Acute stress induces voluntary alcohol intake in mice through anxiety mitigated by toll-like receptor 4 antagonist

Event Abstract Back to Event A study on optimal concentrations of isodiospyrin putative inhibitory actions against exonic splicing enhancers of Dystrophin gene exon 53 skipping in Duchenne Muscular Dystrophy Hussain S. Alzahrani1*, Roslina Rashid2, Muzaimi Mustapha1 and Teguh H. Sasongko2 1 Universiti Sains Malaysia, Department of Neuroscience, School of Medical Sciences, Health Campus, Malaysia 2 Universiti Sains Malaysia, Human Genome Center, School of Medical Sciences, Health Campus, Malaysia Duchene muscular dystrophy (DMD) is an X-linked recessive disorder. It is characterized by rapid loss of muscular tissues due lacking gene of muscle replacement. The DMD gene is responsible for Dystrophin protein expression, which exists within a complex called Dystrophin glycol-protein complex (DGC). Exon mutations within DMD gene cause defective expression of Dystrophin. This study aimed to determine the inhibitory actions of Isodiospyrin targeting splicing factors and SR protein (Serine-arginine rich amino acids) a known topoisomerase inhibitor, which plays a critical role in splice site selection. previous studies demonstrated that Isodiospyrin has antitumor activity and inhibits topoisomerase enzyme from phosphorylating SF2/ASF splicing factor. In the current study we used plasmid of non-mutated exon 53 minigenes, transfected into non-mutated HEK-293 cell lines. Then, observed its actions on cells viability and exon splicing modification. The later was confirmed using RT-PCR, followed by exon 53 sequence software analysis. In consistence with previous studies, concentration of half maximal inhibitory effect (IC50) was 3.58µM, and the optimal inhibitory concentrations were: 1.79, 0.90, and 0.60µM. However, there was no detection of exon 53 skipping when exposing non-mutated HEK-293 cells to the optimal concentrations of Isodiospyrin compound. The results suggest that exon 53 splicing may occur without phosphorylation of SR proteins targeted by Isodiospyrin, which indicated that the splicing of exon 53 occurred independently of SR proteins targeted by the splicing inhibitor Isodiospyrin ,in non-mutated HEK-293 cells. Keywords: Gene Expression, inhibition, in vitro, Exon splicing, Duchenne muscular dystrophy Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Alzahrani HS, Rashid R, Mustapha M and Sasongko TH (2016). A study on optimal concentrations of isodiospyrin putative inhibitory actions against exonic splicing enhancers of Dystrophin gene exon 53 skipping in Duchenne Muscular Dystrophy. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00120 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. Hussain S Alzahrani, Universiti Sains Malaysia, Department of Neuroscience, School of Medical Sciences, Health Campus, Kota Bharu, Kelantan, 16150, Malaysia, hssz_23@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Google Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Google Scholar Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko PubMed Hussain S Alzahrani Roslina Rashid Muzaimi Mustapha Teguh H Sasongko Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Rodent models have explored the transition from controlled goal-directed consumption to habitual/compulsive intake using different procedures. This study evaluates the effect of concurrent presentation of sucrose on alcohol intake using two models that induce high levels of alcohol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and/or stress. In Experiment 1, male mice were exposed to four cycles of CIE or control (air) exposure, and once an increase in voluntary alcohol was observed in CIE mice, mice were offered a choice between alcohol or increasing concentrations of sucrose (from 0.75% to 12%; w/v). In Experiment 2, male mice experienced three cycles of CIE exposure, CIE and forced swim stress, control (air) exposure, or forced swim stress. Once elevated voluntary alcohol intake was observed in mice that experienced both CIE and stress, mice were presented with a choice between alcohol and sucrose (from 1.5% to 6%, w/v increased over consecutive days). Mice that experienced CIE exposure (Experiment 1) or CIE exposure and stress (Experiment 2) showed increased alcohol intake. In Experiment 1, the presentation of sucrose at 3% and 12% reduced alcohol intake in control mice. Only the two highest concentrations of sucrose (6% and 12%) affected alcohol intake in CIE-exposed mice. In Experiment 2, concurrent presentation of a 6% sucrose solution decreased alcohol intake in mice that experienced CIE, stress, or control exposure; however, the presentation of sucrose did not influence alcohol intake in mice that experienced both CIE and stress. The amount of sucrose consumed did not differ between groups in both experiments. These experiments showed that mice that had experienced repeated CIE exposure alone or in combination with stress were more prone to continue their high levels of alcohol intake despite the presence of a sucrose solution as an alternative.

