Vitamin D receptor and binding protein genes variants in patients with migraine.

BACKGROUND/OBJECTIVES: Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25-hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single-nucleotide variants (SNVs) vitamin D receptor (VDR) gene, VDR rs2228570, and VDR rs731236 have shown an association with migraine risk in a previous case-control association study, while an exome sequencing study identified a rare variant in GC vitamin D binding protein gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine. METHODS: We genotyped 290 patients diagnosed with migraine and 300 age-matched controls using specific TaqMan assays for VDR rs2228570, VDR rs731236, VDR rs7975232, VDR rs739837, VDR rs78783628, GC rs7041, and GC rs4588 SNVs. RESULTS: We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The VDR rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007). CONCLUSIONS: In summary, the results of the current study suggest a lack of association between common SNVs in the VDR and GC gene and the risk of developing migraine. The possible relationship between VDR rs731236 and the triggering of migraine episodes with ethanol deserves future studies.

Use of Laughter for the Detection of Parkinson's Disease: Feasibility Study for Clinical Decision Support Systems, Based on Speech Recognition and Automatic Classification Techniques.

Parkinson's disease (PD) is an incurable neurodegenerative disorder which affects over 10 million people worldwide. Early detection and correct evaluation of the disease is critical for appropriate medication and to slow the advance of the symptoms. In this scenario, it is critical to develop clinical decision support systems contributing to an early, efficient, and reliable diagnosis of this illness. In this paper we present a feasibility study for a clinical decision support system for the diagnosis of PD based on the acoustic characteristics of laughter. Our decision support system is based on laugh analysis with speech recognition methods and automatic classification techniques. We evaluated different cepstral coefficients to identify laugh characteristics of healthy and ill subjects combined with machine learning classification models. The decision support system reached 83% accuracy rate with an AUC value of 0.86 for PD-healthy laughs classification in a database of 20,000 samples randomly generated from a pool of 120 laughs from healthy and PD subjects. Laughter could be employed for the efficient and reliable detection of PD; such a detection system can be achieved using speech recognition and automatic classification techniques; a clinical decision support system can be built using the above techniques. Significance: PD clinical decision support systems for the early detection of the disease will help to improve the efficiency of available and upcoming therapeutic treatments which, in turn, would improve life conditions of the affected people and would decrease costs and efforts in public and private healthcare systems.

Current Treatment Options for REM Sleep Behaviour Disorder.

The symptomatic treatment of REM sleep behaviour disorder (RBD) is very important to prevent sleep-related falls and/or injuries. Though clonazepam and melatonin are usually considered the first-line symptomatic therapy for RBD, their efficiency has not been proven by randomized clinical trials. The role of dopamine agonists in improving RBD symptoms is controversial, and rivastigmine, memantine, 5-hydroxytryptophan, and the herbal medicine yokukansan have shown some degree of efficacy in short- and medium-term randomized clinical trials involving a low number of patients. The development of potential preventive therapies against the phenoconversion of isolated RBD to synucleinopathies should be another important aim of RBD therapy. The design of long-term, multicentre, randomized, placebo-controlled clinical trials involving a large number of patients diagnosed with isolated RBD with polysomnographic confirmation, directed towards both symptomatic and preventive therapy for RBD, is warranted.

Métodos de examen en oftalmología para apoyo del diagnóstico y seguimiento en la enfermedad de Alzheimer leve o moderada / Ophthalmological examination for diagnosis and follow-up in mild and moderate Alzheimer disease

Objetivos: evaluar si existen alteraciones en la función visual y en la estructura de la retina y del nervio óptico en pacientes con demencia de tipo Alzheimer (DA). Material y métodos: se incluyeron 61 pacientes con DA leve-moderada y 36 controles sanos. En todos ellos se evaluó la agudeza visual (escala ETDRS), la sensibilidad al contraste (con los tests CSV-1000E y Pelli-Robson), la estereopsis (con el test TNO) y la visión cromática (con los tests Farnsworth 15 D y Lanthony 15 D utilizando el software Vision Color Recorder). La estructura y los espesores de la retina y del nervio óptico se evaluaron mediante tomografía de coherencia óptica (OCT). Comparamos los resultados entre pacientes y controles. Resultados: el grupo de pacientes mostró una disminución estadísticamente significativa en la agudeza visual, la sensibilidad al contraste, la visión cromática y los espesores de las nueve áreas maculares y de la capa de fibras nerviosas de la retina. Conclu siones: la DA causa alteraciones en la función visual así como una reducción de los espesores en la retina y el nervio óptico desde estadios iniciales de la enfermedad. Estos parámetros podrían ser buenos biomarcadores para el diagnóstico y seguimiento de esta enfermedad (AU)

Objective: To analyze visual function alterations and changes in the retina and the optic nerve in mild or moderate Alzheimer disease (AD) patients, compared with healthy subjects. Material and methods: Sixty one mild/moderate AD patients and 36 age-and-sex matched controls were included. All of them underwent assessment of visual acuity (ETDRS scale), contrast sensitivity (CSV-1000E and Pelli-Robson tests), stereopsis (TNO test), and color vision (Farnsworth 15 D and Lanthony 15 D tests using the Vision Color Recorder software). Optical coherence tomography (OCT) of the macula and optic disc was also acquired to evaluate macular and the retinal nerve fiber layer (RNFL) thicknesses. Comparison between patients and healthy controls were analyzed. Results: AD group showed statistical significant decrease in visual acuity, contrast sensitivity color vision, macular thicknesses in the 9 analyzed areas and RNFL thickness. Conclusions: Visual function alterations and reduction of macular and optic nerve thicknesses appear in AD patients since earlier stages. These parameters may be usefull as biomarker in diagnosis and follow-up of AD patients (AU)

Influence of vitamin D-related gene polymorphisms (CYP27B and VDR) on the response to interferon/ribavirin therapy in chronic hepatitis C.

