Obesity is intimately associated with hypertension; increases in blood pressure are closely related to the magnitude of weight gain. The present study aims to determine whether the excitatory amino acid input to rostral ventrolateral medulla (RVLM) contributes to elevated blood pressure in rats with diet-induced obesity. Male Sprague-Dawley rats weighing 280 to 300 grams were fed with a low-fat diet (10% kcal from fat) or moderately high-fat diet (32% kcal from fat) for 16 weeks. At week 16, rats on the moderate high-fat diet were segregated into obesity-prone and obesity-resistant rats based on body weight distribution. Baseline mean arterial pressure (MAP) was significantly higher in obesity-prone rats as compared to obesity-resistant and rats on a low-fat diet. Bilateral injection of kynurenic acid (KYN) (40 nM) into the RVLM of the obesity-prone rats reduced MAP to levels significantly different from those observed in rats on a low-fat diet and obesity-resistant rats (no change in MAP). At a lower concentration (4 nM), KYN injection did not produce any change in MAP in any group. The results obtained suggest that excitatory amino acid input to the RVLM does contribute to the development of hypertension in rats with diet-induced obesity.
Cryptosporidium species are protozoan parasites that infect humans and a wide variety of animals. This study was aimed at identifying Cryptosporidium species and genotypes isolated from avian hosts. A total of 90 samples from 37 different species of birds were collected throughout a 3-month period from April 2008 to June 2008 in the National Zoo of Kuala Lumpur, Malaysia. Prior to molecular characterization, all samples were screened for Cryptosporidium using a modified Ziehl-Neelsen staining technique. Subsequently samples were analysed with nested-PCR targeting the partial SSU rRNA gene. Amplicons were sequenced in both directions and used for phylogenetic analysis using Neighbour-Joining and Maximum Parsimony methods. Although 9 (10%) samples were positive for Cryptosporidium via microscopy, 8 (8.9%) produced amplicons using nested PCR. Phylogenetic trees identified all the isolates as Cryptosporidium parvum. Although C. parvum has not been reported to cause infection in birds, and the role of birds in this study was postulated mainly as mechanical transporters, these present findings highlight the significant public health risk posed by birds that harbour the zoonotic species of Cryptosporidium.
Vaccine development against the blood-stage malaria parasite is aimed at reducing the pathology of the disease. We constructed a recombinant Mycobacterium bovis bacille Calmette Guerin (rBCG) expressing the 19 kDa C-terminus of Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) to evaluate its protective ability against merozoite invasion of red blood cells in vitro. A mutated version of MSP-1(19), previously shown to induce the production of inhibitory but not blocking antibodies, was cloned into a suitable shuttle plasmid and transformed into BCG Japan (designated rBCG016). A native version of the molecule was also cloned into BCG (rBCG026). Recombinant BCG expressing the mutated version of MSP-1(19) (rBCG016) elicited enhanced specific immune response against the epitope in BALB/c mice as compared to rBCG expressing the native version of the epitope (rBCG026). Sera from rBCG016-immunized mice contained significant levels of specific IgG, especially of the IgG2a subclass, against MSP-1(19) as determined by enzyme-linked immunosorbent assay. The sera was reactive with fixed P. falciparum merozoites as demonstrated by indirect immunofluorescence assay (IFA) and inhibited merozoite invasion of erythrocytes in vitro. Furthermore, lymphocytes from rBCG016-immunized mice demonstrated higher proliferative response against the MSP-1(19) antigen as compared to those of rBCG026- and BCG-immunized animals. rBCG expressing the mutated version of MSP-1(19) of P. falciparum induced enhanced humoral and cellular responses against the parasites paving the way for the rational use of rBCG as a blood-stage malaria vaccine candidate.
Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
Clinical studies and research in animals have established that alcohol consumption during pregnancy produces irreversible developmental anomalies. Deficits in fine motor performance are often noted in infants diagnosed with fetal alcohol syndrome. However, the effects of alcohol on the spinal motoneurons have not been examined. In this study, the morphometric alterations in spinal motoneurons were assessed as a result of prenatal alcohol exposure.
Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic indicator in breast carcinoma in the local population.
Pedicle involvement in spinal tuberculosis (TB), the prevertebral abscess formation, severity of vertebral body, and disc collapse were evaluated from magnetic resonance imaging (MRI) of the patients.
The ethanolic extract of Alpinia conchigera Griff. leaves (EACL) was evaluated for its antinociceptive and anti-inflammatory activities in several in vivo experimental models. Antinociceptive activity was determined using the acetic acid-induced abdominal writhing test, the hot plate test and the formalin test. Anti-inflammatory activity was determined using the carrageenan-induced paw edema test. The extract (30, 100 and 300 mg/kg i.p.) was found to possess significant, dose-dependent inhibitory activity in all test models. In addition, the antinociceptive effect of the extract in the acetic acid-induced writhing and hot plate tests was reversed by naloxone, suggesting that this activity is mediated through activation of the opioid system. These findings suggest that EACL presents notable analgesic and anti-inflammatory activities, which support its folkloric use for painful and inflammatory conditions.
ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus niruri Linn. (Euphorbiaceae) is used as folk medicine in South America to treat excess uric acid. Our initial study showed that the methanol extract of Phyllanthus niruri and its lignans were able to reverse the plasma uric acid of hyperuricemic animals.
AIM OF THE STUDY: The study was undertaken to investigate the mechanisms of antihyperuricemic effect of Phyllanthus niruri and its lignan constituents.
MATERIAL AND METHODS: The mechanisms were investigated using xanthine oxidase assay and uricosuric studies in potassium oxonate- and uric acid-induced hyperuricemic rats.
RESULTS: Phyllanthus niruri methanol extract exhibited in vitro xanthine oxidase inhibition with an IC50 of 39.39 microg/mL and a moderate in vivo xanthine oxidase inhibitory activity. However, the lignans display poor xanthine oxidase inhibition in vitro and a relatively weak in vivo inhibitory activity at 10mg/kg. On the other hand, intraperitoneal treatment with Phyllanthus niruri methanol extract showed 1.69 folds increase in urinary uric acid excretion when compared to the hyperuricemic control animals. Likewise, the lignans, phyllanthin, hypophyllanthin and phyltetralin exhibited up to 2.51 and 11.0 folds higher in urinary uric acid excretion and clearance, respectively. The co-administration of pyrazinamide with phyllanthin exhibited a significant suppression of phyllanthin's uricosuric activity resembling that of pyrazinamide with benzbromarone.
CONCLUSIONS: The present study showed that the antihyperuricemic effect of Phyllanthus niruri methanol extract may be mainly due to its uricosuric action and partly through xanthine oxidase inhibition, whereas the antihyperuricemic effect of the lignans was attributed to their uricosuric action.
The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT).
Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow-mediated dilation (FMD) was measured in 56 first-degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age-, sex-, and BMI-matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA(IR)), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4-week double-blind, placebo-controlled trial. The FDRs had significantly impaired FMD (4.4 +/- 8.1% vs. 13.0 +/- 4.2%; P < 0.001), higher HOMA(IR) (1.72 +/- 1.45 vs. 1.25 +/- 0.43; P = 0.002), and elevated levels of plasma markers of inflammation-highly sensitive C-reactive protein (hsCRP) (2.6 +/- 3.8 mg/L vs. 0.7 +/- 1.0 mg/L; P = 0.06), interleukin (IL)-6 (0.07 +/- 0.13 ng/mL vs. 0.03 +/- 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 +/- 30.7 ng/mL vs. 238.2 +/- 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin-treated subjects when compared with the placebo-treated subjects (atorvastatin, from 3.7 +/- 8.5% to 9.8 +/- 7.3%; placebo, from 3.9 +/- 5.6% to 4.7 +/- 4.2%; P = 0.001). There were also reductions in the levels of IL-6 (0.08 +/- 0.02 ng/mL vs. 0.04 +/- 0.01 ng/mL; P < 0.001) and hsCRP (3.0 +/- 3.9 mg/L vs. 1.0 +/- 1.3 mg/L; P = 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.
