A series of six/five member (E/Z)-Goniothalamin analogs were synthesized from commercially available (3,4-dihydro-2H-pyran-2-yl)methanol/5-(hydroxymethyl)dihydrofuran-2(3H)-one in three steps with good to moderate overall yields and their cytotoxicity against lymphoblastic leukemic T cell line (Jurkat E6.1) have been evaluated. Among the synthesized analogs, (Z)-Goniothalamin appeared to be the most active in cytotoxicity (IC50 = 12 μM). Structure-activity relationship study indicates that introducing substituent in phenyl ring or replacing phenyl ring by pyridine/naphthalene, or decreasing the ring size of lactones (from six to five member) do not increase the cytotoxicity.
MeSH terms: Cytotoxins/chemical synthesis*; Cytotoxins/pharmacology*; Drug Evaluation, Preclinical/methods; Humans; Pyrones/chemical synthesis*; Pyrones/pharmacology*; Structure-Activity Relationship; Drug Design*; Jurkat Cells
Self-assembled nanocarriers attract increasing attention due to their wide application in various practical fields; among them, one of the most focused fields is drug delivery. Appropriate selection of surfactant is the basis for preparing a successful nanocarrier. Until now, from phospholipid to synthetic surfactants, many surfactants have been used to explore a suitable drug delivery vehicle for the complex in-vivo environment. Among all, bio surfactants are found to be more suitable due to their bio-origin, less-toxicity, biodegradability, cheaper rate and above all, their versatile molecular structures. This molecular property enables them to self assemble into fascinating structures. Moreover, binding DNA, enhancing pH sensitivity and stability allows novelty over their synthetic counterparts and phospholipid. This review paper focuses on the properties and applications of bio-nano-carriers for drug delivery. Micelle, microemulsion, and vesicle are the three nanocarriers which are discussed herein.
MeSH terms: Emulsions; Micelles; Drug Delivery Systems*; Nanostructures*
The carboxymethyl sago pulp (CMSP) with a degree of substitution of 0.4% was synthesized from sago waste. The CMSP beads with an average diameter of 3.1-4.8 mm were formed by aluminium chloride gelation as well as further cross-linked by irradiation. To evaluate colon targeted release, a model drug, 5-aminosalicylic acid (5-ASA) was encapsulated in CMSP beads. Fourier-transform infrared spectroscopy and X-ray diffraction studies indicated intact and amorphous nature of entrapped drug. A pH dependent drug release was observed, and about 90% of the drug was released only at pH 7.4 over 9 h. Irradiated beads were resisted the drug release in an acidic environment at a higher extent than non-irradiated beads. The drug release from 6% (w/w) of 5-ASA loaded bead followed zero order, whereas, 15 and 22% loaded beads followed first order. The release exponent n value suggests non-fickian transport of 5-ASA from the beads.
Utilization of macroalgae biomass for bioethanol production appears as an alternative source to lignocellulosic materials. In this study, for the first time, Amberlyst (TM)-15 was explored as a potential catalyst to hydrolyze carbohydrates from Eucheuma cottonii extract to simple reducing sugar prior to fermentation process. Several important hydrolysis parameters were studied for process optimization including catalyst loading (2-5%, w/v), reaction temperature (110-130°C), reaction time (0-2.5 h) and biomass loading (5.5-15.5%, w/v). Optimum sugar yield of 39.7% was attained based on the following optimum conditions: reaction temperature at 120°C, catalyst loading of 4% (w/v), 12.5% (w/v) of biomass concentration and reaction time of 1.5h. Fermentation of the hydrolysate using Saccharomyces cerevisiae produced 0.33 g/g of bioethanol yield with an efficiency of 65%. The strategy of combining heterogeneous-catalyzed hydrolysis and fermentation with S. cerevisiae could be a feasible strategy to produce bioethanol from macroalgae biomass.
Vibrio cholerae is a human pathogen that causes mild to severe diarrheal illnesses and has major public health significance. Herein, we present a thermostabilized electrochemical genosensing assay combining the use of magnetic beads as a biorecognition platform and gold nanoparticles as a hybridization tag for the detection and quantification of V. cholerae lolB gene single-stranded asymmetric PCR amplicons as an alternative to the time-consuming classical isolation method. This thermostabilized, pre-mixed, pre-aliquoted and ready-to-use magnetogenosensing assay simplified the procedures and permitted the reaction to be conducted at room temperature. The asymmetric PCR amplicons were hybridized to a magnetic bead-functionalized capture probe and a fluorescein-labeled detection probe followed by tagging with gold nanoparticles. Electrochemical detection of the chemically dissolved gold nanoparticles was performed using the differential pulse anodic stripping voltammetry method. The real-time stability evaluation of thermostabilized assay was found to be stable for at least 180 days at room temperature (25-30°C). The analytical specificity of the assay was 100%, while its analytical sensitivity was linearly related to different concentrations of 200-mer synthetic target, purified genomic DNA, and bacterial culture with a limit of detection (LoD) of 3.9nM, 5pg/µl, and 10(3)CFU/ml, respectively. The clinical applicability of the assay was successfully validated using spiked stool samples with an average current signal-to-cut-off ratio of 10.8. Overall, the precision of the assay via relative standard deviation was <10%, demonstrating its reliability and accuracy.
Receptor for advanced glycation end-product (RAGE) gene polymorphism 2245G/A is associated with diabetic retinopathy (DR). However, the mechanism on how it affects the disease development is still unclear.
