The plant Andrographis paniculata found throughout Southeast Asia contains Andrographolide 1, a diterpenoid lactone, which has antitumour activities against in vitro and in vivo breast cancer models. In the present study, we report on the synthesis of andrographolide derivatives, 3,19-isopropylideneandrographolide (2), 14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide (4), and their in vitro antitumour activities against a 2-cell line panel consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell line). Compounds 2 and 4 were also screened at the US National Cancer Institute (NCI) for their activities against a panel of 60 human cancer cell lines derived from nine cancer types. Compound 2 was found to be selective towards leukaemia and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian and renal cancer cells at all the dose-response parameters. Compounds 2 and 4 showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at different intervals with different concentrations. NCI's COMPARE and SOM mechanistic analyses indicated that the anticancer activities of these new class of compounds were not similar to that of standard anticancer agents, suggesting novel mechanism(s) of action.
We report a case of an 8-year-old aborigine boy referred to our hospital for respiratory insufficiency with skin eruptions over the trunk and limbs. The skin condition was diagnosed as acquired ichthyosis. He also had a non-bleeding form of disseminated intravascular coagulopathy. Radiograph of the lungs showed bilateral perihilar opacities with bilateral pleural effusion. The diagnosis of leptospirosis was confirmed by a 4-fold rise in microagglutinating titre and polymerase chain reaction assay.
In this study, the development and validation of a high-performance liquid chromatography (HPLC) assay for determination of repaglinide concentration in human plasma for pharmacokinetic studies is described. Plasma samples containing repaglinide and an internal standard, indomethacin were extracted with ethylacetate at pH 7.4. The recovery of repaglinide was 92%+/-55.31. Chromatographic separations were performed on Purospher STAR C-18 analytical column (4.8 mm x 150 mm; 5 microm particle size). The mobile phase composed of acetonitrile-ammonium formate (pH 2.7; 0.01 M) (60:40, v/v). The flow rate was 1 ml/min. The retention time for repaglinide and indomethacin were approximately 6.2 and 5.3 min, respectively. Calibration curves of repaglinide were linear in the concentration range of 20-200 ng/ml in plasma. The limits of detection and quantification were 10 ng/ml and 20 ng/ml, respectively. The inter-day precision was from 5.21 to 11.84% and the intra-day precision ranged from 3.90 to 6.67%. The inter-day accuracy ranged 89.95 to 105.75% and intra-day accuracy ranged from 92.37 to 104.66%. This method was applied to determine repaglinide concentration in human plasma samples for a pharmacokinetic study.
MeSH terms: Carbamates/blood*; Carbamates/pharmacokinetics*; Carbamates/chemistry; Chromatography, High Pressure Liquid/instrumentation; Chromatography, High Pressure Liquid/methods*; Drug Stability; Freezing; Humans; Hypoglycemic Agents/blood*; Hypoglycemic Agents/pharmacokinetics*; Hypoglycemic Agents/chemistry; Piperidines/blood*; Piperidines/pharmacokinetics*; Piperidines/chemistry; Reference Standards; Sensitivity and Specificity; Reproducibility of Results; Molecular Structure
Cerebral angioinvasive aspergillosis is a rare manifestation of disseminated aspergillosis which may result in stroke in immunocompromised individuals. Reports of such disease in patients with diabetes mellitus are rare. We describe a 45-year-old man with diabetes mellitus who presented with a three-day history of right-sided limb weakness and aphasia. Cerebral computed tomography showed features of an acute infarct involving the left anterior and middle cerebral arteries. He was initially treated for an acute ischaemic stroke. Further history revealed that he was investigated for a growth in the sphenoid sinus two months earlier. Culture of the biopsied material from the sphenoid sinus grew Aspergillus fumigatus. Magnetic resonance imaging showed an extension of the growth to the brain, causing the acute ischaemic stroke. He was subsequently diagnosed with angioinvasive cerebral aspergillosis and was commenced on intravenous amphotericin B. Unfortunately, he succumbed to his illness despite treatment.
INTRODUCTION: Fibromyalgia syndrome (FMS) is a common but controversial condition. There appears to be different levels of belief of its existence and awareness. We set out to explore the variations of perceptions and awareness of this condition among rheumatologists from Malaysia and Singapore.
METHODS: 48 rheumatologists from Malaysia (28) and Singapore (20) were approached to participate in this survey by answering a specific questionnaire regarding their belief in FMS. 23 respondents from Malaysia and 20 from Singapore completed the questionnaire.