Matched MeSH terms: Genetic Predisposition to Disease
This study was performed to determine the antinociceptive and anti-inflammatory activities of aqueous extract of Kaempferia galanga leaves using various animal models. The extract, in the doses of 30, 100, and 300 mg/kg, was prepared by soaking (1:10; w/v) the air-dried powdered leaves (40 g) in distilled water (dH(2)O) for 72 h and administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot-plate and formalin tests, with activity observed in all tests occurring in a dose-dependent manner. Furthermore, the antinociceptive activity of K. galanga extract was significantly (P < 0.05) reversed when prechallenged with 10 mg/kg naloxone. The extract also produced a significantly (P < 0.05) dose-dependent anti-inflammatory activity when assessed using the carrageenan-induced paw-edema test. In conclusion, this study demonstrated that K. galanga leaves possessed antinociceptive and anti-inflammatory activities and thus supports the Malay's traditional uses of the plant for treatments of mouth ulcer, headache, sore throat, etc.
Acute gastroenteritis (AGE) is a common illness among infants and children contributing to significant mortality and morbidity. As such, appropriate treatment received prior to hospital admission is of utmost importance. This retrospective observational study aimed to determine preadmission management in paediatric patients prior to hospital admission. Two hundred and twenty-two case notes of paediatric AGE patients were reviewed over a 12-month period. One hundred and fifty-four patients received medications prior to admission with 143 (92.9%) patients received known classes of medications. Antipyretic agents were the most commonly prescribed (69.2%), followed by antibiotics (38.5%), anti-emetics (35.7%), oral rehydration salts (29.4%) and antidiarrhoeals (28.0%). The mean duration of stay in hospital was slightly shorter in patients, who received prior medications than those who did not (2.22 vs. 2.32 days respectively). Seventy per cent of children admitted for AGE were treated suboptimally prior to hospital admission with oral rehydration salts being largely under-utilized, despite their proven efficacy and safety. Sex, race and age had no influence on the type of preadmission treatment. A greater effort should be made to educate the general public in the appropriate treatment of AGE.
We were presented with a teenage female who developed superior ophthalmic vein thrombosis and cavernous sinus thrombophlebitis after a 1-week history of a single acne-like lesion or furuncle at the anterior tip of the nose. She was managed aggressively with heparin and intravenous antibiotic. Signs and symptoms improved after 2 weeks of treatment, and she was discharged with an anticoagulant.
The present study described the kinetics of Rat cytomegalovirus (RCMV) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral DNA in the blood (DNAemia) and antibody response. These parameters were evaluated quantitatively using double-antibody sandwich ELISA (DAS-ELISA), real-time PCR, indirect ELISA and virus infectivity assay. For the first time DAS-ELISA was used for detection of RCMV antigen directly from organ samples. The relationships between the presence of viral antigens in the infected organs and antibody levels were established by the Spearman's rank test. It was found that the virus was present in the blood, spleen, liver, lungs, and kidneys earlier than in the salivary glands. Furthermore, the early immunity of the newborn rats led to a delayed seroconversion. We suggested that the prolonged presence of the virus in salivary glands could augment the antibody response that conversely might be responsible for a reduction of viremia. This study expanded our understanding of RCMV pathogenesis leading to improved therapeutic and preventive treatment regimens particularly for the neonatal Human cytomegalovirus (HCMV) infections. Additionally, the detection procedures developed in this study such as DAS-ELISA and real-time PCR could serve as alternative techniques for rapid screening of large number of samples.
Burkholderia pseudomallei is a Gram-negative saprophytic soil bacterium, which is the etiologic agent of melioidosis, a severe and fatal infectious disease occurring in human and animals. Distinct clinical and animal isolates have been shown to exhibit differences in phenotypic trait such as growth rate, colony morphology, antimicrobial resistance, and virulence. This study was carried out to gain insight into the intrinsic differences between 4 clinical and 6 animal B. pseudomallei isolates from Malaysia. The 16S rRNA-encoding genes from these 10 isolates of B. pseudomallei were sequenced to confirm the identity of these isolates along with the avirulent Burkholderia thailandensis. The nucleotide sequences indicated that the 16S rRNA-encoding genes among the 10 B. pseudomallei isolates were identical to each other. However, the nucleotide sequence differences in the 16S rRNA-encoding genes appeared to be B. pseudomallei and B. thailandensis specific. The growth rate of all B. pseudomallei isolates was determined by generating growth curves at 37 degrees C for 72 h. The isolates were found to differ in growth rates with doubling time varying from 1.5 to 2.3 h. In addition, the B. pseudomallei isolates exhibited considerable variation in colony morphology when grown on Ashdown media, brain-heart infusion agar, and Luria-Bertani agar over 9 days of observation. Antimicrobial susceptibility tests indicated that 80% of the isolates examined were Amp(R) Cb(R) Kn(R) Gm(R) Chl(S) Te(S). Virulence of the B. pseudomallei clinical and animal isolates was evaluated in B. pseudomallei-susceptible BALB/c mice. Most of the clinical isolates were highly virulent. However, virulence did not correlate with isolate origin since 2 of the animal isolates were also highly virulent.
