Day 3 :
- Respiratory Tract Infections
Prevention, Cure and Control Management of Lung Disorders
Session Introduction
Amarjit Mishra
National Institutes of Health, USA
Title: Dendritic cell specific DNA-dependent protein kinase mediates Th2 airway inflammatory responses to house dust mite
Time : 09:30-10:00
Biography:
Amarjit Mishra is a Postdoctoral at Laboratory of Asthma and Lung Inflammation working in National Institutes of Health, USA
Abstract:
The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. DNA-dependent protein kinase (DNA-PK) is a nuclear protein serine/threonine kinase that acts as a molecular sensor in DNA damage and mediates ligation of double stranded DNA break repair, V (D) J recombination and telomere stabilization. Yet, the role of DNA-PK in Th2 immune responses to allergic asthma remains to be completely elucidated. Since DNA-PK can regulate innate immunity and pro-inflammatory signaling pathways, we hypothesized that it might also modulate adaptive Th2-mediated immune responses to house dust mite (HDM) antigen. In the present study, we report that DNA-PK regulates myeloid dendritic cell (DC)-dependent allergic sensitization and Th2 immune responses to HDM. We found that HDM induces DNA-PK phosphorylation in DCs via generation of reactive-oxygen species. Next, the adoptive transfer of HDM-pulsed CD11c+ bone marrow-derived DCs (BMDCs) from Prkdcscid mice or CD11c+ BMDCs from wild-type (WT) mice that had been treated with the pharmacologic DNA-PK inhibitor, NU-7441, or the Akt kinase inhibitor, GDC0068 had an impaired ability to induce HDM-specific airway inflammation in HDM-challenged WT recipient mice. This confirms that Akt is downstream of DNA-PK signaling in DCs. CD11c-specific deletion of DNA-PK in mice (DNA-PKfl/fl; CD11c-Cre) displayed a similar phenotype of reduced allergic sensitization and Th2-mediated airway inflammation as compared to DNA-PKcsfl/fl. In addition, adoptive transfer experiments using CD11b+myeloid DCs isolated from mediastinal lymph nodes of HDM-challenged DNA-PKfl/fl; CD11c-Cre mice to WT mice demonstrated impairment in antigen presentation that limits their ability to induce allergic sensitization and Th2-mediated airway inflammation. Moreover, feeding NU7441-containing chow before and after HDM-challenges to WT mice suppressed mucous cell metaplasia as well as airway inflammation and airway hyper-responsiveness. Our findings highlight a novel function for DNA-PK in myeloid DCs where it mediates antigen presentation and the induction of Th2 immune responses to HDM in the lung. Collectively, these data suggest that DNA-PK contributes to airway inflammation and that targeting DNA-PK kinase activity may be a noveltreatment approach for allergic asthma.
Ahmed Al-Jumaily
Auckland University of Technology, New Zealand
Title: Improvements on CPAP treatment for OSA
Time : 10:00-10:30
Biography:
Ahmed Al-Jumail did PhD and MSc from the Ohio State University and BSc from the University of Baghdad. He is a Fellow member of the ASME, and a member of 11 other international professional societies. He is the Editor of the ASME monograph series-Biomedical and Nanomedical Technologies and the Editor in Chief of the Journal of Biomedical Engineering and Technology, and has been on the editorial and refereeing boards for several international journals. He has published more than 270 papers in international journals and conference proceedings including two ASME books on Vibration and Acoustics in Biomedical Applications and a third one on CPAP devices. He has supervised more than 90 Postgraduate students in biomedical applications, vibrations, biomechanics, and electroactive polymers. During his academic career, he forged strong alliances between academia and industries; in particular in the medical devices area. His current research focuses on biomedical applications with particular interest in the application of vibration and acoustics to airways constriction therapies and artery non-invasive diagnostics.
Abstract:
Over the last three decades the continuous positive airway pressure (CPAP) method has been used as an effective tool for the treatment of obstructive sleep apnea (OSA). It provides air at an elevated pressure, which is normally called the titration pressure, through a nasal or facial mask, creating a pneumatic splint that keeps the pharyngeal upper airway (UA) open during inspiration and expiration. In spite of the CPAP therapy effectiveness, a number of drawbacks and negative impacts have been reported with its use. Over 45% of CPAP patients report negative side effects including discomfort, nasal irritation problems and some possible negative physiological impacts caused by the effect of CPAP on cerebral blood flow. The airway binary fluid layer and the structural characteristics of the UA have significant influence on the activity of the airway muscles by changing airway compliance and collapsibility during OSA. However, modulating the titration pressure has been reported to introduce some improvements to remedy some of these problems. This presentation shows how pressure oscillation can modulate the upper airways and improves airway compliance. Computer simulation and clinical trials have demonstrated that incorporating pressure oscillation helps to improve the UA muscle activities, allowing better air delivery and reducing the requirements for a relatively high titration pressure.
