The effect of intravenous paracetamol for the prevention of rocuronium injection pain

Rocuronium is a nondepolarizing neuromuscular blocking agent used in anesthesia induction and is associated with considerable discomfort and burning pain during injection, which is reported to occur in 50–80% of patients. This study was carried out to investigate the effectiveness of intravenous paracetamol pretreatment compared with lidocaine and normal saline to prevent rocuronium injection pain. The study included 150 ASA I–II patients undergoing elective orthopedic, gastrointestinal, and gynecological procedures under general anesthesia. They were allocated into three groups according to pretreatment drugs: lidocaine (40 mg) (n = 50), paracetamol (n = 50), and normal saline group (n = 50). Before anesthesia induction with propofol, all patients were pretreated with rocuronium. The pain caused by the injection was evaluated. Local signs were assessed on the arm at the end of the injection, as well as 24 hours after recovery from anesthesia. There were no patients with blurred speech or vision and there was no respiratory depression in any group after pretreatment with the study drug. The level of pain on injection was statistically lower in those who had received paracetamol compared to normal saline (p = 0.009). There were more patients in the saline group with severe pain (p < 0.001). Paracetamol relieved the rocuronium injection pain better than normal saline but lidocaine was the best of the three drugs (p < 0.001).     

Quantitation of escitalopram and its metabolites by liquid chromatography‐tandem mass spectrometry in psychiatric patients: New metabolic ratio establishment

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC‐MS/MS to analyse quantitative assay of escitalopram (S‐CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S‐CT and its metabolites in the patients’ plasma. A new method with short sample preparation and analysis time was developed and validated using LC‐MS/MS to analyse quantitative assay of S‐CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S‐CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S‐CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S‐CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S‐CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S‐CT.     

Rewiring yeast sugar transporter preference through modifying a conserved protein motif

