Five Malaysian rice (Oryza sativa L.) varieties, MR33, MR52, MR211, MR219, and MR232, were tested in pot culture under different salinity regimes for biochemical response, physiological activity, and grain yield. Three different levels of salt stresses, namely, 4, 8, and 12 dS m(-1), were used in a randomized complete block design with four replications under glass house conditions. The results revealed that the chlorophyll content, proline, sugar content, soluble protein, free amino acid, and yield per plant of all the genotypes were influenced by different salinity levels. The chlorophyll content was observed to decrease with salinity level but the proline increased with salinity levels in all varieties. Reducing sugar and total sugar increased up to 8 dS m(-1) and decreased up to 12 dS m(-1). Nonreducing sugar decreased with increasing the salinity levels in all varieties. Soluble protein and free amino acid also decreased with increasing salinity levels. Cortical cells of MR211 and MR232 did not show cell collapse up to 8 dS m(-1) salinity levels compared to susceptible checks (IR20 and BRRI dhan29). Therefore, considering all parameters, MR211 and MR232 showed better salinity tolerance among the tested varieties. Both cluster and principal component analyses depict the similar results.
The methanolic extracts of 13 accessions of purslane were analyzed for their total phenol content (TPC), total flavonoid contents (TFC), and total carotenoid contents (TCC) and antioxidant activity of extracts was screened using FRAP assay and DPPH radical scavenging methods. The TPC, TFC, and TCC ranged from 0.96 ± 0.04 to 9.12 ± 0.29 mg GAE/g DW, 0.13 ± 0.04 to 1.44 ± 0.08 mg RE/g DW, and 0.52 ± 0.06 to 5.64 ± 0.09 mg (β-carotene equivalent) BCE/g DW, respectively. The DPPH scavenging (IC50) activity varied between 2.52 ± 0.03 mg/mL and 3.29 ± 0.01 mg/mL and FRAP ranged from 7.39 ± 0.08 to 104.2 ± 6.34 μmol TE/g DW. Among all the measured micro- and macrominerals K content was the highest followed by N, Na, Ca, Mg, P, Fe, Zn, and Mn. The overall findings proved that ornamental purslane was richer in antioxidant properties, whereas common purslane possesses more mineral contents than ornamental ones.
2,4',6-Trihydroxy-4-methoxybenzophenone was isolated from the ethyl acetate fraction of Phaleria macrocarpa (Scheff.) Boerl. fruits. It was found to inhibit cell proliferation in HT-29 human colon carcinoma cell line but caused little damage to WRL-68 normal human liver and MRC-5 normal human fibroblast lung cell lines. The compound was found to sharply affect the viability of HT-29 cells in a dose- and time-dependent manner. HT-29 cells treated with the compound showed morphological changes under microscopic examination such as cell shrinkage, membrane blebbing, DNA fragmentation, and the occurrence of apoptotic nuclei. The percentage of early apoptotic, late apoptotic, and dead or necrotic cells was determined by flow cytometry using annexin V-FTIC/PI staining. In addition, flow cytometry showed that, when the HT-29 cells were treated with 115 µM of the compound, it resulted in G0/G1 phase arrest in a time-dependent manner. Western blot revealed an upregulation of PUMA, Bak, Bcl-2, and Mcl-1 proteins suggesting that the compound induced apoptosis in HT-29 cells by regulating these proteins.
We propose a class of attacks on quantum key distribution (QKD) systems where an eavesdropper actively engineers new loopholes by using damaging laser illumination to permanently change properties of system components. This can turn a perfect QKD system into a completely insecure system. A proof-of-principle experiment performed on an avalanche photodiode-based detector shows that laser damage can be used to create loopholes. After ∼1 W illumination, the detectors' dark count rate reduces 2-5 times, permanently improving single-photon counting performance. After ∼1.5 W, the detectors switch permanently into the linear photodetection mode and become completely insecure for QKD applications.
