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Zinc: indications in brain disorders

Prakash A, Bharti K, Majeed AB

Fundam Clin Pharmacol, 2015 Apr;29(2):131-49.
PMID: 25659970 DOI: 10.1111/fcp.12110

Zinc is the authoritative metal which is present in our body, and reactive zinc metal is crucial for neuronal signaling and is largely distributed within presynaptic vesicles. Zinc also plays an important role in synaptic function. At cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Different importers and transporters are involved in zinc homeostasis. ZnT-3 is a main transporter involved in zinc homeostasis in the brain. It has been found that alterations in brain zinc status have been implicated in a wide range of neurological disorders including impaired brain development and many neurodegenerative disorders such as Alzheimer's disease, and mood disorders including depression, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. Furthermore, zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders.
Fulltext Psychiatric aspects of the acquired immunodeficiency syndrome. A case report

Maniam T, Abu Bakar AK

Med J Malaysia, 1988 Jun;43(2):166-9.
PMID: 3237133
Fulltext Transcutaneous bilirubinometry in Malay, Chinese and Indian term neonates

Boo NY, Abu Bakar A

Med J Malaysia, 1984 Mar;39(1):35-7.
PMID: 6513837

The transcutaneous (Tc) bilirubinometer was evaluated in 105 jaundiced neonates, comprising 38 Malays, 37 Chinese and 30 Indians, who had not been treated with phototherapy or exchange transfusion. Tc bilirubin index and serum bilirubin concentration correlated at statistically significant levels in all the three racial groups. Unlike the Chinese and Malay babies, the action levels, using Tc bilirubin index, in the Indian babies are not reliable due to the wide variation of skin pigmentation. Neonatal jaundice is conventionally monitored by estimation of serum bilirubin level. This involves blood sampling. The transcutaneous (Tc) bilirubinometer, however, is non-invasive, small and portable. In this study, the use of the Tc bilirubinometer in the management of neonatal jaundice' in the three racial groups was evaluated.
Fulltext Psychosocial support for healthcare frontliners during COVID-19 pandemic in Malaysia

Bakar AYA, Ramli S

Asian J Psychiatr, 2020 Dec;54:102272.
PMID: 32653851 DOI: 10.1016/j.ajp.2020.102272
Fulltext Evaluation of Melaleuca cajuputi (Family: Myrtaceae) Essential Oil in Aerosol Spray Cans against Dengue Vectors in Low Cost Housing Flats

Abu Bakar A, Sulaiman S, Omar B, Mat Ali R

J Arthropod Borne Dis, 2012;6(1):28-35.
PMID: 23293776

Melaleuca cajuputi essential oil in aerosol spray was evaluated against the dengue vectors Aedes aegypti and Ae. albopictus at low cost housing flats in Section 10, Setapak, Kuala Lumpur, Malaysia.
Job satisfaction and perceived future roles of Malaysian dental therapists: findings from a national survey

Abu Bakar A, Mohd Nor NA, Ab-Murat N, Jaafar N

Int J Dent Hyg, 2015 Aug;13(3):199-205.
PMID: 25040653 DOI: 10.1111/idh.12095

OBJECTIVE: To assess Malaysian dental therapists' perceptions of their job satisfaction and future roles.
METHODS: A nationwide postal survey involving all Malaysian dental therapists who met the inclusion criteria (n = 1726).
RESULTS: The response rate was 76.8%. All respondents were females; mean age 35.4 years (SD = 8.4). Majority were married (85.5%) and more than one-half had a working experience of <10 years (56.1%). Majority worked in community dental service (94.3%) and in urban areas (61.7%). Overall, they were highly satisfied with most aspects of their career. However, they were least satisfied with administrative workload (58.1%), career advancement opportunities (51.9%) and remuneration package; specifically income (45.2%), allowances (45.2%) and non-commensurate between pay and performance (44.0%). Majority perceived their role as very important in routine clinical tasks such as examination and diagnosis, preventive treatment, extraction of deciduous teeth and oral health promotion. However, fewer than one-half consider complex treatment such as placement of preformed crowns on deciduous teeth (37.1%) and extraction of permanent teeth (37.2%) as very important tasks.
CONCLUSION: Majority expressed high career satisfaction with most aspects of their employment but expressed low satisfaction in remuneration, lack of career advancement opportunities and administrative tasks. We conclude that most Malaysian dental therapists have positive perceptions of their current roles but do not favour wider expansion of their roles. These findings imply that there was a need to develop a more attractive career pathway for therapists to ensure sustainability of effective primary oral healthcare delivery system for Malaysia's children.
Fulltext Splenorrhaphy: omental pouch

Lazim TR, Salleh M, Bakar AS

Med J Malaysia, 1995 Jun;50(2):145-9.
PMID: 7565184

This work studies the efficacy of an autogenous viable omental pouch as a means of splenorrhaphy for saving the traumatised spleen. One sheep and 9 goat spleens were mobilised and their vascular pedicles clamped. All spleens were subjected to AAST grade IV trauma. The injured spleens were put into omental pouches and manual pressure was applied for 10 minutes after removal of the vascular clamp. Bleeding was controlled in 8 animals which became fully active 12-36 hours postoperatively. Two animals died, one due to aspiration of gastric contents during surgery and the other due to bleeding 24 hours postoperatively. All remaining spleens were harvested after 6 weeks. They were surrounded by a fibrous capsule and the previously inflicted injuries were easily identifiable. Viable omental pouch based on left epiploic vascular pedicle offers itself as a good autogenous alternative other methods used for saving the injured spleen. This method has been used in two humans so far.
Fulltext Religious beliefs in relation to smoking: a cross-sectional study among muslim males in the month of Ramadan

Abu Bakar A Majid, Lokman H Johari, Amal M Nasir, Anselm, S.T., Chan, W.H., Noraziah A Rahman, et al.

Malaysian Journal of Public Health Medicine, 2002;2(2):32-35.
MyJurnal

A cross—sectional study conducted in the fasting month of Ramadan targeting muslim males assessed their religious beliefs in relation to smoking and their intentions t0 quit smoking in Ramadan. It was found that there law; is a strong association between their perceptions on the religious ruling of smoking as haram (prohibited) in relation to their smoking status. Among the non smokers and ex smokers, 87.8% and 73.6% respectively accept the ruling on smoking as prohibitea'(haram), while only 31.6% of smokers accept smoking as prohibited. Among the smokers, 97.7% smoke a lesser number of cigarettes during Ramadan, while 96.7% of them felt that it is easier to quit during the fasting month. The findings suggest that the religious department needs to provide more information and education to the Muslim population as to the reasons of the ruling on smoking as haram(prohibited) on religious grounds . It was also found that the majority felt it is easier to quit during quit smoking programmes can be emphasized and carried out on a bigger scale during fasting months in the future.
Village midwives in Malaysia

Peng JY, Laily N, Bakar A, Bin Marzuki A

Stud Fam Plann, 1972 Feb;3(2):25-8.
PMID: 4656053 DOI: 10.2307/1965087

PIP: 292 village midwives (bidans) in Malaysia were interviewed between January 1969 and December 1970 as they came to report for training. The mean age was 47.3, 80% had had no schooling, 43% had practiced less than 10 years (32% between 10 and 20 years, 21% between 20 and 30 years, and 4% more than 30 years). On the average each bidan reported attending 3 deliveries during the past month and 26 during the past year. The average charge per delivery was about U.S.$2.00. Of 267 who responded to a question concerning other services they provided, 50% said they performed massages, 30% performed massages combined with other services, 12% said they did not do anything other than midwifery and 7% prescribed herbs and performed abortions. 67% said they first had contact with the mother during the seventh to ninth month of pregnancy, 42% between the fourth and sixth month, and 7% at or before the third month. 40% said the postpartum care lasted less than 1 week, 40% from 1-2 weeks and 19% between 2-7 weeks. Only 2 out of 198 bidans disapproved of family planning services. 99% were not worried that this would affect their job in conducting deliveries. 62% had been approached by women about family planning information services during the last 3 months. 95% thought they could help to promote the government's program by recruiting patients and distributing contraceptives. Since oral contraceptives are the most frequently used contraceptive in Malaysia, bidans could resupply the women with the pill. They could play an important role in promoting contraceptive continuation in rural areas by providing women with a continuous motivation through their constant contact. The success of using bidans in rural family planning services will greatly depend on their supervision. They can be paid with a flat salary-type payment, with an incentive scheme alone, or a combination of the two.
Cyp2a5 Promoter-based Gene Reporter Assay: A Novel Design of Cell-based Bioassay for Toxicity Prediction