Utilization of exogenous sugars found in lignocellulosic biomass hydrolysates, such as xylose, must be improved before yeast can serve as an efficient biofuel and biochemical production platform. In particular, the first step in this process, the molecular transport of xylose into the cell, can serve as a significant flux bottleneck and is highly inhibited by other sugars. Here we demonstrate that sugar transport preference and kinetics can be rewired through the programming of a sequence motif of the general form G-G/F-XXX-G found in the first transmembrane span. By evaluating 46 different heterologously expressed transporters, we find that this motif is conserved among functional transporters and highly enriched in transporters that confer growth on xylose. Through saturation mutagenesis and subsequent rational mutagenesis, four transporter mutants unable to confer growth on glucose but able to sustain growth on xylose were engineered. Specifically, Candida intermedia gxs1 Phe³⁸Ile³⁹Met⁴⁰, Scheffersomyces stipitis rgt2 Phe³⁸ and Met⁴⁰, and Saccharomyces cerevisiae hxt7 Ile³⁹Met⁴⁰Met³⁴⁰ all exhibit this phenotype. In these cases, primary hexose transporters were rewired into xylose transporters. These xylose transporters nevertheless remained inhibited by glucose. Furthermore, in the course of identifying this motif, novel wild-type transporters with superior monosaccharide growth profiles were discovered, namely S. stipitis RGT2 and Debaryomyces hansenii 2D01474. These findings build toward the engineering of efficient pentose utilization in yeast and provide a blueprint for reprogramming transporter properties.Molecular transporter proteins facilitate monosaccharide uptake and serve as the first step in catabolic metabolism. In this capacity, the preferences, regulation, and kinetics of these transporters ultimately dictate total carbon flux (1–3); and optimization of intracellular catabolic pathways only increases the degree to which transport exerts control over metabolic flux (4, 5). Thus, monosaccharide transport profiles and rates are important design criteria and a driving force to enable metabolic engineering advances, ultimately resulting in a biorefinery concept whereby biomass is converted via microbes into a diverse set of molecules (6–10). Among possible host organisms, Saccharomyces cerevisiae is an emerging industrial organism with well-developed genetic tools and established industrial processes and track record (11–16). However, S. cerevisiae lacks an endogenous xylose catabolic pathway and thus is unable to natively use the second most abundant sugar in lignocellulosic biomass. Decades of research have been focused on improving xylose catabolic pathways in recombinant S. cerevisiae (17–22), but less work has been focused on the first committed step of the process—xylose transport, an outstanding limitation in the efficient conversion of lignocellulosic sugars (23, 24).In S. cerevisiae, monosaccharide uptake is mediated by transporters belonging to the major facilitator superfamily (MFS) (25, 26), a ubiquitous group of proteins found across species (27). The predominant transporters in yeast are members of the HXT family (28) and are marked by efficient hexose transport (29) with lower affinities to xylose thus contributing to diauxic growth and flux limitation when attempting pentose utilization in recombinant S. cerevisiae (30). Previous efforts have attempted to identify heterologous transporters with a higher affinity for xylose over glucose (31–36). However, the vast majority of these transporters are either nonfunctional, not efficient, or not xylose specific (24, 37). Furthermore, nearly all known wild-type transporters that enable growth on xylose in yeast confer higher growth rates on glucose than on xylose (24, 37). As an alternative to bioprospecting, we have previously reported that xylose affinity and exponential growth rates on xylose can be improved via directed evolution of Candida intermedia glucose-xylose symporter 1 (GXS1) and Scheffersomyces stipitis xylose uptake 3 (XUT3) (38). These results demonstrated that mutations at specific residues (e.g., Phe⁴⁰ in C. intermedia GXS1) can have a significant impact on the carbohydrate selectivity of these MFS transporters. The fact that single amino acid substitutions can have such a significant impact on transport phenotype (38–40) indicates how simple homology based searches can be ineffective at identifying efficient xylose transporters (35, 36). However, evidence of natural xylose exclusivity is seen in the Escherichia coli xylE transporter that has recently been crystallized (41). The sequence-function flexibility of MFS transporters potentiates the capability to rewire hexose transporters from being glucose favoring, xylose permissive into being xylose-exclusive transporters.In this work, we report on the discovery of a conserved Gly³⁶-Gly³⁷-Val³⁸-Leu³⁹-Phe⁴⁰-Gly⁴¹ motif surrounding the previously identified Phe⁴⁰ residue of C. intermedia GXS1 that controls transporter efficiency and selectivity. By evaluating 46 different heterologously expressed transporters, we find that this motif is conserved among functional transporters and highly enriched in transporters that confer growth on xylose, taking the general form G-G/F-XXX-G. We conduct saturation mutagenesis on Val³⁸, Leu³⁹, and Phe⁴⁰ within the variable region of this motif in C. intermedia GXS1 to demonstrate control of sugar selectivity. Next, we combine xylose-favoring mutations to create a unique mutant version of gxs1 that transports xylose, but not glucose. Finally, we demonstrate the importance of this motif in the capacity to rewire the sugar preference of other hexose transporters including S. cerevisiae hexose transporter 7 (HXT7) and S. stipitis glucose transporter/sensor (RGT2, similar to S. cerevisiae RGT2). This work serves to increase our understanding of the structure–function relationships for molecular transporter engineering and demonstrates complete rewiring of hexose transporters into transporters that prefer xylose as a substrate.     

The relationship between vitamin D and PTH levels and cardiovascular risk in the elderly hypertensives

Introduction and objective: In this study, we aimed to investigate the relationship between vitamin D, parathyroid hormone (PTH) and cardiovascular risk (CVR) in hypertensive patients aged 65 years and over.

Patients and methods: This study was performed with 84 hypertensive patients and 68 normotensive control group in Afyon Kocatepe University Faculty of Medicine Hospital. The determined cardiovascular risk degrees and the stages of blood pressure were compared with the levels of 25-(OH) vitamin D and PTH.

