House crows (Corvus splendens) in Selangor, Malaysia were examined for the presence of Campylobacter species, Salmonella species, Mycoplasma gallisepticum and Mycoplasma synoviae by serology, culture and pcr. For the detection of Campylobacter and Salmonella species swabs were taken either from the intestine or cloaca. For the detection of mycoplasmas, swabs were taken either from the choanal cleft or trachea for culture and pcr and serum samples were tested by the rapid serum agglutination (rsa) and monoclonal antibody-blocking elisa (mbelisa) for antibodies to M gallisepticum and M synoviae. For campylobacter, 25.3 per cent of the crows were positive by culture, and the species identified were Campylobacter jejuni and Campylobacter coli. No Salmonella species were isolated. Four of 24 swabs were positive for M gallisepticum dna but none gave positive results for M synoviae dna. No M gallisepticum or M synoviae antibodies were detected by rsa but 60 per cent of the sera gave positive reactions for M gallisepticum and 13 per cent gave positive reactions for M synoviae by mbelisa.
AIM: The main objective of this study is to elucidate the role of immunoglobulin A (IgA) rheumatoid factor (RF) in predicting the clinical response to tumour necrosis factor α inhibitors (TNFi) among patients with rheumatoid arthritis (RA).
METHOD: We recruited all patients with RA who were ever on TNFi for a minimum duration of 3 months at our centre. Based on the European League Against Rheumatism response criteria, subjects were further divided into responders and non-responders. Age-matched RA patients who were on conventional disease-modifying anti-rheumatic drugs and in remission were enrolled as controls. Subjects were tested for quantitative values of IgA, IgM, IgG RF and anti-citrulinated cyclic peptides (CCP). Further, all subjects were assessed for the disease activity score that includes 28 joints (DAS28) and Stanford Health Assessment Questionnaire (HAQ) 8-item Disability Index (HAQ-DI).
RESULTS: A total of 31 subjects with RA who had received TNFi and 15 controls were enrolled in this study. There was a trend for the non-responders (n = 10) to have higher levels of all isotypes of RF and anti-CCP. However, only the IgA RF and anti-CCP levels were significantly higher in the non-responder group compared to the responders and controls (P = 0.001, P = 0.034, respectively). On multivariate analysis, only the IgA RF remained significant (OR 0.989; 95% CI 0.980-0.999; P = 0.026).
CONCLUSION: IgA RF is potentially a novel predictor of response to TNFi in RA patients. Testing for pretreatment IgA RF levels could be a reasonable consideration before commencement of TNFi.
Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Aim: This study aimed to assess the cost-effectiveness of starting insulin therapy with biphasic insulin aspart 30 (BIAsp 30) in people with type 2 diabetes inadequately controlled on oral glucose-lowering drugs in Saudi Arabia, India, Indonesia, and Algeria.
Methods: The IMS CORE Diabetes Model was used to evaluate economic outcomes associated with starting BIAsp 30, using baseline characteristics and treatment outcomes from the A(1)chieve study. Time horizons of 1 and 30 years were applied, with country-specific costs for complications, therapies, and background mortality. Incremental cost-effectiveness ratios (ICERs) are expressed as cost per quality-adjusted life-year (QALY) in local currencies, USD, and fractions of local GDP per capita (GDPc). Cost-effectiveness was pre-defined using the World Health Organization definition of <3.0 times GDPc. Comprehensive sensitivity analyses were performed.
Results: In the primary 30-year analyses, starting BIAsp 30 was associated with a projected increase in life expectancy of >1 year and was highly cost-effective, with ICERs of -0.03 (Saudi Arabia), 0.25 (India), 0.48 (India), 0.47 (Indonesia), and 0.46 (Algeria) GDPc/QALY. The relative risk of developing selected complications was reduced in all countries. Sensitivity analyses including cost of self-monitoring, treatment costs, and deterioration of glucose control with time showed the results to be robust. In a 1-year analysis, ICER per QALY gained was still cost-effective or highly cost-effective.
Conclusion: Starting BIAsp 30 in people with type 2 diabetes in the A(1)chieve study was found to be cost-effective across all country settings at 1- and 30-year time horizons, and usefully increased predicted life expectancy.
Hepatocellular carcinoma (HCC) is an important cancer in Malaysia. This study aimed to determine the epidemiological characteristics and clinical presentations of patients in a multiracial population consisting of three major Asian races: Malays, Chinese and Indians.