Abu-Bakar A, Hu H, Lang MA

Basic Clin Pharmacol Toxicol, 2018 Sep;123 Suppl 5:72-80.
PMID: 29788535 DOI: 10.1111/bcpt.13046

The murine cytochrome P450 2a5 (Cyp2a5) gene is regulated by complex interactions of various stress-activated transcription factors (TFs). Elevated Cyp2a5 transcription under chemical-induced stress conditions is achieved by interplay between the various TFs - including as aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2) - at the 'stress-responding' cluster of response elements on the Cyp2a5 promoter, as well as through mRNA stabilization mediated by interaction of the stress-activated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with the 3'-UTR of the CYP2A5 mRNA. We designed a unique toxicity pathway-based reporter assay to include regulatory regions from both the 5' and the 3' untranslated regions of Cyp2a5 in a luciferase reporter plasmid to reflect in vivo responses to chemical insult. Human breast cancer MCF-7 cells were stably transfected with pGL4.38-Cyp2a5_Wt3k (wild-type) or mutant - pGL4.38-Cyp2a5_StREMut and pGL4.38-Cyp2a5_XREMut - reporter gene to monitor chemical-induced cellular response mediated by AhR and Nrf2 signalling. The recombinant cells were treated with representative of AhR agonist, polycyclic aromatic hydrocarbons, brominated flame retardant, fluorosurfactant, aromatic organic compound and metal, to determine the sensitivity of the Cyp2a5 promoter-based gene reporter assays to chemical insults by measuring the LC50 and EC50 of the respective chemicals. The three assays are sensitive to sublethal cellular responses of chemicals, which is an ideal feature for toxicity pathway-based bioassay for toxicity prediction. The wild-type reporter responded well to chemicals that activate crosstalk between the AhR and Nrf2, whilst the mutant reporters effectively gauge cellular response driven by either Nrf2/StRE or AhR/XRE signalling. Thus, the three gene reporter assays could be used tandemly to determine the predominant toxicity pathway of a given compound.
Fulltext Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin

Nna VU, Bakar ABA, Ahmad A, Mohamed M

Andrology, 2019 01;7(1):110-123.
PMID: 30515996 DOI: 10.1111/andr.12567

BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.
OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.
MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.
RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.
DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.
Fulltext Machine Learning Predictions on Outpatient No-Show Appointments in a Malaysia Major Tertiary Hospital

Ahmad Hamdan AF, Abu Bakar A

Malays J Med Sci, 2023 Oct;30(5):169-180.
PMID: 37928795 DOI: 10.21315/mjms2023.30.5.14

INTRODUCTION: A no-show appointment occurs when a patient does not attend a previously booked appointment. This situation can cause other problems, such as discontinuity of patient treatments as well as a waste of both human and financial resources. One of the latest approaches to address this issue is predicting no-shows using machine learning techniques. This study aims to propose a predictive analytical approach for developing a patient no-show appointment model in Hospital Kuala Lumpur (HKL) using machine learning algorithms.
METHODS: This study uses outpatient data from the HKL's Patient Management System (SPP) throughout 2019. The final data set has 246,943 appointment records with 13 attributes used for both descriptive and predictive analyses. The predictive analysis was carried out using seven machine learning algorithms, namely, logistic regression (LR), decision tree (DT), k-near neighbours (k-NN), Naïve Bayes (NB), random forest (RF), gradient boosting (GB) and multilayer perceptron (MLP).
RESULTS: The descriptive analysis showed that the no-show rate was 28%, and attributes such as the month of the appointment and the gender of the patient seem to influence the possibility of a patient not showing up. Evaluation of the predictive model found that the GB model had the highest accuracy of 78%, F1 score of 0.76 and area under the curve (AUC) value of 0.65.
CONCLUSION: The predictive model could be used to formulate intervention steps to reduce no-shows, improving patient care quality.
Apoptosis induced by desmethyl-lasiodiplodin is associated with upregulation of apoptotic genes and downregulation of monocyte chemotactic protein-3