Results: Mean systolic and diastolic blood pressure (BP) levels of the patients with vitamin D deficiency (VDD) were significantly higher than those without VDD (p?p?=?0.012, p?=?0.036, respectively). CVR was reversely correlated with vitamin D but the correlation with hyperparathyroidism did not reach statistically significant level (r?=?–0.752, p?r?=?0.210, p?=?0.055), respectively.

Conclusion: These results indicate that the presence of hypertension is associated with VDD, as well as the stage of hypertension contributes to insufficiency, hyperparathyroidism and increased CVR. Clinicians should be aware and perhaps more aggressive for the treatment of HT and VDD in patients over 65 years of age.     

Low Prevalence of Hepatitis C Virus Infection Among HIV-Positive Patients: Data From a Large-Scale Cohort Study in Istanbul,Turkey

Background:

Rate of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) varies in different countries. This may be attributable to common transmission routes as well as social, economic, and cultural factors.

Objectives:

The purpose of this study was to investigate the prevalence and risk factors of HCV infection among HIV-positive patients in Istanbul, Turkey.

Patients and Methods:

Since January 2006 to November 2013, 949 HIV-positive patients that were enrolled in this study by ACTHIV-IST (Action Against HIV in Istanbul) Study Group, which consists of five centers to follow up HIV-positive patients in Istanbul. Epidemiologic and clinical data were collected retrospectively from medical records and were transferred to an HIV database system.

Results:

Among 949 patients, 84% were men and the mean age was 37.92 ± 11.54 years (range, 17-79). The most frequent route of transmission was heterosexual intercourse (48.8%), followed by men having sex with men (30.5%). Only nine patients (0.9%) had history of injection drug use (IDU). The prevalence of HIV/HCV coinfection was 0.9% (9:949). The IDU rate was 44.4% (4:9) in patients with HIV/HCV coinfection (three of them were not Turkish citizens), whereas this rate was only 0.6% (5:881) in patients with only HIV infection (P < 0.01). Genotypes 1b, 2a/2c, and 3 were determined in five, one, and two patients, respectively. Genotype could not be determined in one patient. History of residence in a foreign country (P < 0.01) and imprisonment (P < 0.01) were also considered as risk factors in terms of HIV/HCV coinfection.

Conclusions:

Prevalence of HIV/HCV coinfection is considerably low in Turkey. The extremely rare prevalence of IDU might have a role in this low prevalence.     

Clinical trial: transcutaneous interferential electrical stimulation in individuals with irritable bowel syndrome - a prospective double-blind randomized study

Background: The exact etiology of irritable bowel syndrome (IBS) remains unclear. Curative treatment is not available and current treatment modalities are mainly directed against the predominant symptoms. There are a few studies reporting the beneficial effects of transcutaneous electrical stimulation in patients with chronic constipation, gastroparesis, and functional dyspepsia. Aim: To investigate whether transcutaneous electrical stimulation is an effective procedure in IBS patients. Methods: IBS patients were randomly placed in vacuum interferential current (IFC) and placebo groups. Both treatments consisted of 12 sessions administered over 4 weeks. Symptoms due to IBS were documented via questionnaires, including the IBS Global Assessment of Improvement Scale, numeric rating scales, visual analogue scale, and IBS Quality of Life Scale at the beginning of, end of, and 1 month after the treatment. Results: Patients in the therapy (29 cases) and placebo (29 cases) groups were homogeneous with respect to demographic data and gastrointestinal system symptoms. When compared to the beginning scores, severity of abdominal discomfort, bloating, and abdominal distension and rumbling improved significantly in either interference or placebo groups at both the end of treatment and 1 month after treatment. In the IFC group, severity of symptoms continued to decrease significantly at 1 month after treatment when compared to scores at just the end of treatment, whereas in the placebo group severity of these symptoms did not change significantly on numeric severity scales. Also, the visual analogue scale of the first month after treatment continued to decrease significantly when compared to the level at the end of treatment in the IFC group. Total quality score increased significantly in the IFC group. Conclusions: Vacuum IFC therapy can significantly improve symptoms and quality of life in patients with IBS. It may represent a novel treatment modality for drug-refractory IBS patients.