Patsalis P.C.,The Cyprus Institute of Neurology and Genetics
Applied and Translational Genomics | Year: 2012
During the last decade, the area of non-invasive prenatal diagnosis (NIPD) has rapidly evolved. Several methodological approaches have been presented and demonstrated a proof of concept for the NIPD of chromosomal aneuploidies. The two most promising methods are NIPD using next generation sequencing technologies and NIPD using Methylation DNA Immunoprecipitation (MeDIP) with real time qPCR. Both approaches have been validated with blind studies and have >. 99% accuracy. NIPD using next generation sequencing is achieved by high throughput shotgun sequencing of DNA from plasma of maternal women followed by ratio comparisons of each chromosome sequence tag density over the median tag density of all autosomes (z-score analysis). The MeDIP real time qPCR method, which is described in this review in more detail, is based on the identification of differentially methylated regions (DMRs) and their use in discriminating normal from abnormal cases. More than 10,000 DMRs were identified for chromosomes 13, 18, 21, X and Y using high resolution oligo-arrays that can be potentially used for the NIPD of aneuploidies for chromosomes 13, 18, 21, X and Y. Both NIPD methods have several advantages and limitations and it is believed that they will soon be implemented in clinical practice. With the continuous advancements of genetic methodologies and technologies, we predict that within the next 10. years we will be able to provide NIPD for all common and rare genetic disorders where the molecular basis is known. © 2012 Elsevier B.V.
Vasquez M.I.,University of Cyprus |
Lambrianides A.,The Cyprus Institute of Neurology and Genetics |
Schneider M.,Luneburg University |
Kummerer K.,Luneburg University |
Fatta-Kassinos D.,University of Cyprus
Journal of Hazardous Materials | Year: 2014
Cocktails of pharmaceuticals are released in the environment after human consumption and due to the incomplete removal at the wastewater treatment plants. Pharmaceuticals are considered as contaminants of emerging concern and, a plethora of journal articles addressing their possible adverse effects have been published during the past 20 years. The emphasis during the early years of research within this field, was on the assessment of acute effects of pharmaceuticals applied singly, leading to results regarding their environmental risk, potentially not realistic or relevant to the actual environmental conditions. Only recently has the focus been shifted to chronic exposure and to the assessment of cocktail effects. To this end, this review provides an up-to-date compilation of 57 environmental and human toxicology studies published during 2000-2014 dealing with the adverse effects of pharmaceutical mixtures. The main challenges regarding the design of experiments and the analysis of the results regarding the effects of pharmaceutical mixtures to different biological systems are presented and discussed herein. The gaps of knowledge are critically reviewed highlighting specific future research needs and perspectives. © 2014 Elsevier B.V.
Kleopa K.A.,The Cyprus Institute of Neurology and Genetics
Current Neuropharmacology | Year: 2011
Ion channels are complex transmembrane proteins that orchestrate the electrical signals necessary for normal function of excitable tissues, including the central nervous system, peripheral nerve, and both skeletal and cardiac muscle. Progress in molecular biology has allowed cloning and expression of genes that encode channel proteins, while compara- ble advances in biophysics, including patch-clamp electrophysiology and related techniques, have made the functional assessment of expressed proteins at the level of single channel molecules possible. The role of ion channel defects in the pathogenesis of numerous disorders has become increasingly apparent over the last two decades. Neurological channelo- pathies are frequently genetically determined but may also be acquired through autoimmune mechanisms. All of these autoimmune conditions can arise as paraneoplastic syndromes or independent from malignancies. The pathogenicity of autoantibodies to ion channels has been demonstrated in most of these conditions, and patients may respond well to immunotherapies that reduce the levels of the pathogenic autoantibodies. Autoimmune channelopathies may have a good prognosis, especially if diagnosed and treated early, and if they are non-paraneoplastic. This review focuses on clinical, pathophysiologic and therapeutic aspects of autoimmune ion channel disorders of the nervous system. © 2011 Bentham Science Publishers.
Papacostas S.S.,The Cyprus Institute of Neurology and Genetics
Hippokratia | Year: 2015
Background: Sudden unexpected death in epilepsy (SUDEP) affects 0.09-9.3 per 1,000 person-years depending on the population studied and constitutes the most common cause of death in people with epilepsy. The purpose of this study was to analyze epidemiological data of patients with SUDEP, identify possible risk factors in the population of a tertiary referral center and provide a review of the literature aiming to raise awareness of this phenomenon. Methods: Data for this study originate from the records of the Cyprus Institute of Neurology and Genetics in Nicosia Cyprus. We performed a systematic review of patients with epilepsy who had died between 1997 and 2012 and identified those whose death circumstances met the definition of SUDEP. Information was collected regarding sex, age, type of seizures, anti-epileptic therapies, and circumstances of death. Ethical approval was obtained from the institutional medical ethics committee. Results: Four hundred and forty four new patients were diagnosed with epilepsy among referrals to the epilepsy clinic and were followed to the end of the study period. Seven patients, six males, were identified who met criteria for SUDEP. The average age was 30 years. All patients had had either primary or secondary tonic-clonic seizures. Most were on polypharmacy, and two had Vagus Nerve Stimulation implanted. Most deaths were unwitnessed and nocturnal. The overall incidence rate for SUDEP in this population was 2.13 deaths/1000 person-years. Overall Cumulative Incidence (or lifetime risk) was calculated at 15.76 SUDEP deaths/1,000 patients.Conclusions: In our series, SUDEP was primarily a nocturnal and unwitnessed event that affected primarily young males. Among both males and females patients, 36.8% of all deaths were due to SUDEP. The major risk factor identified was the occurrence of generalized tonic-clonic seizures signifying that every effort should be made to control this type of seizures. © 2015, Lithografia Antoniadis I - Psarras Th G.P. All rights reserved.
Demetriou C.A.,Imperial College London |
Demetriou C.A.,The Cyprus Institute of Neurology and Genetics |
Vineis P.,Imperial College London
Journal of Thoracic Disease | Year: 2015
The association between ambient air pollution (AAP) exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution can cause lung cancer. Biomarkers can enhance research on the health effects of air pollution by improving exposure assessment, increasing the understanding of mechanisms, and enabling the investigation of individual susceptibility. In this review, we assess DNA adducts as biomarkers of exposure to AAP and early biological effect, and DNA methylation as biomarker of early biological change and discuss critical issues arising from their incorporation in AAP health impact evaluations, such as confounding, individual susceptibilities, timing, intensity and duration of exposure, and investigated tissue. DNA adducts and DNA methylation are treated as paradigms. However, the lessons, learned from their use in the examination of AAP carcinogenicity, can be applied to investigations of other biomarkers involved in AAP carcinogenicity. © Journal of Thoracic Disease.