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Ozonation of metoprolol in aqueous solution: ozonation by-products and mechanisms of degradation

Tay KS, Rahman NA, Abas MR

Environ Sci Pollut Res Int, 2013 May;20(5):3115-21.
PMID: 23054788 DOI: 10.1007/s11356-012-1223-3

This study investigated the degradation pathway of metoprolol, a widely used β-blocker, in the ozonation via the identification of generated ozonation by-products (OPs). Structure elucidation of OPs was performed using HPLC coupled with quadrupole time-of-flight high-resolution mass spectrometry. Seven OPs were identified, and four of these have not been reported elsewhere. Identified OPs of metoprolol included aromatic ring breakdown by-products; aliphatic chain degraded by-products and aromatic ring mono-, di-, and tetrahydroxylated derivatives. Based on the detected OPs, metoprolol could be degraded through aromatic ring opening reaction via reaction with ozone (O3) and degradation of aliphatic chain and aromatic ring via reaction with hydroxyl radical (•OH).
Fulltext Distribution of Flavonoids and Cyclohexenyl Chalcone Derivatives in Conventional Propagated and In Vitro-Derived Field-Grown Boesenbergia rotunda (L.) Mansf

Tan BC, Tan SK, Wong SM, Ata N, Rahman NA, Khalid N

Evid Based Complement Alternat Med, 2015;2015:451870.
PMID: 25883671 DOI: 10.1155/2015/451870

The distribution patterns of flavonoids and cyclohexenyl chalcone derivatives in conventional propagated (CP) and in vitro-derived (CPA) field-grown plants of an important medicinal ginger, Boesenbergia rotunda, are described. A total of eight compounds were extracted from six organs (rootlet, rhizome, shoot base, maroon stem, stalk, and leaf) of the CP and CPA plants. Five major chromatographic peaks, namely, alpinetin, pinocembrin, pinostrobin, 4-hydroxypanduratin A, and panduratin A, were consistently observed by high performance liquid chromatography. Nonaerial organs had higher levels of flavonoids than the aerial ones for all types of samples. Among the compounds detected, pinostrobin and 4-hydroxypanduratin A were the most abundant flavonoid and cyclohexenyl chalcone derivative, respectively. The distribution and abundance of the bioactive compounds suggested that the shoot base could be more potentially useful for medicinal application than other organs of the plant and may be the site of storage or occurrence of biosynthetic enzymatic activities.
Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors

Takhi M, Sreenivas K, Reddy CK, Munikumar M, Praveena K, Sudheer P, et al.

Eur J Med Chem, 2014 Sep 12;84:382-94.
PMID: 25036796 DOI: 10.1016/j.ejmech.2014.07.036

A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.
Fulltext Flavonoids with M1 muscarinic acetylcholine receptor binding activity

Swaminathan M, Chee CF, Chin SP, Buckle MJ, Rahman NA, Doughty SW, et al.

Molecules, 2014 Jun 27;19(7):8933-48.
PMID: 24979399 DOI: 10.3390/molecules19078933

Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer's disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki=40-110 µM), comparable to that of acetylcholine (Ki=59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.
Fulltext Analogues of 2'-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase

Sukumaran SD, Nasir SB, Tee JT, Buckle MJC, Othman R, Rahman NA, et al.

J Enzyme Inhib Med Chem, 2021 Dec;36(1):130-137.
PMID: 33243025 DOI: 10.1080/14756366.2020.1847100

A series of C4-substituted tertiary nitrogen-bearing 2'-hydroxychalcones were designed and synthesised based on a previous mixed type acetylcholinesterase inhibitor. Majority of the 2'-hydroxychalcone analogues displayed a better inhibition against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound 4c was identified as the most potent AChE inhibitor (IC50: 3.3 µM) and showed the highest selectivity for AChE over BuChE (ratio >30:1). Molecular docking studies suggested that compound 4c interacts with both the peripheral anionic site (PAS) and catalytic anionic site (CAS) regions of AChE. ADMET analysis confirmed the therapeutic potential of compound 4c based on its blood-brain barrier penetrating. Overall, the results suggest that this 2'-hydroxychalcone deserves further investigation into the therapeutic lead for Alzheimer's disease (AD).
Fulltext Presentation of retinoblastoma patients in Malaysia

Subramaniam S, Rahmat J, Rahman NA, Ramasamy S, Bhoo-Pathy N, Pin GP, et al.