BACKGROUND AND AIMS: Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC). METHODS: Single nucleotide polymorphisms (SNPs) in CYP27B-1260 gene promoter (rs10877012AC) and in vitamin D receptor (VDR) gene rs2228570TC, rs1544410CT, rs7975232AC and rs731236AT were analyzed in a cohort of 238 Caucasian CHC patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV). Multivariate analyses were performed to exclude confounding effects of well-known baseline predictors of response to therapy (HCV genotype and load, IL28B genotype, age, and GGT and serum cholesterol). RESULTS: Three SNPs at the VDR gene (rs1544410, rs7975232 and rs731236) were in strong linkage disequilibrium, with the CCA haplotype predicting therapeutic failure [Odds ratio 2.743; (95% C.I. 1.313-5.731), p = 0.007]. The carrier state of the VDR rs2228570 T allele was inversely related to the probability of therapeutic failure [Odds ratio 0.438; 95 C.I. (0.204-0.882), p = 0.021]. No relation existed between CYP27B-1260 rs10877012 polymorphism and response to therapy. The area under the operating curve (AUROC) based on the model including all variables significantly related to the response to therapy was 0.846 (95% confidence interval = 0.793-0.899). CONCLUSION: VDR gene polymorphisms are independently related to the response to Peg-IFN+RBV therapy in chronic hepatitis C and could be used as complementary biomarkers of response when included in a prediction algorithm in association with demographic, virologic, biochemical and genetic traits.

Metabolic considerations of drugs in the treatment of allergic diseases.

INTRODUCTION: The clinical management of allergic diseases involves a number of drugs, most of which are extensively metabolized. This review aims to analyze the metabolism and the clinical implications of altered metabolism for these drugs. AREAS COVERED: The authors present an overview of current knowledge of the metabolism of: antihistamine drugs, glucocorticoids, inhaled ß-2 bronchodilators, anticholinergics and other drugs used in allergic diseases, such as cromoglycate, omalizumab, montelukast and epinephrine. Polymorphic drug metabolism is relevant for chlorpheniramine, loratadine and montelukast. Inhibition of drug metabolism is relevant for loratadine, methylprednisolone, fluticasone, mometasone, triamcinolone or prednisolone. Polymorphic pre-systemic metabolism may be relevant to budesonide, fluticasone, beclomethasone, mometasone or salmeterol. The authors also discuss the current information on gene variations according to the 1,000 genomes catalog and other databases. Finally, the authors review the clinical implications of these variations with a particular regard to drugs used in the management of allergic diseases. EXPERT OPINION: Most drugs used in allergic diseases are extensively metabolized. Drug interaction or adverse reactions related to altered metabolism are relevant issues that should be considered in the management of allergic diseases. However, much additional research is required before defining pharmacogenomic biomarkers for the management of drugs used in allergic diseases.

Acquired resistance to the anticancer drug paclitaxel is associated with induction of cytochrome P450 2C8.

INTRODUCTION: We have previously shown that human colorectal cancer tissue is able to inactivate the anticancer drug paclitaxel through cytochrome P450 (CYP)2C8 and CYP3A4 metabolisms. The aim of this study was to evaluate whether changes in the expression levels of genes coding for such enzymes are related to anticancer drug resistance after long-term exposure to the drug. METHODS: Human colorectal cancer cells (Caco-2) that are sensitive to paclitaxel were exposed to increasing concentrations of the drug from 0-250 nM during one year, in order to select paclitaxel-resistant cells. Subsequently, we compared the sensitivity to paclitaxel and the extent of expression of the CYP2C8, CYP3A4 and CYP3A5 genes in original and resistant cells. RESULTS: Resistant cancer cells displayed a 246-fold increased lethal dose (LD)50 to paclitaxel (p < 0.004) as compared with original cancer cells. A 4.4-fold (p = 0.005) enhancement of CYP2C8 expression and a 5.6-fold (p = 0.001) increase of multidrug resistance (MDR)1 expression was observed in resistant cells exposed to paclitaxel. When paclitaxel was removed from the culture medium, CYP2C8, but not MDR1 expression, reverted to basal levels and the resistance to paclitaxel decreased 3.2-fold (p = 0.005). No major changes in the expression levels of CYP3A4 and CYP3A5 were observed. CONCLUSIONS: Caco-2 cells are capable of increasing the expression levels of CYP2C8 as a response to long-term exposure to paclitaxel. This study provides evidence for a mechanism of acquired resistance to anticancer therapy based on the induction of anticancer-metabolizing enzymes.