The quinoline compound, S4 effectively antagonizes alcohol intake in mice: Possible association with the histone H3 modifications

Alcohol use disorder (AUD) is a chronic condition associated with devastating socioeconomic consequences. Yet, pharmacotherapies to treat behavioral phenotypes such as uncontrolled heavy drinking are limited. Studies in rodents suggest that the mammalian target of rapamycin complex 1 (mTORC1) plays an important role in mechanisms underlying alcohol drinking behaviors as well as alcohol seeking and relapse. These preclinical evidence suggest that mTORC1 may be a therapeutic target for the treatment of AUD. Thus, the aim of the present study was to test the potential use of newly developed mTORC1 inhibitors, RapaLink-1 and MLN0128, in preclinical mouse models of AUD. First, we used the intermittent access to 20 percent alcohol in a two-bottle choice paradigm and tested the efficacy of the drugs to reduce alcohol intake in mice with a history of binge drinking and withdrawal. We found that both inhibitors reduce excessive alcohol intake and preference with RapaLink-1 exhibiting higher efficacy. We further observed that RapaLink-1 attenuates alcohol consumption during the first alcohol-drinking session in naïve mice, and interestingly, the effect was still present 14days after the initial treatment with the drug. We also found that RapaLink-1 did not alter the consumption of water or saccharin, revealing a specific effect of the inhibitor on alcohol intake. Finally, we report that RapaLink-1 blocks the retrieval but not acquisition of alcohol place preference without affecting locomotion. Together, our findings suggest that RapaLink-1 may be developed as a new medication to treat and prevent the development of AUD.

Department of Orthopaedics, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia Correspondence to Abdul R. Sulaiman, MD, Department of Orthopaedics, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia Tel: +60 976 76398; fax: +60 976 53370; e-mail: [email protected]

Cyclic AMP (cAMP)-dependent signaling is highly implicated in the pathophysiology of alcohol use disorder (AUD), with evidence supporting the efficacy of inhibiting the cAMP hydrolyzing enzyme phosphodiesterase 4 (PDE4) as a therapeutic strategy for drinking reduction. Off-target emetic effects associated with non-selective PDE4 inhibitors has prompted the development of selective PDE4 isozyme inhibitors for treating neuropsychiatric conditions. Herein, we examined the effect of a selective PDE4B inhibitor A33 (0–1.0 mg/kg) on alcohol drinking in both female and male mice from two genetically distinct C57BL/6 substrains. Under two different binge-drinking procedures, A33 pretreatment reduced alcohol intake in male and female mice of both substrains. In both drinking studies, there was no evidence for carry-over effects the next day; however, we did observe some sign of tolerance to A33’s effect on alcohol intake upon repeated, intermittent, treatment (5 injections of 1.0 mg/kg, every other day). Pretreatment with 1.0 mg/kg of A33 augmented sucrose intake by C57BL/6NJ, but not C57BL/6J, mice. In mice with a prior history of A33 pretreatment during alcohol-drinking, A33 (1.0 mg/kg) did not alter spontaneous locomotor activity or basal motor coordination, nor did it alter alcohol’s effects on motor activity, coordination or sedation. In a distinct cohort of alcohol-naïve mice, acute pretreatment with 1.0 mg/kg of A33 did not alter motor performance on a rotarod and reduced sensitivity to the acute intoxicating effects of alcohol. These data provide the first evidence that selective PDE4B inhibition is an effective strategy for reducing excessive alcohol intake in murine models of binge drinking, with minimal off-target effects. Despite reducing sensitivity to acute alcohol intoxication, PDE4B inhibition reduces binge alcohol drinking, without influencing behavioral sensitivity to alcohol in alcohol-experienced mice. Furthermore, A33 is equally effective in males and females and exerts a quantitatively similar reduction in alcohol intake in mice with a genetic predisposition for high versus moderate alcohol preference. Such findings further support the safety and potential clinical utility of targeting PDE4 for treating AUD.