The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.
Matched MeSH terms: Genetic Predisposition to Disease
The p27 V109G polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 230 breast cancer patients and 200 normal and healthy women who had no history of breast disease or breast cancer. We evaluated the association between the p27 polymorphism and breast cancer risk, and clinico-pathological parameters in the population. The distribution of genotype and allele frequencies of p27 V109G polymorphism were not significantly different between the breast cancer cases and normal subjects (P=0.376). Women who were homozygous (OR=1.73; 95% CI, 0.62-4.92) or heterozygous (OR=1.26; 95% CI, 0.75-2.12) for G allele, or carriers of G allele genotype (OR=1.34; 95%, 0.83-2.16) or G allele (OR=1.36; 95% CI, 0.90-2.05) were not associated with breast cancer risk. No significant correlation was noted between G allele genotype and breast cancer risk among patients under 50 (OR=1.28; 95% CI, 0.62-2.66) or 50 years and older (OR=1.38; 95% CI, 0.71-2.66) at diagnosis. The G allele genotype was significantly associated with lymph node metastases but independent of ER status and histological grade. In conclusion, the polymorphic variant at codon 109 of p27 gene may not be a marker for determining patients' risk of developing breast cancer but it may be a potential genetic marker for poor prognosis, thereby a marker for tumor prognosis.
Matched MeSH terms: Genetic Predisposition to Disease
The pathogenesis of cisplatin-induced renal failure is related to reduced renal blood flow due to severe tubular damage and enhanced renovascular resistance. It is also known that alpha(1)-adrenoceptors, the major subtype of alpha-adrenoceptors in renal vasculature play the pivotal role in regulating renal hemodynamics. With this background, we have hypothesized that the altered renal hemodynamics and enhanced renovascular resistance in cisplatin-induced renal failure might be caused by the altered alpha-adrenergic responsiveness with a possible involvement of alpha(1)-adrenoceptors in the renal vasculature. In a unique experimental approach with anesthetized rats, this study has therefore examined if there is any shift in the renovascular responsiveness to renal nerve stimulation and a series of alpha-adrenergic agonists in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats with cisplatin-induced renal failure in comparison with their body weight-matched normal controls. Thirty-two male rats of both WKY (n=16) and SHR (n=16) origin with body weight 236+/-7.9 g received cisplatin (5mg/kg i.p.). The renal failure was confirmed in terms of significantly reduced renal blood flow, reduced creatinine clearance, increased fractional excretion of sodium, increased kidney index (all P<0.05) and tubular damage. After 7 days of cisplatin, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The changes in the vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by electrical renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine and methoxamine. It was observed that in the cisplatin-treated renal failure WKY and SHR rats there were significant (all P<0.05) reductions in the renal blood flow along with significantly (P<0.05) higher renal adrenergic responsiveness as compared with their non-renal failure controls. The data showed that in the renal failure WKY and SHR rats, the altered renal hemodynamics might be caused by an augmented renal adrenergic responsiveness. The results obtained further led us to suggest that the augmented renal adrenergic responsiveness in the cisplatin-induced renal failure rats were possibly mediated by the alpha(1)-adrenoceptors.
The objective of this study was to determine the anti cancer effects of red spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study, microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were carried out to determine the severity of hepatocarcinogenesis. The result found that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to normal rats did not show any significant difference towards normal control (P <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05). However, it was found that the supplementation of A. gangeticus aqueous extract in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer potential in in vitro and in vivo studies.