Hazalin NA, Lim SM, Cole AL, Majeed AB, Ramasamy K

Anticancer Drugs, 2013 Sep;24(8):852-61.
PMID: 23764760 DOI: 10.1097/CAD.0b013e3283635a47

There is growing interest in the discovery of bioactive metabolites from endophytes as an alternative source of therapeutics. Identification of their therapeutic targets is essential in understanding the underlying mechanisms and enhancing the resultant therapeutic effects. As such, bioactive compounds produced by endophytic fungi from plants at the National Park, Pahang, Malaysia, were investigated. Five known compounds were identified using LC-UV-MS-NMR and they include trichodermol, 7-epi-brefeldin A, (3R,4S)-4-hydroxymellein, desmethyl-lasiodiplodin and cytochalasin D. The present study went on to investigate the potential anticancer effects of these compounds and the corresponding molecular mechanisms of the lead compound against human breast adenocarcinoma, MCF-7. For the preliminary screening, the cytotoxicity and apoptotic effects of these compounds against MCF-7 were examined. The compounds were also tested against noncarcinogenic hepatocytes (WRL68). The differential cytotoxicity was then determined using the MTT assay. Desmethyl-lasiodiplodin was found to suppress the growth of MCF-7, yielding an inhibitory concentration (IC50) that was seven-fold lower than that of the normal cells. The cytotoxic effect of desmethyl-lasiodiplodin was accompanied by apoptosis. Subsequent analysis demonstrated increased expression levels of caspase 3, c-myc and p53. Further, desmethyl-lasiodiplodin resulted in inhibition of monocyte chemotactic protein (MCP)-3, a cytokine involved in cell survival and metastasis. Hence, this study proposed that desmethyl-lasiodiplodin inhibited growth and survival of MCF-7 through the induction of apoptosis. This anticancer effect is mediated, in part, by upregulation of apoptotic genes and downregulation of MCP-3. As desmethyl-lasiodiplodin elicited minimal impact against normal hepatocytes, our findings also imply its potential use as a specific apoptotic agent in breast cancer treatment.
Mitochondrial targeting of bilirubin regulatory enzymes: An adaptive response to oxidative stress

Muhsain SN, Lang MA, Abu-Bakar A

Toxicol Appl Pharmacol, 2015 Jan 1;282(1):77-89.
PMID: 25478736 DOI: 10.1016/j.taap.2014.11.010

The intracellular level of bilirubin (BR), an endogenous antioxidant that is cytotoxic at high concentrations, is tightly controlled within the optimal therapeutic range. We have recently described a concerted intracellular BR regulation by two microsomal enzymes: heme oxygenase 1 (HMOX1), essential for BR production and cytochrome P450 2A5 (CYP2A5), a BR oxidase. Herein, we describe targeting of these enzymes to hepatic mitochondria during oxidative stress. The kinetics of microsomal and mitochondrial BR oxidation were compared. Treatment of DBA/2J mice with 200mgpyrazole/kg/day for 3days increased hepatic intracellular protein carbonyl content and induced nucleo-translocation of Nrf2. HMOX1 and CYP2A5 proteins and activities were elevated in microsomes and mitoplasts but not the UGT1A1, a catalyst of BR glucuronidation. A CYP2A5 antibody inhibited 75% of microsomal BR oxidation. The inhibition was absent in control mitoplasts but elevated to 50% after treatment. An adrenodoxin reductase antibody did not inhibit microsomal BR oxidation but inhibited 50% of mitochondrial BR oxidation. Ascorbic acid inhibited 5% and 22% of the reaction in control and treated microsomes, respectively. In control mitoplasts the inhibition was 100%, which was reduced to 50% after treatment. Bilirubin affinity to mitochondrial and microsomal CYP2A5 enzyme is equally high. Lastly, the treatment neither released cytochrome c into cytoplasm nor dissipated membrane potential, indicating the absence of mitochondrial membrane damage. Collectively, the observations suggest that BR regulatory enzymes are recruited to mitochondria during oxidative stress and BR oxidation by mitochondrial CYP2A5 is supported by mitochondrial mono-oxygenase system. The induced recruitment potentially confers membrane protection.
Fulltext Advances in bio-tactile sensors for minimally invasive surgery using the fibre Bragg grating force sensor technique: a survey