The homeostatic role of adenosine in regulating intraocular pressure (IOP) is now widely recognized, and hence, the drugs targeting adenosine receptors have become the focus of investigation. In this review, we summarize the adenosine receptor signaling pathways, which could be potential therapeutic targets for the management of glaucoma.
BACKGROUND: Provision of post stroke care in developing countries is hampered by discoordination of services and limited access to specialised care. Albeit shortcomings, primary care continues to provide post-stroke services in less than favourable circumstances. This paper aimed to review provision of post-stroke care and related problems among Family Medicine Specialists managing public primary health care services.
METHODS: A semi-structured questionnaire was distributed to 121 Family Physicians servicing public funded health centres in a pilot survey focused on improving post stroke care provision at community level. The questionnaire assessed respondents background and practice details i.e. estimated stroke care burden, current service provision and opinion on service improvement. Means and frequencies described quantitative data. For qualitative data, constant comparison method was used until saturation of themes was reached.
RESULTS: Response rate of 48.8% was obtained. For every 100 patients seen at public healthcentres each month, 2 patients have stroke. Median number of stroke patients seen per month is 5 (IQR 2-10). 57.6% of respondents estimated total stroke patients treated per year at each centre was less than 40 patients. 72.4% lacked a standard care plan although 96.6% agreed one was needed. Patients seen were: discharged from tertiary care (88.1%), shared care plan with specialists (67.8%) and patients who developed stroke during follow up at primary care (64.4%). Follow-ups were done at 8-12 weekly intervals (60.3%) with 3.4% on 'as needed' basis. Referrals ranked in order of frequency were to physiotherapy services, dietitian and speech and language pathologists in public facilities. The FMS' perceived 4 important 'needs' in managing stroke patients at primary care level; access to rehabilitation services, coordinated care between tertiary centres and primary care using multidisciplinary care approach, a standardized guideline and family and caregiver support.
CONCLUSIONS: Post discharge stroke care guidelines and access to rehabilitation services at primary care is needed for post stroke patients residing at home in the community.
MeSH terms: Adult; Ambulatory Care Facilities; Cross-Sectional Studies; Family Practice/standards*; Female; Health Facilities; Humans; Malaysia; Malaysia/ethnology; Male; Practice Patterns, Physicians'*; Primary Health Care; Public Health; Surveys and Questionnaires; Stroke/therapy*; Self Report*
The purpose of this study was to clarify the changes in the kinematics of the knee that result from isolated deficiency of the anteromedial (AM) or posterolateral (PL) bundle.
The introduction and success of imatinib mesylate (IM) has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, the high efficacy of IM has been hampered by the issue of clinical resistance that might due to pharmacogenetic variability. In the current study, the contribution of three common single nucleotide polymorphisms (SNPs) of ABCB1 (T1236C, G2677T/A and C3435T) and two SNPs of ABCG2 (G34A and C421A) genes in mediating resistance and/or good response among 215 CML patients on IM therapy were investigated. Among these patients, the frequency distribution of ABCG2 421 CC, CA and AA genotypes were significantly different between IM good response and resistant groups (P=0.01). Resistance was significantly associated with patients who had homozygous ABCB1 1236 CC genotype with OR 2.79 (95%CI: 1.217-6.374, P=0.01). For ABCB1 G2677T/A polymorphism, a better complete cytogenetic remission was observed for patients with variant TT/AT/AA genotype, compared to other genotype groups (OR=0.48, 95%CI: 0.239-0.957, P=0.03). Haplotype analysis revealed that ABCB1 haplotypes (C1236G2677C3435) was statistically linked to higher risk to IM resistance (25.8% vs. 17.4%, P=0.04), while ABCG2 diplotype A34A421 was significantly correlated with IM good response (9.1% vs. 3.9%, P=0.03). In addition, genotypic variant in ABCG2 421C>A was associated with a major molecular response (MMR) (OR=2.20, 95%CI: 1.273-3.811, P=0.004), whereas ABCB1 2677G>T/A variant was associated with a significantly lower molecular response (OR=0.49, 95%CI: 0.248-0.974, P=0.04). However, there was no significant correlation of these SNPs with IM intolerance and IM induced hepatotoxicity. Our results suggest the usefulness of genotyping of these single nucleotide polymorphisms in predicting IM response among CML patients.