Extensively Drug-Resistant Mycobacterium tuberculosis in Kelantan East Coast of Malaysia: First Two Cases

Journal Article Pneumonia, Pericarditis, and Endocarditis in a Child with Corynebacterium xerosis Septicemia Get access A. S. Malik, A. S. Malik Department of Paediatrics and Microbiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Reprints or correspondence: Dr. Alam Sher Malik, Department of Paediatrics, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150 Kelantan, Malaysia. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. R. Johari M. R. Johari Department of Paediatrics and Microbiology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 20, Issue 1, January 1995, Pages 191–192, https://doi.org/10.1093/clinids/20.1.191-a Published: 01 January 1995

Ivermectin (IVM), an FDA approved anthelmintic agent, can significantly reduce ethanol intake in mice following acute administration. The current study evaluates the sustainability and safety of multiday IVM administration in reducing 10% v/v ethyl alcohol (10E) intake in mice at a dose shown to be safe in humans. We tested the effect of 10-day administration of IVM (3.0 mg/kg/day; intraperitoneally) on reducing 10E intake in C57BL/6J mice using a 24-h, two-bottle choice paradigm. On the 10th day of IVM administration, mice were sacrificed at 0, 0.5, 2, 8, 32, 48, and 72 h after injection. Brain tissue and plasma samples were collected and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Analysis of variance (ANOVA) was used to assess the effect of 10-day IVM administration on 10E intake, 10E preference, water intake, and total fluid intake with Dunnett's multiple comparison post-hoc test. Individual Student's t-tests were also used to further quantify changes in these dependent variables. IVM significantly decreased 10E intake over a 9-day period (P<0.01). Pre-IVM 10E intake was 9.1±3.2 g/kg/24 h. Following the 9th day of IVM injections, intake dropped by almost 30% (P<0.05). IVM had no effect on total water intake or mouse weight throughout the study; however, there was a significant decrease in both preference for 10E (P<0.01) and total fluid intake (P<0.05). Multiday administration of IVM significantly reduces 10E intake and preference in animals without causing any apparent adverse effects at a dose shown to be safe in humans.

Background: The weekly held clinical pathologic case conference popularly known as CPC provides an effective and regular educational media of collaborative learning for inter-disciplinary exchange of knowledge among the faculty members of an institution. CPC has been routinely practiced for the last two decades in School of medical Sciences (SMS) at Universiti Sains Malaysia (USM). An hour session primarily involves a case presentation hiding the diagnosis followed by discussion on differential diagnosis and floor interaction on interesting clinical cases. It also gives an opportunity to new teaching staff in the institution to experience an in-house practice of presenting the clinical cases; witch can readily be reproduced as a case report for publication. An effort to follow the original format of CPC is comprehended as an essential outcome of this study to keep up the sanctity of CPC as a case method of learning medicine in future. Methodology: A questionnaire-based survey was recently conducted to evaluate the weekly held CPC in SMS. It was a cross sectional survey in which a questionnaire comprising of 23 items was administered to a targeted population of faculty members of School of Medical Sciences. The items in questionnaire were grouped into 5 clusters. All respondents were adequately briefed through a letter addressing the objectives and importance of survey and its appraisal aiming to revamp the CPC guided by the out-come of study. Questionnaires were administered to 240 academic staff, covering > 80% of the target population of 294 faculty members. 159 (66.2%) members of sample population completed the questionnaires. Total non-responses were 81 (33.7%) and item non-responses were 320 (8.7%) Result: All the items in questionnaire were found significant ( p 0.016) except those two items related to, observing a difference in preparing for a case presentation verses a formal CPC presentation and its promotion ( p 0.556 and 0.197 respectively). It was also established that the major respondents were unaware of the original format of CPC ( p 0.003) in which a presenter select and prepares a case, which is discussed with participating faculty members for its differential diagnoses. 51.6% faculty members did not follow the formal CPC format (p 0.016) in their presentations. A lack of awareness about the format of CPC was shown by (61.0%) faculty members ( p 0.003). Conclusion : It was concluded that emphasis to discuss the differential diagnosis by a competent discussant was lacking, as presenters did not follow the formal CPC format. It was critically observed that a number of presentations made in this weekly program deviate from the original format adapted by SMS in USM. However, the out-come appraisal of this survey was the pledge shown by the majority faculty members to adapt the guidelines as a reverence to the formal CPC format.

