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Fulltext Glutathione (GSH) improves sperm quality and testicular morphology in streptozotocin-induced diabetic mice

Abdullah F, Khan Nor-Ashikin MN, Agarwal R, Kamsani YS, Abd Malek M, Bakar NS, et al.

Asian J Androl, 2021 1 22;23(3):281-287.
PMID: 33473013 DOI: 10.4103/aja.aja_81_20

Diabetes mellitus (DM) is known to cause reproductive impairment. In men, it has been linked to altered sperm quality and testicular damage. Oxidative stress (OS) plays a pivotal role in the development of DM complications. Glutathione (GSH) is a part of a nonenzymatic antioxidant defense system that protects lipid, protein, and nucleic acids from oxidative damage. However, the protective effects of exogenous GSH on the male reproductive system have not been comprehensively examined. This study determined the impact of GSH supplementation in ameliorating the adverse effect of type 1 DM on sperm quality and the seminiferous tubules of diabetic C57BL/6NTac mice. GSH at the doses of 15 mg kg-1 and 30 mg kg-1 was given intraperitoneally to mice weekly for 6 consecutive weeks. The mice were then weighed, euthanized, and had their reproductive organs excised. The diabetic (D Group) showed significant impairment of sperm quality and testicular histology compared with the nondiabetic (ND Group). Diameters of the seminiferous lumen in diabetic mice treated with 15 mg kg-1 GSH (DGSH15) were decreased compared with the D Group. Sperm motility was also significantly increased in the DGSH15 Group. Improvement in testicular morphology might be an early indication of the protective roles played by the exogenous GSH in protecting sperm quality from effects of untreated type 1 DM or diabetic complications. Further investigation using different doses and different routes of GSH is necessary to confirm this suggestion.
Fulltext Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes

Sadikan MZ, Abdul Nasir NA, Bakar NS, Iezhitsa I, Agarwal R

BMC Complement Med Ther, 2023 Jun 02;23(1):179.
PMID: 37268913 DOI: 10.1186/s12906-023-04005-9

BACKGROUND: Diabetic retinopathy (DR) is the second commonest microvascular complication of diabetes mellitus. It is characterized by chronic inflammation and angiogenesis. Palm oil-derived tocotrienol-rich fraction (TRF), a substance with anti-inflammatory and anti-angiogenic properties, may provide protection against DR development. Therefore, in this study, we investigated the effect of TRF on retinal vascular and morphological changes in diabetic rats. The effects of TRF on the retinal expression of inflammatory and angiogenic markers were also studied in the streptozotocin (STZ)-induced diabetic rats.
METHODS: Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.
RESULTS: TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p
Fulltext Trends of completed suicide rates among Malaysian elderly between 1995 and 2020

Abu Bakar NS, Zainuddin NA, Seman Z, Khamal NR, Ismail MH

BMC Public Health, 2023 Feb 10;23(1):303.
PMID: 36765292 DOI: 10.1186/s12889-023-15185-x

BACKGROUND: Suicide among the elderly has become a global public health concern. This study was carried out to determine the trend of completed suicide rates according to age, sex, and ethnicity and the suicidal methods among the elderly in Malaysia.
METHODS: All suicide-related deaths in elderly aged 60 years and above from the Year 1995 to 2020 reported to the National Registration Department (NRD) were analyzed. Causes of death for suicide were coded based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The completed suicide rate was calculated by dividing the completed suicide number by the total elderly population for the respective year.
RESULTS: Overall, the analysis of 1,600 suicide-related deaths was investigated over 26 years. Male was seen to be correlated with higher suicidal risk, with a male-female relative risk (RR) = 1.89 (95%CI:1.46,2.45). The risk of suicide was also found to be significantly higher for those aged 60 to 74 years old and Chinese, with RR = 4.26 (95%CI:2.94, 6.18) and RR = 5.81 (95%CI: 3.70, 9.12), respectively. Hanging was found to be a statistically significant suicide method (IRR:4.76, 95%CI:2.34,9.65) as compared to pesticide poisoning. The completed suicide rate was fluctuating over the years.
CONCLUSIONS: In conclusion, it is believed that Malaysia's elderly suicide rate has reached an alarmingly high incidence. By identifying the crucial criteria of sociodemographic factors, the government and responsible agencies have the essential and additional information to put together a more effective strategy and approach to overcome the issue in the future.
Treatment of African catfish, Clarias gariepinus wastewater utilizing phytoremediation of microalgae, Chlorella sp. with Aspergillus niger bio-harvesting

