Comparative sequence analysis of representative foot-and-mouth disease virus genomes from Southeast Asia

Foot-and-mouth disease (FMD) is endemic in mainland Southeast Asia where up to seven genetically distinct viral lineages co-circulate (O/SEA/Mya-98, O/SEA/Cam-94, O/ME-SA/PanAsia, O/ME-SA/PanAsia-2, O/CATHAY, A/ASIA/Sea-97, and serotype Asia 1). The aim of this study was to analyse the sequence variability between representative complete genomes for these seven lineages. The genome sequences varied from 8130 to 8192 nucleotides in length and shared nucleotide identities ranging from 91.8 to 78.9%. Broad-scale differences such as block and codon deletions observed in these genomes paralleled features that have been reported previously for other FMDV sequences from Southeast Asia. Comparison between these sequences revealed the presence of 2501 variant sites which were more evident in regions encoding surface capsid proteins (VP2, VP3 and VP1) compared to regions encoding non-structural proteins. Specific comparisons between closely related O/ME-SA sequences showed that the distribution of variant sites was focussed particularly at the 5′ end of the genome indicating that recombination may have occurred during the evolution of the O/ME-SA/PanAsia-2 lineage. These sequences provide insights into the evolutionary mechanisms by which new lineages generate genetic and antigenic novelty in the region and will form the basis of studies to define the spatio-temporal epidemiology of FMDV.     

Microwave modified non-crosslinked pectin films with modulated drug release

The effects of microwave on drug release properties of pectin films carrying sulfanilamide (SN-P), sulfathiazole (ST-P) and sulfamerazine (SM-P) of high to low aqueous solubilities were investigated. These films were prepared by solvent evaporation technique and treated by microwave at 80?W for 5-40?min. Their profiles of drug dissolution, drug content, matrix interaction and matrix crystallinity were determined by drug dissolution testing, drug content assay, differential scanning calorimetry, X-ray diffractometry and scanning electron microscopy techniques. Microwave induced an increase in matrix amorphousness but lower drug release propensity with a greater retardation extent in SN-P films, following a rise in strength of matrix interaction. A gain in amorphous structure does not necessarily increase the drug release of film. Microwave can possibly retard drug release of pectin film carrying water-soluble drug through modulating its state of matrix interaction.     

Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype causing vasoconstriction in the kidney of the rat

This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.     

Antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract in experimental animal models

The antinociceptive and anti-inflammatory properties of Corchorus capsularis leaves chloroform extract were investigated in experimental animal models. The antinociceptive activity was measured using the writhing, hot plate and formalin tests, while the anti-inflammatory activity was measured using the carrageenan-induced paw edema test. The extract, obtained after 72 h soaking of the air-dried leaves in chloroform followed by in vacuo evaporation to dryness, was weighed and prepared by serial dilution in DMSO in the doses of 20, 100 and 200 mg/kg. The extract was administered (s.c.) 30 min prior to subjection to the respective assays. The extract was found to exhibit significant (p < 0.05) antinociceptive and anti-inflammatory activities. As a conclusion, the present study confirmed the traditional claims of using C. capsularis to treat various ailments related to inflammation and pain.     

Thalassemia among blood donors at the Hospital Universiti Sains Malaysia

The aim of this study was to screen and identify the types of thalassemia among blood donors at the Hospital Universiti Sains Malaysia (HUSM). Thalassemia screening was performed by hemoglobin electrophoresis. A total number of 80 blood samples were obtained from donors at the Transfusion Medicine Unit, HUSM. The ethnic origins of the donors were Malays (n=73, 91.3%) and non-Malays (n=7, 8.75%). Males comprised 88.1% of the donors. Thalassemia was detected in 16.25% (n=13) of the blood donors. Of those with thalassemia, 46.2% (6/13) were anemic. Microcytosis and hypochromia were detected in 84.6% (n=l1) and 84.6% (n=l1) of these donors, respectively. The types of thalassemias detected were Hb E, 11.25% (n=9/80) and beta thalassemia trait, 5% (n=4/80). Among the thalassemias detected, the Hb E hemoglobinopathy was comprised of Hb E/ alpha-thalassemia (38.5%: n=5), Hb E /beta-thalassemia (23.1%: n=3), Hb E trait (7.6%: n=1) and beta-thalassemia (30.8%: n=4). In conclusion, screening for thalassemia trait should be included as part of a standard blood testing before blood donation. Further studies are required to look at the effects of donated thalassemic blood.     

A retrospective prevalence study of malaria in an aborigine hospital in Gombak, Selangor, Malaysia

This was a five-year retrospective study (1999-2004) on the prevalence of malaria at the Aborigine Hospital, Gombak, Malaysia. A total of 94 malaria cases was analysed. The highest case reports were for the year 2000, with 32 cases (34%), and the lowest was in 2004, with only 1 (1%). The majority of cases reported were among the Semai tribe (44%), followed by the Temiar tribe (34%) and the unspecified tribe (s) (20%). Females (53%) were more commonly affected than males (47%). The majority of cases were within the age group 1-5 years (51%). Plasmodium falciparum was the most common species reported in this study, at 57%, followed by Plasmodium vivax (38%) and 5% mixed infection of P. falciparum and P. vivax. Most patients (27%) stayed for more than one month in hospital. Most patients came from Kuala Lipis, Pahang, (78%). The most common complication was anemia (38%) followed by splenomegaly (18%); only 2% had cerebral malaria. All patients were treated with the standard anti-malarial drugs. No deaths were reported in this study.     

Enteral donor pre-treatment with ursodeoxycholic acid protects the liver against ischaemia-reperfusion injury in rats

Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36±13% in pre-treated rats, causing higher bile flow (P=0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group (P<0.02 and P<0.05). In conclusion, augmented bile salt-dependent bile flow is preserved in the liver after cold storage. Enteral donor pre-treatment with UDCA protects the liver against ischaemia-reperfusion injury.     

The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B-cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols

We investigated 390 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated according to NOPHO ALL 2008, regarding copy number alterations (CNA) of eight loci associated with adverse prognosis, including IKZF1. The impact on outcome was investigated for each locus individually, combined as CNA profiles and together with cytogenetic information. The presence of IKZF1 deletion or a poor-risk CNA profile was associated with poor outcome in the whole cohort. In the standard-risk group, IKZF1-deleted cases had an inferior probability of relapse-free survival (pRFS) (p ≤ 0.001) and overall survival (pOS) (p ≤ 0.001). Additionally, among B-other patients, IKZF1 deletion correlated with poor pRFS (60% vs. 90%) and pOS (65% vs. 89%). Both IKZF1 deletion and a poor-risk CNA profile were independent factors for relapse and death in multivariable analyses adjusting for known risk factors including measurable residual disease. Our data indicate that BCP-ALL patients with high-risk CNA or IKZF1 deletion have worse prognosis despite otherwise low-risk features. Conversely, patients with both a good CNA and cytogenetic profile had a superior relapse-free (p ≤ 0.001) and overall survival (p ≤ 0.001) in the cohort, across all risk groups. Taken together, our findings highlight the potential of CNA assessment to refine stratification in ALL.