Dimosthenis Lykouras

Bio: Dimosthenis Lykouras is an academic researcher from University of Patras. The author has contributed to research in topics: Obstructive sleep apnea & COPD. The author has an hindex of 10, co-authored 34 publications receiving 276 citations. Previous affiliations of Dimosthenis Lykouras include Guy's Hospital.

Human genes in TB infection : their role in immune response

Abstract: Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and Thelper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving.

The impact of obstructive sleep apnea syndrome severity on physical performance and mental health. The use of SF-36 questionnaire in sleep apnea.

Abstract: OBJECTIVES Obstructive sleep apnea syndrome (OSAS) is a common disorder defined by repeated episodes of airflow cessation (apneas)leading to arterial hypoxemia and sleep disruption. OSAS has been associated with increased morbidity, mortality and diminished quality of life so far. This cross-sectional study aimed to assess the impact of OSAS on patients' Quality of Life, as measured by the Medical Outcomes Study Short Form-36 (SF-36). PATIENTS AND METHODS Two hundred and forty five subjects referred to the sleep laboratory and underwent full polysomnography overnight. Prior to sleep study onset, we registered height and weight, medical history, smoking habit, drug consumption. Afterwards, each patient completed the SF-36. Eighty subjects not diagnosed with sleep apnea [apnea hypopnea index (AHI < 5)] were excluded. Therefore, 165 subjects (121 male and 44 female) remained. RESULTS AND CONCLUSIONS Statistical analysis revealed that in patients with respiratory disturbance index (RDI) ≥ 15, (n = 115), RDI was independently associated with lower performance in role limitations due to physical problems (p = 0.005). Additionally, RDI was the only factor associated with decreased vitality (p = 0.014) and mental health scores (p = 0.047). In the same patient subgroup, body mass index (BMI) and age were associated with poorer scores in physical functioning (p < 0.001 and p = 0.003, respectively). BMI was an independent clinical predictor of worse scores in bodily pain (p = 0.006) general health (p = 0.006), social functioning (p = 0.025) and role limitations due to emotional problems (p = 0.004).

DNA sequence variations of metalloproteinases: their role in asthma and COPD.

Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are complex genetic diseases that cause considerable morbidity and mortality worldwide. Genetic variability interacting with environmental and ethnic factors is presumed to cause tobacco smoke susceptibility and to influence asthma severity. A disintegrin and metalloproteinase 33 (ADAM33) and matrix metalloproteinase-9 (MMP9) appear to have important roles in asthma and COPD pathogenesis. ADAM33 and MMP9 genetic alterations could possibly contribute to the establishment and progression of these multifactorial diseases, although their association with the clinical phenotypes has not yet been elucidated. However, the occurrence of these alterations does not always result in clear disease, implying that either they are an epiphenomenon or they are in proximity to the true causative alteration. This review summarises the most recent literature dealing with the genetic variations of metalloproteinases and outlines their potential pathogenetic outcome.

The role of Endothelin-1 in obstructive sleep apnea syndrome and pulmonary arterial hypertension: pathogenesis and Endothelin-1 antagonists.

Abstract: Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.

Association of the adam33 gene with asthma and bronchial hyperresponsiveness

Abstract: Van Eerdewegh P, Little RD, Dupuis J, et al Nature 2002;418:426–430 To identify novel genetic polymorphisms associated with bronchial hyperresponsiveness (BHR) in asthma Four hundred sixty white affected sib-pair families from the United States and the United Kingdom with current asthma A genetic linkage analysis was performed for current asthma and BHR Case-control, transmission disequilibrium, and haplotype analyses were conducted to identify the gene(s) most commonly associated with asthma Novel genes of interest were …

Федеральное государственное бюджетное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний» Сибирского отделения Российской академии медицинских наук, Кемерово, Россия

Abstract: Results. The incidence rate of significant non-cardiac occlusive stenotic lesions in patients with coronary artery disease (CAD), who had to undergo CABG, was 15,84 %. Simultaneous revascularization of coronary and non-coronary arteries was performed in 2,46 % of patients with CAD and PolyVD and multi-stage surgical proced ures were chosen in other cases. Conclusions. The outcomes of CAD surgical treatment were improved in this group of patients due to the implementation of a mul-

Endothelin-1 gene regulation

Abstract: Over two decades of research have demonstrated that the peptide hormone endothelin-1 (ET-1) plays multiple, complex roles in cardiovascular, neural, pulmonary, reproductive, and renal physiology. Differential and tissue-specific production of ET-1 must be tightly regulated in order to preserve these biologically diverse actions. The primary mechanism thought to control ET-1 bioavailability is the rate of transcription from the ET-1 gene (edn1). Studies conducted on a variety of cell types have identified key transcription factors that govern edn1 expression. With few exceptions, the cis-acting elements bound by these factors have been mapped in the edn1 regulatory region. Recent evidence has revealed new roles for some factors originally believed to regulate edn1 in a tissue or hormone-specific manner. In addition, other mechanisms involved in epigenetic regulation and mRNA stability have emerged as important processes for regulated edn1 expression. The goal of this review is to provide a comprehensive overview of the specific factors and signaling systems that govern edn1 activity at the molecular level.—Stow, L. R., Jacobs, M. E., Wingo, C. S., Cain, B. D. Endothelin-1 gene regulation.

Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review.

Abstract: It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, suggests that this is biologically plausible, particularly in the light of the current understanding of asthma as a complex disease with a variety of phenotypes. The epidemiological evidence for associations between ambient levels of air pollutants and asthma prevalence at a whole community level is unconvincing; meta-analysis confirms a lack of association. In contrast, a meta-analysis of cohort studies found an association between asthma incidence and within-community variations in air pollution (largely traffic dominated). Similarly, a systematic review suggests an association of asthma prevalence with exposure to traffic, although only in those living very close to heavily trafficked roads carrying a lot of trucks. Based on this evidence, the UK's Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic. Nonetheless, the effect on public health is unlikely to be large: air pollutants are likely to make only a small contribution, compared with other factors, in the development of asthma, and in only a small proportion of the population.

Epidemiology of chronic obstructive pulmonary disease

Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability in many countries over the world. Prevalence of COPD is difficult to evaluate because of clinical similarity to bronchial asthma, and changes in diagnostic standards. Actually about 8-35% patients are suffering because of COPD. In Poland this problem was described only in some regional trials. For this reason the program for prevalence of COPD has to be established according to contemporary diagnostic and therapeutic standards.