Literature Watch
Cystic fibrosis: Identification and frequency of mutations in a mixed population from a low-income region in Northeastern Brazil.
Cystic fibrosis: Identification and frequency of mutations in a mixed population from a low-income region in Northeastern Brazil.
Pediatr Pulmonol. 2018 May 04;:
Authors: Mota LR, de Castro LL, da Anunciação Ferreira T, de Lima RLLF, Toralles MBP, Souza EL
PMID: 29727070 [PubMed - as supplied by publisher]
Estimating regions of air trapping from electrical impedance tomography data.
Estimating regions of air trapping from electrical impedance tomography data.
Physiol Meas. 2018 May 04;:
Authors: Mueller JL, Muller PA, Mellenthin M, Murthy R, Capps M, Alsaker M, Deterding R, Sagel SD, DeBoer E
Abstract
OBJECTIVE: Electrical impedance tomography (EIT) has been shown as a viable non-invasive, bedside imaging modality to monitor lung function.This paper introduces a method for identifying regions of air trapping from EIT data collected during tidal breathing and breath-holding maneuvers.
APPROACH: Ventilation-perfusion index maps are computed from dynamic EIT images. These maps are then used to identify regions of air trapping in the area of the lung as regions that are poorly ventilated but well perfused throughout the breathing and cardiac cycles. These EIT-identified regions are then compared with independently identified regions of low attenuation, or air trapping, on chest CT. Results of this method are demonstrated in two children with cystic fibrosis and on a healthy control subject.
MAIN RESULTS: In both CF children, the EIT-identified regions of air trapping matched the regions indicated from the chest CT. The EIT-based method is only validated with CT scans within 4 cm of the chest cross-section defined by the electrode plane.
SIGNIFICANCE: The results indicate the potential use of EIT-derived ventilation-perfusion index maps as a non-invasive method for identifying regions of air trapping.
PMID: 29726838 [PubMed - as supplied by publisher]
Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.
Congruence Between Pulmonary Function and Computed Tomography Imaging Assessment of Cystic Fibrosis Severity.
Adv Exp Med Biol. 2018 May 04;:
Authors: Rybacka A, Goździk-Spychalska J, Rybacki A, Piorunek T, Batura-Gabryel H, Karmelita-Katulska K
Abstract
In cystic fibrosis, pulmonary function tests (PFTs) and computed tomography are used to assess lung function and structure, respectively. Although both techniques of assessment are congruent there are lingering doubts about which PFTs variables show the best congruence with computed tomography scoring. In this study we addressed the issue by reinvestigating the association between PFTs variables and the score of changes seen in computed tomography scans in patients with cystic fibrosis with and without pulmonary exacerbation. This retrospective study comprised 40 patients in whom PFTs and computed tomography were performed no longer than 3 weeks apart. Images (inspiratory: 0.625 mm slice thickness, 0.625 mm interval; expiratory: 1.250 mm slice thickness, 10 mm interval) were evaluated with the Bhalla scoring system. The most frequent structural abnormality found in scans were bronchiectases and peribronchial thickening. The strongest relationship was found between the Bhalla sore and forced expiratory volume in 1 s (FEV1). The Bhalla sore also was related to forced vital capacity (FVC), FEV1/FVC ratio, residual volume (RV), and RV/total lung capacity (TLC) ratio. We conclude that lung structural data obtained from the computed tomography examination are highly congruent to lung function data. Thus, computed tomography imaging may supersede functional assessment in cases of poor compliance with spirometry procedures in the lederly or children. Computed tomography also seems more sensitive than PFTs in the assessment of cystic fibrosis progression. Moreover, in early phases of cystic fibrosis, computed tomography, due to its excellent resolution, may be irreplaceable in monitoring pulmonary damage.
PMID: 29725972 [PubMed - as supplied by publisher]
Dietary intake of energy-dense, nutrient-poor and nutrient-dense food sources in children with cystic fibrosis.
Dietary intake of energy-dense, nutrient-poor and nutrient-dense food sources in children with cystic fibrosis.