Janet M Urban
Tobacco Treatment and Wellness Services, USA
Title: What are the current facts and evidence-based theories about smoking cessation
Time : 10:55-11:25
Biography:
Janet M Urban is a lifelong resident of Central New York and currently resides in Nedrow. She holds an MS in Special Education and has taught for OCM BOCES for the past fifteen years. She holds certifications as a Tobacco Treatment Specialist from the Mayo Clinic Nicotine Dependence Center, Rochester, MN and as a Facilitator for the “Freedom from Smoking” program through the American Lung Association. She also holds certification as: Personal Trainer through WITS (World Instruction Training Schools), “Practical Yoga for Personal Trainers” and “Holistic Fitness Specialist” through the Academy of Holistic Fitness. She is also certified as a Work-Based Learning Coordinator through SUNY Buffalo. She provides individual consultations, customized treatment plans and group counseling smoking cessation services.
Abstract:
There is much literature on smoking cessation. As a future worker in the substance abuse field, it is necessary to gain insight into the facts, implications and treatments for smoking cessation. The website used for this paper is the most current on the topic as it enables an individual to earn clock hours toward their substance abuse certificate and to become certified in “Smoking Cessation”. Areas to be addressed in this paper include the following: Attitudes, values and beliefs about smoking, history of smoking, rationale for smoking, tobacco dependence and part 856; assessment, diagnosis and the CO monitor, stages of change readiness, and pharmacotherapy basics; motivational interviewing; cognitive behavioral therapy and relapse prevention; facilitating a tobacco awareness group; treatment planning basics; comorbidity and treating the whole patient
Bishoy Y A El-Aarag
Menoufia University, Egypt
Title: Anti-tumor effect of novel thalidomide dithiocarbamate analogs on human lung cancer A549 cells
Time : 11:25-11:55
Biography:
Dr. Bishoy El-Aarag has awarded PhD degree in the field of medical Biochemistry (Cancer Science and Therapy) through a scientific channel between Egypt (Menoufia University) and Japan (Okayama University). He works as a lecturer of Biochemistry at Faculty of Science, Menoufia University, Egypt.
Abstract:
Lung cancer is the leading cause of cancer-related mortality in the word and non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Numerous evidences had shown that thalidomide has potential for the inhibition and therapy of cancer. The present study aimed to investigate the anti-tumor effect of novel two thalidomide dithiocarbamate analogs towards human lung cancer A549 cells. The anti-proliferative, apoptotic and migration effects of lung cancer cells induced by thalidomide analogs were examined. Also, A549 cells were studied in tumor xenograft model. Our results revealed that thalidomide analogs exhibited anti-proliferative and apoptotic effect more than thalidomide itself. Also, analogs 1 and 2 suppressed the expression levels of VEGF165 by 42% and 53.25% and MMP-2 by 45% and 52% respectively. Moreover, thalidomide analogs 1 and 2 showed potent anti-tumor activity in vivo as they reduced the tumor volume by 30.11% and 53.52% respectively while thalidomide recorded 10.3% compared to vehicle control. Taken together, our study improved that thalidomide dithiocarbamate analogs are more potent anti-tumor and anti-angiogenic agents with more pronounced effect than thalidomide itself.
S M Rathnasiri Bandara
Teaching Hospital Gampola, Sri Lanka
Title: Migraine and respiratory disorders, consideration of sinus hypoxic nitric oxide theory: A review article
Time : 11:55-12:25
Biography:
S M Rathnasiri Bandara is pursuing his PhD in 2017 at Faculty of Medicine, University of Peradeniya in Sri Lanka on paranasal nitric oxide and migraine and working as second incharge in youth friendly clinic at Teaching Hospital Kandy, Sri Lanka. He has published 2 papers on hypoxic nitric oxide theory (SHNOT) for migraine and psychiatric disorders in a reputed journal. This was related to a new hypothesis connected to pranasal sinus nitric oxide and neuropsychiatric disorders. He also has served as the President of Human Protection Foundation in Sri Lanka since 2005.
Abstract:
Migraine is an extremely common disorder and has co morbidity with many respiratory illnesses. After reviewing the respiratory physiological, pathology of respiratory illnesses and association of biochemical basis on the research findings of migraine and respiratory disorders, I present to the best of my knowledge the first para-nasal sinus nitric oxide mediated respiratory biophysiological explanation for many respiratory disorders. The etiology of respiratory illnesses is mainly due to infections, immunological disturbances; degenerative changes in acute and chronic inflammation and effects of hypo NO levels and genetic predisposition. According to this para nasal sinus nitric oxide based description, those effects are mainly brought on by the excess sinorhinogenic NO (s NO) distribution of the upper and lower respiratory track except genetic predisposition. Indeed this article explains a new pathophysiological initiation between sinorhinogenic nitric oxide effects and respiratory disorders and provides an etiologically important neuro vascular impulse generating pathway to cause or aggravate migraine as well as respiratory disorders. Therefore the patients who are clinically suspected of having migraine headache and respiratorydisorders or along with susceptible respiratory disorders should receive comprehensive sinorhinological examination and evaluation based on the sinus hypoxic nitric oxide phenomena. A standard surgical and medical management of migraine that links with the sinus hypoxic nitric oxide theory are suggested to be used for even respiratory disorder as a new treatment to prevent or reduce aggravation or cure respiratory disorders locally and to prevent the dysfunction of central specific neural circuitsin migraine centrally. It warrants clinical testing.
