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Fulltext Developing and prototyping of empty fruit bunch high density board

J. Sahari, Shah, M. K. M, Nuratiqah, M.N., Rao, M.M.

Journal of Advanced Research Design, 2014;3(1):1-8.
MyJurnal

Empty fruit bunches and wastepaper together with urea formaldehyde (UF) were
evaluated to figure out potential applications in engineering field. The purpose of this project is to
determine the mechanical properties of a new high density board. This composite was manufactured
by hot-press technique with 3 different ratios i.e. 10:0, 6.67:3.33 and 9.33:0.67. The mechanical
properties were evaluated using the GOTECH/AI-7000M Electronic Mechanical Testing. Tensile tests
were carried out according to ASTM D638. The results were analysed to calculate the tensile
strength. Tensile strength at break ranged from 4.712 N/mm2 to 12.941 N/mm2 while hardness
number obtained ranged from 6.76 RHN to 75.84 RHN. This fibreboard has better properties when
reinforced with wastepaper compared to that of 100% empty fruit bunches. It is also found that the
hardness number is higher, which means that this fibreboard can withstand any load not more than
75.84 RHN. Finally, through Scanning Electron Microscope (SEM), the surface structure of the new
high density board has been studied in terms of their surface morphology.
Caseous lymphadenitis in sheep imported from Australia for slaughter in Malaysia

Sheikh-Omar AR, Shah M

Aust. Vet. J., 1984 Dec;61(12):410.
PMID: 6534363
Fulltext Prehypertensive state, mild hypertension, metabolic syndrome and cardiovascular risk factors among young adults in rural Malaysia

Abdullah Aszrin, Shah M. Azarisman, Rahman A. Jamaluddin, Razak A. Tariq, Noor M. Noriah

International Medical Journal Malaysia, 2018;17(1):47-54.
MyJurnal

Introduction: Prehypertension precedes overt hypertension and has been acknowledged by many guidelines.
Hypertension is an important risk factor for cardiovascular disease in Malaysia. Hypertension prevalence is
at 42.6% and population-based control is poor at 26.8%. The objective of the study is to ascertain the
cardiovascular risk profile of prehypertensive and mildly hypertensive young adults against age-matched
controls in rural Malaysia. Methods: 484 (four hundred and eighty four) subjects attending primary care
clinic were screened. 91 (Ninety one) young adults with pre/mild hypertension and normotensive, agematched controls were enrolled. The blood pressure and biochemical profiles for both groups were assessed
and compared. Results: Fifty-four subjects and 37 controls were enrolled. Amongst subjects, 46.3% had
prehypertension and 53.7% had mild hypertension. Mean values compared to age-matched controls for MAP
were 102.68 ± 7.48 vs 83.25 ± 6.08 mmHg (p< 0.001), LDL 3.75 ± 0.95 vs 3.32 ± 0.93 mmol/L (p=0.03), FBG
4.65 ± 0.54 vs 4.33 ± 0.42 mmol/L (p=0.03), BMI 28.81 ± 5.16 vs 24.12 ± 4.91 (p< 0.001). The mean BP was
significantly associated with BMI, FBG, triglycerides, HDL and the TC/HDL ratio. Conclusions: Greater BMI,
FBG, HDL, triglyceride levels and TC/HDL ratio characterised the young adults with pre/mild hypertension.
The data suggests that hypertension in young adults is secondary to metabolic syndrome.
Fulltext Development of Samarium-153 labelled radiotracer for gamma scintigraphy of whole gastric-intestinal transit study

