Dengue virus infection has been posing alarming economic and social burden on affected nations. It is estimated that 50-100 million dengue infections occur annually with over 2.5 billion people at risk for endemic transmission. In the effort to develop effective antiviral agents, we previously reported potential antiviral activities from selected array of natural products and compounds against dengue virus serotype 2 (DV2). In this study, we report the synthesis of two efficacious novel compounds, YK51 and YK73, and their activities against DV2 replication. Both compounds were chemically synthesised from nicotinic acid using a modified method for the synthesis of dihydropyridine. The products were tested with cell-based assays against DV2 followed by a serine protease assay. As a result, both YK51 and YK73 exhibited intriguing antiviral properties with EC50 of 3.2 and 2.4 µM, respectively. In addition, YK51 and YK73 were found to attenuate the synthesis of intracellular viral RNA and protect the switching of non-classic mechanism of protein translation. These compounds demonstrated inhibitory properties toward the activity of DV2 serine protease in a dose dependent manner. These findings demonstrate that both YK51 and YK73 serve as DV2 serine protease inhibitors that abrogate viral RNA synthesis and translation. Further investigation on these compounds to corroborate its therapeutic properties towards dengue is warranted.

The aim of this study was to assess the wear of tungsten carbide burs and round rotary diamond instruments through measurements of rake angle and visual observations respectively under a f ield emission scanning electron microscope. Sixty short and long head pear-shaped tungsten carbide burs and 18 round rotary diamond instruments that had been used to complete < 5, > 5 and > 10 cavity preparations (n=10/ group) were selected from the 3rd and 4th year dental students, Faculty of Dentistry, University of Malaya. There were two control groups consisting of long and short tungsten carbide burs of ten each. Two-way ANOVA was used to analyse the rake angle data. The data from the two control groups were collectively analysed following multiple paired t-test (p > .05) which showed no significant difference between the two types of tungsten carbide bur (short and long head). The mean rake angle of the control group was significantly higher (p < .05) compared to the < 5, > 5 and > 10 cavity preparation groups. The rake angle of the > 10 cavity preparation group was significantly lower than the other two test groups (p < .05). Round rotary diamond instruments in the < 5 cavity preparation group showed intact diamond particles with distinct cutting facets comparable to the control group. However, diamonds instruments in the > 5 and > 10 cavity preparation groups showed blunt diamond particles. In conclusion, wear of tungsten carbide burs and round rotary diamond instruments were evident after repeated use. Wear was more pronounced when instruments were used to prepare more than ten cavities.

Background: The high prevalence and impacts of orofacial pain (OFP) have caused major sufferings to individuals and society. The purpose of the study was to investigate the problems and impacts of OFP among a group of Malaysian aborigines. The objectives were to determine (i) the prevalence, aetiology, duration, severity, types and persistence of OFP during the past 3 months preceding the study; (ii) its associated impact on daily performance; and (iii) the measures taken for pain relief. Methods: This is a cross sectional study carried out in Kuala Lipis, Pahang involving 6 villages of Orang Asli Bateq and Semai. Study sample was chosen using convenient sampling including adults aged 16 years and above. Participants were invited for an interview using structured questionnaire followed by clinical examination. Data analysis was carried out using SPSS ver12. Results: Response rate was low at 20% (n = 140). Over one-quarter (26.4%) of the sample experienced OFP in the previous 3 months. Toothache was found to be the main aetiology (83.3%) followed by gingival pain (18.9%), temporomandibular joint (10.8%) and facial pain (8.1%). Mean duration of pain was 9.8 days for toothache, 162.4 days for gingival pain, 7.3 days for TMJ and 5.7 days for facial pain. Of those who had OFP, over half rated the pain as moderate (37.8%) and severe (29.7%) and most of the pain was ‘intermittent’ in nature (81.1%). Over half (62.2%) admitted the pain had disappeared during the interview. In terms of pain relief, 56.8% of the sample used traditional medicine. The pain had impacted on the chewing ability (70.3%, p=0.01), ability to sleep at night (73.0%, p<0.001), levels of anxiety (70.3%), ability to perform daily chores (33.3%) and social life (35.1%) of the Orang Asli sample. Conclusion: This study suggests the prevalence of OFP was high among the Orang Asli sample, which imposed considerable physical and psychological impacts on daily life.

This study assessed the effectiveness of a biorational control approach using 2% hydramethylnon gel bait on German cockroaches, Blattella germanica (L.) in some residential and hospital buildings in South Western Iran. In total, three buildings consisting of 150 apartment units and 101 hospital units were monitored weekly via sticky trap for German cockroach infestations over a period of eight months. These infested units were randomly subjected to intervention and control treatments. Pamphlets and posters were provided and lectures were given to support the educational programmes as a tactic of the biorational system. Survey on cockroach index for intervention units showed 67-94% recovery to achieve clean level of infestation for intervention units of the residential buildings and 83% for the hospital. Mean percentage reductions for treatment groups throughout the 15-week treatment period were 76.8% for the residential buildings and 88.1% for the hospital, showing significant differences compared to the control groups. Linear regression of infestation rates were recorded weekly after treatment and their negative slope for treatment groups substantiated significant reductions for interventions. The results of this study showed that biorational control method, using gel bait, educational programmes and sanitation, is an effective way to manage German cockroach infestation.