Nasir NM, Bakar NS, Lananan F, Abdul Hamid SH, Lam SS, Jusoh A

Bioresour Technol, 2015 Aug;190:492-8.
PMID: 25791330 DOI: 10.1016/j.biortech.2015.03.023

This study focuses on the evaluation of the performance of Chlorella sp. in removing nutrient in aquaculture wastewater and its correlation with the kinetic growth of Chlorella sp. The treatment was applied with various Chlorella sp. inoculation dosage ranging from 0% to 60% (v/v) of wastewater. The optimum inoculation dosage was recorded at 30% (v/v) with effluent concentration of ammonia and orthophosphate recording at 0.012mgL(-1) and 0.647mgL(-1), respectively on Day 11. The optimum dosage for bio-flocculation process was obtained at 30mgL(-1) of Aspergillus niger with a harvesting efficiency of 97%. This type of development of phytoremediation with continuous bio-harvesting could promote the use of sustainable green technology for effective wastewater treatment.
Fulltext Lymphocytic interstitial pneumonia with tiny cysts of peribronchovascular distribution on CT

Hanafiah M, Johari B, Abdul Kadir RF, Bakar NS, Baharuddin H

Clin Case Rep, 2020 Dec;8(12):3565-3566.
PMID: 33363980 DOI: 10.1002/ccr3.3206

Cysts are a common finding of lymphocytic interstitial pneumonia (LIP) on imaging. Usually, they are limited in number and size. Tiny and numerous cysts of peribronchovascular distribution are less typical but a recognized appearance in LIP.
Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

Bakar NS

Drug Metab Pers Ther, 2021 Mar 19;36(3):173-181.
PMID: 34412170 DOI: 10.1515/dmpt-2020-0153

Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.
Pharmacogenetics of common SNP affecting drug metabolizing enzymes: comparison of allele frequencies between European and Malaysian/Singaporean

Bakar NS

Drug Metab Pers Ther, 2021 Mar 18.
PMID: 33735954 DOI: 10.1515/dmdi-2020-0153

Compared to Europe, data on genetic variation in genes transcribing drug metabolizing enzymes among Asian is limited due to ethnic diversity. Here we compare frequencies for clinically relevant single nucleotide polymorphism (SNP) commonly observed in drug metabolizing enzymes between European and Malaysian/Singaporean. Minor allele frequencies (MAF) for the indicated SNPs for European, South Asian and East Asian populations were obtained from the NCBI website (https://www.ncbi.nlm.nih.gov/snp). The SNP prevalence among Malaysian/Singaporean was characterized from gene association studies. Generally, some SNPs in CYP2D6 and CYP2C19 do not show good agreement between the two populations as to the MAF value obtained. CYP2D6*4 tends to be more common among European, whereas CYP2D6*10 is more common in Malays and Chinese among Singaporean. Regardless of different phenotype, MAF of CYP2D6*4 for Indians is similar to that seen by the European. Singaporeans show smaller MAF for CYP2C19*17 but higher CYP2C19*2 frequencies as opposed to European ones. Following growing attention to the contribution of CYP3A4/5, N-acetyltransferases (NAT2), thiopurine methyltransferase (TPMT) and uridine diphosphate glucuronosyltransferases (UGT)2B7 in predicting drug response across Europe, there are limited pharmacogenetics (PGx) studies examining the gene-drug interaction among Malaysian/Singaporean. To better understand the heterogeneity of the drug response, PGx studies for the abovementioned enzymes between ethnics in Malaysian/Singaporean should be identified.
Effects of magnesium taurate on the onset and progression of galactose-induced experimental cataract: in vivo and in vitro evaluation

Agarwal R, Iezhitsa I, Awaludin NA, Ahmad Fisol NF, Bakar NS, Agarwal P, et al.

Exp Eye Res, 2013 May;110:35-43.
PMID: 23428743 DOI: 10.1016/j.exer.2013.02.011

Cataract, a leading cause of blindness, is characterized by lenticular opacities resulting from denaturation of lens proteins due to activation of calcium-dependent enzyme, calpain. Magnesium (Mg(2+)) plays an important role not only in maintaining a low lenticular calcium (Ca(2+)) and sodium concentration but also in preserving the lens redox status. Taurine has also been shown to reduce lenticular oxidative stress. Present study evaluated the anticataract effects of magnesium taurate in vivo and in vitro. Among the five groups of 9 Sprague Dawley rats each, two groups received 30% galactose diet with topical (GDMT) or oral treatment (GDMO) with magnesium taurate. Two groups received 30% galactose diet with topical (GDT) or oral vehicle (GDO). Remaining 1 group received normal diet (ND). Weekly slit lamp examination was done during 21 days experimental period and then all rats were sacrificed; Ca/Mg ratio and antioxidant parameters including reduced glutathione (GSH), catalase and superoxide dismutase (SOD) activities were measured in the isolated lenses using ELISA. In the in vitro study, 2 groups of 10 normal rat lenses were incubated in Dulbecco's Modified Eagle's Medium (DMEM) with galactose while 1 similar group was incubated in DMEM without galactose. In one of the groups, galactose containing medium was supplemented with magnesium taurate. After 48 h of incubation, lenses were photographed and Ca(2+)/Mg(2+) ratio and antioxidant parameters were measured as for in vivo study. The in vivo study, at the end of experimental period, demonstrated delay in the development of cataract with a mean opacity index of 0.53 ± 0.04 and 0.51 ± 0.03 in GDMO (p < 0.05 versus GDO) and GDMT (p < 0.01 versus GDT) respectively. Histopathological grading showed a lower mean value in treated groups, however, the differences from corresponding controls were not significant. Lenticular Ca(2+)/Mg(2+) ratio with a mean value of 1.20 ± 0.26 and 1.05 ± 0.26 in GDMO and GDMT was significantly lower than corresponding controls (p < 0.05) and in GDMT no significant difference was observed from ND. Lenticular GSH and catalase activities were significantly lower and SOD activity was significantly higher in all galactose fed groups. However, in GDMT, GSH and catalase were significantly higher than corresponding control with mean values of 0.96 ± 0.30 μmol/gm lens weight and 56.98 ± 9.86 μmol/g lens protein respectively (p < 0.05 for GSH and p < 0.01 for catalase). SOD activity with mean values of 13.05 ± 6.35 and 13.27 ± 7.61 units/mg lens protein in GDMO and GDMT respectively was significantly lower compared to corresponding controls (p < 0.05) signifying lesser upregulation of SOD due to lesser oxidative stress in treated groups. In the in vitro study, lenses incubated in magnesium taurate containing medium showed less opacity and a lower mean Ca(2+)/Mg(2+) ratio of 1.64 ± 0.03, which was not significantly different from lenses incubated in DMEM without galactose. Lens GSH and catalase activities were restored to normal in lenses incubated in magnesium taurate containing medium. Both in vivo and in vitro studies demonstrated that treatment with magnesium taurate delays the onset and progression of cataract in galactose fed rats by restoring the lens Ca(2+)/Mg(2+) ratio and lens redox status.
Supraglottic Schwannoma: Dilemma and Challenges in Management

Al-Yahya SN, Saifudin N, Rahim NA, Mansor M, Din S, Bakar NS

Indian J Otolaryngol Head Neck Surg, 2022 Dec;74(Suppl 3):5172-5176.
PMID: 36742766 DOI: 10.1007/s12070-021-03027-4

Laryngeal schwannomas are rare lesions that represent less than 1.5% of all benign laryngeal tumors. Its slow and submucosal growth may cause a delay in consultation and management. Herein, a case of right supraglottic schwannoma is diagnosed in a 34-year-old lady who was unconcerned about hoarseness for 10 years. She was referred to otorhinolaryngology clinic for assessment when hoarseness was detected during consultation for a gynecology surgery. Apart from hoarseness, there were no noisy breathing, shortness of breath or aspiration symptoms. Flexible nasopharyngolaryngoscopy showed a submucosal bulge at the right vestibular fold obscuring the vocal fold causing an airway concern. Computer tomography scan of the neck revealed a heterogenous enhancing mass centered at the right supraglottis measuring 2.6 × 2.7 × 2.7 cm. There were no erosions of the adjacent thyroid and arytenoid cartilages. Subsequently, complete excision of the lesion was done endoscopically. Definitive diagnosis of schwannoma was obtained via histopathology examination. This paper presents our approach and operative steps in the excision of this lesion using microlaryngoscopy with cold instruments.
Fulltext Factors Affecting the Use of Private Outpatient Services among the Adult Population in Malaysia

Anis-Syakira J, Jawahir S, Abu Bakar NS, Mohd Noh SN, Jamalul-Lail NI, Hamidi N, et al.

Int J Environ Res Public Health, 2022 Oct 21;19(20).
PMID: 36294242 DOI: 10.3390/ijerph192013663

The proportion of Malaysians of all ages who use private outpatient services has dropped over time, highlighting the overstretched condition of public outpatient facilities compared to their private counterparts. This paper aims to determine the prevalence of outpatient care, characteristics of outpatient care users by sector, and the factors affecting the utilisation of private outpatient services among the adult population of Malaysia using Andersen's behavioural model. Data from the National Health Morbidity Survey 2019 (NHMS 2019), a nationwide survey, were analysed. Logistic regression analysis was performed to explore the association of predisposing (locality, age, sex, ethnicity, education level, and marital status), enabling (working status, health care coverage, and household income), and need factors (perceived and evaluated needs) with the use of private outpatient services. Variables with a statistical significance ≤ 0.25 in the univariate regression analysis were included in the final multivariable logistic regression analysis. A total of 11,674 respondents, estimated to represent 22.4 million adults aged 18 years and above in Malaysia, were included for analysis. Overall, 8.3% of the adult population of Malaysia used outpatient care and 33.9% used the private sector. Those living in urban areas (OR = 1.80, 95% CI = 1.02, 3.18), non-Malays (OR = 1.74, 95% CI = 1.04, 2.93), those working (OR = 2.47, 95% CI = 1.48, 4.10), those with employer coverage (OR = 4.73, 95% CI = 2.79, 8.01), and those with health problems (OR = 2.26, 95% CI = 1.26, 4.05) were more likely to utilise private outpatient services. Those who self-rated their health status as fair (OR = 0.54, 95% CI = 0.33, 0.91) and who had diabetes, hypertension, or hypercholesterolemia (OR = 0.56, 95% CI = 0.31, 1.02) were less likely to utilise private outpatient services. The predisposing and enabling factors were associated with the use of private outpatient services, and the need factors were strong predictors of private outpatient care utilisation among adults. Understanding the factors associated with the utilisation of private outpatient services could aid in the development of effective initiatives designed to enhance outpatient care access among the population of Malaysia and balance the burden of outpatient care provision on the public and private sector.
Dose-dependent effects of NMDA on retinal and optic nerve morphology in rats

Lambuk L, Jafri AJA, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, et al.

Int J Ophthalmol, 2019;12(5):746-753.
PMID: 31131232 DOI: 10.18240/ijo.2019.05.08

AIM: To investigate dose-dependent effects of N-methyl-D-aspartate (NMDA) on retinal and optic nerve morphology in rats.
METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and 4 were intravitreally administered with vehicle and NMDA at the doses 80, 160 and 320 nmol respectively. Seven days after injection, rats were euthanized, and their eyes were taken for optic nerve toluidine blue and retinal hematoxylin and eosin stainings. The TUNEL assay was done for detecting apoptotic cells.
RESULTS: All groups treated with NMDA showed significantly reduced ganglion cell layer (GCL) thickness within inner retina, as compared to control group. Group NMDA 160 nmol showed a significantly greater GCL thickness than the group NMDA 320 nmol. Administration of NMDA also resulted in a dose-dependent decrease in the number of nuclei both per 100 µm GCL length and per 100 µm2 of GCL. Intravitreal NMDA injection caused dose-dependent damage to the optic nerve. The degeneration of nerve fibres with increased clearing of cytoplasm was observed more prominently as the NMDA dose increased. In accordance with the results of retinal morphometry analysis and optic nerve grading, TUNEL staining demonstrated NMDA-induced excitotoxic retinal injury in a dose-dependent manner.
CONCLUSION: Our results demonstrate dose-dependent effects of NMDA on retinal and optic nerve morphology in rats that may be attributed to differences in the severity of excitotoxicity and oxidative stress. Our results also suggest that care should be taken while making dose selections experimentally so that the choice might best uphold study objectives.
Polypharmacy and potentially inappropriate medications among hospitalized older adults with COVID-19 in Malaysian tertiary hospitals

Chang CT, Mohd Shariff SM, Abu Bakar NS, Ramzuzzaman NS, Lim CK, Lim EYJ, et al.

J Pharm Policy Pract, 2023 Jan 12;16(1):2.
PMID: 36635766 DOI: 10.1186/s40545-022-00504-1

INTRODUCTION: Older adults are among the most vulnerable groups during the COVID-19 epidemic, contributing to a large proportion of COVID-19-related death. Medication review and reconciliation by pharmacist can help reduce the number of potentially inappropriate medications but these services were halted during COVID-19.
AIM: To assess the prevalence and factors associated with inappropriate medicine use among older populations with COVID-19.
METHODS: This was a cross-sectional, retrospective analysis of medications among hospitalized older adults with COVID-19. Potentially inappropriate medication use was categorized using the Beer's and STOPP criteria.
RESULTS: Combining both criteria, 181 (32.7%) of the 553 patients were identified to have used at least one or more potentially inappropriate medication. A marginally higher number of inappropriate medications was documented using the Beers 2019 criteria (151 PIM in 124 patients) compared to STOPP criteria (133 PIMS in 104 patients). The long-term use of proton pump inhibitors (n = 68; 12.3%) and drugs which increases the risk of postural hypotension were the most commonly reported PIM (n = 41; 7.4%). Potentially inappropriate medication use was associated with previous history of hospital admission in the past 12 months (Odds ratio [OR]: 2.27; 95% CI 1.29-3.99) and higher number of discharge medications.
CONCLUSIONS: Nearly, one in three older adults with COVID-19 had been prescribed a PIM, and the proportion of older adults with polypharmacy increased after discharge. This highlights the importance of having clinical pharmacist conducting medication reviews to identify PIMs and ensure medication appropriateness.
Protective effect of magnesium acetyltaurate against endothelin-induced retinal and optic nerve injury

Arfuzir NN, Lambuk L, Jafri AJ, Agarwal R, Iezhitsa I, Sidek S, et al.

Neuroscience, 2016 06 14;325:153-64.
PMID: 27012609 DOI: 10.1016/j.neuroscience.2016.03.041

Vascular dysregulation has long been recognized as an important pathophysiological factor underlying the development of glaucomatous neuropathy. Endothelin-1 (ET1) has been shown to be a key player due to its potent vasoconstrictive properties that result in retinal ischemia and oxidative stress leading to retinal ganglion cell (RGC) apoptosis and optic nerve (ON) damage. In this study we investigated the protective effects of magnesium acetyltaurate (MgAT) against retinal cell apoptosis and ON damage. MgAT was administered intravitreally prior to, along with or after administration of ET1. Seven days post-injection, animals were euthanized and retinae were subjected to morphometric analysis, TUNEL and caspase-3 staining. ON sections were stained with toluidine blue and were graded for neurodegenerative effects. Oxidative stress was also estimated in isolated retinae. Pre-treatment with MgAT significantly lowered ET1-induced retinal cell apoptosis as measured by retinal morphometry and TUNEL staining. This group of animals also showed significantly lesser caspase-3 activation and significantly reduced retinal oxidative stress compared to the animals that received intravitreal injection of only ET1. Additionally, the axonal degeneration in ON was markedly reduced in MgAT pretreated animals. The animals that received MgAT co- or post-treatment with ET1 also showed improvement in all parameters; however, the effects were not as significant as observed in MgAT pretreated animals. The current study showed that the intravitreal pre-treatment with MgAT reduces caspase-3 activation and prevents retinal cell apoptosis and axon loss in ON induced by ET1. This protective effect of ET1 was associated with reduced retinal oxidative stress.
Neuroprotective Effect of Magnesium Acetyltaurate Against NMDA-Induced Excitotoxicity in Rat Retina

Lambuk L, Jafri AJ, Arfuzir NN, Iezhitsa I, Agarwal R, Rozali KN, et al.

Neurotox Res, 2017 01;31(1):31-45.
PMID: 27568334 DOI: 10.1007/s12640-016-9658-9

Glutamate excitotoxicity plays a major role in the loss of retinal ganglion cells (RGCs) in glaucoma. The toxic effects of glutamate on RGCs are mediated by the overstimulation of N-methyl-D-aspartate (NMDA) receptors. Accordingly, NMDA receptor antagonists have been suggested to inhibit excitotoxicity in RGCs and delay the progression and visual loss in glaucoma patients. The purpose of the present study was to examine the potential neuroprotective effect of Mg acetyltaurate (MgAT) on RGC death induced by NMDA. MgAT was proposed mainly due to the combination of magnesium (Mg) and taurine which may provide neuroprotection by dual mechanisms of action, i.e., inhibition of NMDA receptors and antioxidant effects. Rats were divided into 5 groups and were given intravitreal injections. Group 1 (PBS group) was injected with vehicle; group 2 (NMDA group) was injected with NMDA while groups 3 (pre-), 4 (co-), and 5 (post-) treatments were injected with MgAT, 24 h before, in combination or 24 h after NMDA injection respectively. NMDA and MgAT were injected in PBS at doses 160 and 320 nmol, respectively. Seven days after intravitreal injection, the histological changes in the retina were evaluated using hematoxylin & eosin (H&E) staining. Optic nerves were dissected and stained in Toluidine blue for grading on morphological neurodegenerative changes. The extent of apoptosis in retinal tissue was assessed by TUNEL assay and caspase-3 immunohistochemistry staining. The estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors and caspase-3 activity in retina was done using enzyme-linked immunosorbent assay (ELISA) technique. The retinal morphometry showed reduced thickness of ganglion cell layer (GCL) and reduction in the number of retinal cells in GCL in NMDA group compared to the MgAT-treated groups. TUNEL and caspase-3 staining showed increased number of apoptotic cells in inner retina. The results were further corroborated by the estimation of neurotrophic factor, oxidative stress, pro/anti-apoptotic factors, and caspase-3 activity in retina. In conclusion, current study revealed that intravitreal MgAT prevents retinal and optic nerve damage induced by NMDA. Overall, our data demonstrated that the pretreatment with MgAT was more effective than co- and posttreatment. This protective effect of MgAT against NMDA-induced retinal cell apoptosis could be attributed to the reduction of retinal oxidative stress and activation of BDNF-related neuroprotective mechanisms.
Antiapoptotic effect of taurine against NMDA-induced retinal excitotoxicity in rats

Lambuk L, Iezhitsa I, Agarwal R, Bakar NS, Agarwal P, Ismail NM

Neurotoxicology, 2019 01;70:62-71.
PMID: 30385388 DOI: 10.1016/j.neuro.2018.10.009

OBJECTIVE: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure.
METHODOLOGY: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique.
RESULTS: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p
Synergy of flavone with vancomycin and oxacillin against vancomycin-intermediate Staphyloccus aureus

Bakar NS, Zin NM, Basri DF

Pak J Pharm Sci, 2012 Jul;25(3):633-8.
PMID: 22713953

This study evaluated in vitro activity of 9 flavonoids in combination with vancomycin or oxacillin against vancomycin-intermediate Staphylococcus aureus (VISA) ATCC 700699 by employing the checkerboard method to obtain Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index. Six flavonoids namely hesperitin, rutin, naringenin, flavones, naringin and 3, 7-dihyroxyflavone which exhibited notable inhibitory activity (MIC values < 3200 μg/ml) were further evaluated for combination assay with antibiotics. The combinations of vancomycin+flavone and oxacillin+flavone were found synergistic with the FIC index value 0.094 and 0.126, respectively. Other combinations showed an additive interaction (FIC index = 1.063) but no antagonistic reaction (FIC index > 4) were observed. In time kill studies, oxacillin-flavone combination at synergistic concentration demonstrated bactericidal effect at 24 h period with concentration-dependent manner on the VISA strain. Following 1 h exposure, the combination also produced persistent effect on the bacteria growth for 2.9 hrs at 1x sub-MIC and more than 24 h at 5x of sub-MIC and there was a significant difference between both concentrations (p<0.05). Vancomycin-flavone combination, however, showed no concentration-dependent effect and lower PAE values (1.159 h and 2.322 h at 1x and 5x sub-MIC, respectively) on the VISA strain. In conclusion, flavone markedly intensifies the susceptibility of oxacillin against VISA and the combination can be implicated for further interaction studies at molecular level.
Fulltext Philanthotoxin-343 attenuates retinal and optic nerve injury, and protects visual function in rats with N-methyl-D-aspartate-induced excitotoxicity

Fazel MF, Abu IF, Mohamad MHN, Agarwal R, Iezhitsa I, Bakar NS, et al.

PLoS One, 2020;15(7):e0236450.
PMID: 32706792 DOI: 10.1371/journal.pone.0236450

Retinal ganglion cell (RGC) loss and optic neuropathy, both hallmarks of glaucoma, have been shown to involve N-methyl-D-aspartate receptor (NMDAR)-mediated excitotoxicity. This study investigated the neuroprotective effects of Philanthotoxin (PhTX)-343 in NMDA-induced retinal injury to alleviate ensuing visual impairments. Sprague-Dawley rats were divided into three; Group I was intravitreally injected with phosphate buffer saline as the control, Group II was injected with NMDA (160 nM) to induce retinal excitotoxic injury, while Group III was injected with PhTX-343 (160 nM) 24 h prior to excitotoxicity induction with NMDA. Rats were subjected to visual behaviour tests seven days post-treatment and subsequently euthanized. Rat retinas and optic nerves were subjected to H&E and toluidine blue staining, respectively. Histological assessments showed that NMDA exposure resulted in significant loss of retinal cell nuclei and thinning of ganglion cell layer (GCL). PhTX-343 pre-treatment prevented NMDA-induced changes where the RGC layer morphology is similar to the control. The numbers of nuclei in the NMDA group were markedly lower compared to the control (p<0.05). PhTX-343 group had significantly higher numbers of nuclei within 100 μm length and 100 μm2 area of GCL (2.9- and 1.7-fold, respectively) compared to NMDA group (p<0.05). PhTX-343 group also displayed lesser optic nerve fibres degeneration compared to NMDA group which showed vacuolation in all sections. In the visual behaviour test, the NMDA group recorded higher total distance travelled, and lower total immobile time and episodes compared to the control and PhTX-343 groups (p<0.05). Object recognition tests showed that the rats in PhTX-343 group could recognize objects better, whereas the same objects were identified as novel by NMDA rats despite multiple exposures (p<0.05). Visual performances in the PhTX-343 group were all comparable with the control (p>0.05). These findings suggested that PhTX-343 inhibit retinal cell loss, optic nerve damage, and visual impairments in NMDA-induced rats.
Leptin-induced increase in blood pressure and markers of endothelial activation during pregnancy in Sprague Dawley rats is prevented by resibufogenin, a marinobufagenin antagonist

Hassan MJM, Bakar NS, Aziz MA, Basah NK, Singh HJ

Reprod Biol, 2020 Jun;20(2):184-190.
PMID: 32253169 DOI: 10.1016/j.repbio.2020.03.004