Recent reports indicate Neospora caninum has a possible role in causing abortions in sheep in New Zealand. Knowledge about the epidemiology of neosporosis in sheep is limited. This study aimed to adapt and validate a commercially available ELISA assay as an IgG avidity assay to discriminate between acute (primary and re-inoculated) and chronic N. caninum infections in sheep. In addition, it was used to compare the antibody avidity values between lambs from ewes inoculated with N. caninum either during the pregnancy or in the previous year. The avidity assay was undertaken by using 6M urea for the first wash after incubation with the primary antibody in the commercial ELISA (Chekit* Neospora antibody test kit, IDEXX Laboratories, Australia). Sequential serum samples were obtained from naïve ewes (n=16) experimentally inoculated with live N. caninum tachyzoites. All ewes were seropositive by two weeks post-inoculation and remained seropositive for 20 weeks post-inoculation. There was a linear relationship between time after inoculation and avidity values (p<0.05) over the first 24 weeks. In Week 4, all animals had avidity values <35% and by Week 8, 8/16 animals had avidity values of >35%. These results suggest that an avidity value of <35% indicates a recent primary infection while a value of >35% is indicative of a chronic infection. The assay was then validated using samples from other groups of experimentally inoculated sheep as well as samples from naturally infected ewes. When comparing sample to positive ratio (S/P) and avidity values from lambs born from recently inoculated ewes with those from ewes inoculated the previous year and re-inoculated in the current year, it was possible to differentiate the lambs at 2 weeks of age. Lambs from recently inoculated ewes had low S/P and avidity values at 2 weeks of age which increased by 12 weeks of age. In comparison, lambs from re-inoculated ewes had high S/P and avidity values at 2 weeks of age, due to maternal antibody influence but values were similar to those from lambs that were born from recently inoculated ewes at 12 weeks of age. Avidity values for four naturally infected ewes were all >60% indicating chronic infection. These results suggest that the assay is able to discriminate between recent and chronic infection in sheep as well as able to differentiate lambs with maternal immunity compared to their own de novo immunity. As such it can be utilized to understand the kinetics of N. caninum infection in sheep.
Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.
Traditional healers in Sarawak, Malaysia, use plants such as Picria fel-terrae, Linariantha bicolor and Lansium domesticum to treat gastrointestinal infections. This study aimed to test whether their nematocidal activities could be confirmed in vitro using highly standardised Caenorhabditis elegans models. We applied eight different ethanol solubilised plant extracts and two commercial anthelmintic drugs to larval and adult stages of C. elegans in vitro. Seven C. elegans strains were evaluated, one wild type and six strains with GFP-tagged stress response pathways to help characterise and compare the pathways affected by plant extracts. Our in vitro screen confirmed that both of the commercial anthelmintic drugs and five of the eight traditionally used plant extracts had significant nematocidal activity against both larval and adult C. elegans. The most effective extracts were from P. fel-terrae. The plant extracts triggered different stress response pathways from the commercial anthelmintic drugs. This study showed that using traditional knowledge of plant medicinal properties in combination with a C. elegans in vitro screen provided a rapid and economical test with a high hit rate compared with the random screening of plants for nematocidal activities. The use of transgenic C. elegans strains may allow this approach to be refined further to investigate the mode of action of active extracts.
Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have similarity with those of prostaglandin analogs. The present study investigated the involvement of matrix metalloproteinases (MMPs) and cytokine activity modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor. Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering effect of ACEI. Topical treatment with single drop of enalaprilat resulted in significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h post-instillation. Treatment with losartan resulted in a peak IOP reduction of 13.3%, which was significantly lower than enalaprilat, indicating involvement of mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin II type 1 receptor stimulation and modulation of MMP and cytokines activities.