J Cyst Fibros. 2018 Apr 30;:
Authors: Sutherland R, Katz T, Liu V, Quintano J, Brunner R, Tong CW, Collins CE, Ooi CY
Abstract
BACKGROUND: Prescription of a high-energy, high-fat diet is a mainstay of nutrition management in cystic fibrosis (CF). However, families may be relying on energy-dense, nutrient-poor (EDNP) foods rather than nutrient-dense (ND) foods to meet dietary targets. We aimed to evaluate the relative contribution of EDNP and ND foods to the usual diets of children with CF and identify sociodemographic factors associated with higher EDNP intakes.
METHODS: This is a cross-sectional comparison of children with CF aged 2-18 years and age- and gender-matched controls. Dietary intake was assessed using the Australian Child and Adolescent Eating Survey (ACAES) food frequency questionnaire.
RESULTS: Children with CF (n = 80: 37 males; mean age 9.3 years) consumed significantly more EDNP foods than controls (mean age 9.8 years) in terms of both total energy (median [IQR]: 1301 kcal/day (843-1860) vs. 686 kcal/day (480-1032); p < 0.0001), and as a proportion of energy intake (median [IQR]: 44% (34-51) vs. 31% (24-43); p < 0.0001). Although children with CF met their estimated energy requirements (median [IQR]: 158% (124-187) vs. 112% (90-137); p < 0.0001) and their diets were high in fat (median [IQR]: 38% (35-41) vs. 34% (32-36); p < 0.0001), this was largely attributable to EDNP foods. High EDNP intakes (≥10 serves/day) were associated with socioeconomic disadvantage (p = 0.01) and rural residential location (p = 0.03).
DISCUSSION: The energy- and fat-dense CF diet is primarily achieved by overconsumption of EDNP foods, rather than ND sources. This dietary pattern may not be optimal for the future health of children with CF, who are now expected to survive well into adulthood.
PMID: 29724576 [PubMed - as supplied by publisher]
Treatment compliance in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection treated with tobramycin inhalation powder: The FREE study.
Treatment compliance in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection treated with tobramycin inhalation powder: The FREE study.
Respir Med. 2018 May;138:88-94
Authors: Blasi F, Carnovale V, Cimino G, Lucidi V, Salvatore D, Messore B, Bartezaghi M, Muscianisi E, Porpiglia PA, FREE study group
Abstract
BACKGROUND: A high treatment burden with nebulised therapies in cystic fibrosis (CF) patients is the major limitation for treatment compliance; moreover, studies on treatment compliance with inhaled antibiotics are limited. This study assessed compliance to TOBI® Podhaler™ (TIP) treatment in CF patients with chronic Pseudomonas aeruginosa (Pa) infections in a real-world setting using the Italian Treatment Adherence CF Questionnaire (ITA-CFq).
METHODS: This longitudinal, multicentre, cohort study included 2 follow-up (FU) visits: FU-1 at 3-months±15-days from the baseline visit and FU-2 at the end of third TIP cycle (or 6-months after enrolment, whichever occurred first). The effect of TIP on quality-of-life (QoL) and treatment satisfaction were evaluated using Cystic Fibrosis Questionnaire-Revised (CFQ-R) and Treatment Satisfaction Questionnaire for Medication (TSQM), respectively. Overall compliance to treatments was assessed using ITA-CFq.
RESULTS: Eighty-two patients (mean age, 24.8 ± 7.9 years), including 22 paediatric patients (age, <18 years), were enrolled in the study; 56 (68.3%) patients, including 17 paediatric patients, completed the study. At baseline, the mean compliance score to aerosol antibiotic treatment was 7.8 ± 3.2; upon introducing TIP, the compliance score improved to 9.4 ± 1.2 at the FU-1 and thereafter remained stable at 9.5 ± 1.2. TSQM was higher for the convenience domain (74.2 ± 17.1 at enrolment and slightly improved to 77.8 ± 15.9 at FU-2) following TIP initiation. No substantial effect of TIP was observed on the QoL when measured using the revised CFQ-R. The safety profile was in line with previous findings.
CONCLUSION: TIP was convenient to use and led to improved treatment adherence in CF patients with chronic Pa-infection.
PMID: 29724399 [PubMed - in process]
Management and grading of EGFR inhibitor-induced cutaneous toxicity.
Management and grading of EGFR inhibitor-induced cutaneous toxicity.
