Displaying publications 41 - 60 of 166 in total

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  1. Fulltext Antiviral cationic peptides as a strategy for innovation in global health therapeutics for dengue virus: high yield production of the biologically active recombinant plectasin peptide
    Rothan HA, Mohamed Z, Suhaeb AM, Rahman NA, Yusof R
    OMICS, 2013 Nov;17(11):560-7.
    PMID: 24044366 DOI: 10.1089/omi.2013.0056
    Dengue virus infects millions of people worldwide, and there is no vaccine or anti-dengue therapeutic available. Antimicrobial peptides have been shown to possess effective antiviral activity against various viruses. One of the main limitations of developing these peptides as potent antiviral drugs is the high cost of production. In this study, high yield production of biologically active plectasin peptide was inexpensively achieved by producing tandem plectasin peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was assessed as a target to inhibit dengue virus replication in Vero cells. Single units of recombinant plectasin were collected after applying consecutive steps of refolding, cleaving by Factor Xa, and nickel column purification to obtain recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the recombinant peptide against Vero cells was 20 μM (100 μg/mL). The reaction velocity of DENV2 NS2B-NS3pro decreased significantly after increasing concentrations of recombinant plectasin were applied to the reaction mixture. Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of 5.03 ± 0.98 μM. The percentage of viral inhibition was more than 80% at the MNTD value of plectasin. In this study, biologically active recombinant plectasin which was able to inhibit dengue protease and viral replication in Vero cells was successfully produced in E. coli in a time- and cost- effective method. These findings are potentially important in the development of potent therapeutics against dengue infection.
  2. Current approaches in antiviral drug discovery against the Flaviviridae family
    Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.
    Curr Pharm Des, 2014;20(21):3428-44.
    PMID: 24001228
    Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.
  3. Fulltext Sandstorm appearance of pulmonary alveolar microlithiasis incidentally detected in a young, asymptomatic male
    Ch'ng LS, Bux SI, Liam CK, Rahman NA, Ho CY
    Korean J Radiol, 2013 Sep-Oct;14(5):859-62.
    PMID: 24043987 DOI: 10.3348/kjr.2013.14.5.859
    Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of symptoms in contrast to the imaging findings. We present a case of a 24-year-old Malay man having an incidental abnormal pre-employment chest radiograph of dense micronodular opacities giving the classical "sandstorm" appearance. High-resolution computed tomography of the lungs showed microcalcifications with subpleural cystic changes. Open lung biopsy showed calcospherites within the alveolar spaces. The radiological and histopathological findings were characteristic of PAM.
  4. Fulltext Validation of quantitative structure-activity relationship (QSAR) model for photosensitizer activity prediction
    Frimayanti N, Yam ML, Lee HB, Othman R, Zain SM, Rahman NA
    Int J Mol Sci, 2011;12(12):8626-44.
    PMID: 22272096 DOI: 10.3390/ijms12128626
    Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r(2) value, r(2) (CV) value and r(2) prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC(50) values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r(2) prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.
  5. Comparison of telomere length and telomerase activation between breast fibroadenoma and infiltrating ductal carcinoma in Malaysian women
    Looi LM, Cheah PL, Ng MH, Yip CH, Mun KS, Rahman NA
    Asian Pac J Cancer Prev, 2010;11(3):713-6.
    PMID: 21039041
    A study was initiated to explore possible differences in handling telomere attrition in the most common lignant and benign tumours of the breast in Malaysian women. Infiltrating ductal carcinoma (IDC) and fibroadenoma (FA) represented the malignant and benign prototypes respectively. 29 IDC, 28 FA and 22 benign non-lesional control (BNL) breast tissue samples were analysed for telomerase activation using a Telomerase PCR ELISA kit (Boehringer Mannheim). In addition, 23 IDC, 12 FA and 14 BNL were subjected to telomere length determination with a TeloTAGGG Telomere Length Assay Kit (Roche Diagnostic GmbH, Germany), following digestion of genomic DNA by frequently cutting restriction enzymes RsaI and HinfI. Mean telomerase activity in IDC (A450nm=0.3338), but not FA (A450nm=0.0003) was significantly raised (p<0.05) compared with BNL (A450nm=0.0031). Similarly IDC (1.2 kb), but not FA (2.2 kb), showed significant telomere shortening (p<0.05) relative to BNL (2.9 kb). The findings imply that telomere attrition and telomerase activation differ between malignant and benign tumours of the breast and may be important for targeted therapy.