Wong, Y. H., Kasbollah, A., Md. Shah M. N., Abdullah, B. J. J., Yeong, Chai Hong

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):23-23.
MyJurnal

Introduction: Constipation is affecting a quarter of human population at any one time in all age groups. However, a proper gamma scintigraphic study of whole GI transit is rarely performed in Malaysia due to the lack of suitable radiopharmaceutical. Hence, this study was taken to develop a suitable radiotracer formulation for gamma scintigraphy study of whole gastric-intestinal transit. Methods: The biocompatible polystyrene (PS) incorporated with 152Sm2O3 (5%, w/v) will be used to synthesize the radiotracer. The 152Sm-labelled PS particles was neutron activated to 153Sm in a nuclear reactor for 5 minutes. Characterization of the physicochemical properties, gamma spectrometry and in-vitro radiolabeling studies in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out to study the properties and stability of the radiotracer before and after neutron activation. Results: Scanning electron microscope (SEM) and particle size analysis showed that size, shape and surface morphology of the particles remained after neutron activation. The synthesized 153Sm-labelled PS radiotracer (100 mg) particles achieved an activity of 3.7 MBq after 46 hrs. As indicated by the gamma spectrometry result, there is no long half-life radioimpuirties present in the samples. The 153Sm-labelled PS particles achieved radiolabeling efficiency of more than 95% in both SGF and SIF over 72 hrs. Conclusions: A 153Sm-labelled radiotracer particles formulation has been successfully developed from biocompatible PS. The proposed formulation has the advantage of cheaper, easier to be produced and reduced radiation exposure to staff. Further studies are required to validate the in-vivo performance of 153Sm-labelled formulation for assessing GI motility and transit in clinical use.
Fulltext Role of cardiovascular magnetic resonance in assessment of acute coronary syndrome

Azarisman SM, Teo KS, Worthley MI, Worthley SG

World J Cardiol, 2014 Jun 26;6(6):405-14.
PMID: 24976912 DOI: 10.4330/wjc.v6.i6.405

Cardiovascular disease (CVD) is the leading cause of death in the western world and is becoming more important in the developing world. Recently, advances in monitoring, revascularisation and pharmacotherapy have resulted in a reduction in mortality. However, although mortality rates have declined, the burden of disease remains large resulting in high direct and indirect healthcare costs related to CVDs. In Australia, acute coronary syndrome (ACS) accounts for more than 300000 years of life lost due to premature death and a total cost exceeding eight billion dollars annually. It is also the main contributor towards the discrepancy in life expectancy between indigenous and non-indigenous Australians. The high prevalence of CVD along with its associated cost urgently requires a reliable but non-invasive and cost-effective imaging modality. The imaging modality of choice should be able to accelerate the diagnosis of ACS, aid in the risk stratification of de novo coronary artery disease and avail incremental information of prognostic value such as viability which cardiovascular magnetic resonance (CMR) allows. Despite its manifold benefits, there are limitations to its wider use in routine clinical assessment and more studies are required into assessing its cost-effectiveness. It is hoped that with greater development in the technology and imaging protocols, CMR could be made less cumbersome, its imaging protocols less lengthy, the technology more inexpensive and easily applied in routine clinical practice.
Fulltext Myocardial infarction induced by appetite suppressants in Malaysia

Azarisman SM, Magdi YA, Noorfaizan S, Oteh M

N Engl J Med, 2007 Nov 1;357(18):1873-4.
PMID: 17978302 DOI: 10.1056/NEJMc070990
Fulltext Cardiac magnetic resonance assessment of diastolic dysfunction in acute coronary syndrome

Azarisman SM, Teo KS, Worthley MI, Worthley SG

J Int Med Res, 2017 Dec;45(6):1680-1692.
PMID: 29239257 DOI: 10.1177/0300060517698265

Chest pain is an important presenting symptom. However, few cases of chest pain are diagnosed as acute coronary syndrome (ACS) in the acute setting. This results in frequent inappropriate discharge and major delay in treatment for patients with underlying ACS. The conventional methods of assessing ACS, which include electrocardiography and serological markers of infarct, can take time to manifest. Recent studies have investigated more sensitive and specific imaging modalities that can be used. Diastolic dysfunction occurs early following coronary artery occlusion and its detection is useful in confirming the diagnosis, risk stratification, and prognosis post-ACS. Cardiac magnetic resonance provides a single imaging modality for comprehensive evaluation of chest pain in the acute setting. In particular, cardiac magnetic resonance has many imaging techniques that assess diastolic dysfunction post-coronary artery occlusion. Techniques such as measurement of left atrial size, mitral inflow, and mitral annular and pulmonary vein flow velocities with phase-contrast imaging enable general assessment of ventricular diastolic function. More novel imaging techniques, such as T2-weighted imaging for oedema, T1 mapping, and myocardial tagging, allow early determination of regional diastolic dysfunction and oedema. These findings may correspond to specific infarcted arteries that may be used to tailor eventual percutaneous coronary artery intervention.
Impact of educational outreach intervention on enhancing health care providers' knowledge about statin therapy prescribing in Malaysian patients with type 2 diabetes mellitus