Future Oncol. 2018 May 04;:
Authors: Beech J, Germetaki T, Judge M, Paton N, Collins J, Garbutt A, Braun M, Fenwick J, Saunders MP
Abstract
Cutaneous toxicities associated with EGFR inhibitors (EGFRIs) have a significant impact on patient treatment continuation, quality of life and healthcare resource utilization. This paper reviews the current prophylaxis and management of EGFRI-induced cutaneous toxicities in patients with colorectal cancer, and combines these findings with the authors' clinical expertise to define a novel algorithm for healthcare professionals managing patients receiving EGFRIs. This tool includes a grading system based on the location, severity and psychological impact, and provides a standard prescription pack, advice on prophylaxis/self-management of cutaneous symptoms for patients initiating EGFRIs, and essential guidance on subsequent review and treatment escalation. It aims to optimize treatment of metastatic colorectal cancer by minimizing cutaneous toxicities to maintain dose intensity and efficacy of EGFRI-based chemotherapy.
PMID: 29727211 [PubMed - as supplied by publisher]
A Phase 1 dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors.
A Phase 1 dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors.
Ann Oncol. 2018 May 03;:
Authors: Ferrarotto R, Eckhardt G, Patnaik A, LoRusso P, Faoro L, Heymach JV, Kapoun AM, Xu L, Munster P
Abstract
Background: Brontictuzumab is a monoclonal antibody that targets Notch1 and inhibits pathway activation. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, immunogenicity and preliminary efficacy of brontictuzumab in patients with solid tumors.
Patients ans Methods: Subjects with selected refractory solid tumors were elegible. Brontictuzumab was administered intravenously at various dose levels and schedule during dose escalation, and at 1.5mg/kg every three weeks (Q3W) during expansion. Evidence of Notch1 pathway activation as determined by an immunohistochemistry assay was required for entry in the expansion cohort. Adverse events were graded according to the NCI-CTCAE v 4.03. Efficacy was assessed by RECIST 1.1.
Results: Forty-eight subjects enrolled (33 in dose escalation and 15 in the expansion phase). The MTD was 1.5 mg/kg Q3W. Dose-limiting toxicities were grade 3 diarrhea in two subjects and grade 3 fatigue in one subject. The most common drug-related adverse events of any grade were diarrhea (71%), fatigue (44%), nausea (40%), vomiting (21%), and AST increase (21%). Brontictuzumab exhibited nonlinear PK with dose-dependent terminal half-life ranging 1-4 days. Clinical benefit was seen in six out of 36 (17%) evaluable subjects: two had unconfirmed partial response (PR) and four subjects had prolonged (≥ 6 months) disease stabilization (SD). Both PRs and three prolonged SD occurred in adenoid cystic carcinoma (ACC) subjects with evidence of Notch1 pathway activation. Pharmacodynamic effects of brontictuzumab was seen in patients' blood and tumor.
Conclusion: Brontictuzumab was well tolerated at the MTD. The main toxicity was diarrhea, an on-target effect of Notch1 inhibition. An efficacy signal was noted in subjects with ACC and Notch1 pathway activation.
ClinicalTrials.gov Identifier: NCT01778439.
PMID: 29726923 [PubMed - as supplied by publisher]
Systematic Evaluation of Corticosteroid Use in Obese and Non-obese Individuals: A Multi-cohort Study.
Systematic Evaluation of Corticosteroid Use in Obese and Non-obese Individuals: A Multi-cohort Study.
Int J Med Sci. 2017;14(7):615-621
Authors: Savas M, Wester VL, Staufenbiel SM, Koper JW, van den Akker ELT, Visser JA, van der Lely AJ, Penninx BWJH, van Rossum EFC
Abstract
Background: Although the use of corticosteroids has been linked to high incidence of weight gain, no data are available concerning the differences in corticosteroid use between a diverse obese population and non-obese individuals. The main purpose of this study was to systematically explore the use of corticosteroids in obese subjects compared to non-obese controls. In addition, we also explored self-reported marked weight gain within obese subjects. Methods: Two hundred seventy-four obese outpatients (median [range] BMI: 40.1 kg/m2 [30.5-67.0]), and 526 non-obese controls (BMI: 24.1 kg/m2 [18.6-29.9]) from two different Dutch cohort studies were included. Corticosteroid use at the time of clinic or research site visit for up to the preceding three months was recorded in detail. Medical records and clinical data were evaluated with regard to age and body mass index in relation to corticosteroid use, single or multiple type use, and administration forms. Results: Recent corticosteroid use was nearly twice as high for obese subjects than for non-obese controls (27.0% vs. 11.9% and 14.8%, both P<.001). Largest differences were found for use of local corticosteroids, in particular inhaled forms, and simultaneous use of multiple types. Marked weight gain was self-reported during corticosteroid use in 10.5% of the obese users. Conclusion: Corticosteroid use, especially the inhaled agents, is higher in obese than in non-obese individuals. Considering the potential systemic effects of also local corticosteroids, caution is warranted on the increasing use in the general population and on its associations with weight gain.