  6. A retrospective study of oral and maxillofacial injuries in Seremban Hospital, Malaysia
    Ramli R, Rahman NA, Rahman RA, Hussaini HM, Hamid AL
    Dent Traumatol, 2011 Apr;27(2):122-6.
    PMID: 21281443 DOI: 10.1111/j.1600-9657.2010.00968.x
    Aetiology of oral and maxillofacial injuries in this country includes motorvehicle accident (MVA), fall, industrial accidents and others. Among these causes, MVA accident is the predominant cause of injury in Malaysia.
  7. The effect of mild hearing loss on academic performance in primary school children
    Khairi Md Daud M, Noor RM, Rahman NA, Sidek DS, Mohamad A
    Int J Pediatr Otorhinolaryngol, 2010 Jan;74(1):67-70.
    PMID: 19913305 DOI: 10.1016/j.ijporl.2009.10.013
    To determine the prevalence of mild hearing loss and its association with academic performance among primary school children.
  8. The sternalis muscle in cadavers: anatomical facts and clinical significance
    Rahman NA, Das S, Maatoq Sulaiman I, Hlaing KP, Haji Suhaimi F, Latiff AA, et al.
    Clin Ter, 2009;160(2):129-31.
    PMID: 19452102
    The sternalis is an anomalous muscle located in the anterior wall of thorax and several past reports have described its presence with clinical implications. The sternalis muscle may be incidentally detected during routine cadaveric dissections and autopsies. We observed the presence of anomalous sternalis muscle on both sides of the anterior chest wall in 25 cadavers (n = 50), over a span of three years. Out of a 50 cases, we observed a single case of sternalis on the right side of the 55-year-old male cadaver (2%). The sternalis was found to be absent in the rest 49 cases (98%). The sternalis muscle displayed an oblique course in the anterior wall of the thorax. The muscle originated near the seventh costal cartilage extending obliquely upwards to insert into the second costal cartilage close to the sternum. The originating portion of the muscle was located at a distance of 3.5 cm lateral to the mid-sternal plane. The vertical length and the maximum width of the anomalous sternalis muscle measured 9 cm and 1.9 cm, respectively. The fibers of the muscle vertically ascended upwards. No other associated anomalies were observed in the same cadaver. The presence of sternalis muscle is considered to be a rare variation with no earlier studies being performed in the Malaysian population. The anomalous sternalis muscle may be important for reconstructive surgeons performing mastectomy and radiologists interpreting mammograms. Thus, the sternalis muscle may be academically, anthropologically and surgically important.
  9. Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites
    Othman R, Kiat TS, Khalid N, Yusof R, Newhouse EI, Newhouse JS, et al.
    J Chem Inf Model, 2008 Aug;48(8):1582-91.
    PMID: 18656912 DOI: 10.1021/ci700388k
    A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.
  10. Maxillofacial trauma of pediatric patients in Malaysia: a retrospective study from 1999 to 2001 in three hospitals
    Rahman RA, Ramli R, Rahman NA, Hussaini HM, Idrus SM, Hamid AL
    Int J Pediatr Otorhinolaryngol, 2007 Jun;71(6):929-36.
    PMID: 17442408
    Maxillofacial trauma in children is not common worldwide. Domestic injuries are frequently seen in younger children while older children are mostly involved in motor vehicle accidents (MVA). The objective of this study was to analyze the pattern of maxillofacial injuries in pediatric patients referred to three government main hospitals in different areas of West Malaysia.
  11. Fulltext 2-(3,5-Di-tert-butyl-4-hydroxy-benzyl-sulfan-yl)nicotinic acid
    Mansor S, Yehye WA, Ariffin A, Rahman NA, Ng SW
    Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 9):o1778.
    PMID: 21201758 DOI: 10.1107/S1600536808026056
    Two mol-ecules of the title compound, C(21)H(27)NO(3)S, are disposed about a center of inversion, generating an O-H⋯O hydrogen-bonded dimer.
  12. Maxillofacial trauma with emphasis on soft-tissue injuries in Malaysia
    Hussaini HM, Rahman NA, Rahman RA, Nor GM, Ai Idrus SM, Ramli R
    Int J Oral Maxillofac Surg, 2007 Sep;36(9):797-801.