Multislice computed tomography (MSCT) is the imaging modality of choice in assessing clinically stable patients with blunt abdominal trauma. This study assessed the role of MSCT in the detection of intra abdominal injury caused by blunt trauma in our centre within a two-year-period (2008-2009). A total of 151 patients had MSCT abdomen for blunt abdominal trauma within this study period. Positive scan were seen in 126 patients (83.4%). Out of these positive scans, liver, spleen and renal injuries were seen in 42.1% (n=53), 34.9% (n=44) and 30.0% (n=34) of cases respectively. Laparotomies were performed in 45 patients. Out of these 45 laparotomies, 10 patients had surgically significant injuries that were missed on CT scan findings. The injuries were bowel perforation (n=4), serosal tear of bowel (n=1), mesenteric injuries with active haemorrhage (n=3), spleen injury (n=1) and liver injury (n=1).

Japanese encephalitis virus (JEV), a member of the family Flaviviridae, causes severe neurological disorders in humans. JEV infections represent one of the most widely spread mosquito-borne diseases, and therefore, it has been considered as an endemic disease. An effective antiviral drug is still unavailable to treat JEV, and current drugs only provide supportive treatment to alleviate the symptoms and stabilize patients’ conditions. This study was designed to evaluate the antiviral activity of the sulphated polysaccharides “Carrageenan,” a linear sulphated polysaccharide that is extracted from red edible seaweeds against JEV replication in vitro. Viral inactivation, attachment, and post-infection assays were used to determine the mode of inhibition of Carrageenan. Virus titters after each application were evaluated by plaque formation assay. MTT assay was used to determine the 50% cytotoxic concentration (CC50), and ELISA-like cell-based assay and immunostaining and immunostaining techniques were used to evaluate the 50% effective concentration (EC50). This study showed that Carrageenan inhibited JEV at an EC50 of 15 µg/mL in a dose-dependent manner with CC50 more than 200 µg/mL in healthy human liver cells (WRL68). The mode of inhibition assay showed that the antiviral effects of Carrageenan are mainly due to their ability to inhibit the early stages of virus infection such as the viral attachment and the cellular entry stages. Our investigation showed that Carrageenan could be considered as a potent antiviral agent to JEV infection. Further experimental and clinical studies are needed to investigate the potential applications of Carrageenan for clinical intervention against JEV infection.

Chikungunya virus (CHIKV) infection is the cause of acute symptoms and chronic symmetrical polyarthritis associated with long-term morbidity and mortality. Currently, there is no available licensed vaccine or particularly useful drug for human use against CHIKV infection. This study was conducted to evaluate the efficacy of antibodies produced by papaya mosaic virus (PapMV) nanoparticles fused to E2EP3 peptide of CHIKV envelope as a recombinant CHIKV vaccine. PapMV, PapMV-C- E2EP3, and E2EP3-N-PapMV were produced in E. coli with an approximate size of 27 to 30 kDa. ICR mice (5 to 6 weeks of age) were injected subcutaneously with 25 micrograms of vaccine construct, and ELISA measured the titer of CHIKV specific IgG antibodies. The results showed that both recombinant proteins E2EP3-N-PapMV and PapMVC-E2EP3 were able to induce IgG antibodies production in immunized mice against CHIKV while immunization with recombinant PapMV showed no IgG antibodies induction. The neutralizing activity of the antibodies generated by either E2EP3-N-PapMV or PapMV-C-E2EP3 exhibited similar inhibition to CHIKV replication in Vero cells using the cells based antibody neutralizing assay and analyzed by plaque formation assay. This study showed the effectiveness of nanoparticles vaccine generated by fusing epitope peptide of CHIKV envelope to papaya mosaic virus envelope in inducing a robust immune response in mice against CHIKV. The data showed that levels of neutralizing antibodies correlate with a protective immune response CHIKV replication

The hepatitis C virus (HCV) consists of eight genotypes and 90 subtypes, with genotype (GT) 3 being the second most common globally and is linked to higher incidences of steatosis and rapid development of fibrosis and cirrhosis. The NS3/4A serine protease, a heterodimer complex of two HCV non-structural proteins, is an effective target for pharmaceutical intervention due to its essential roles in processing HCV polyproteins and inhibiting innate immunity. This study combines structure-based virtual screening (SBVS) of predefined compound libraries, pharmacokinetic prediction (ADME/T) and in vitro evaluation to identify potential low molecular weight (<500 Dalton) inhibitors of the NS3/4A serine protease (GT3). In silico screening of ZINC and PubChem libraries yielded five selected compounds as potential candidates. Dose-dependent inhibition of the NS3/4A serine protease and HCV replication in HuH-7.5 cells revealed that compound A (PubChem ID No. 16672637) exhibited inhibition towards HCV GT3 with an IC50 of 106.7µM and EC50 of 25.8µM, respectively. Thus, compound A may be developed as a potent, low molecular weight drug against the HCV NS3/4A serine protease of GT3.

Dengue fever is one of major health problem around the world including Malaysia. It is caused by the arthropode-borne flavivirus and transmitted by the bite of the Aedes aegypti or Aedes albopictus mosquito infected with one of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, or DENV-4). In this study, a screening exercise of various Malaysian medicinal plants showed that the extracts of Lawsonia inermis, Dryobalanops aromatica, Punica granatum, Zizyphus jujuba Lam. and Zingiber zerumbet exhibited potent inhibitory activity against NS2B-NS3 serine protease. The methanol extracts of Dryobalanops aromatica showed inhibition of 99.70 % at concentration of 200 μg/mL with IC50 value of 0.30 ± 0.16 μg/mL.