Asian Pac J Cancer Prev, 2014;15(18):7863-7.
PMID: 25292078

BACKGROUND: Retinoblastoma is a rare type of cancer that usually develops in early childhood. If left untreated it can cause blindness and even death. The aim of this study is to determine sociodemographic and clinical features of retinoblastoma patients and also to determine the treatment pattern and outcome in Malaysia.

MATERIALS AND METHODS: Data for this study were retrieved from the Retinoblastoma Registry of the National Eye Database (NED) in Malaysia. Hospital Kuala Lumpur, Hospital Umum Kuching, Sarawak and Hospital Queen Elizabeth, Kota Kinabalu were the major source data providers for this study. Data collected in the registry cover demography, clinical presentation, modes of treatment, outcomes and complications.

RESULTS: The study group consisted of 119 patients (162 eyes) diagnosed with retinoblastoma between 2004 and 2012. There were 68 male (57.1%) and 51 (42.9%) female. The median age at presentation was 22 months. A majority of patients were Malays (54.6%), followed by Chinese (18, 5%), Indians (8.4%), and indigenous races (15.9%). Seventy six (63.8%) patients had unilateral involvement whereas 43 patients had bilateral disease (36.1%). It was found that most children presented with leukocoria (110 patients), followed by strabismus (19), and protopsis (12). Among the 76 with unilateral involvement (76 eyes), enucleation was performed for a majority (79%). More than half of these patients had extraocular extension. Of the 40 who received chemotherapy, 95% were given drugs systemically. Furthermore, in 43 patients with bilateral involvement (86 eyes), 35 (41%) eyes were enucleated and 17 (49%) showed extraocular extension. Seventy-two percent of these patients received systemic chemotherapy. The patients were followed up 1 year after diagnosis, whereby 66 were found to be alive and 4 dead. Sixteen patients defaulted treatment and were lost to follow-up, whereas follow-up data were not available in 33 patients.

CONCLUSIONS: Patients with retinoblastoma in this middle-income Asian setting are presenting at late stages. As a result, a high proportion of patients warrant aggressive management such as enucleation. We also showed that a high number of patients default follow-up. Therefore, reduction in refusal or delay to initial treatment, and follow-up should be emphasized in order to improve the survival rates of retinoblastoma in this part of the world.
Primary Melanoma of the Third Metatarsal

Singh VA, Lim CY, Yan HC, Rahman NA

J Foot Ankle Surg, 2017 06 26;56(6):1292-1297.
PMID: 28659241 DOI: 10.1053/j.jfas.2017.05.005

Melanoma is a well-known malignant neoplasm of the skin, although it can also arise from other structures. Bone metastasis is not an uncommon event associated with melanoma, although primary osseous melanoma is very rare. In the present report, we describe a case of primary melanoma arising from the left third metatarsal in an adult male. The lesion was treated with surgical excision without adjunct chemotherapy, and recurrence developed approximately 12 months after the foot surgery. The patient died of the cancer 34 months after it had been identified. Primary melanoma arising in a metatarsal is rare, and we wished to highlight this unusual presentation.
Saccharification of polysaccharide content of palm kernel cake using enzymatic catalysis for production of biobutanol in acetone-butanol-ethanol fermentation

Shukor H, Abdeshahian P, Al-Shorgani NK, Hamid AA, Rahman NA, Kalil MS

Bioresour Technol, 2016 Feb;202:206-13.
PMID: 26710346 DOI: 10.1016/j.biortech.2015.11.078

In this work, hydrolysis of cellulose and hemicellulose content of palm kernel cake (PKC) by different types of hydrolytic enzymes was studied to evaluate monomeric sugars released for production of biobutanol by Clostridium saccharoperbutylacetonicum N1-4 (ATCC 13564) in acetone-butanol-ethanol (ABE) fermentation. Experimental results revealed that when PKC was hydrolyzed by mixed β-glucosidase, cellulase and mannanase, a total simple sugars of 87.81±4.78 g/L were produced, which resulted in 3.75±0.18 g/L butanol and 6.44±0.43 g/L ABE at 168 h fermentation. In order to increase saccharolytic efficiency of enzymatic treatment, PKC was pretreated by liquid hot water before performing enzymatic hydrolysis. Test results showed that total reducing sugars were enhanced to 97.81±1.29 g/L with elevated production of butanol and ABE up to 4.15±1.18 and 7.12±2.06 g/L, respectively which represented an A:B:E ratio of 7:11:1.
Production of butanol by Clostridium saccharoperbutylacetonicum N1-4 from palm kernel cake in acetone-butanol-ethanol fermentation using an empirical model

Shukor H, Al-Shorgani NK, Abdeshahian P, Hamid AA, Anuar N, Rahman NA, et al.

Bioresour Technol, 2014 Oct;170:565-73.
PMID: 25171212 DOI: 10.1016/j.biortech.2014.07.055

Palm kernel cake (PKC) was used for biobutanol production by Clostridium saccharoperbutylacetonicum N1-4 in acetone-butanol-ethanol (ABE) fermentation. PKC was subjected to acid hydrolysis pretreatment and hydrolysates released were detoxified by XAD-4 resin. The effect of pH, temperature and inoculum size on butanol production was evaluated using an empirical model. Twenty ABE fermentations were run according to an experimental design. Experimental results revealed that XAD-4 resin removed 50% furfural and 77.42% hydroxymethyl furfural. The analysis of the empirical model showed that linear effect of inoculums size with quadratic effect of pH and inoculum size influenced butanol production at 99% probability level (P<0.01). The optimum conditions for butanol production were pH 6.28, temperature of 28°C and inoculum size of 15.9%. ABE fermentation was carried out under optimum conditions which 0.1g/L butanol was obtained. Butanol production was enhanced by diluting PKC hydrolysate up to 70% in which 3.59g/L butanol was produced.
Enhanced mannan-derived fermentable sugars of palm kernel cake by mannanase-catalyzed hydrolysis for production of biobutanol

Shukor H, Abdeshahian P, Al-Shorgani NK, Hamid AA, Rahman NA, Kalil MS

Bioresour Technol, 2016 Oct;218:257-64.
PMID: 27372004 DOI: 10.1016/j.biortech.2016.06.084

Catalytic depolymerization of mannan composition of palm kernel cake (PKC) by mannanase was optimized to enhance the release of mannan-derived monomeric sugars for further application in acetone-butanol-ethanol (ABE) fermentation. Efficiency of enzymatic hydrolysis of PKC was studied by evaluating effects of PKC concentration, mannanase loading, hydrolysis pH value, reaction temperature and hydrolysis time on production of fermentable sugars using one-way analysis of variance (ANOVA). The ANOVA results revealed that all factors studied had highly significant effects on total sugar liberated (P<0.01). The optimum conditions for PKC hydrolysis were 20% (w/v) PKC concentration, 5% (w/w) mannanase loading, hydrolysis pH 4.5, 45°C temperature and 72h hydrolysis time. Enzymatic experiments in optimum conditions revealed total fermentable sugars of 71.54±2.54g/L were produced including 67.47±2.51g/L mannose and 2.94±0.03g/L glucose. ABE fermentation of sugar hydrolysate by Clostridium saccharoperbutylacetonicum N1-4 resulted in 3.27±1.003g/L biobutanol.
Association between cognitive reserve with cognitive impairment, social and occupational functioning, and quality of life in schizophrenia: A preliminary study in the Malaysian population

Sharip S, Zairani MI, Ing LP, Baharom NN, Asarapoo NS, Rahman NA, et al.

Asian J Psychiatr, 2020 Oct;53:102230.
PMID: 32585635 DOI: 10.1016/j.ajp.2020.102230
Fulltext Descriptive distribution and phylogenetic analysis of feline infectious peritonitis virus isolates of Malaysia

Sharif S, Arshad SS, Hair-Bejo M, Omar AR, Zeenathul NA, Fong LS, et al.

Acta Vet Scand, 2010 Jan 06;52:1.
PMID: 20053278 DOI: 10.1186/1751-0147-52-1

The descriptive distribution and phylogeny of feline coronaviruses (FCoVs) were studied in cats suspected of having feline infectious peritonitis (FIP) in Malaysia. Ascitic fluids and/or biopsy samples were subjected to a reverse transcription polymerase chain reaction (RT-PCR) targeted for a conserved region of 3'untranslated region (3'UTR) of the FCoV genome. Eighty nine percent of the sampled animals were positive for the presence of FCoV. Among the FCoV positive cats, 80% of cats were males and 64% were below 2 years of age. The FCoV positive cases included 56% domestic short hair (DSH), 40% Persian, and 4% Siamese cats. The nucleotide sequences of 10 selected amplified products from FIP cases were determined. The sequence comparison revealed that the field isolates had 96% homology with a few point mutations. The extent of homology decreased to 93% when compared with reference strains. The overall branching pattern of phylogenetic tree showed two distinct clusters, where all Malaysian isolates fall into one main genetic cluster. These findings provided the first genetic information of FCoV in Malaysia.
Study on the physical and chemical composition of agro wastes for the production of 5-hydroxymethylfurfural