    PMID: 17630250
    Soft-tissue injuries with or without facial bone involvement are the most common presentation following maxillofacial trauma. The objective of this study was to look at the distribution, pattern and type of soft-tissue injury in relation to aetiology. Records of patients over a period of 5 years (1998-2002), who sustained maxillofacial injuries and were treated at Kajang Hospital, a secondary referral hospital, were reviewed. Out of 313 patients with maxillofacial injuries, 295 patients sustained soft-tissue injuries. Males (79%) between 21 and 30 years old (34%) were the majority of patients. Road-traffic accident was the main cause of soft-tissue injuries (75%) with motorcycle accident being the most frequent (40%). The upper lips (23%) and the lower lips (18%) were the most common extraoral site involved, while the labial mucosa and sulcular areas, both accounting for 21%, were the most common intraoral sites. Stringent road-traffic regulations should be practiced in developing countries, as morbidity arising from road-traffic accidents poses a national economic and social problem.
  13. Fulltext Di-n-butyl-ammonium 2-(3,5-di-tert-butyl-4-hydroxy-benzyl-sulfan-yl)nicotinate
    Mansor S, Yehye WA, Ariffin A, Rahman NA, Ng SW
    Acta Crystallogr Sect E Struct Rep Online, 2008;64(Pt 9):o1799.
    PMID: 21201778 DOI: 10.1107/S1600536808026202
    The asymmetric unit of the title compound, C(8)H(20)N(+)·C(21)H(26)NO(3)S(-), contains two indpendent ion pairs which are disposed about a psuedo-inversion center, generating an ammonium-carboxylate N-H⋯O hydrogen-bonded four-component cluster. In the crystal structure, adjacent clusters are linked by hydr-oxy-carboxylate O-H⋯O hydrogen bonds, forming a chain.
  14. Facial Fractures in Kajang Hospital, Malaysia: A 5-Year Review
    Rahman RA, Hussaini HM, Rahman NA, Rahman SR, Nor GM, Ai Idrus SM, et al.
    Eur J Trauma Emerg Surg, 2007 Feb;33(1):90-5.
    PMID: 26815981 DOI: 10.1007/s00068-007-5154-5
    The objective of this study was to determine the demographic data as well as other relevant data pertaining to the management of patients with maxillofacial injury in a Malaysian government regional hospital.
  15. Distributions and health risks of polycyclic aromatic hydrocarbons (PAHs) in atmospheric aerosols of Kuala Lumpur, Malaysia
    Omar NY, Mon TC, Rahman NA, Abas MR
    Sci Total Environ, 2006 Oct 1;369(1-3):76-81.
    PMID: 16766020
    The concentrations and distributions of particle bound polycyclic aromatic hydrocarbons (PAHs) collected over a 10 month period in ambient environment, at street levels as well as during a hazy episode are reported. Ambient and street level distributions of PAHs were similar and their occurrence was attributed to vehicular emissions. However, in haze particles, a different pattern of PAHs was observed, characterized by relatively low levels of benzo[a]pyrene (BaP) and high levels of benzofluoranthenes (BFs). The BaP equivalency results showed that the potential health risk associated with haze smoke particles was 4 times higher than that of street level particles whereas the lowest health risk was associated with ambient atmospheric particles.
  16. Fulltext Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1
    Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R
    BMC Infect Dis, 2012;12:314.
    PMID: 23171075 DOI: 10.1186/1471-2334-12-314
    Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not available at the moment. In this study, we report retrocyclin-1 (RC-1) production in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro.
  17. Rational discovery of dengue type 2 non-competitive inhibitors
    Heh CH, Othman R, Buckle MJ, Sharifuddin Y, Yusof R, Rahman NA
    Chem Biol Drug Des, 2013 Jul;82(1):1-11.