Abushagur AA, Arsad N, Reaz MI, Bakar AA

Sensors (Basel), 2014;14(4):6633-65.
PMID: 24721774 DOI: 10.3390/s140406633

The large interest in utilising fibre Bragg grating (FBG) strain sensors for minimally invasive surgery (MIS) applications to replace conventional electrical tactile sensors has grown in the past few years. FBG strain sensors offer the advantages of optical fibre sensors, such as high sensitivity, immunity to electromagnetic noise, electrical passivity and chemical inertness, but are not limited by phase discontinuity or intensity fluctuations. FBG sensors feature a wavelength-encoding sensing signal that enables distributed sensing that utilises fewer connections. In addition, their flexibility and lightness allow easy insertion into needles and catheters, thus enabling localised measurements inside tissues and blood. Two types of FBG tactile sensors have been emphasised in the literature: single-point and array FBG tactile sensors. This paper describes the current design, development and research of the optical fibre tactile techniques that are based on FBGs to enhance the performance of MIS procedures in general. Providing MIS or microsurgery surgeons with accurate and precise measurements and control of the contact forces during tissues manipulation will benefit both surgeons and patients.
Fulltext Pituitary apoplexy: a rare cause of middle cerebral artery infarction

Hassan R, Sharis Othman S, Ahmad Mukari SA, Abu Bakar A

Med J Malaysia, 2013 Jun;68(3):264-6.
PMID: 23749020 MyJurnal

Pituitary apoplexy is a well-known complication of a pituitary adenoma. However, an ischaemic event caused by pituitary apoplexy is rare. We reported a case of pituitary apoplexy with middle cerebral artery infarction in a 44-year old man who presented with a sudden onset of altered sensorium. Vasospasm is the most likely underlying cause of the infarction in this case secondary to transdiaphragmatic rupture of the sella tumour into the subarachnoid space.
Synthesis and characterization of poly(p-phenylene vinylene)

Abd Rashid MY, Abu Bakar A, Mohd Asri MT, Iskandar SM

Med J Malaysia, 2004 May;59 Suppl B:135-6.
PMID: 15468855

Poly (p-phenylene vinylene) (PPV) was synthesized from p-xylylene bis(tetrahydrothiophenium chloride) using the Wessling route and characterized by Fourier Transform Infra-Red (FTIR) and UV-visible (UV-VIS) spectroscopic techniques. The significance of thermal treatment along with evolution of precursor polymer to polymer PPV was also studied through these spectroscopic techniques. Thermally Stimulated Current (TSC) measurements indicated the presence of crystallization, sulphonium group which occurred through the evolution from precursor polymer to polymer PPV during thermal treatment.
Raised leptin concentrations in feto-placental tissues from women with preeclampsia

Singh HJ, Abu Bakar A, Che Romli A, Nila A

Hypertens Pregnancy, 2005;24(2):191-9.
PMID: 16036403

The aim of this study was to estimate the levels of leptin in the amnion, chorion laeve, and placenta and to examine for any differences in leptin levels in these tissues from preeclamptic and normotensive pregnant women.
Fulltext Quantitating proteinuria using the urinary protein creatinine index

Norella Kong CT, Chin JH, Izham Cheong IK, Abu Bakar A

Med J Malaysia, 1988 Jun;43(2):134-7.
PMID: 3237129
Concurrent stroke and ST-elevation myocardial infarction: Is it a contraindication for intravenous tenecteplase?

Wan Asyraf WZ, Elengoe S, Che Hassan HH, Abu Bakar A, Remli R

Med J Malaysia, 2020 03;75(2):169-170.
PMID: 32281601

Acute ischemic stroke (AIS) and acute ST-elevation myocardial infarction (STEMI) are leading causes of mortality worldwide. Concurrent AIS presentation with STEMI is rare and potentially fatal. Most importantly to date many centres in Malaysia are still not aware on how to treat this condition. We report a case of AIS, which was treated with intravenous tenecteplase (TNK) according to ischemic stroke dosage and lead to improvement of neurological deficit.

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