Shamsul NS, Kamarudin SK, Rahman NA

Bioresour Technol, 2018 Jan;247:821-828.
PMID: 30060418 DOI: 10.1016/j.biortech.2017.09.140

Treated sludge, goat manure, sugarcane bagasse, empty fruit bunches of oil palm (EFBP) and dry leaves are agro wastes that have high potential for use as feedstocks for the production of 5-hydroxymethylfurfural (5-HMF). The focus of this study is to investigate the production of 5-HMF from agro wastes via co-hydrothermal (CHT) treatment and extraction. Present study include examine on agro waste's physical and chemical properties and also their thermal degradation behaviour. The analysis of the bio-oil products is conducted by FTIR and GC-MS. Co-hydrothermal experiments were conducted at a temperature of 300°C with an experimental time of 15min, followed by alcohol extraction. Highest carbon and hydrogen content are 45.94% and 6.49% (dry leaves) with maximum high heating value 18.39MJ/kg (dry leaves) and fix carbon value 6.60 (goat manure). Through CHT about 39% 5-HMF, 22.97% carboxylic acids, 0.97% of aromatic and 0.73% aldehyde obtained.
Fulltext Effects of Low-Level Laser Therapy and Bracket Systems on Root Resorption during Orthodontic Treatment: A Randomized Clinical Trial

Shahid F, Nowrin SA, Alam MK, Khamis MF, Husein A, Rahman NA

Healthcare (Basel), 2023 Mar 15;11(6).
PMID: 36981521 DOI: 10.3390/healthcare11060864

This study aimed to assess the outcomes of low-level laser therapy (LLLT) with the conventional bracket (CB) and self-ligating (SL) bracket systems on root resorption (RR) during orthodontic treatment. A total of 32 patients were included in this randomized clinical trial. All the patients were randomly divided into four individual groups (SLL: self-ligating laser, CBL: conventional bracket laser, SLNL: self-ligating non-laser, CBNL: conventional bracket non-laser). RR was measured from the cone-beam computed tomography (CBCT) radiographs which were taken at two stages of the orthodontic treatment: pre-treatment (T1) and after leveling and alignment stage (T2). Wilcoxon rank test for the comparison was conducted to compare the RR at T1 and T2 stages within each group and showed a significant difference (p < 0.05) for various variables. Mann Whitney test compared the RR in laser and non-laser groups irrespective of the bracket systems and exhibited no significant differences except the left lateral incisor. Moreover, CB and SL groups showed no significant difference in RR among any tooth. Kruskal Wallis test was performed to compare the RR among all groups which presented no significant differences. LLLT and bracket systems have no consequences on RR until the leveling and alignment stage of orthodontic treatment.
Fulltext Feeding Behaviour of Cynopterus sphinx (Pteropodidae) Under Captive Conditions

Shafie NJ, Rahman NA, Sah SA, Rosely NF, Sufian M

Trop Life Sci Res, 2014 Dec;25(2):53-9.
PMID: 27073599 MyJurnal

We examined the olfactory and visual abilities of megachiropteran bats, Cynopterus sphinx, for discrimination of the odour and shape of the banana fruit, Musa sp. We conducted the experiments in captive conditions by offering a selection of ripe bananas, blended bananas and artificial bananas. The behaviour of the bats was observed visually, and the percentage of activity and rest, duration of the first foraging bout, number of feeding attempts and the average duration of successful attempts was recorded for each bat. The bats exhibited an increased number of visits to ripe bananas and blended banana fruits. However, the artificial fruit did not evoke any response. Our study suggests that odour cues are more important than visual cues for the location of fruits by C. sphinx.
Fulltext Cost analysis of facial injury treatment in two university hospitals in Malaysia: a prospective study

Saperi BS, Ramli R, Ahmed Z, Muhd Nur A, Ibrahim MI, Rashdi MF, et al.