Elnaem MH, Nik Mohamed MH, Zaman Huri H, Azarisman SM

J Eval Clin Pract, 2018 06;24(3):521-527.
PMID: 29508492 DOI: 10.1111/jep.12903

RATIONALE: Previous research reported underutilization of statin therapy among patients with type 2 diabetes mellitus. Improving health care providers' awareness and understanding of the benefits and risks of statin treatment could be of assistance in optimizing the statin prescribing process.
AIMS AND OBJECTIVES: This study aimed to assess health care providers' knowledge related to statin therapy and the impact of educational outreach intervention based on the perceived knowledge.
METHODS: This was a cross-sectional study based on educational outreach intervention targeting physicians and pharmacists in 1 major tertiary hospital in the state of Pahang, Malaysia. Participants responded to a 12-item, validated questionnaire both prior to and after the outreach educational program. Two sessions were conducted separately for 2 cohorts of pharmacists and physicians. The knowledge scores prior to and after the educational intervention were calculated and compared using a paired-samples t-test.
RESULTS: The response rate to both pre-and post-educational outreach questionnaires was 91% (40/44). Prior to the intervention, around 84% (n37) of the participants decided to initiate statin therapy for both pre-assessment clinical case scenarios; however, only 27% (n12) could state the clinical benefits of statin therapy. Forty-five percent (n20) could state the drug to drug interactions, and 52.3% (n23) could identify the statin therapy that can be given at any time day/evening. The educational outreach program increased participants' knowledge scores of 1.450 (95% CI, 0.918 to 1.982) point, P
Fulltext Preparation of theranostic 153 Samarium-labelled polystyrene microspheres for hepatic radioembolization

Tan, H. Y., Wong, Y. H., Kasbollah A., Md. Shah M. N., Abdullah B. J. J., Yeong, Chai Hong

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):21-21.
MyJurnal

Introduction: Hepatic radioembolization is a minimally invasive procedure involving intrarterial administration of radioembolic microspheres for the treatment of liver tumours. In this study, a biocompatible polystyrene (PS) microspheres formulation containing radioactive Samarium-153 (153Sm) was synthesized and tested. The 153Sm emits both diagnostic gamma energy and therapeutic beta radiation, renders the synthesized microspheres an ideal theranostic radioembolic agent for hepatic radioembolization. Methods: First, the 152Sm2O3 (20 – 50%, w/v) was encapsulated in PS microspheres using solid-in-oil-in-water solvent evaporation method. The 152Sm-labelled PS microspheres were then activated to 153Sm (Eβmax = 807.6 keV, half-life = 46.3 hours) via 152Sm (n,γ) 153Sm reaction in a nuclear reactor with a neutron flux of 2.0 x 1012 n.cm-2.s-1. Physicochemical characterization, gamma spectroscopy and in-vitro radiolabeling studies were carried out to study the properties and stability of the microspheres before and after neutron activation. Results: The 153Sm -labelled PS microspheres achieved a nominal activity of 4.0 GBq.g-1 after 6 hours of neutron activation. Scanning electron microscope (SEM) and particle size analysis show that the microspheres remained spherical with diameters within 15 – 60 μm after neutron activation. No long half-life radioimpurities were found in the samples as revealed by the gamma spectroscopy results. The 153Sm-labelled PS microspheres achieved radiolabeling efficiency of more than 95% in saline and blood plasma over 480 hours. Conclusion: A biocompatible 153Sm-radiolabelled PS microspheres formulation has been successfully developed. The formulation achieved desirable properties for theranostic treatment of liver tumours. The formulation is relatively cheaper, easier to be produced and more readily available.
A bicycle safety index for evaluating urban street facilities

Asadi-Shekari Z, Moeinaddini M, Zaly Shah M

Traffic Inj Prev, 2015;16:283-8.
PMID: 24983474 DOI: 10.1080/15389588.2014.936010

The objectives of this research are to conceptualize the Bicycle Safety Index (BSI) that considers all parts of the street and to propose a universal guideline with microscale details.
Characterisation of Myocardial Injury via T1 Mapping in Early Reperfused Myocardial Infarction and its Relationship with Global and Regional Diastolic Dysfunction

Azarisman SM, Carbone A, Shirazi M, Bradley J, Teo KS, Worthley MI, et al.

