Requirements for Muscle Relaxants during Radical Retropubic Prostatectomy

Background: The need for the routine use of muscle relaxants to provide an adequate surgical field for intraabdominal surgery has not been established. This study tested the hypothesis that vecuronium decreases the frequency of unacceptable operating conditions for patients undergoing radical retropubic prostatectomy who are anesthetized with isoflurane and fentanyl.

Methods: After obtaining informed consent, patients in this blinded, placebo-controlled study were randomized to receive either an infusion of vecuronium or saline (placebo) beginning 5 min after fascial incision during the maintenance of anesthesia with at least 1 minimum alveolar concentration end-tidal isoflurane and fentanyl infusion. The surgical field was graded from 1 (excellent) to 4 (unacceptable) by the surgeons at 15-min intervals. If a grade 4 rating occurred (defined as a treatment failure), the patient received rescue vecuronium.

Results: A total of 120 patients are included in this report (59 in the vecuronium group and 61 in the placebo group). The frequency of treatment failure in the placebo group was 17 of 61 (27.9%) versus 1 of 59 (1.7%) in the control group who received vecuronium (P < 0.001). Thirty-eight patients (62.3%) in the placebo group and 52 patients (88.1%) in the vecuronium group had surgical field ratings of <= 2 (good to excellent) at each time assessed throughout the procedure.     

Endothelial Dysfunction and Oxidant Status in Pediatric Patients with Hemoglobin E-β Thalassemia

Thalassemia major is characterized by anemia, iron overload, and oxidant damage to major organs, especially the cardiovascular system. Oxidative stress is ultimately involved in endothelial dysfunction, a condition which is evident in adults suffering from various cardiovascular diseases including thalassemia. We investigated endothelial function in pediatric patients with hemoglobin E-β thalassemia (HbE-β thalassemia), who have been exposed to excessive iron and oxidative stress for much shorter period than adults with thalassemia. We recruited 22 blood transfusion-dependent HbE-β thalassemia patients aged 11.8 ± 2.9 years and 20 healthy controls aged 12.1 ± 1.7 years. Oxidant status was determined, and endothelial function was assessed by a forearm blood flow technique. Oxidative stress was increased in the thalassemic patients, as blood glutathione (GSH) and ratios of reduced GSH to GSH disulfide were markedly reduced, and superoxide anion released from blood cells was highly elevated. Oxidative stress response, assessed by γ-glutamylcysteine ligase activity, was increased approximately twofold in thalassemia patients. Basal forearm blood flow was significantly increased in patients compared with controls (7.3 ± 1.8 vs 6.0 ± 1.8 ml/100 ml tissue/min, respectively), whereas forearm vasodilatory response to reactive hyperemia was depressed by 50% in patients compared with controls. Endothelial function is impaired in young thalassemia patients, and impaired endothelial function is associated with oxidant stress.     

Reducing mutans streptococci and caries development by Lactobacillus paracasei SD1 in preschool children: a randomized placebo-controlled trial

Objective: To examine a reducing effect of Lactobacillus paracasei SD1 on MS and caries in preschool children.

Materials and methods: A total of 124 children, aged 1.5–5 years old, participated and were randomly assigned to the probiotic or control group. The probiotic group received L. paracasei SD1-milk and the control group received standard-milk once daily for 3 months. MS/lactobacilli were enumerated and the caries score was examined. Association between probiotic consumption and bacterial level, or caries progression was assessed by a multivariate logistic regression. This study was registered at the Thai-Clinical-Trials-Registry (TCTR20140903001).

Results: Probiotic was found to be a factor associated with the MS level. Children in the probiotic group had a significantly lower risk of an increase in the MS level than in the control group after receiving the probiotic milk at 3- and 4-months with p?p?=?.040, respectively. Probiotic significantly reduced the risk for caries compared to the control group (p?=?.016). There were no adverse effects or non-compliance reported in either group.

Conclusions: Consumption of milk powder containing L. paracasei SD1 resulted in a reduction of both salivary MS and delayed new caries development, and the strain is safe for use in young children. Results suggest that L. paracasei SD1 may be an alternative way for caries prevention in young children.     

Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives

The antioxidant activities of curcumin, its natural demethoxy derivatives (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC; octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging activity compared to curcumin and a reference antioxidant, trolox. The scavenging activity significantly decreased in the order THC>HHC=OHC>trolox>curcumin>Dmc>Bdmc. Stronger antioxidant activities toward lipid peroxidation and red blood cell hemolysis were also demonstrated in the hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the stoichiometric number of peroxyl radical that can be trapped per molecule (n) of hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC, respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively, which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH induced red blood cell hemolysis significantly decreased in the order OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower antioxidant activity of the demethoxy derivatives, suggesting the ortho-methoxyphenolic groups of curcumin are involved in antioxidant activities. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance antioxidant activity.     