Informed consent of prospective donors should include information about the quality of life (QoL) of existing donors, especially those within the relevant country. This study aimed to provide information on Malaysian organ donors' QoL relative to a control group.
MeSH terms: Adult; Female; Follow-Up Studies; Health Status*; Humans; Informed Consent/psychology*; Malaysia; Male; Middle Aged; Quality of Life/psychology*; Surveys and Questionnaires; Kidney Transplantation/psychology*; Living Donors/psychology*; Control Groups
Glycyrrhiza glabra L. (Fabaceae), commonly known as 'liquorice', is one of the most popular ingredients in several traditional herbal medicinal preparations, and glycyrrhizin is the major glycoside present in this plant. The content of glycyrrhizin may vary among G. glabra samples collected from various geographical origins, which may affect the therapeutic efficacy. Thus, quantification of glycyrrhizin in G. glabra samples is important.
The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations.
MeSH terms: Adult; Amoxicillin/adverse effects*; Amoxicillin/blood; Amoxicillin/pharmacokinetics*; Amoxicillin/chemistry; Blood Pressure/drug effects; Chromatography, High Pressure Liquid; Drug Stability; Heart Rate/drug effects; Humans; Malaysia/epidemiology; Male; Random Allocation; Sensitivity and Specificity; Therapeutic Equivalency; Reproducibility of Results; Cross-Over Studies; Area Under Curve; Young Adult
We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.
Andrographolides, the diterpene lactones, are major bioactive phytochemicals which could be found in different parts of the medicinal herb Andrographis paniculata. A number of such compounds namely andrographolide (AG), neoandrographolide (NAG), and 14-deoxy-11,12-didehydroandrographolide (DDAG) have already attracted a great deal of attention due to their potential therapeutic effects in hard-to-treat diseases such as cancers and HIV. Recently, they have also been considered as substrates for the discovery of novel pharmaceutical compounds. Nevertheless, there is still a huge gap in knowledge on the genetic pattern of the biosynthesis of these bioactive compounds. Hence, the present study aimed to investigate the genetic mechanisms controlling the biosynthesis of these phytochemicals using a diallel analysis. The high performance liquid chromatography analysis of the three andrographolides in 210 F1 progenies confirmed that the biosynthesis of these andrographolides was considerably increased via intraspecific hybridization. The results revealed high, moderate and low heterosis for DDAG, AG and NAG, respectively. Furthermore, the preponderance of non-additive gene actions was affirmed in the enhancement of the three andrographolides contents. The consequence of this type of gene action was the occurrence of high broad-sense and low narrow-sense heritabilities for the above mentioned andrographolides. The prevalence of non-additive gene action suggests the suitability of heterosis breeding and hybrid seed production as a preferred option to produce new plant varieties with higher andrographolide contents using the wild accessions of A. paniculata. Moreover, from an evolutionary point of view, the occurrence of population bottlenecks in the Malaysian accessions of A. paniculata was unveiled by observing a low level of additive genetic variance (VA ) for all the andrographolides.
Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
MeSH terms: Adult; Aged; Breast Neoplasms/metabolism*; Breast Neoplasms/pathology*; Female; Humans; Immunohistochemistry; Middle Aged; Prognosis; Receptors, Estrogen/metabolism*; Biomarkers, Tumor/metabolism; Carcinoma, Ductal, Breast/metabolism*; Carcinoma, Ductal, Breast/pathology*; Receptor, ErbB-2/metabolism; Ki-67 Antigen/metabolism*; Young Adult
Phenylhydrazine, a hemolytic agent, is widely used as a model of experimental hyperbilirubinemia. Palm tocotrienol-rich fraction (TRF) was shown to exert beneficial effects in hyperbilirubinemic rat neonates.