Heart Lung Circ, 2016 Nov;25(11):1094-1106.
PMID: 27210302 DOI: 10.1016/j.hlc.2016.03.011

BACKGROUND: Cardiovascular magnetic resonance (CMR) advances in imaging techniques, permits the ability to accurately characterise tissue injury post myocardial infarction. Pre-contrast T1 mapping enables this through measurement of pre-contrast T1 relaxation times. We investigate the relationship between T1 characterisation of myocardial injury with global and regional diastolic function.
METHODS: Revascularised acute myocardial infarction patients with normal left ventricular (LV) systolic function on TTE were assessed by 1.5T CMR. Acute regional diastolic wall motion abnormalities, global diastolic function measurements, acute segmental damage fraction with LGE and mean segmental pre-contrast T1 values were assessed on matching short axis slices.
RESULTS: Forty-four patients were analysed. Mean LVEF was 62.1±9.4%. No difference between NSTEMI (22/44) and STEMI in mean pre-contrast T1 values of infarcted (1025.0±109.2 vs 1011.0±81.6ms, p=0.70), adjacent (948.3±45.3 vs 941.1±46.6ms, p=0.70) and remote (888.8±52.8 vs 881.2±54.5ms, p=0.66) segments was detected. There was no correlation between pre-contrast T1 of infarcted segments with global diastolic dysfunction (E/A, r(2)=0.216, p=0.06; S/D, r(2)=0.243, p=0.053; E/E', r(2)=0.240, p=0.072), but there was significantly positive, moderate correlation with circumferential diastolic strain rate, (r(2)=0.579, p<0.01) with excellent agreement and reproducibility.
CONCLUSION: Cardiac magnetic resonance evaluation of pre-contrast T1 values revealed no difference between NSTEMI and STEMI patients in terms of tissue characterisation post-myocardial infarction. However, pre-contrast T1 of infarcted tissue is significantly correlated with regional diastolic circumferential strain rate.
Immediate postpartum cardiorespiratory collapse: a management quandary

Azarisman SM, Liza RA, Radhiana H, Sujana SS, Maskon O, Rosli MA, et al.

Blood Coagul Fibrinolysis, 2010 Sep;21(6):601-4.
PMID: 20581659 DOI: 10.1097/MBC.0b013e32833c2b9f

A 35-year-old multiparous woman was found unresponsive, tachypnoeic, hypoxic and in shock 4 h postpartum. The ECG revealed S1 Q3 T3, a right bundle branch block pattern and right-axis deviation. The computed tomography of her pulmonary arteries revealed bilateral pulmonary artery thrombosis with dilated right ventricle. She was fibrinolyzed with intravenous Tenecteplase 30 mg bolus. Her saturation and tachypnoea improved and her ECG reverted to sinus rhythm subsequently. We discuss our use of off-label Tenecteplase in postpartum pulmonary embolism and review the literature.
Fulltext Statin Therapy Prescribing for Patients with Type 2 Diabetes Mellitus: A Review of Current Evidence and Challenges

Elnaem MH, Mohamed MHN, Huri HZ, Azarisman SM, Elkalmi RM

J Pharm Bioallied Sci, 2017 Apr-Jun;9(2):80-87.
PMID: 28717329 DOI: 10.4103/jpbs.JPBS_30_17

Use of statin therapy in patients with type 2 diabetes mellitus (T2DM) has been recommended by most clinical guidelines. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among T2DM patients. It has been proved that statins are effective for primary or secondary CVD prophylaxis. Reports have highlighted the underutilization of statins in clinical practice and the suboptimal adherence to guideline recommendations. This review article points to summarize the current evidence confirming the role of statins in T2DM patients and to provide an overview of factors that may affect statins' prescribing patterns and compliance in clinical practice. Initiatives to enhance statin therapy prescribing should recognize the comprehensive nature of the prescribing process. Attempts to assure proper statin prescribing and utilization can help in achieving better clinical outcomes of statin therapy.
Review on pharmacological activities of Cinnamomum iners Reinw. ex Blume

Mustaffa F, Indurkar J, Shah M, Ismail S, Mansor SM

Nat Prod Res, 2013;27(10):888-95.
PMID: 22574706 DOI: 10.1080/14786419.2012.678347