Thailand's national strategic plan on antimicrobial resistance: progress and challenges

Antimicrobial resistance is a serious threat that affects all countries. The Global Action Plan on antimicrobial resistance and the United Nations Political Declaration on antimicrobial resistance set standards for countries to resolve antimicrobial resistance challenges under the One Health approach. We assess progress and challenges in implementing Thailand’s national strategic plan on antimicrobial resistance 2017–2022, discuss interim outcomes and share lessons learnt. Major progress includes: establishing a national governance mechanism that leads high-impact policy on antimicrobial resistance and consolidates actions and multisectoral collaboration; creating a monitoring system and platform to track implementation of the strategic plan; and converting strategies of the strategic plan into actions such as controlling the distribution and use of antimicrobials in humans and animals. Interim results indicate that antimicrobial consumption in animals has nearly halved (exceeding the national goal of a 30% reduction) whereas other goals have not yet reached their targets. We have learnt that elevating antimicrobial resistance to high-level visibility and establishing a national governance mechanism is an important first step, and a monitoring and evaluation system should be developed in parallel with implementation. Securing funds is crucial. Policy coherence is needed to avoid duplication of actions. Highly ambitious goals, although yet to be achieved, can advance actions beyond expectations. Political commitment and collaboration across different sectors will continue to play important roles but might not be sustained without a well-designed governance structure to support long-term actions to address antimicrobial resistance.     

Capsaicin induces heme oxygenase-1 expression in HepG2 cells via activation of PI3K-Nrf2 signaling: NAD(P)H:quinone oxidoreductase as a potential target

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a major pungent ingredient of red pepper, is reported to have antimutagenic and anticarcinogenic properties. However, the mechanisms underlying its chemoprotective effects remain largely unresolved. In the present study, we found that capsaicin induced expression of heme oxygenase-1 (HO-1) in HepG2 cells. Capsaicin treatment resulted in a transient increase in the phosphorylation of Akt and subsequently nuclear translocation of NF-E2-related factor 2 (Nrf2), enhancing its binding to antioxidant response element (ARE). HepG2 cells treated with capsaicin exhibited increased production of reactive oxygen species (ROS). Prior exposure of cells to N-acetyl-L -cysteine blocked not only the ROS production but also the nuclear translocation of Nrf2 and its ARE binding, as well as HO-1 induction by capsaicin. Immunoblot analysis showed that whereas the level of HO-1 protein was elevated, that of NAD(P)H:quinone oxidoreductase (NQO1) was decreased after the treatment with capsaicin or the inhibitor of NQO1, dicumarol. We hypothesize that quinone metabolites or other reactive forms of capsaicin may bind covalently to NQO1 and thereby inhibit its activity, leading to production of ROS. This, in turn, would trigger the activation of Akt via phosphorylation, increase the nuclear translocation and ARE binding of Nrf2, and upregulate the expression of HO-1.     

Umbelliferone Improves an Impaired Glucose and Lipid Metabolism in High‐Fat Diet/Streptozotocin‐Induced Type 2 Diabetic Rats

Umbelliferone (UMB) is a natural product that has several pharmacological effects including antihyperglycemic activity in diabetic rats. Thus, the objective of this study was to investigate the effect of UMB on insulin resistance and on the regulation of glucose and lipid metabolism in type 2 diabetic rats. Type 2 diabetes was induced in rats by feeding a high‐fat diet (45 kcal% fat) and a single dose of streptozotocin injection. After 8 weeks of treatment, UMB significantly reduced the elevated blood glucose levels and insulin resistance and increased the liver glycogen and serum adiponectin. Moreover, the serum lipid and the storages of triglyceride and non‐esterified fatty acid in liver tissue were reduced. From histological examination, the lipid droplets in liver tissue were clearly decreased, and the fat cell size in the fat tissue was smaller in diabetic rats treated with UMB. Interestingly, UMB increased fat cell adiponectin, plasma membrane glucose transporter 4 (GLUT4) and peroxisome proliferator‐activated receptor gamma (PPARγ), and liver PPARα protein expressions. Our findings demonstrate that UMB improves glucose and lipid metabolism in type 2 diabetes by stimulating the insulin secretion and the related mechanisms via stimulating expression of adiponectin, GLUT4, PPARγ, and PPARα‐protein expressions. Copyright © 2015 John Wiley & Sons, Ltd.     

Effects of Atorvastatin on the Pharmacokinetics of Everolimus Among Kidney Transplant Recipients

Background

Hyperlipidemia occurs in up to 50% of kidney transplant (KT) recipients who take everolimus (EVL). As a result of this, statins are the most commonly prescribed lipid-lowering drugs among these patients. However, we are concerned whether there are any drug interactions between EVL and statins, because both of these drugs use the same pharmacokinetics pathway. Therefore, we assessed the effects of concomitant use of EVL and atorvastatin.

Methods

In this randomized, open-label, crossover study, 20 KT patients were assigned (1:1) to receive EVL with or without 20 mg atorvastatin for 1 month. One-month washout period was used before crossover. Plasma EVL concentrations were measured by homogeneous particle-enhanced turbidimetric immunoassay. Twelve-hour area under the time-concentration curve (AUC_0–12) of EVL was calculated with the use of whole-blood EVL concentrations from 10 different time points (0, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours).

Results

The mean (SD) AUC_0–12 for EVL and EVL plus atorvastatin was 155.9 (41.6) ng·h/mL and 151.3 (51.4) ng·h/mL, respectively (P > .05; paired t test). No difference of EVL Cmax or Tmax was found after atorvastatin coadministration. Even though the EVL AUC_0–12 levels were not affected by atorvastatin coadministration in one-half of the subjects, for the rest of the patients, there were unpredictable changes in the EVL AUC_0–12 levels. This may be due to the high intrapatient variability of EVL drug concentration (coefficient of variation ranges from 9.8% to 34.1%).

Conclusions

Coadministration of atorvastatin with EVL in KT recipients did not affect the pharmacokinetics of EVL.