The objective of this study was to determine fractional absorption of exogenous zinc and intestinal excretion of endogenous zinc in women of childbearing age whose habitual dietary zinc intake was marginal. The target population (L group) comprised residents of a remote farming village in northeast China and the control subjects (M group) were residents of Beijing. Mean (+/-SE) calculated dietary zinc intakes were 5.2 +/- 0.2 and 8.1 +/- 0.2 mg/d, respectively. The phytate-zinc molar ratio in the diet of both groups was approximately 10:1. 70Zn was administered intravenously before breakfast and 67Zn orally with three main meals in 1 d. Subsequently, all feces were collected quantitatively until the second visible marker had been excreted and 12-h urine samples were collected on days 3-9. Fractional absorption was determined by measuring cumulative fecal excretion of nonabsorbed 67Zn and endogenous fecal zinc by isotope-dilution technique (70Zn). Fractional absorption values for L and M groups, respectively, were 0.31 +/- 0.03 and 0.34 +/- 0.03 (P=0.45). Corresponding figures for endogenous fecal zinc were 1.30 +/- 0.07 and 2.34 +/- 0.20 mg Zn/d (P<0.001). Both the estimated total size of the pools of zinc that exchange with zinc in plasma within 2 d (r=0.762, P<0.001) and the excretion of endogenous zinc in the feces (r=0.706, P<0.0001) were positively correlated with calculated total daily zinc absorption. We conclude that fractional absorption of zinc does not differ between women consuming marginal and adequate quantities of zinc in their diets, but endogenous zinc is conserved effectively by the intestine in women whose habitual dietary zinc is marginal.

Dasatinib is a tyrosine kinase inhibitor (including BCR-ABL and the SRC family) that is effective in patients with chronic myeloid leukemia. Dasatinib has pH-dependent solubility and is bioavailable as an oral formulation. The effect of gastric pH modifiers on dasatinib pharmacokinetics is evaluated in an open-label, randomized, 3-period, 3-treatment crossover study. Twenty-four healthy subjects receive treatment A (2 doses of dasatinib 50 mg separated by 12 hours), treatment B (famotidine 40 mg given 2 hours after dasatinib 50 mg and 10 hours before another dose of dasatinib 50 mg), and treatment C (30 mL of an antacid containing aluminum/magnesium hydroxides given 2 hours before dasatinib 50 mg and concomitantly with dasatinib 50 mg 12 hours after the previous dasatinib dose); a 7-day washout separates each treatment period. When famotidine is administered 2 hours after dasatinib, dasatinib exposure is similar to dasatinib administered alone. However, dasatinib exposure is reduced by approximately 60% when famotidine is administered 10 hours before dasatinib dosing. In contrast, dasatinib exposure is unchanged when antacid (Maalox) is administered 2 hours before dasatinib; but when the antacid is coadministered with dasatinib, dasatinib exposure is reduced by approximately 55% to 58%. This indicates that H(2)-receptor antagonists should not be coadministered with dasatinib. Dasatinib may be administered with acid-neutralizing antacids if the doses are temporally separated by at least 2 hours.

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Background:Little is known about the long-term outcomes of severe acute respiratory distress syndrome (ARDS) patients requiring extracorporeal membrane oxygenation (ECMO). This study aimed to investigate the 1-year outcomes of these patients or patients receiving mechanical ventilation (MV) and compare their health-related quality of life (HRQoL) to the general population.Methods:Severe ARDS survivors admitted to two ICUs in China between January 2012 and January 2014 were enrolled. Of the severe ARDS survivors enrolled, 1-year postdischarge, HRQoL assessment using the Short-Form 36 (SF-36) and EuroQol questionnaire dimensions, 6-min walking distance, chest computed tomography scan, pulmonary function, and arterial blood gas analysis were compared for ARDS patients with or without ECMO.Results:ARDS patients receiving ECMO had a significantly higher Acute Physiology and Chronic Health Evaluation II score (30.3 ± 6.7 vs. 26.5 ± 7.3, P = 0.036), lung injury score (3.3 ± 0.4 vs. 2.8 ± 0.5, P = 0.000), Sequential Organ Failure Assessment score (10.8 ± 3.5 vs. 7.9 ± 3.1, P = 0.000), lower PaO2/FiO2 ratio ([mmHg, 1 mmHg = 0.133 kPa], 68.3 ± 16.1 vs. 84.8 ± 16.5, P = 0.000), and increased extrapulmonary organ failure (2 [1, 3] vs. 1 [1, 1], P = 0.025) compared with patients not receiving ECMO. ECMO and non-ECMO survivors showed similar pulmonary function, morphological abnormalities, resting arterial blood gas values, and 6-min walking distance. Mild pulmonary dysfunction and abnormal morphology were observed in a few survivors. In addition, ECMO and non-ECMO survivors showed a similar quality of life. ECMO survivors showed lower SF-36 physical functioning and role-physical domain scores (minimum clinically significant difference at least 5 points), and non-ECMO survivors had similar outcome.Conclusions:One-year posthospital discharge, severe ARDS survivors receiving ECMO or MV demonstrated comparable outcomes. Compared with the general population, ARDS survivors showed reduced HRQoL. Pulmonary function and lung morphology revealed sufficient recovery with minor lung impairment.