This review describes the morphological, phytochemical and pharmacological properties of Cinnamomum iners Reinw. ex Blume (Lauraceae). The plant grows wild in the lowland of Malaysia, India, Myanmar, Indonesia, Thailand, Singapore, Brunei and Philippines. This plant is commonly used for its carminative, analgesic and antipyretic properties, for postpartum treatment, rheumatism and digestive ailments. This article enumerates an overview of phytochemical and pharmacological aspects that is useful to researchers for further exploration necessary for the development of this potential herb.
Fulltext An antimicrobial compound isolated from Cinnamomum iners leaves with activity against methicillin-resistant Staphylococcus aureus

Mustaffa F, Indurkar J, Ismail S, Shah M, Mansor SM

Molecules, 2011 Apr 08;16(4):3037-47.
PMID: 21478819 DOI: 10.3390/molecules16043037

This study was designed to investigate the antimicrobial activity of Cinnamomum iners standardized leave methanolic extract (CSLE), its fractions and isolated compounds. CSLE and fractions were subjected to disc diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests using different Gram positive and Gram negative bacteria and yeast. Within the series of fractions tested, the ethyl acetate fraction was the most active, particularly against methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli, with MIC values of 100 and 200 µg/mL, respectively. The active compound in this fraction was isolated and identified as xanthorrhizol [5-(1, 5-dimethyl-4-hexenyl)-2-methylphenol] by various spectroscopic techniques. The overall results of this study provide evidence that Cinnamomum iners leaves extract as well as the isolated compound xanthorrhizol exhibit antimicrobial activity for both Gram negative and Gram positive pathogens, especially against MRSA strains.
Fulltext Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii

Anwar A, Siddiqui R, Raza Shah M, Khan NA

J Microbiol Biotechnol, 2019 May 28;29(5):713-720.
PMID: 31030451 DOI: 10.4014/jmb/1903.03009

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.
The Effect of H2S Pressure on the Formation of Multiple Corrosion Products on 316L Stainless Steel Surface

Shah M, Ayob MTM, Rosdan R, Yaakob N, Embong Z, Othman NK

ScientificWorldJournal, 2020;2020:3989563.
PMID: 32774180 DOI: 10.1155/2020/3989563

H2S gas when exposed to metal can be responsible for both general and localized corrosion, which depend on several parameters such as H2S concentration and the corrosion product layer formed. Therefore, the formation of passive film on 316L steel when exposed to H2S environment was investigated using several analysis methods such as FESEM and STEM/EDS analyses, which identified a sulfur species underneath the porous structure of the passive film. X-ray photoelectron spectroscopy analysis demonstrated that the first layer of CrO3 and Cr2O3 was dissolved, accelerated by the presence of H2S-Cl-. An FeS2 layer was formed by incorporation of Fe and sulfide; then, passivation by Mo took place by forming a MoO2 layer. NiO, Ni(OH)2, and NiS barriers are formed as final protection for 316L steel. Therefore, Ni and Mo play an important role as a dual barrier to maintain the stability of 316L steel in high pH2S environments. For safety concern, this paper is aimed to point out a few challenges dealing with high partial pressure of H2S and limitation of 316L steel under highly sour condition for the oil and gas production system.
Fulltext Is autonomy a universal value of human existence? Scope of autonomy in medical practice: a comparative study between western medical ethics and islamic medical ethics

Rathor MY, Azarisman Shah MS, Hasmoni MH

International Medical Journal Malaysia, 2016;15(1):81-88.
MyJurnal

The practice of contemporary medicine has been tremendously influenced by western ideas and it is assumed by many that autonomy is a universal value of human existence. In the World Health Report 2000, the World Health Organization (WHO) considered autonomy a “universal” value of human life against which every health system in the world should be judged. Further in Western bioethics, patient autonomy and self -determination prevails in all sectors of social and personal life, a concept unacceptable to some cultures. In principle, there are challenges to the universal validity of autonomy, individualism and secularism, as most non-Western cultures are proud of their communal relations and spiritualistic ethos and, thereby imposing Western beliefs and practices as aforementioned can have deleterious consequences. Religion lies at the heart of most cultures which influences the practice patterns of medical professionals in both visible and unconscious ways. However, religion is mostly viewed by scientists as mystical and without scientific proof. Herein lies the dilemma, whether medical professionals should respect the cultural and religious beliefs of their patients? In this paper we aim to discuss some of the limitations of patient's autonomy by comparing the process of reasoning in western medical ethics and Islamic medical ethics, in order to examine the possibility and desirability of arriving at a single, unitary and universally acceptable notion of medical ethics. We propose a more flexible viewpoint that accommodates different cultural and religious values in interpreting autonomy and applying it in an increasingly multilingual and multicultural, contemporaneous society in order to provide the highest level of care possible.
Association of the drug of abuse in road traffic collision death in Hospital Kuala Lumpur