Levels of leptin and marinobufagenin (MBG), a cardiotonic steroid, are elevated in the serum of women with pre-eclampsia. Besides this, leptin administration to pregnant rats increases systolic blood pressure (SBP), urinary protein excretion and serum markers of endothelial activation. The link between leptin and MBG is unknown and it is also unclear if leptin-induced increases in blood pressure and proteinuria in the pregnant rat could be prevented by an MBG antagonist. To ascertain this link, this study investigated the effect of resibufogenin (RBG), a marinobufagenin antagonist, on leptin-induced increases in blood pressure and proteinuria during pregnancy in rats. Four groups of Sprague-Dawley rats, aged 12 weeks, were given either normal saline (CONTROL) or 120 μg/kg/day of leptin (LEP), or 120 μg/kg/day of leptin+30 μg/kg/day of resibufogenin (L + RBG) or 30 μg/kg/day of resibufogenin (RBG) from Day 1-20 of pregnancy. Systolic blood pressure and urinary protein excretion (UPE) were measured during the study period. Animals were euthanized on day 21 of pregnancy and vascular cell adhesion molecule 1, (VCAM-1), soluble intracellular cell adhesion molecule 1 (sICAM-1), E-selectin and endothelin-1 (ET-1) were estimated in the serum. SBP, UPE, VCAM-1, sICAM-1 and ET-1 were significantly higher only in the LEP group when compared with those in CONT and in L + RBG and RBG groups. The prevention by RBG of leptin-induced increases in SBP, proteinuria, and endothelial activation during pregnancy seem to suggest a potential role for MBG in leptin-induced adverse effects on blood pressure, urinary protein excretion and endothelial activity during pregnancy in the rat.
Fulltext Cystic teratoma mimicking recurrent pleural effusion, complicated by Mycobacterium abscessus infection

Mohd Esa NY, Mohd Radzi AA, Bakar NS, Mohd Khalid MS, Ismail AI, Abdul Rani MF

Respirol Case Rep, 2016 May;4(3):e00155.
PMID: 27516884 DOI: 10.1002/rcr2.155

Teratomas of anterior mediastinum are rare. They are often slow growing, asymptomatic, and detected incidentally on chest imaging. Mycobacterium abscessus (M. abscessus) is an acid-fast bacillus that is classified as a pathogenic "rapid growing" non-tuberculous mycobacteria. It is an uncommon cause of human pathology, which may cause skin and soft tissue infection after skin injury following inoculation, minor trauma, and surgery. Here, we present an unusual case of benign cystic teratoma mimicking recurrent pleural effusion, which was subsequently complicated by M. abscessus infection following thoracotomy. Cystic teratoma is rare, but it needs to be considered whenever clinical and investigative work-up fails to provide a convincing diagnosis. A combined clinical, radiological, surgical, and histopathological assessment is important to arrive at the correct diagnosis. Rapidly growing mycobacteria needs to be included in the differential diagnosis of patients with non-resolving infected post-thoracotomy wound and who do not respond to broad-spectrum antibiotics.
Fulltext Effects of home visits on quality of life among older adults: a systematic review protocol

Tay YL, Abu Bakar NS, Tumiran R, Ab Rahman NH, Mohd Ma'amor NAA, Yau WK, et al.

Syst Rev, 2021 Dec 06;10(1):307.
PMID: 34872589 DOI: 10.1186/s13643-021-01862-8

BACKGROUND: Home visiting services for older adults have been offered for decades to maintain and promote health and independent functioning, thus enhancing quality of life. Previous systematic reviews have provided a mixed picture of the benefits of home visiting programmes in older adults, primarily because of heterogeneity in study designs, targeted populations, and intervention strategies. These reviews may also become out of date; thus, an updated synthesis of relevant studies is warranted. Our objective is to perform a systematic review of recently published primary studies on the effectiveness of multi-professional home visits on quality of life among older adults.
METHODS: We will perform a comprehensive search for studies investigating the effect of a multi-professional home visit approach on quality of life among older adults. We will conduct the literature search in selected electronic databases and relevant research websites from January 2010 onwards. We will include randomised controlled trials (RCTs), cluster randomised controlled trials (cluster RCTs), and observational studies that enrolled older adults without dementia over 60 years old, along with studies involving multi-professional preventive-promotive home visit approaches not related to recent hospital discharge. We will report our planned review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We will retrieve and record relevant data in a standardised data extraction form and evaluate the quality of the included articles using the Cochrane risk of bias tool and the quality assessment tool for studies with diverse designs (QATSDD). Where appropriate, outcomes will be pooled for meta-analysis using a random-effects model. The main outcomes include quality of life, incidence of falls, depression, dementia, and emergency department admissions.
DISCUSSION: This review may provide evidence for the effectiveness of home visits in improving older adults' quality of life. It will potentially benefit health care professionals, policymakers, and researchers by facilitating the design and delivery of interventions related to older generations and improve service delivery in future.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234531 .

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