RESULTS: 91 percent of Malaysian rheumatologists and 95 percent of the Singaporean believe that FMS is a distinct clinical entity and that this condition is considered an illness rather than a disease. 87 percent and 90 percent of rheumatologists from Malaysia and Singapore, respectively, believe that FMS is a mixture of medical and psychological illness. However, not many of those in the university setting include FMS in their undergraduate teaching. 87 percent and 80 percent of the respondents from Malaysia and Singapore, respectively, also ordered blood tests to exclude other serious pathologies, and 100 percent of the respondents from both countries also prescribed some form of drugs to their FMS patients.
CONCLUSION: This study confirmed that there was a variation of perceptions and knowledge of FMS among rheumatologists from Malaysia and Singapore. The majority of rheumatologists recognise that FMS is a distinct clinical entity, and is diagnosed by excluding other well-defined clinical diseases through a combination of clinical evaluation and screening tests.
MeSH terms: Awareness*; Fibromyalgia/diagnosis*; Humans; Health Knowledge, Attitudes, Practice*; Malaysia; Perception*; Practice Patterns, Physicians'; Surveys and Questionnaires; Rheumatology*; Singapore; Syndrome
INTRODUCTION: Breast cancer is the commonest female cancer in Singapore. It is steadily rising with an incidence of 53.1 cases per 100,000 persons per year among women. Screening for detection of early lesions which are highly curable helps to reduce mortality.
METHODS: Over three afternoon sessions in December 2003, 224 female patients aged 40-65 years, participated in interviews conducted by the National Healthcare Group Polyclinics, Singapore. The survey sought information on mammographic screening history, the time interval since the previous mammographic screening, and the reasons for not going for the screening.
RESULTS: The survey found that only 26.4 percent (28 out of 106) among those aged 40 to 49 years had mammographic screening done within the past one year, and 43.2 percent (51 out of 118) among those aged 50 to 65 years had screening done within the last two years. Chinese women were twice more likely than Malay women to have a mammogram done. The commonest reasons for not wanting to have mammographic screening among women who did not have a mammogram done or had mammogram done more than two years ago, were lack of time (42.5 percent), fear of pain during the procedure (26.9 percent), and the belief that cancer would not happen to them (24.6 percent).
CONCLUSION: Despite publicity on breast cancer being the commonest cancer among women in Singapore and cure being possible if the malignancy was detected early, close to half of the women aged 40-65 years old who attended the National Healthcare Group Polyclinics did not have mammographic screening done. One-quarter of the women who did not have mammogram screening did not do so as they did not think cancer would happen to them.
Study site: NHG Polyclinics, Singapore
MeSH terms: Adult; Aged; Ambulatory Care/methods*; Ambulatory Care Facilities; Breast Neoplasms/epidemiology; Breast Neoplasms/radiography*; Female; Follow-Up Studies; Humans; Malaysia/ethnology; Mammography*; Mass Screening/methods*; Middle Aged; Outpatients/statistics & numerical data*; Population Surveillance*; Retrospective Studies; Singapore; Incidence
INTRODUCTION: This retrospective review evaluates the prognostic indicators in the management of sudden sensorineural hearing loss (SSNHL) in otorhinolaryngology patients admitted to Brunei RIPAS Hospital.
METHODS: The review covered data collected from 1996 to 1998, and included patients who were treated with naftidrofuryl and dexamethasone. Their hearing improvement (more than 20 dB) in relation to pure tone audiogram patterns, hearing loss severity, vertigo, age of the patients and duration from symptom onset to time of treatment, were evaluated.
RESULTS: After exclusion of three patients with known causes of hearing loss, 50 patients with idiopathic SSNHL were reviewed. Six audiogram patterns were observed with good prognostic indicators in patterns 1 and 4, where respectively, 95 percent and 100 percent of the patients improved. The hearing improvement was noted in the majority of the patients with mild or moderate degree of hearing loss, especially noticeable in audiogram patterns 1 and 4. Initial vertigo gave poor prognosis in hearing (more than 33 percent patients with vertigo improved versus 88 percent patients without vertigo improved). Patients aged between 21 and 60 years appear to have better prognosis of hearing improvement compared to those who are outside of this age range. 92 percent patients whose treatment started within the first week of onset of hearing loss experienced hearing improvement compared to 84 percent patients whose treatment started in the second week after onset.
CONCLUSION: Fairly consistent with the previously-reported prognostic indicators are hearing loss severity, vertigo, age and duration of onset to treatment, though there was reasonably good prognosis when the patients were treated in the second week from hearing loss onset. Further findings of note were the six audiogram patterns and the good prognostic indicators in patterns 1 and 4.
The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients.
MeSH terms: Child; Child, Preschool; Chromosome Deletion*; Female; Humans; Infant; Infant, Newborn; Malaysia; Male; Nerve Tissue Proteins/genetics*; Spinal Muscular Atrophies of Childhood/genetics*; RNA-Binding Proteins/genetics*; Cyclic AMP Response Element-Binding Protein/genetics*; Asian Continental Ancestry Group/genetics*; Neuronal Apoptosis-Inhibitory Protein/genetics*; SMN Complex Proteins; Survival of Motor Neuron 1 Protein
1. The present study was performed in order to determine the amino acid and fatty acid composition of an aqueous extract of the freshwater fish Channa striatus, obtained by soaking (1:2, w/v) fresh fillets overnight in a chloroform:methanol (2:1, v/v) solvent, to elucidate the mechanism responsible for its antinociceptive activity and to clarify the relationship between the presence of the amino and fatty acids and the expected activity. 2. The aqueous extract was found to contain all amino acids with the major amino acids glycine, alanine, lysine, aspartic acid and proline making up 35.77 +/- 0.58, 10.19 +/- 1.27, 9.44 +/- 0.56, 8.53 +/- 1.15 and 6.86 +/- 0.78% of the total protein, respectively. 3. In addition, the aqueous extract was found to have a high palmitic acid (C16:0) content, which contributed approximately 35.93 +/- 0.63% to total fatty acids. The other major fatty acids in the aqueous extract were oleic acid (C18:1), stearic acid (C18:0), linoleic acid (C18:2) and arachidonic acid (C20:4), contributing 22.96 +/- 0.40, 15.31 +/- 0.33, 11.45 +/- 0.31 and 7.44 +/- 0.83% of total fatty acids, respectively. 4. Furthermore, the aqueous extract was demonstrated to possess concentration-dependent antinociceptive activity, as expected, when assessed using the abdominal constriction test in mice. 5. It is concluded that the aqueous extract of C. striatus contains all the important amino acids, but only some of the important fatty acids, which are suggested to play a key role in the observed antinociceptive activity of the extract, as well as in the traditionally claimed wound healing properties of the extract.
Nitrogen mustard alkylating agents are important cancer drugs. Much interest has been focused on redirecting their covalent adducts from the N7 atoms of guanine in the major groove of DNA to the N3 atoms of adenine in the minor groove by attaching mustard groups to AT-selective minor groove binding ligands. Here we describe the use of electrospray ionization and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry to study the structure of the DNA complexes of two minor groove binding polybenzamide mustards, alkamin and alkamini; the former is a bis-half-mustard in which reactive groups are disposed at each end of the ligand, and the latter is its monofunctional analog. Alkamin is potently cytotoxic and active in experimental mouse tumor models, whereas alkamini is not. We have studied their interaction with the DNA dodecamer d(CGCGAATTCGCG)(2), designated A2T2, and we provide a detailed analysis of the observed DNA-ligand adduct ions and their fragmentation products. We find that alkamini alkylates A2T2 at guanine G4 and adenines A5 and A6 in a manner consistent with covalent attack on purine N3 atoms from the minor groove of the AT tract. Alkamin also forms monofunctional adducts at G4 and both adenines in which the second mustard arm is hydrolyzed but, in addition, forms a variety of interstrand cross-links between adenines A5/A6 and A5'/A6', an interstrand cross-link between G4 and A6', and an intrastrand cross-link between G4 and A6. We conclude that the marked cytotoxicity of alkamin and its experimental antitumor activity could be the consequence of its ability to cross-link cellular DNA at AT tract sequences.
MeSH terms: Alkylating Agents/pharmacokinetics; Antineoplastic Agents/pharmacokinetics; Antineoplastic Agents/chemistry; Base Sequence; Binding Sites; DNA Damage; Nitrogen Mustard Compounds/pharmacokinetics*; Nucleic Acid Conformation; Oligodeoxyribonucleotides/metabolism*; Oligodeoxyribonucleotides/chemistry; Mass Spectrometry/methods
Coptotermes gestroi, the Asian subterranean termite (AST), is an economically important structural and agricultural pest that has become established in many areas of the world. For the first time, phylogeography was used to illuminate the origins of new found C. gestroi in the US Commonwealth of Puerto Rico; Ohio, USA; Florida, USA; and Brisbane, Australia. Phylogenetic relationships of C. gestroi collected in indigenous locations within Malaysia, Thailand, and Singapore as well as from the four areas of introduction were investigated using three genes (16S rRNA, COII, and ITS) under three optimality criteria encompassing phenetic and cladistic assumptions (maximum parsimony, maximum likelihood, and neighbor-joining). All three genes showed consistent support for a close genetic relationship between C. gestroi samples from Singapore and Ohio, whereas termite samples from Australia, Puerto Rico, and Key West, FL were more closely related to those from Malaysia. Shipping records further substantiated that Singapore and Malaysia were the likely origin of the Ohio and Australia C. gestroi, respectively. These data provide support for using phylogeography to understand the dispersal history of exotic termites. Serendipitously, we also gained insights into concerted evolution in an ITS cluster from rhinotermitid species in two genera.
Nonalcoholic fatty liver disease (NAFLD) is increasing rapidly in the Asia-Pacific region. There has been a paucity of studies from the region. The aims of this study were to define the demographic, anthropometric, metabolic and histological characteristics of patients with NAFLD in our local population and to determine independent predictors of severe liver fibrosis.
A simple analytical method using HPLC with fluorescence detection was developed for the simultaneous determination of four lignans, phyllanthin (1), hypophyllanthin (2), phyltetralin (3) and niranthin (4) from Phyllanthus niruri L. in plasma. The method recorded limits of detection for 1, 2, 3 and 4 as 1.22, 6.02, 0.61 and 1.22 ng/ml, respectively, at a signal-to-noise ratio of 5:1 whereas their limits of quantification were 4.88, 24.41, 4.88 and 9.76 ng/ml, respectively, at a signal-to-noise ratio of 12:1. These values were comparable to those of other sensitive methods such as gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography-MS (HPLC-MS) and HPLC-electrochemical detection (HPLC-ECD) for the analysis of plasma lignans. A further advantage over known methods was its simple protocol for sample preparation. The within-day and between-day accuracies for the analysis of the four lignans were between 87.69 and 110.07% with precision values below 10.51%. Their mean recoveries from extraction were between 91.39 and 114.67%. The method was successfully applied in the pharmacokinetic study of lignans in rats. Following intravenous administration, the lignans were eliminated slowly from the body with a mean clearance of 0.04, 0.01, 0.03 and 0.02 l/kg h and a mean half-life of 3.56, 3.87, 3.35 and 4.40 h for 1, 2, 3 and 4, respectively. Their peak plasma concentration upon oral administration was 0.18, 0.56, 0.12 and 0.62 microg/ml, respectively, after 1h. However, their absorption was incomplete with a calculated absolute oral bioavailability of 0.62, 1.52, 4.01 and 2.66% for 1, 2, 3 and 4, respectively.
MeSH terms: Animals; Chromatography, High Pressure Liquid/methods*; Male; Sensitivity and Specificity; Spectrometry, Fluorescence/methods*; Rats, Sprague-Dawley; Lignans/blood*; Lignans/pharmacokinetics; Phyllanthus/chemistry*; Rats
BACKGROUND: Data comparing the effect of losartan and perindopril on aortic stiffness among hypertensive subjects without A(1166)C polymorphism was not available.
METHODS: The short-term and long-term effects of losartan (50 mg) and perindopril (4 mg) on aortic stiffness measured as carotid femoral pulse wave velocity (PWV) were compared in 39 middle-aged Malay subjects with mild-to-moderate hypertension in a 4-month, double-blind, randomized, controlled, parallel-design study.
RESULTS: Four-month treatment with both drugs showed a significant reduction in blood pressure (BP) (P < .005) and PWV (P < .05) as compared to the baseline. On the other hand 1-month treatment showed a significant reduction in BP only in perindopril group (P < .05) but not in the losartan group. There was no significant reduction in pulse pressure and PWV after 1 month treatment by both drugs. No significant difference was seen in reduction in BP after 1 month and 4 months treatment between the two drugs. Similarly no significant difference was seen in reduction in PWV between the two drugs after 1 month (P = .613) and 4 months (P = .521) of treatment. Reduction in PWV by losartan (r = 0.470) and perindopril (r = 0.457) correlated significantly only with reduction in DBP (P < .05) and remained significant even after controlling for reduction in DBP (P < .05). Reduction in PWV by both losartan and perindopril was independent of reduction in BP by these drugs.
CONCLUSIONS: These results showed that long-term treatment with losartan shows similar pressure independent reduction in PWV as perindopril among Malay hypertensive subjects with a homogenous "AA" genotype for angiotensin II type 1 receptor and may serve as a suitable alternative to perindopril.
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.
Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.
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.
Pheochromocytomas are rare neuroendocrine tumors that produce, metabolize, and usually secrete catecholamines. Although hypertension is a common presenting feature of pheochromocytoma, the tumors occur (or are present) in only 0.1% of patients with hypertension. The variability of symptoms and rarity of occurrence render these tumors difficult to diagnose; many are discovered incidentally during radiological examination or at autopsy. A patient is presented with a pheochromocytoma that was discovered incidentally when she presented with abdominal pain and a normal blood pressure.