.ResultsIn boys with testicular volume < 4 ml, the hip-to-height ratio (HHR) was positively correlated with BSQ score (β = 8.17, P < 0.01). In boys with testicular volume ≥4 ml and nonfirst spermatorrhea, the HHR and SST were positively correlated with BSQ score (β = 2.51, P = 0.04; β = 4.98, P < 0.01). In boys with first spermatorrhea, weight was positively correlated with BSQ score (β = 10.30, P < 0.01). In girls with breast development < Tanner stage II, waist-to-height ratio (WHtR) was positively correlated with BSQ score (β = 5.12, P < 0.01); In girls with breast development ≥ Tanner stage II and nonmenarche, chest-to-sitting height ratio (CSHR) was positively correlated with BSQ score (β = 10.82, P < 0.01), and waist-to-hip ratio (WHR) was negatively correlated with BSQ score (β = −3.61, P = 0.04). In girls with menarche, WHtR and sitting height-to-height ratio (SHHR) were positively correlated with BSQ score (β = 6.09, P < 0.01; β = 2.05, P = 0.02).ConclusionThe associations between body image dissatisfaction and anthropometric indices among Chinese children and adolescents at different developmental stages are different

Determination of sulpiride in rabbit plasma by LC-ESI-MS and its application to a pharmacokinetic study

A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method for determination of sulpiride in rabbit plasma was developed and validated. The analyte and internal standard (IS) were extracted from plasma by liquid-liquid extraction using ethyl acetate, and chromatography involved Agilent Extend-C18 column (2.1 mm x 50 mm, 3.5 μm) using 0.2 % formic acid in water and acetonitrile (60: 40, v/v) as a mobile phase. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragmentions m/z 342.0 for sulpiride and m/z 294.8 for estazolam (internal standard, IS). The assay was linear over the range of 10-2000 ng/mL for sulpiride, with a lower limit of quantitation (LLOQ) of 10 ng/mL for sulpiride. Intraand inter-day precisions were less than 12 % and the accuracies were in the range of 94.1-108.7 % for sulpiride. This developed method was successfully applied for the determination of sulpiride in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of meropenem in rabbit plasma by LC-MS/MS

A sensitive and selective liquid chromatography tandem mass spectrometry (LC–MS/MS) method for determination of meropenem in rabbit plasma was developed. After addition of triazolam as internal standard (IS), protein precipitation by acetonitrile was used in sample preparation. Chromatographic separation was achieved on a Restek Allure (TM) PFP Propyl (2.1 mm × 100 mm, 5 μm) column with acetonitrile-0.1 % formic acid as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used to quantification using target fragment ions m/z 384.1 → 339.9 for meropenem and m/z 342.7 → 307.8 for the IS. Calibration plots were linear over the range of 0.1-40 μg/mL for meropenem in plasma. Lower limit of quantification (LLOQ) for meropenem was 0.1 μg/mL. Mean recovery of meropenem from plasma was in the range 85.6 %-96.5 %. CV of intra-day and inter-day precision were both less than 15 %. This method is simple and sensitive enough to be used in pharmacokinetic research for determination of meropenem in rabbit plasma.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Two novel TSC2 mutations in renal epithelioid angiomyolipoma sensitive to everolimus.

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus