Displaying publications 181 - 200 of 292 in total

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  1. Fulltext Brain-Derived Neurotrophic Factor-Mediated Neuroprotection in Glaucoma: A Review of Current State of the Art
    Lambuk L, Mohd Lazaldin MA, Ahmad S, Iezhitsa I, Agarwal R, Uskoković V, et al.
    Front Pharmacol, 2022;13:875662.
    PMID: 35668928 DOI: 10.3389/fphar.2022.875662
    Retinal ganglion cells (RGCs) are neurons of the visual system that are responsible for transmitting signals from the retina to the brain via the optic nerve. Glaucoma is an optic neuropathy characterized by apoptotic loss of RGCs and degeneration of optic nerve fibers. Risk factors such as elevated intraocular pressure and vascular dysregulation trigger the injury that culminates in RGC apoptosis. In the event of injury, the survival of RGCs is facilitated by neurotrophic factors (NTFs), the most widely studied of which is brain-derived neurotrophic factor (BDNF). Its production is regulated locally in the retina, but transport of BDNF retrogradely from the brain to retina is also crucial. Not only that the interruption of this retrograde transport has been detected in the early stages of glaucoma, but significantly low levels of BDNF have also been detected in the sera and ocular fluids of glaucoma patients, supporting the notion that neurotrophic deprivation is a likely mechanism of glaucomatous optic neuropathy. Moreover, exogenous NTF including BDNF administration was shown reduce neuronal loss in animal models of various neurodegenerative diseases, indicating the possibility that exogenous BDNF may be a treatment option in glaucoma. Current literature provides an extensive insight not only into the sources, transport, and target sites of BDNF but also the intracellular signaling pathways, other pathways that influence BDNF signaling and a wide range of its functions. In this review, the authors discuss the neuroprotective role of BDNF in promoting the survival of RGCs and its possible application as a therapeutic tool to meet the challenges in glaucoma management. We also highlight the possibility of using BDNF as a biomarker in neurodegenerative disease such as glaucoma. Further we discuss the challenges and future strategies to explore the utility of BDNF in the management of glaucoma.
  2. Fulltext Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1β -/- hearts
    Ahmad S, Valli H, Edling CE, Grace AA, Jeevaratnam K, Huang CL
    Pflugers Arch, 2017 Dec;469(12):1579-1590.
    PMID: 28821956 DOI: 10.1007/s00424-017-2054-3
    A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β -/- mice. Simultaneous electrocardiographic and intracellular microelectrode recordings were made through successive trains of 100 regular stimuli at progressively incremented heart rates. Aged Pgc-1β -/- hearts displayed an increased incidence of arrhythmia compared to other groups. Young and aged Pgc-1β -/- hearts showed higher incidences of alternans in both AP activation (maximum AP upshoot velocity (dV/dt)max and latency), recovery (action potential duration (APD90) and resting membrane potential (RMP) characteristics compared to WT hearts. This was particularly apparent at lower pacing frequencies. These findings accompanied reduced (dV/dt)max and increased AP latency values in the Pgc-1β -/- hearts. APs observed prior to termination of the protocol showed lower (dV/dt)max and longer AP latencies, but indistinguishable APD90 and RMPs in arrhythmic compared to those in non-arrhythmic hearts. APD restitution analysis showed that Pgc-1β -/- and WT hearts showed similar limiting gradients. However, Pgc-1β -/- hearts had shortened plateau AP wavelengths, particularly in aged Pgc-1β -/- hearts. Pgc-1β -/- hearts therefore show pro-arrhythmic instabilities attributable to altered AP conduction and activation rather than recovery characteristics.
  3. A randomized control trial evaluating the prevalence of obstetrical anal sphincter injuries in primigravida in routine versus selective mediolateral episiotomy
    Sulaiman AS, Ahmad S, Ismail NA, Rahman RA, Jamil MA, Mohd Dali AZ
    Saudi Med J, 2013 Aug;34(8):819-23.
    PMID: 23974453
    To evaluate the prevalence of obstetrical anal sphincter injuries (OASIS), which include third and fourth degree perineal tears in primigravida in routine versus selective mediolateral episiotomy. Secondly, to determine the rate of episiotomy in local settings.
  4. Fulltext Highlighting the forgotten: Tuberculosis amidst the humanitarian crisis and COVID-19 in Afghanistan
    Essar MY, Nemat A, Ahmad S, Zil-E-Ali A, Marzo RR, Head M
    Ann Med Surg (Lond), 2022 May;77:103671.
    PMID: 35502225 DOI: 10.1016/j.amsu.2022.103671
  5. Acetylsalicylic acid-sulfa drugs conjugates as potential urease inhibitors and anti-inflammatory agents: bio-oriented drug synthesis, molecular docking, and dynamics simulation studies
    Ahmad S, Abdul Qadir M, Ahmed M, Imran M, Yousaf N, Asari A, et al.
    J Biomol Struct Dyn, 2023 Aug 29.
    PMID: 37643014 DOI: 10.1080/07391102.2023.2252083
    To explore the new mode of action and reduce side effects, making conjugates of existing drugs is becoming an attractive tool in the realm of medicinal chemistry. In this work, we exploited this approach and synthesized new conjugates to assess their activities against the enzymes involved in different pathological conditions. Specifically, we design and synthesized conjugates involving acetylsalicylic acid and sulfa drugs, validating the newly crafted conjugates using techniques like IR, 1HNMR, 13CNMR, and elemental analysis. These conjugates underwent assessment for their ability to inhibit cyclooxygenase-2 (COX-2), urease enzymes, and their anti-inflammatory potential. A competitive mode of urease inhibition was observed for acetylsalicylic acid conjugated with sulfanilamide, sulfacetamide, and sulfadiazine with IC50 of 2.49 ± 0.35 µM, 6.21 ± 0.28 µM, and 6.57 ± 0.44 µM, respectively. Remarkably, the acetylsalicylic acid-sulfamethoxazole conjugate exhibited exceptional anti-inflammatory activity, effectively curtailing induced edema by 83.7%, a result akin to the reference anti-inflammatory drug indomethacin's performance (86.8%). Additionally, it demonstrated comparable COX-2 inhibition (75.8%) to the reference selective COX-2 inhibitor celecoxib that exhibited 77.1% inhibition at 10 µM concentration. To deepen our understanding, we employed molecular docking techniques to predict the binding interactions of competitive inhibitors with COX-2 and urease receptors. Additionally, MD simulations were carried out, confirming the stability of inhibitor-target complexes throughout the simulation period, devoid of significant conformational changes. Collectively, our research underscores the potential of coupling approved medicinal compounds to usher in novel categories of pharmacological agents, holding promise for addressing a wide spectrum of pathological disorders involving COX-2 and urease enzymes.Communicated by Ramaswamy H. Sarma.
  6. First Report of Fruit Rot Caused by Fusarium incarnatum-equiseti species complex on Greenhouse Bell Pepper in Malaysia
    Ishak NF, Wan Azhar WMA, Ahmad S, Khairuddin AU, Laboh R
    Plant Dis, 2023 Oct 19.
    PMID: 37858968 DOI: 10.1094/PDIS-06-23-1076-PDN
    In Malaysia, bell pepper (Capsicum annuum var. grossum), also known as sweet pepper or paprika, is one of the highly imported vegetable crops. In 2021 alone, Malaysia imported nearly 74 thousand metric tons of its chilies, including bell peppers, from other countries (DOSM, 2022). Often, farmers grow the bell peppers in moderate to cool conditions within highland regions for local commercial purposes. In June 2022, the Malaysian Agricultural Research and Development Institute (MARDI) in Serdang, Selangor, conducted a research study to grow lowland bell peppers under a glasshouse rain protection system. A disease inspection carried out found fruit rot on approximately 30% of mature bell pepper fruits in the greenhouse. Symptoms appeared as firm and sunken black lesions covered with white to light pink spore masses on the outer surface, which eventually fell off. Infected fruit parts were disinfected with 10% hypochlorite (NaOCl) for 2 min, followed by double washing with sterile distilled water, air-dried, and placed onto potato dextrose agar (PDA). After 3 days of incubation, the fungal colonies that grew from the symptomatic tissue pieces were transferred onto new PDA to obtain pure cultures. The pure fungal colony appeared dense, whitish aerial mycelium that slowly became cream to pinkish-orange after 7 days of incubation at room temperature (25±2 °C). To examine the morphology features, the pure cultures were subbed onto carnation leaf agar (CLA) and incubated at 25±2°C for 14 days. Macroconidia were abundant, slightly curved with tapered apical cells, 3- to 5-septate, and ranged between 21.8 and 34.0 x 3.0 and 5.1 μm. Microconidia were single-celled, often 1-septate, and ranged between 10.0 and 12.6 x 2.1 and 3.4 μm. Chlamydospores were globose and in chains. The fungus was identified as Fusarium sp. according to Fusarium key by Leslie and Summerell (2006). PCR amplification and DNA sequencing were performed using primers EF1F/EF2R and ITS1/ITS4 (O'Donnell et al., 1998; White et al., 1990) to amplify the partial elongation factor 1-alpha (TEF1-α) gene and internal transcribed spacer region (ITS), respectively. The TEF1-α and ITS sequences of this isolate were deposited in GenBank as OQ672911 and OR349657. BLAST analysis with TEF1-α gene sequences revealed 99.74% and 99.33% sequence identity with F. pernambucanum (accession no. ON330424) and Fusarium isolate NRRL 25134 (accession no. JF740755), respectively; both belonged to the Fusarium incarnatum-equiseti species complex (FIESC). BLAST search of the TEF1-α sequence in the database of the International Mycological Association (www.mycobank.org) showed 99.18% identity with FIESC (NRRL 36548). The ITS sequences were 100% identical to those of F. incarnatum (MT563420, MT563419, and MT563418). Pathogenicity test was conducted on three unwounded and three wounded mature red bell pepper fruits (SP299 Red Masta variety). Two healthy bell peppers were used as controls for each treatment. Prior to inoculation, the fruits were surface-sterilized by dipping in 70% ethanol and rinsed twice with sterile distilled water. Unwounded fruits were inoculated with fungal mycelium disks (5 mm diameter), whereas control fruits were inoculated with sterile PDA agar disks. For wound method, 6 µl of spore suspension (1x106 spores/ml) was obtained from 7-day-old cultures and injected (1 mm depth) into the fruit wall using a sterile syringe needle. Control fruits were inoculated with sterile distilled water only. Each fruit was inoculated with the inoculum at three distinct spots and kept in a humid chamber at a temperature of 25±2 °C. The pathogenicity test was done twice. Five days post-inoculation, the control fruits showed no symptoms, whereas all inoculated wounded and non-wounded fruits developed necrotic lesions with white mycelium growing on the inoculation points. The pathogen was successfully re-isolated from the infected fruits and morphologically identified as FIESC, fulfilling Kochs postulates. It has been reported previously that the members of FIESC are responsible for the fruit rot of bell peppers under greenhouse conditions (Ramdial et al., 2016). To the best of our knowledge, this is the first report of FIESC causing fruit rot on greenhouse bell peppers in Malaysia. This fruit rot disease may impose significant constraints on bell pepper production in Malaysia; hence, effective strategies to control the pathogen and prevent disease dispersal should be implemented.
  7. Fulltext Fragment-based in silico design of SARS-CoV-2 main protease inhibitors
    Ahmad S, Usman Mirza M, Yean Kee L, Nazir M, Abdul Rahman N, Trant JF, et al.
    Chem Biol Drug Des, 2021 Oct;98(4):604-619.
    PMID: 34148292 DOI: 10.1111/cbdd.13914
    3CLpro is essential for SARS-CoV-2 replication and infection; its inhibition using small molecules is a potential therapeutic strategy. In this study, a comprehensive crystallography-guided fragment-based drug discovery approach was employed to design new inhibitors for SARS-CoV-2 3CLpro. All small molecules co-crystallized with SARS-CoV-2 3CLpro with structures deposited in the Protein Data Bank were used as inputs. Fragments sitting in the binding pocket (87) were grouped into eight geographical types. They were interactively coupled using various synthetically reasonable linkers to generate larger molecules with divalent binding modes taking advantage of two different fragments' interactions. In total, 1,251 compounds were proposed, and 7,158 stereoisomers were screened using Glide (standard precision and extra precision), AutoDock Vina, and Prime MMGBSA. The top 22 hits having conformations approaching the linear combination of their constituent fragments were selected for MD simulation on Desmond. MD simulation suggested 15 of these did adopt conformations very close to their constituent pieces with far higher binding affinity than either constituent domain alone. These structures could provide a starting point for the further design of SARS-CoV-2 3CLpro inhibitors with improved binding, and structures are provided.
  8. Fulltext Improving Erectile Dysfunction Management Among Asian Men With Diabetes Using the Knowledge Translation Intervention
    Muin MRA, Ahmad S, Jasman MH, Aziz AFA, Ali MF, Zainuddin ZM
    Ann Fam Med, 2023;21(6):502-507.
    PMID: 38012042 DOI: 10.1370/afm.3030
    PURPOSE: Erectile dysfunction (ED) is frequently undermanaged due to communication barriers, particularly among Asian men. We looked at how ED discussion and treatment were affected by the patient's prompt sheet and the Knowledge Translation Tools in the Management of Erectile Dysfunction (LASTED).

    METHODS: We conducted a quasi-experimental study in a primary care clinic in Kedah, Malaysia involving 120 Asian men with diabetes. In the intervention group, patients were given a prompt sheet to indicate their intention to discuss or receive ED treatment, and physicians were provided with LASTED to assist with ED consultation. The control group patients received standard care from their physicians.

    RESULTS: The intervention increased the initiation of ED discussion up to 66.7% compared with 8.3% in the control group. In the intervention group, 57.5% of patients were prescribed phosphodiesterase-5 inhibitors and men with ED of moderate severity were more likely to be prescribed oral ED medication. Use of the LASTED flipchart was associated with prescription of phosphodiesterase-5 inhibitors (P = .011) and patient satisfaction with ED consultation (P

  9. Towards understanding the role of nanomedicine in targeting TNFR2 in rheumatoid arthritis
    Lambuk F, Nordin NA, Mussa A, Lambuk L, Ahmad S, Hassan R, et al.
    Immunology, 2024 Aug 27.
    PMID: 39191474 DOI: 10.1111/imm.13855
    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium and progressive joint destruction which significantly affects both quality of life and socioeconomic status. Admittedly, various treatments are available, but they are usually accompanied by various side effects, from mild to severe, and potentially with adverse events. Tumour necrosis factor-alpha (TNF-α) plays a crucial role in the pathophysiology of RA. It promotes inflammatory, apoptosis and necroptosis via TNF receptor-1 (TNFR1) but elicit anti-inflammatory effects via TNFR2. Herein, targeting TNFR2 has gained attention in RA studies. Understanding the role of nanomedicine in modulating TNFR2 signalling may be the instrument in development of RA therapies. Nanotechnology has made a significant progress in treating various conditions of diseases since its inception. Due to this, nanomedicine has emerged as a promising therapeutics approach for RA. Recent studies have demonstrated the potential of nanomedicine in RA theranostics, combining therapy and diagnostics for improved treatment outcomes. Owing to the challenges and advancements in the field of nanotechnology, nanoparticles are seen as an applicable candidate in the treatment of RA. In this review, we provide an overview of the role of nanomedicine in targeting TNFR2 for the treatment of RA and highlight the limitations of current therapies as well as the potential of nanocarriers with controlled drug release and active targeting abilities.
  10. Fulltext Acute Oral, Subacute, and Developmental Toxicity Profiling of Naphthalene 2-Yl, 2-Chloro, 5-Nitrobenzoate: Assessment Based on Stress Response, Toxicity, and Adverse Outcome Pathways
    Anwar F, Saleem U, Rehman AU, Ahmad B, Ismail T, Mirza MU, et al.
    Front Pharmacol, 2021;12:810704.
    PMID: 35126145 DOI: 10.3389/fphar.2021.810704
    The U.S. National Research Council (NRC) introduced new approaches to report toxicity studies. The NRC vision is to explore the toxicity pathways leading to the adverse effects in intact organisms by the exposure of the chemicals. This study examines the toxicity profiling of the naphthalene-2-yl 2-chloro-5-dinitrobenzoate (SF5) by adopting the vision of NRC that moves from traditional animal studies to the cellular pathways. Acute, subacute, and developmental toxicity studies were assayed according to the Organization for Economic Cooperation and Development (OECD) guidelines. The stress response pathway, toxicity pathway, and adverse effects outcome parameters were analyzed by using their standard protocols. The results showed that the acute toxicity study increases the liver enzyme levels. In a subacute toxicity study, alkaline phosphatase (ALP) levels were raised in both male and female animals. SF5 significantly increases the normal sperm count in the male animals corresponding to a decrease in the abnormality count. Developmental toxicity showed the normal skeletal and morphological parameters, except little hydrocephalus was observed in developmental toxicity. Doses of 20 mg/kg in males and 4 mg/kg in females showed decreased glutathione (GSH) levels in the kidney and liver. MDA levels were also increased in the kidney and liver. However, histopathological studies did not show any cellular change in these organs. No statistical difference was observed in histamine levels, testosterone, nuclear factor erythroid two-related factor-2 (Nrf2), and nuclear factor-kappa B (NF-κB), which showed no initiation of the stress response, toxicity, and adverse effect pathways. Immunomodulation was observed at low doses in subacute toxicity studies. It was concluded that SF5 did not produce abrupt and high-toxicity levels in organs and biochemical parameters. So, it is safe for further studies.
  11. Unequal distribution of COVID-19 vaccine: A looming crisis
    Sawal I, Ahmad S, Tariq W, Tahir MJ, Essar MY, Ahmed A
    J Med Virol, 2021 09;93(9):5228-5230.
    PMID: 33942326 DOI: 10.1002/jmv.27031
  12. Assessment of the reliability of a novel self-sampling device for performing cervical sampling in Malaysia
    Latiff LA, Rahman SA, Wee WY, Dashti S, Andi Asri AA, Unit NH, et al.
    Asian Pac J Cancer Prev, 2015;16(2):559-64.
    PMID: 25684487
    BACKGROUND: The participation of women in cervical cancer screening in Malaysia is low. Self-sampling might be able to overcome this problem.The aim of this study was to assess the reliability of self-sampling for cervical smear in our country.

    MATERIALS AND METHODS: This cross-sectional study was conducted on 258 community dwelling women from urban and rural settings who participated in health campaigns. In order to reduce the sampling bias, half of the study population performed the self-sampling prior to the physician sampling while the other half performed the self-sampling after the physician sampling, randomly. Acquired samples were assessed for cytological changes as well as HPV DNA detection.

    RESULTS: The mean age of the subjects was 40.4±11.3 years. The prevalence of abnormal cervical changes was 2.7%. High risk and low risk HPV genotypes were found in 4.0% and 2.7% of the subjects, respectively. A substantial agreement was observed between self-sampling and the physician obtained sampling in cytological diagnosis (k=0.62, 95%CI=0.50, 0.74), micro-organism detection (k=0.77, 95%CI=0.66, 0.88) and detection of hormonal status (k=0.75, 95%CI=0.65, 0.85) as well as detection of high risk (k=0.77, 95%CI=0.4, 0.98) and low risk (K=0.77, 95%CI=0.50, 0.92) HPV. Menopausal state was found to be related with 8.39 times more adequate cell specimens for cytology but 0.13 times less adequate cell specimens for virological assessment.

    CONCLUSIONS: This study revealed that self-sampling has a good agreement with physician sampling in detecting HPV genotypes. Self-sampling can serve as a tool in HPV screening while it may be useful in detecting cytological abnormalities in Malaysia.

  13. In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot)
    Isa NM, Abdelwahab SI, Mohan S, Abdul AB, Sukari MA, Taha MM, et al.
    Braz. J. Med. Biol. Res., 2012 Jun;45(6):524-30.
    PMID: 22358425
    The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.
  14. The methanolic extract of Boesenbergia rotunda (L.) Mansf. and its major compound pinostrobin induces anti-ulcerogenic property in vivo: possible involvement of indirect antioxidant action
    Abdelwahab SI, Mohan S, Abdulla MA, Sukari MA, Abdul AB, Taha MM, et al.
    J Ethnopharmacol, 2011 Sep 2;137(2):963-70.
    PMID: 21771650 DOI: 10.1016/j.jep.2011.07.010
    Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated.
  15. Fulltext Phytochemicals from Mangifera pajang Kosterm and their biological activities
    Ahmad S, Sukari MA, Ismail N, Ismail IS, Abdul AB, Abu Bakar MF, et al.
    BMC Complement Altern Med, 2015;15:83.
    PMID: 25887035 DOI: 10.1186/s12906-015-0594-7
    Mangifera pajang Kosterm is a plant species from the mango family (Anacardiaceae). The fruits are edible and have been reported to have high antioxidant content. However, the detailed phytochemical studies of the plant have not been reported previously. This study investigates the phytochemicals and biological activities of different parts of Mangifera pajang.
  16. Fulltext Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes
    Valli H, Ahmad S, Sriharan S, Dean LD, Grace AA, Jeevaratnam K, et al.
    Clin Exp Pharmacol Physiol, 2018 03;45(3):278-292.
    PMID: 29027245 DOI: 10.1111/1440-1681.12870
    Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca2+ homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na+ current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na+ currents. Plots of peak current against depolarisation from resting potential gave pretreatment maximum atrial and ventricular currents of -20.23 ± 1.48 (17) and -29.8 ± 2.4 (10) pA/μm2 (mean ± SEM [n]). Challenge by 8-CPT (1 μmol/L) reduced these currents to -11.21 ± 0.91 (12) (P  .05). Assessment of the inactivation that followed by applying subsequent steps to a fixed voltage 100 mV positive to resting potential gave concordant results. Half-maximal inactivation voltages and steepness factors, and time constants for Na+ current recovery from inactivation in double-pulse experiments, were similar through all the pharmacological conditions. Intracellular sharp microelectrode membrane potential recordings in intact Langendorff-perfused preparations demonstrated concordant variations in maximum rates of atrial and ventricular action potential upstroke, (dV/dt)max . We thus demonstrate an acute, reversible, Na+ channel inhibition offering a possible mechanism for previously reported pro-arrhythmic slowing of AP propagation following modifications of Ca2+ homeostasis, complementing earlier findings from chronic alterations in Ca2+ homeostasis in genetically-modified RyR2-P2328S hearts.
  17. Fulltext Age-dependent atrial arrhythmic phenotype secondary to mitochondrial dysfunction in Pgc-1β deficient murine hearts
    Valli H, Ahmad S, Chadda KR, Al-Hadithi ABAK, Grace AA, Jeevaratnam K, et al.
    Mech Ageing Dev, 2017 Oct;167:30-45.
    PMID: 28919427 DOI: 10.1016/j.mad.2017.09.002
    INTRODUCTION: Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF).

    MATERIALS AND METHODS: Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3-4 month) and aged (>12 month), wild type (WT) and peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES).

    RESULTS AND DISCUSSION: The Pgc-1β-/- genotype was associated with a pro-arrhythmic phenotype progressing with age. Young and aged Pgc-1β-/- hearts showed compromised maximum action potential (AP) depolarization rates, (dV/dt)max, prolonged AP latencies reflecting slowed action potential (AP) conduction, similar effective refractory periods and baseline action potential durations (APD90) but shortened APD90 in APs in response to extrasystolic stimuli at short stimulation intervals. Electrical properties of APs triggering arrhythmia were similar in WT and Pgc-1β-/- hearts. Pgc-1β-/- hearts showed accelerated age-dependent fibrotic change relative to WT, with young Pgc-1β-/- hearts displaying similar fibrotic change as aged WT, and aged Pgc-1β-/- hearts the greatest fibrotic change. Mitochondrial deficits thus result in an arrhythmic substrate, through slowed AP conduction and altered repolarisation characteristics, arising from alterations in electrophysiological properties and accelerated structural change.

  18. Fulltext Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
    Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.
    Molecules, 2020 Jul 28;25(15).
    PMID: 32731323 DOI: 10.3390/molecules25153403
    Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
  19. Gestational diabetes mellitus in primigravidae: a mild disease
    Ismail NA, Aris NM, Mahdy ZA, Ahmad S, Naim NM, Siraj HH, et al.
    Acta Medica (Hradec Kralove), 2011;54(1):21-4.
    PMID: 21542419 DOI: 10.14712/18059694.2016.12
    This prospective observational study was done to analyse the prevalence of gestational diabetes mellitus (GDM) among primigravidae and its outcome. All healthy primigravidae with singleton pregnancies were offered universal glucose tolerance testing between 16 and 28 weeks gestation. GDM and non GDM groups were managed according to hospital protocol. The antenatal features and pregnancy outcomes were analysed. Out of 616 primigravidae, 113 (18.34%) were GDM with slightly older (27.9 +/- 4.2 versus 26.32 +/- 3.3, p < 0.001) age. The mean fasting and two hours postprandial blood glucose in both groups were 4.99 +/- 1.08 mmol/l, 8.86 +/- 1.41 mmol/l(GDM) and 4.36 +/- 0.43 mmol/l, 5.71 +/- 1.11 mmol/l (Non GDM), respectively. Maternal family history of diabetes mellitus, weight exceeding 80 Kg, polyhydramnios (2.65% versus 0.2%, p = 0.028) and neonatal hyperbilirubinaemia (9.73% versus 2.98%, p = 0.01) occurred significantly more frequent in the GDM group compared to normal. There was no significant difference in other pregnancy outcomes and complications between the two groups. In conclusion GDM in primigravidae was detected at a relatively young age with more frequent maternal family history of DM, weight exceeding 80 Kg, polyhydromnions and neonatal hyperbilirubinaemia. The degree of disease was mild and treatment led to no significant complication.
  20. Vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers in Malaysia
    Kalok A, Loh SYE, Chew KT, Abdul Aziz NH, Shah SA, Ahmad S, et al.
    Vaccine, 2020 02 24;38(9):2183-2189.
    PMID: 32001070 DOI: 10.1016/j.vaccine.2020.01.043
    BACKGROUND: Vaccine hesitancy is a complex behaviour which involves various degrees of indecision about specific vaccines or vaccination uptake. Access to antenatal care had been associated with positive vaccine behavior.

    OBJECTIVE: To determine the prevalence of vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers and the associated socio-demographic factors.

    METHODS: A cross-sectional study was conducted among 1081 women who received antenatal care at a teaching hospital in Kuala Lumpur. Vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines (PACV) Survey in both English and validated Malay versions. The sociodemographic data of the mothers and their partners, source of vaccine information and reasons for hesitancy were analysed.

    RESULTS: Eighty-six (8.0%) pregnant mothers were vaccine hesitant. Ethnicity, religion, number of children, educational level and employment status were significantly associated with vaccine hesitancy. Multivariable analysis showed that a low level of education was the most significant risk factor (p 

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