In this model of VIDD, autophagy is induced by MV but is not responsible for diaphragmatic weakness. The authors propose that autophagy may instead be a beneficial adaptive response that can potentially be exploited for therapy of VIDD.

Background:There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data.Methods:A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC).Results:The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659–1.010, P = 0.007) and 0.762 (95% CI, 0.558–0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571–1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge.Conclusions:The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients’ data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.

1211S axagliptin is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor, specifically designed for extended inhibition of the DPP-4 enzyme. DPP-4 is an enzyme that selectively cleaves dipeptides such as the key insulinotropic hormone glucagonlike peptide-1 (GLP-1), converting it from the intact and active form to the inactive form, and is responsible for the short half-life of intact GLP-1 in vivo. 1 Inhibitors of DPP-4 increase levels of endogenous intact GLP-1 and prolong its physiological actions, augmenting postprandial insulin secretion and improving the glycemic profile in patients with type 2 diabetes. 2 Because GLP-1 stimulates insulin secretion in a glucose-dependent manner, DPP-4 inhibitors are expected to present lower risks of hypoglycemia and may not lead to weight gain.Saxagliptin is a Biopharmaceutics Classification System (BCS) class III compound (high solubility/low permeability) but exhibits class-I−like characteristics. Clinical studies have shown that saxagliptin is rapidly and almost completely absorbed following oral administration. 3 Saxagliptin is metabolized by cytochrome P450 enzymes 3A4 and 3A5 (CYP3A4 and CYP3A5) to the pharmacologically active major metabolite BMS-510849. 4 In vitro experiments indicate that saxagliptin is a weak substrate for the efflux transporter P-glycoprotein (P-gp). 5 The terminal half-life of saxagliptin in humans is approximately 2.5 hours. 3 Food-drug interactions can result in 2 predominant clinical effects. The first is decreased bioavailability, resulting in the increased possibility of treatment failure; conversely, there is the possibility of increased bioavailability, with increased risk of adverse events and toxicities. 6 A classic example of a food-drug interaction resulting in decreased bioavailability with eventual treatment failure is that of tetracycline administration with milk. The calcium ions present in milk sequester the tetracycline, thereby decreasing its absorption from the gastrointestinal (GI) tract and leading to subtherapeutic systemic exposures, predisposing patients to treatment failure. 7 Another important food-drug interaction involves the effects of food or its constituents on metabolic enzyme activity. Most commonly observed with foods such as grapefruit juice, red wine, and tea are metabolic CYP3A4-based food-drug interactions. These foods contain furanocoumarins and flavonoids, which have been shown to inhibit the CYP3A4 enzyme system, 8 consequently slowing drug metabolism and increasing systemic drug exposure.In a preliminary study with a capsule formulation of saxagliptin, administration of single oral doses of 5 to 20 mg of saxagliptin following a highfat meal resulted in modest effects, including a maximum decrease of 28% in the maximum (peak) plasma drug concentration (C max ) of saxagliptin and a 32% increase in the area under the plasma concentration-time curve from time zero to infinity (AUC ∞ ) of saxagliptin compared with the fasted state. The time to reach C max (T max ) was increased by approximately 1.25...

Zinc balance, including zinc secreted in breast milk, was maintained at approximately 2 mo of lactation in women whose habitual diet was low in zinc. Homeostasis was achieved by high fractional absorption of zinc and intestinal conservation of endogenous fecal zinc.