PMID: 28824292 [PubMed - indexed for MEDLINE]
Statin myopathy: over-rated and under-treated?
Statin myopathy: over-rated and under-treated?
Curr Opin Cardiol. 2016 Jul;31(4):417-25
Authors: Maghsoodi N, Wierzbicki AS
Abstract
PURPOSE OF REVIEW: Statins are recommended as first-line therapy for cardiovascular disease. Unfortunately, a proportion of patients cannot tolerate these drugs because of muscle-related side-effects. This review summarizes the definition of statin-related muscle disorders, aetiological factors, and recommended management strategies.
RECENT FINDINGS: A number of consensus groups have defined and classified statin-related muscle disorders, whereas others have suggested diagnostic and management strategies. Mechanisms behind statin-related muscle toxicity have been identified. Therapeutic and clinical investigation pathways have been reviewed and algorithms defined. New drugs have become available to reduce low-density lipoprotein cholesterol levels that are not associated with causing muscle side-effects.
SUMMARY: Statin-related muscle side-effects are common. Secondary causes of muscle disease unmasked by statin therapy should be identified. Most patients can be managed by adjustment of standard treatment protocols.
PMID: 27258372 [PubMed - indexed for MEDLINE]
NIOSH Occupational Safety and Health Research (R01)
"systems biology"; +30 new citations
30 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/04
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy.
Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy.
Expert Opin Investig Drugs. 2018 May 03;:
Authors: Schcolnik-Cabrera A, Chávez-Blanco A, Domínguez-Gómez G, Taja-Chayeb L, Cardenas-Barcenas R, Trejo-Becerril C, Perez-Cardenas E, Gonzalez-Fierro A, Dueñas-González A
Abstract
INTRODUCTION: Cancer cells have increased glycolysis and glutaminolysis. Their third feature is increased de novo lipogenesis. As such, fatty acid (FA) synthesis enzymes are over-expressed in cancer and their depletion causes antitumor effects. As fatty acid synthase (FASN) plays a pivotal role in this process, it is an attractive target for cancer therapy. Areas covered: This is a review of the lipogenic phenotype of cancer and how this phenomenon can be exploited for cancer therapy using inhibitors of FASN, with particular emphasis on orlistat as a repurposing drug. Expert opinion: Disease stabilization only has been observed with a highly selective FASN inhibitor used as a single agent in clinical trials. It is too early to say whether the absence of tumor responses other than stabilization results because even full inhibition of FASN is not enough to elicit antitumor responses. The FASN inhibitor orlistat is a "dirty" drug with target-off actions upon at least seven targets with a proven role in tumor biology. The development of orlistat formulations suited for its intravenous administration is a step ahead to shed light on the concept that drug promiscuity can or not be a virtue.
PMID: 29723075 [PubMed - as supplied by publisher]
Repurposing the Selective Oestrogen Receptor Modulator Tamoxifen for the Treatment of Duchenne Muscular Dystrophy.
Repurposing the Selective Oestrogen Receptor Modulator Tamoxifen for the Treatment of Duchenne Muscular Dystrophy.
Chimia (Aarau). 2018 Apr 25;72(4):238-240
Authors: Gayi E, Neff LA, Ismail HM, Ruegg UT, Scapozza L, Dorchies OM
Abstract
Drug discovery is a long, expensive and risky process. Evaluating drugs that have already been proved safe for use in humans and testing them for a new indication greatly reduces the time and monetary costs involved in finding treatments for life-threatening conditions. Here tamoxifen, a drug that is used for the treatment of breast cancer, is investigated in a mouse model of Duchenne muscular dystrophy. Tamoxifen was efficacious in countering the symptoms of the disease without affecting the underlying genetic cause. Based on these results, tamoxifen has been tested in other forms of muscle disease with success. Drug repurposing may not only be a cost-effective manner for treating a variety of diseases, it may also help us uncover common mechanisms between conditions that were previously thought to be unrelated.