© www.eduimed.com | e1 CORRESPONDING AUTHOR: Prof. Dr. Rogayah Ja’afar, Department of Medical Education, School of Medical Sciences, Universiti Sains Malaysia, 1650, Kubang Kerian, Kelantan, Malaysia. Email: rogayah@kb.usm.my © Medical Education Department, School of Medical Sciences, Universiti Sains Malaysia. All rights reserved. Two decades of championing faculty development: Is it worth the effort?

FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest

Event Abstract Back to Event Evaluation of human amniotic membrane as a scaffold for periodontal tissue engineering: An in vitro study Asrar Elahi1*, Haslina Taib1, Zurairah Berahim1, Azlina Ahmad2 and Suzina S. AbHamid3 1 Universiti Sains Malaysia, Periodontics Unit, School of Dental Sciences, Malaysia 2 Universiti Sains Malaysia, Molecular Biology, School of Dental Sciences, Malaysia 3 Universiti Sains Malaysia, Tissue Bank, School of Medical Sciences, Malaysia Human amniotic membrane (HAM) has many biological properties suitable for periodontal tissue regeneration such as low immunogenicity, anti-fibrosis, anti-inflammation and rich in extracellular matrix component. It is biocompatible and provides good characteristic for cells attachment and proliferation. It has been used as a scaffold/substrate for periodontal ligament stem cells (PDLSCs)[1], human adipose-derived stem cells (ADSCs)[2], periosteal-derived cell sheet[3] and human dental pulp-derived cells[4. This study aimed to evaluate the ability of this membrane as a scaffold for the growth of the main cells in periodontal regeneration, human periodontal ligament fibroblasts (hPDLFs). In this study, commercially available hPDLFs (Lonza, USA) were cultured in α-MEM till passage 6. The hPDLFs (5.0×104 cells) were then seeded on 1 cm2 glycerol preserved HAM (USM Tissue Bank, Malaysia) in 6-well plate at 37°C with 5% CO2. HAM only was used as a control. Proliferation test using alamarBlue® assay was done for the assessment of cell viability and the hPDLFs attachment and proliferation were observed through scanning electron microscopy (SEM) analysis at day 1, 3, 7, 14 and 21. P<0.05 was considered as significant. The proliferation assay showed that hPDLFs viability on HAM had increased significantly compared to control from day 3 to 7 (p=0.003) (Table 1). However, the proliferation of cells on HAM showed significant reduction at day 14 (p=0.002) and day 21 (p=0.005). SEM analysis demonstrated that hPDLFs had attached appropriately on HAM surface at day 1 to day 3 and became overlapping at day 7, while maintaining their flat shape (Fig. 1). Consistent with the reduction of cell activities, some of the cells demonstrated alteration in their morphology and later became rounded at day 14 and 21. This study showed that HAM is able to function well as a scaffold for hPDLFs within 7 days. Retardation of cellular growth later on could be due to possible reason such as density dependent inhibition of growth[5] which may eventually lead to cell death and detachment. In conclusion, the findings suggest that HAM could be a promising scaffold for periodontal regeneration. However, cells’ behaviour in relation to the membrane over longer culture duration requires further investigations. Figure 1 Acknowledgements This research was supported by Universtiti Sains Malaysia Research Universiti Grant (1001/PPSG/812168). Keywords: Regeneration, Tissue Engineering, Tissue Scaffolds, Amniotic membrane, Periodontal Conference: 6th Malaysian Tissue Engineering and Regenerative Medicine Scientific Meeting (6th MTERMS) 2016 and 2nd Malaysian Stem Cell Meeting, Seberang Jaya, Penang, Malaysia, 17 Nov - 18 Nov, 2016. Presentation Type: Oral Topic: Biomaterials and Tissue Regeneration Citation: Elahi A, Taib H, Berahim Z, Ahmad A and AbHamid SS (2016). Evaluation of human amniotic membrane as a scaffold for periodontal tissue engineering: An in vitro study. Front. Bioeng. Biotechnol. Conference Abstract: 6th Malaysian Tissue Engineering and Regenerative Medicine Scientific Meeting (6th MTERMS) 2016 and 2nd Malaysian Stem Cell Meeting. doi: 10.3389/conf.FBIOE.2016.02.00021 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Dec 2016; Published Online: 19 Dec 2016. * Correspondence: Dr. Asrar Elahi, Universiti Sains Malaysia, Periodontics Unit, School of Dental Sciences, Kubang Kerian, Kelantan, 16150, Malaysia, asrarelahi@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Asrar Elahi Haslina Taib Zurairah Berahim Azlina Ahmad Suzina S AbHamid Google Asrar Elahi Haslina Taib Zurairah Berahim Azlina Ahmad Suzina S AbHamid Google Scholar Asrar Elahi Haslina Taib Zurairah Berahim Azlina Ahmad Suzina S AbHamid PubMed Asrar Elahi Haslina Taib Zurairah Berahim Azlina Ahmad Suzina S AbHamid Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The School of Medical Sciences of Universiti Sains Malaysia (USM) is the launching pad for this journal. From the school’s humble beginning at the USM Main Campus in Pulau Pinang, Malaysia, it has grown in stature at its current location in the USM Health Campus, Kubang Kerian, Kelantan, Malaysia. Commemorating its 40th anniversary, this editorial aims to recollect, although not exhaustively, the wealth of returns for the USM, as well as for the nation, which the school has managed to deliver in that period. Resolute to its vision and mission, this article highlights the outstanding accomplishments in various core aspects of the school’s academic, research and professional growth as we continually strive to train globally competitive and compassionate medical graduates, medical specialists and scientists, skilled to serve nation’s needs and broader markets worldwide. Currently guided by the Malaysian Higher Education Blueprint (2015–2025), the school shall remain ingenious in its duties in the many more years to come, as we head for a world-class trajectory.