Joanna Floros
The Penn State University, USA
Title: Differential regulation and function of SP-A1 and SP-A2: Proteins of lung innate immunity
Time : 12:25-12:55
Biography:
Joanna Floros completed her PhD and working as a Professor in department of Pediatrics and Obstetrics and Gynecology at The Penn State University, College of Medicine, Hershey PA, USA
Abstract:
Surfactant protein A(SP-A) plays an important role in innate immunity and surfactant-related functions. Dysregulation of immunity and/or surfactant function occur in most pulmonary diseases. Because levels and genetic variants of the surfactant protein A have been associated with susceptibility in several pulmonary diseases it is imperative that we understand their regulatory mechanisms with the hope of identifying points of therapeutic intervention. Two functional genes (hSP-A1; hSP-A2) encode SP-A in humans, and several genetic and splice variants have been identified for each gene. Functional and regulatory differences have been observed between hSP-A1 and hSP-A2. Both 5’ and 3’ untranslated regions (UTR) play important roles in the translational regulation and mRNA stability of SP-A1 and SP-A2. The 5’UTRs exhibit alternative splicing of untranslated exons resulting in different splice variants for hSP-A1 and hSP-A2, and the 3’UTRs exhibit sequence variability. The SP-A2 ABD/ABD’ 5’UTR contains exon B (eB) which is absent from the SP-A1 AD 5’UTR. eB is an enhancer of transcription and translation and contains cis regulatory elements. Specific trans-acting factors including several members of the 14-3-3 family of proteins bind eB and inhibition of specific members of the 14-3-3 family results in a decrease of the SP-A2 protein, but not SP-A1, indicating the role and specificity of 14-3-3 in the differential regulation of SP-A1 and SP-A2. Polymorphisms at the 3’UTR are involved in the regulation of SP-A1 and SP-A2 variants as these provide differential binding sites for miRNAs, noncoding RNAs, shown previously to regulate gene expression by affecting mRNA stability and/or translation. The available data indicate that both 5’ and 3’UTR are important regulators of SP-A1 and SP-A2 as these contain cis-elements for trans-acting protein and/or miRNA binding. A better understanding of the SP-A1 and SP-A2 may provide points for therapeutic intervention in disease where there is an SP-A-dependent derangement of innate immunity and/or surfactant. Because SP-A variants differentially affect the function and protein expression profile of the alveolar macrophage, the sentinel cell of lung innate immunity, the knowledge gained may further help to better understand macrophage functions such as phagocytosis and clearance of bacteria and inflammatory processes.
Uzoewulu Ngozi G
University of Benin,Nigeria
Title: Sensitivity of direct smear microscopy for the diagnosis of TB in high HIV prevalent population Nnewi
Biography:
Uzoewulu Ngozi G obtained his PhD in Medical Microbiology and Diploma in Medical Laboratory Science with specialty in Medical Parasitology from University of Benin, Edo state and University of Nigeria Enugu respectively. He is now working in Department of Medical Microbiology and Parasitology Nnamdi Azikiwe University Teaching Hospital Nnewi Anambra state, Nigeria as a Microbiologist.
Abstract:
Background: Diagnosis of tuberculosis (TB) amongst HIV patients is a great challenge due to the low density of Acid Fast bacilli (AFB) in their sputum. Objective: The study was conducted to determine the sensitivity of direct smear microscopy (DSM) for TB diagnosis in HIV endemic setting using culture as a gold standard. Method: Sputum specimen of 550 TB suspects were screened microscopically for AFB using Ziehl-Nielsen method at NAUTH Nnewi and positive samples subjected to culture on Lowenstein-Jensen medium with each patient also screened for HIV status. Result: They comprised of 238 (43%) DSM TB positive cases and 312 (57%) DSM TB negative cases. Out of 238 DSM TB positive cases, 180(33%) were culture positive cases with 12(2.1%) culture negative cases, 13(2.4%) contaminated specimen, 3(0.5%) NTM and 30(5.5%) lost specimen resulting in 58 (10.5%) specimen which were excluded from analysis respectively. Among the 180 culture positive TB cases 34(19%) were HIV-positive patients while 146(81%) were HIV Negative culture positive TB cases, 109(61%) males as compared to 71(39%) females within 21-40 years age group mostly affected. Findings from this study showed that the difference in the detection of PTB between these two methods was statistically significant (p=0.0001), identifying high sensitivity case detection rate of DSM as compared to specificity by culture detection more especially in HIV positive persons. Conclusion: To improve TB case detection for effective treatment, we recommend the use of culture as back up to enhance the specificity and accuracy of DSM especially in HIV positive persons.