    PMID: 23421589 DOI: 10.1111/cbdd.12122
    Various works have been carried out in developing therapeutics against dengue. However, to date, no effective vaccine or anti-dengue agent has yet been discovered. The development of protease inhibitors is considered as a promising option, but most previous works have involved competitive inhibition. In this study, we focused on rational discovery of potential anti-dengue agents based on non-competitive inhibition of DEN-2 NS2B/NS3 protease. A homology model of the DEN-2 NS2B/NS3 protease (using West Nile Virus NS2B/NS3 protease complex, 2FP7, as the template) was used as the target, and pinostrobin, a flavanone, was used as the standard ligand. Virtual screening was performed involving a total of 13 341 small compounds, with the backbone structures of chalcone, flavanone, and flavone, available in the ZINC database. Ranking of the resulting compounds yielded compounds with higher binding affinities compared with the standard ligand. Inhibition assay of the selected top-ranking compounds against DEN-2 NS2B/NS3 proteolytic activity resulted in significantly better inhibition compared with the standard and correlated well with in silico results. In conclusion, via this rational discovery technique, better inhibitors were identified. This method can be used in further work to discover lead compounds for anti-dengue agents.
  18. Fulltext Inflammatory reaction to fish oil coated polypropylene mesh used for laparoscopic incisional hernia repair: a case report
    Kong CY, Lai LL, Khoo AYY, Rahman NA, Chin KF
    BMC Surg, 2016 Feb 11;16:8.
    PMID: 26864939 DOI: 10.1186/s12893-016-0123-8
    BACKGROUND: Polypropylene meshes are widely used in hernia repairs. Hernia meshes have been developed incorporating coatings of active agents. One commercially available mesh has a fish oil coating which is promoted as having anti-inflammatory properties. We report a case, a symptomatic foreign body granuloma reaction associated with a fish oil coated polypropylene mesh, which required eventual mesh explantation.

    CASE PRESENTATION: A 61-year old lady with previous peptic ulcer disease underwent a laparoscopic intraperitoneal placement of mesh for incisional hernia utilising a fish oil coated polypropylene mesh. The patient presented 3 months after the procedure complaining of dyspepsia and pain at the operative site. There was no discharge. The patient was managed conservatively. She presented 10 months post-operatively with progressively worsening symptoms and a hard palpable mass in the epigastrium. Abdominal laparoscopy revealed dense adhesive disease around the mesh with exudates. Adhesiolysis, mesh explantation and a partial gastrectomy was performed. Histopathological examination revealed a foreign body granuloma formation to the mesh.

    CONCLUSION: In-vivo studies looking at intraperitoneal mesh placement with fish oil coatings including data on surgical outcomes such as fistula and adhesive characteristics are scarce in the literature. Further monitoring and studies are required to investigate the safety and efficacy profile of this mesh type in in-vivo models.

  19. Understanding the chemistry behind the antioxidant activities of butylated hydroxytoluene (BHT): a review
    Yehye WA, Rahman NA, Ariffin A, Abd Hamid SB, Alhadi AA, Kadir FA, et al.
    Eur J Med Chem, 2015 Aug 28;101:295-312.
    PMID: 26150290 DOI: 10.1016/j.ejmech.2015.06.026
    Hindered phenols find a wide variety of applications across many different industry sectors. Butylated hydroxytoluene (BHT) is a most commonly used antioxidant recognized as safe for use in foods containing fats, pharmaceuticals, petroleum products, rubber and oil industries. In the past two decades, there has been growing interest in finding novel antioxidants to meet the requirements of these industries. To accelerate the antioxidant discovery process, researchers have designed and synthesized a series of BHT derivatives targeting to improve its antioxidant properties to be having a wide range of antioxidant activities markedly enhanced radical scavenging ability and other physical properties. Accordingly, some structure-activity relationships and rational design strategies for antioxidants based on BHT structure have been suggested and applied in practice. We have identified 14 very sensitive parameters, which may play a major role on the antioxidant performance of BHT. In this review, we attempt to summarize the current knowledge on this topic, which is of significance in selecting and designing novel antioxidants using a well-known antioxidant BHT as a building-block molecule. Our strategy involved investigation on understanding the chemistry behind the antioxidant activities of BHT, whether through hydrogen or electron transfer mechanism to enable promising anti-oxidant candidates to be synthesized.
  20. Fulltext A combination of doxycycline and ribavirin alleviated chikungunya infection
    Rothan HA, Bahrani H, Mohamed Z, Teoh TC, Shankar EM, Rahman NA, et al.
    PLoS One, 2015;10(5):e0126360.
    PMID: 25970853 DOI: 10.1371/journal.pone.0126360
    Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease.
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