PMID: 29720316 [PubMed - in process]
Looking Back, Looking Forward at Halogen Bonding in Drug Discovery.
Looking Back, Looking Forward at Halogen Bonding in Drug Discovery.
Molecules. 2017 Aug 24;22(9):
Authors: Mendez L, Henriquez G, Sirimulla S, Narayan M
Abstract
Halogen bonding has emerged at the forefront of advances in improving ligand: receptor interactions. In particular the newfound ability of this extant non-covalent-bonding phenomena has revolutionized computational approaches to drug discovery while simultaneously reenergizing synthetic approaches to the field. Here we survey, via examples of classical applications involving halogen atoms in pharmaceutical compounds and their biological hosts, the unique advantages that halogen atoms offer as both Lewis acids and Lewis bases.
PMID: 28837116 [PubMed - indexed for MEDLINE]
H Syndrome: A Rare Genodermatosis Imaged With 18F-FDG PET/CT.
H Syndrome: A Rare Genodermatosis Imaged With 18F-FDG PET/CT.
Clin Nucl Med. 2018 Jan;43(1):36-37
Authors: Turpin S, Patey N, Beaudin M, Mitchell G, Lambert R
Abstract
H syndrome (OMIM 612391) is an extremely rare autosomal recessive genodermatosis, characterized by extensive skin infiltration. We report a case imaged with F-FDG PET/CT.
PMID: 29189375 [PubMed - indexed for MEDLINE]
Promoting innovation in small markets: Evidence from the market for rare and intractable diseases.
Promoting innovation in small markets: Evidence from the market for rare and intractable diseases.
J Health Econ. 2017 Jul;54:56-65
Authors: Iizuka T, Uchida G
Abstract
In many medical care markets with limited profit potential, firms often have little incentive to innovate. These include the market for rare diseases, "neglected" tropical diseases, and personalized medicine. Governments and not-for-profit organizations promote innovation in such markets but empirical evidence on the policy effect is limited. We study this issue by analyzing the impact of a demand-side policy in Japan, which reduces the cost sharing of patients with some rare and intractable diseases and attempts to establish and promote the treatment of those diseases. Using clinical trials data taken from public registries, we identify the effect of the policy using a difference-in-difference approach. We find that the demand-side policy increased firms' incentive to innovate: firm-sponsored clinical trials increased 181% (0.16 per disease per year) when covered by the policy. This result indicates that the demand-side policy can be an important part of innovation policies in markets with limited profit potential.
PMID: 28448950 [PubMed - indexed for MEDLINE]
Pharmacogenomic biomarkers: Interpretation of information included in United States and Japanese drug labels.
Pharmacogenomic biomarkers: Interpretation of information included in United States and Japanese drug labels.
J Clin Pharm Ther. 2018 May 02;:
Authors: Shimazawa R, Ikeda M
Abstract
WHAT IS KNOWN AND OBJECTIVES: Many drug labels contain information on pharmacogenomic biomarkers (PGBMs), but the information is not necessarily actionable. Pharmacogenomics Knowledgebase (PharmGKB) aims to clarify the level of action for PGBMs (PGx levels) implied in each label as issued by the US Food and Drug Administration. We wished to evaluate the association between the PGx level for US and Japanese drug labels and the insurance coverage for PGBM testing or approval for in vitro diagnostics (IVDs) in each country.
METHODS: We investigated the information on PGBMs in US and Japanese drug labels with PGx levels, insurance coverage of PGBM tests and IVD approval in the US and Japan. We analysed the relationship of PGx levels with insurance coverage.
RESULTS: A total of 243 labels were listed by PharmGKB, and 215 (88%) had PGx levels for US labels and 52 (21%) for Japanese labels. Of the 215 US labels, 54 were designated as "Testing Required" in PGx levels. PGx levels in US labels were strongly associated with coverage of PGBM testing. Tests in 52 (96%) of the 54 labels with Testing Required had insurance coverage, 2 (50%) of 4 in "Testing Recommended," 38 (38%) of 100 in "Actionable PGx," 11 (19%) of 57 in "Informative PGx" and 3 (11%) of 28 in "No Level." In Japanese labels, only 14 of 52 were listed as Testing Required, and all were covered by the National Health Insurance in Japan.