Clinicoecon Outcomes Res, 2017;9:107-113.
PMID: 28223831 DOI: 10.2147/CEOR.S119910

OBJECTIVE: Facial injury (FI) may occur in isolation or in association with injuries to other parts of the body (facial and other injury [FOI]). The objective of this study was to determine the direct treatment costs incurred during the management of facial trauma.
MATERIALS AND METHODS: A prospective cohort study on treatment cost for FIs and FOIs due to road-traffic crashes in two university hospitals in Malaysia was conducted from July 2010 to June 2011. The patients were recruited from emergency departments and reviewed after 6 months from the date of initial treatment. Direct cost analysis, comparison of cost and length of hospital stay, and Injury Severity Score (ISS) were performed.
RESULTS: A total of 190 patients were enrolled in the study, of whom 83 (43.7%) had FI only, and 107 (56.3%) had FOI. The mean ISS was 5.4. The mean length of stay and costs for patients with FI only were 5.8 days with a total cost of US$1,261.96, whereas patients with FOI were admitted for 7.8 days with a total cost of US$1,716.47. Costs doubled if the treatment was performed under general anesthesia compared to local anesthesia.
CONCLUSION: Treatment of FI and FOI imposes a financial burden on the health care system in Malaysia.
Recent advances in celluloses and their hybrids for stimuli-responsive drug delivery

Sampath Udeni Gunathilake TM, Ching YC, Chuah CH, Rahman NA, Liou NS

Int J Biol Macromol, 2020 May 07;158:670-688.
PMID: 32389655 DOI: 10.1016/j.ijbiomac.2020.05.010

The limitations of existing drug delivery systems (DDS) such as non-specific bio-distribution and poor selectivity have led to the exploration of a variety of carrier platforms to facilitate highly desirable and efficient drug delivery. Stimuli-responsive DDS are one of the most versatile and innovative approach to steer the compounds to the intended sites by exploiting their responsiveness to a range of various triggers. Preparation of stimuli-responsive DDS using celluloses and their derivatives offer a remarkable advantage over conventional polymer materials. In this review, we highlight on state-of-art progress in developing cellulose/cellulose hybrid stimuli-responsive DDS, which covers the preparation techniques, physicochemical properties, basic principles and, mechanisms of stimuli effect on drug release from various types of cellulose based carriers, through recent innovative investigations. Attention has been paid to endogenous stimuli (pH, temperature, redox gradient and ionic-strength) responsive DDS and exogenous stimuli (light, magnetic field and electric field) responsive DDS, where the cellulose-based materials have been extensively employed. Furthermore, the current challenges and future prospects of these DDS are also discussed at the end.
Evaluation of Microleakage Between Different Post and Core Systems Under Gradual Loading: an In-Vitro Study

Salim NA, Muttlib NAA, Alawi R, Rahman NA, Ariffin Z

Acta Stomatol Croat, 2018 Sep;52(3):218-226.
PMID: 30510297 DOI: 10.15644/asc52/3/5

Objective: This study aimed to compare the difference in marginal dye penetration between everStick, Parapost XP, Parapost fiber white and control groups under gradual loading.
Materials and Methods: Sixty-eight human maxillary permanent incisors were divided into four groups. Each specimen was endodontically treated with step-back technique and prepared for each post system according to experimental groups, subsequently cemented in the canal. Composite resin cores were built and laboratory fabricated metal crowns were cemented. All specimens except those in the control group were subjected to thermal cycling. All groups were subjected to gradual loading from 0N-50N for 100 cycles. Specimens were sectioned transversely and the depths of dye penetration along the post were measured. Data were entered in SPSS ver. 22 and analyzed using two-way ANOVA test.
Results: There was no significant difference in marginal dye penetration between each group (p-value>0.05). However, there was a significant difference in percentage of marginal dye penetration between all groups (p-value<0.05); post-hoc comparison showed significant difference between Fiber White and Control groups (p-value=0.009).
Conclusion: All the groups showed dye penetration but the percentage was significant only between Parapost Fiber White and the control groups.
The awareness of oral cancer in adult patients attending School of Dental Sciences, Universiti Sains Malaysia: a preliminary study

Saini R, Ghani ZI, Rahman NA

Singapore Dent J, 2006 Dec;28(1):34-9.
PMID: 17378340

Lack of awareness of signs and symptoms and risk factors of oral cancer can lead to late presentation of the disease that contributes to poor survival of patients who contract it. This study aims to determine the level of awareness regarding oral cancer in adult patients attending School of Dental Sciences, Universiti Sains Malaysia.
Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus

Rothan HA, Bahrani H, Shankar EM, Rahman NA, Yusof R

Antiviral Res, 2014 Aug;108:173-80.
PMID: 24929084 DOI: 10.1016/j.antiviral.2014.05.019

Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

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