Hepatitis B virus (HBV) is a deadly pathogen that has killed countless people worldwide. Saccharomyces cerevisiae-derived HBV vaccines based upon hepatitis B surface antigen (HBsAg) is highly effective. However, the emergence of vaccine escape mutants due to mutations on the HBsAg and polymerase genes has produced a continuous need for the development of new HBV vaccines. In this study, the "a" determinant within HBsAg was displayed on the recombinant capsid protein of Macrobrachium rosenbergii nodavirus (MrNV), which can be purified easily in a single step through immobilized metal affinity chromatography (IMAC). The purified protein self-assembled into virus-like particles (VLPs) when observed under a transmission electron microscope (TEM). Immunization of BALB/c mice with this chimeric protein induced specific antibodies against the "a" determinant. In addition, it induced significantly more natural killer and cytotoxic T cells, as well as an increase in interferon gamma (IFN-γ) secretion, which are vital for virus clearance. Collectively, these findings demonstrated that the MrNV capsid protein is a potential carrier for the HBV "a" determinant, which can be further extended to display other foreign epitopes. This paper is the first to report the application of MrNV VLPs as a novel platform to display foreign epitopes.
This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.
To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART).
AIM: This pilot study evaluated the short-term benefits of a telemonitoring-supplemented focused diabetic education compared with education alone in participants with Type 2 diabetes who were fasting during Ramadan.
METHODS: In this pilot mixed-method study, we identified 37 participants and randomly allocated them to either a telemonitoring group (n = 18) or a group receiving Ramadan-focused pre-education only (usual care; n = 19). The telemonitoring group received goal-setting and personalized feedback.
RESULTS: The telemonitoring group was less likely to experience hypoglycaemia than the usual care group (odds ratio: 0.1273; 95% confidence interval: 0.0267-0.6059). No significant differences were noted in glycaemic control at the end of study. Participants viewed telemedicine as a more convenient alternative although technological barriers remain a concern.
CONCLUSIONS: The results of this study reinforce the need for monitoring as well as educational initiatives for Muslims with diabetes who fast during Ramadan. Telemonitoring offers an attractive option requiring further research. (Clinical Trial Registry No. NCT02189135).
Matched MeSH terms: Diabetes Mellitus, Type 2/blood
This study was conducted to determine the occurrence of Anaplasma spp. in the blood samples of cattle, goats, deer and ticks in a Malaysian farm. Using polymerase chain reaction (PCR) and sequencing approach, Anaplasma spp. was detected from 81(84.4%) of 96 cattle blood samples. All blood samples from 23 goats and 22 deer tested were negative. Based on the analysis of the Anaplasma partial 16S ribosomal RNA gene, four sequence types (genotypes 1 to 4) were identified in this study. Genotypes 1-3 showed high sequence similarity to those of Anaplasma platys/ Anaplasma phagocytophilum, whilst genotype 4 was identical to those of Anaplasma marginale/ Anaplasma centrale/ Anaplasma ovis. Anaplasma DNA was detected from six (5.5%) of 109 ticks which were identified as Rhipicephalus (formely known as Boophilus) microplus ticks collected from the cattle. This study reported for the first time the detection of four Anaplasma sequence types circulating in the cattle population in a farm in Malaysia. The detection of Anaplasma DNA in R. microplus ticks in this study provides evidence that the ticks are one of the potential vectors for transmission of anaplasmosis in the cattle.
Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.
Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100μM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10μM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10μM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.
Aims: To explore how health care professionals (HCPs) assess patients when initiating insulintherapy in type 2 diabetes.
Methods: Focus group discussions and in-depth interviews were conducted with 41 healthcare professionals in Malaysia in 2010–2011. A semi-structured topic guide was used for theinterview. The interviews were transcribed verbatim and analysed using the Nvivo9 softwarebased on a thematic approach.
Results: HCPs were less likely to initiate insulin therapy in patients who were older, withirregular dietary patterns and poor financial status. They also assessed patients’ knowl-edge, views and misconceptions of insulin. However, there was a variation in how doctors assessed patients’ comorbidities before starting insulin therapy. Medical officers were more likely to initiate insulin therapy in patients with comorbidities and complications, whereas family medicine specialists were more cautious. In addition, most HCPs considered patients’ psychosocial status, including self-care ability, social support and quality of life.