A cross-sectional study to assess job strain and its associated factors among lecturers of the School of Medical Sciences, Universiti Sains Malaysia (USM) and Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM) was undertaken between August 2001 and May 2002. The original English version of the Job Content Questionnaire (JCQ) version 1.7 (revised 1997) by Robert Karasek based on the Job Strain Model was self-administered to 73 (response rate 58.4%) and 80 (response rate 41.7%) lecturers in the medical faculties of USM and UKM respectively. The prevalence of job strain (defined by low decision latitude and high psychological demand) in USM and UKM was 23.3% and 17.5%, respectively; the difference was not significant (p 2 0.05). Analysis showed that the associated factors of job strain in USM lecturers were psychological stressors (adjusted OR 1.2, 95% CI: 1.0, 1.4), created skill (adjusted OR 0.4, 95% CI: 0.2, 0.8), working in clinical-based departments (adjusted OR 18.9, 95% CI: 1.6, 22.7). The risk factors of job strain in UKM lecturers were created skill (adjusted OR 0.3, 95% CI: 0.1, 0.9), psychological stressors (adjusted OR 1.2, 95% CI: 1.0, 1.5) and co-worker support (adjusted OR 0.3, 95% CI: 0.1, 0.9). We conclude psychological stressors and created skill were nonprotective and protective, respectively, against job strain in both USM and UKM lecturers.