WHAT IS NEW AND CONCLUSION: The PGx level given in drug labels provides information on availability of PGBM testing. Higher PGx levels, based on better evidence of usefulness of PGBM testing, provide a route to broader test coverage.
PMID: 29722046 [PubMed - as supplied by publisher]
Pharmacogenomic survey of Qatari populations using whole-genome and exome sequences.
Pharmacogenomic survey of Qatari populations using whole-genome and exome sequences.
Pharmacogenomics J. 2018 May 03;:
Authors: Sivadas A, Scaria V
Abstract
The Arabs represent one of the most genetically heterogeneous populations characterized by a high prevalence of Mendelian disorders due to consanguinity. Population-scale genomic datasets provide a unique opportunity to understand the epidemiology of variants associated with differential therapeutic response. We analyzed publicly available genomic data for 1005 Qatari individuals encompassing five subpopulations. The frequencies of known and novel pharmacogenetic variants were compared with global populations. Impact of genetic substructure on the pharmacogenetic landscape of the population was studied. We report an average of three clinically actionable pharmacogenetic variants with FDA-recommended genetic testing per Qatari individual regardless of their genetic ancestry. We observed extensive differences in the frequencies of clinically actionable pharmacogenetic variants among the Qatari subpopulations. Our analysis revealed 3579 deleterious pharmacogenetic variants potentially altering the function of 1163 genes associated with 1565 drugs. This study has thus compiled the first comprehensive landscape of pharmacogenetic variants for any Arab population.
PMID: 29720721 [PubMed - as supplied by publisher]
Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.
Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome.
Pharmacogenomics J. 2018 May 03;:
Authors: Jiménez-Jiménez FJ, Esguevillas G, Alonso-Navarro H, Zurdo M, Turpín-Fenoll L, Millán-Pascual J, Adeva-Bartolomé T, Cubo E, Navacerrada F, Amo G, Rojo-Sebastián A, Rubio L, Díez-Fairén M, Pastor P, Calleja M, Plaza-Nieto JF, Pilo-de-la-Fuente B, Arroyo-Solera M, García-Albea E, Agúndez JAG, García-Martín E
Abstract
The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.
PMID: 29720720 [PubMed - as supplied by publisher]
A LC/MS/MS method for determination of tenofovir in human plasma and its application to toxicity monitoring.
A LC/MS/MS method for determination of tenofovir in human plasma and its application to toxicity monitoring.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 May 15;1085:89-95
Authors: Wiriyakosol N, Puangpetch A, Manosuthi W, Tomongkon S, Sukasem C, Pinthong D
Abstract
Tenofovir disoproxil fumarate is a pro-drug of the active metabolite tenofovir widely used against the HIV1, HIV2, and Hepatitis B virus. Several studies have been conducted and found kidney injury associated with tenofovir exposure. High tenofovir plasma concentration correlated with kidney injury in tenofovir-exposed patients. The present study developed and validated a simple and cost-effective LC/MS/MS method to determine tenofovir level in human plasma. A small plasma volume of 80 μl is utilized for the sample preparation. The samples were separated by Luna C18 (100 mm × 2.0 mm, 3 μm) using gradient elution with a mobile phase consisting of water (containing 0.1% formic acid) and acetonitrile (90:10, v/v). The detection was achieved through multiple reaction monitoring using positive ionization mode on the triple quadrupole mass spectrometer with a run time of 10 min. The monitoring transitions were set at m/z 288.0 → 176.1 and 136.1 for tenofovir and m/z 226.1 → 152.0 for acyclovir (as the internal standard). This standard curve was linear from 10 to 640 ng/ml, with the lower limit of quantification of 10 ng/ml. The inter- and intra-day precision results were less than 12.3% and their accuracies were within the acceptable range of 84.9-113.1%. The validated method was successfully applied to the study of tenofovir induced kidney injury in HIV-1 infected patients taking 300 mg once daily for more than 4 weeks.
PMID: 29635209 [PubMed - indexed for MEDLINE]
Pages