Subramaniam K, Mohd Shah M, Fatin Farisha F, Poh SL, Nor Fadhilah M, Hilmi S

Med J Malaysia, 2018 10;73(5):272-275.
PMID: 30350803 MyJurnal

INTRODUCTION: The role of pathologist not only confined in performing post mortem but also can assist in prevention. The aim of this study to determine the prevalence and association of drug of abuse (DoA) in road traffic collision (RTC) at Hospital Kuala Lumpur.
METHODS: This is a retrospective study of post mortem cases at Hospital Kuala Lumpur from 2014 to 2016. Deaths from RTC were included while decomposed and homicide cases were excluded. We performed Spearman Correlation statistical test to relate RTC and positive DoA results.
RESULTS: A total of 523 RTC cases were identified in which either blood or urine or both samples were taken for toxicology. 93 cases were positive for both DoA and therapeutic drugs. A total of 37 cases were positive for DoA. Alcohol was present in 5 out of 37 DoA positive cases. Most of the cases seen among 16 to 45 years old (69%) and predominantly in males (93.1%). 29 out of 37 were motorcyclist and the rest were pillion rider and pedestrian. Spearman Correlation statistical test showed a negative relationship between RTC and positive DoA results.
DISCUSSION AND CONCLUSION: Majority of the DoA cases in RTC were identified in the younger age group and among the motorcyclist. Spearman Correlation statistical test showed that more cases of DoA died in natural or suicidal manner compared to RTC. However, this doesn't reflect the true association of DoA in RTC. This is because of mainly two factors which the delayed effect of DoA that gives negative toxicology test and also the influence of other road users on DoA.
Clinically Approved Drugs against CNS Diseases as Potential Therapeutic Agents To Target Brain-Eating Amoebae

Anwar A, Rajendran K, Siddiqui R, Raza Shah M, Khan NA

ACS Chem Neurosci, 2019 01 16;10(1):658-666.
PMID: 30346711 DOI: 10.1021/acschemneuro.8b00484

Central nervous system (CNS) infections caused by free-living amoebae such as Acanthamoeba species and Naegleria fowleri are rare but fatal. A major challenge in the treatment against the infections caused by these amoebae is the discovery of novel compounds that can effectively cross the blood-brain barrier to penetrate the CNS. It is logical to test clinically approved drugs against CNS diseases for their potential antiamoebic effects since they are known for effective blood-brain barrier penetration and affect eukaryotic cell targets. The antiamoebic effects of clinically available drugs for seizures targeting gamma-amino butyric acid (GABA) receptor and ion channels were tested against Acanthamoeba castellanii belonging to the T4 genotype and N. fowleri. Three such drugs, namely, diazepam (Valium), phenobarbitone (Luminal), phenytoin (Dilantin), and their silver nanoparticles (AgNPs) were evaluated against both trophozoites and cysts stage. Drugs alone and drug conjugated silver nanoparticles were tested for amoebicidal, cysticidal, and host-cell cytotoxicity assays. Nanoparticles were synthesized by sodium borohydride reduction of silver nitrate with drugs as capping agents. Drug conjugated nanoconjugates were characterized by ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopies and atomic force microscopy (AFM). In vitro moebicidal assay showed potent amoebicidal effects for diazepam, phenobarbitone, and phenytoin-conjugated AgNPs as compared to drugs alone against A. castellanii and N. fowleri. Furthermore, both drugs and drug conjugated AgNPs showed compelling cysticidal effects. Drugs conjugations with silver nanoparticles enhanced their antiacanthamoebic activity. Interestingly, amoeba-mediated host-cell cytotoxicity was also significantly reduced by drugs alone as well as their nanoconjugates. Since, these drugs are being used to target CNS diseases, their evaluation against brain-eating amoebae seems feasible due to advantages such as permeability of the blood-brain barrier, established pharmacokinetics and dynamics, and United States Food and Drug Administration (FDA) approval. Given the limited availability of effective drugs against brain-eating amoebae, the clinically available drugs tested here present potential for further in vivo studies.

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