Conclusions: HCPs’ assessment of patients’ need to start insulin therapy depends on their perception rather than objective evaluation of patients’ background, knowledge, perception and abilities. The background and the type of practice of HCPs influence their assessment.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood
Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p<0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20-22% vs. ∼11-15% and ∼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p<0.05). These findings demonstrated that H2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.
This study was aimed to investigate the effects of dietary fatty acids on the accretion pattern of major fat pads, inguinal fat cellularity, and their relation with plasma leptin concentration. Forty Sprague-Dawley rats were randomly assigned into four groups and received the following diets for 22 weeks: (1) standard rat chow diet (CTRL), (2) CTRL + 10% (w/w) butter (HFAR), (3) CTRL + 3.33% (w/w) menhaden fish oil + 6.67% (w/w) soybean oil (MFAR), and (4) CTRL + 6.67% (w/w) menhaden fish oil + 3.33% (w/w) soybean oil (LFAR). Inguinal fat cellularity and plasma leptin concentration were measured in this study. Results for inguinal fat cellularity showed that the mean adipocyte number for the MFAR (9.2 ∗ 10⁵ ± 3.6) and LFAR (8.5 ∗ 10⁵ ± 5.1) groups was significantly higher (P < 0.05) than the rest, while the mean adipocyte diameter of HFAR group was larger (P < 0.05) (46.2 ± 2.8) than the rest. The plasma leptin concentration in the HFAR group was higher (P < 0.05) (3.22 ± 0.32 ng/mL), than the other groups. The higher inguinal fat cellularity clearly indicated the ability of the polyunsaturated fatty acids (PUFA) and butter supplemented diets to induce hyperplasia and hypertrophy of fat cells, respectively, which caused adipocyte remodeling due to hyperleptinemia.
In the present study, we evaluated the effect of brown seaweeds Sargassum muticum methanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines proliferation. This algae extract was also evaluated for reducing activity and total polyphenol content. The MTT assay results indicated that the extracts were cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50 of 22 μg/ml for MCF-7 and 55 μg/ml for MDA-MB-231 cell lines. The percentages of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the concentration of the SMME. The antiproliferative efficacy of this algal extract was positively correlated with the total polyphenol contents, suggesting a causal link related to extract content of phenolic acids. Cell cycle analysis showed a significant increase in the accumulation of SMME-treated cells at sub-G1 phase, indicating the induction of apoptosis by SMME. Further apoptosis induction was confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into fertilized chicken eggs induced dose-related antiangiogenic activity in the chorioallantoic membrane (CAM). Our results imply a new insight on the novel function of Sargassum muticum polyphenol-rich seaweed in cancer research by induction of apoptosis, antioxidant, and antiangiogenesis effects.
Catechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Several polyphenolic compounds reported as antioxidants such as quercetin, catechins and gallic acid have been highlighted to have pro-oxidant activity at high doses. Therefore, the present study was conducted to investigate the antioxidant and pro-oxidant effects of chronically administering high dose of OPLE (1000 mg kg⁻¹) in an animal model of diabetic nephropathy (DN).
The retromolar foramen (RMF) and retromolar canal (RMC) are the anatomical structures of the mandible located in retromolar fossa behind the third molar tooth. This foramen and canal contain neurovascular structures which provide accessory/additional innervation to the mandibular molars and the buccal area. These neurovascular contents of the canal gain more importance in medical and dental practice, because these elements are vulnerable to damage during placement of osteointegrated implants, endodontic treatment and sagittal split osteotomy surgeries and a detailed knowledge of this anatomical variation would be vital in understanding failed inferior alveolar nerve blockage, spread of infection and also metastasis. Although few studies have been conducted in the past showing the incidence and types in different population groups, a lacunae in comprehensive review of this structure is lacking. Though this variation posed challenging situations for the practicing surgeons, it has been quite neglected and the incidence of it is not well presented in all the textbooks. Hence, we made an attempt to provide a consolidated review regarding variations and clinical applications of the RMF and RMC.
Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO) in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C), SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME)]. Rats (SHRC) were administered with Clonidine (0.5 mg kg(-1) day(-1)) from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg(-1) day(-1)) from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP) was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS) (P < 0.001) and reduced the thibarbituric acid reactive substances (TBARS) (P < 0.001) and protein carbonyl content (PCO) (P < 0.05). These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME.
BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.
METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.
RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.
CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).
Note: Malaysia is a study site (Author: Yusoff K)
The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12-week, randomized, open-label, two-arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group.
Matched MeSH terms: Diabetes Mellitus, Type 2/blood