INTRODUCTION: Cervical cancer is the third most common cancer among Malaysian women. However, the uptake of cervical cancer screening--Pap smear--by women in Malaysia has been low and remains a challenge. This study was conducted to assess the cervical screening practices of rural women in Malaysia and to examine the factors associated with such practices.
METHODS: A cross-sectional survey was conducted in five rural districts in Perak, Malaysia. 1,000 households were selected through multistage random sampling. Women aged 20-64 years were interviewed by trained enumerators using structured questionnaires. Binomial logistic regression was used to identify predictors of cervical screening through univariate and multivariate analyses.
RESULTS: Among the 959 respondents, only 48.9% had undergone Pap smear at least once in the past three years. Women in the age group 40-49 years (odds ratio 3.027, 95% confidence interval 1.546-5.925; p < 0.005) were found to be significantly more likely to attend cervical cancer screening as compared to those in the age group 20-29 years. Other significant predictors were being married with children, having knowledge of cervical cancer symptoms, receiving relevant information regarding cervical cancer from health personnel or campaigns, being engaged in family planning and receiving encouragement from husbands.
CONCLUSION: Efforts to boost the uptake of Pap smear screening among the rural population should be targeted toward the predictors of positive uptake.
MeSH terms: Adult; Uterine Cervical Neoplasms/diagnosis*; Uterine Cervical Neoplasms/epidemiology*; Cross-Sectional Studies; Female; Health Education; Humans; Health Knowledge, Attitudes, Practice; Malaysia; Mass Screening/methods; Middle Aged; Patient Acceptance of Health Care/statistics & numerical data*; Risk Factors; Rural Population; Social Class; Vaginal Smears/statistics & numerical data; Early Detection of Cancer/statistics & numerical data*; Young Adult; Papanicolaou Test/statistics & numerical data
Breast metastases are uncommon and typically spread from contralateral breast carcinomas. Breast metastases that spread from extramammary malignancies are even less common, and account for 0.5%-6.6% of all malignant breast disease. As extrapulmonary metastases from osteosarcoma are uncommon, breast metastasis from osteosarcoma is extremely rare. We report a case of breast and peritoneal metastases from a tibial osteosarcoma 18 months after diagnosis, and 9 months after surgery and adjuvant chemotherapy. Computed tomography findings of multiple calcified and noncalcified tumour deposits in the lungs, pleura, peritoneum, chest wall and both breasts are described.
MeSH terms: Adolescent; Bone Neoplasms/diagnosis*; Bone Neoplasms/pathology*; Breast Neoplasms/secondary*; Female; Humans; Neoplasm Metastasis; Peritoneal Neoplasms/secondary*; Osteosarcoma/diagnosis*; Osteosarcoma/pathology*; Tomography, X-Ray Computed
Genetic markers are now routinely used in a wide range of applications, from forensic DNA analysis to marker-assisted plant and animal breeding. The usual practice in such work is to extract the DNA, prime the markers of interest, and sift them out by electrically driving them through an appropriate matrix, usually a gel. The gels, made from polyacrylamide or agarose, are of high cost, limiting their greater applications in molecular marker work, especially in developing countries where such technology has great potential. Trials using superfine resolution (SFR) agarose for SSR marker screening showed that it is capable of resolving SSR loci and can be reused up to 14 times, thus greatly reducing the cost of each gel run. Furthermore, for certain applications, low concentrations of agarose sufficed and switching to lithium borate buffer, instead of the conventional Tris-borate-ethylenediaminetetraacetic acid buffer, will further save time and cost. The 2.5% gel was prepared following the Agarose SFR(TM) manual by adding 2.5 g agarose powder into 100 mL 1X lithium borate buffer in a 250-mL flask with rapid stirring. Two midigels (105 x 83 mm, 17 wells) or 4 minigels (50 x 83 mm, 8 wells), 4 mm thickness can be prepared from 100 mL gel solution. A total of 1680 PCR products amplified using 140 SSR markers from oil palm DNA samples were tested in this study using SFR recycled gel. As average, the gel can be recycled 8 times with good resolution, but can be recycled up to 14 times before the resolutions get blurred.
MeSH terms: Electrophoresis, Agar Gel/methods*; Sepharose/chemistry*; Recycling*
Practice plays an important role in skill acquisition, although not all practice is of equal quality. We examined the types of team practice activities in four groups of youth cricket players. The groups were recreational- and elite-children (9 to 12 years of age) and recreational- and elite-adolescent players (13 to 17 years of age). Time motion analysis recorded the duration in two types of practice activities, namely, Training Form and Playing Form. Training Form is mainly drill-type activities, whereas Playing Form is mainly games-based activities. Training Form activity is thought to contain fewer opportunities to develop the perceptual, cognitive and motor skills required for successful performance in competition when compared to Playing Form. Session duration was a mean value of 95, s = 29 min. All players combined spent 69% of session time in Training Form activity and 19% in Playing Form, with the remaining percentage of time spent in transition between activities. Recreational-children spent around half of their time in Playing Form activity, whereas both elite and adolescent groups spent little or no time in this activity. Findings from this research highlight a gap between research and practice that may not be optimal for skill acquisition.
Work-related musculoskeletal disorders are one of the main occupational health hazards affecting dental practitioners. This study was conducted to assess the prevalence of Work-related Musculoskeletal Disorder (WMSD) amongst dental students. Possible correlations with the working environment and ergonomics taught in Malaysian dental schools were also sought.
To evaluate the outcome of intravitreal bevacizumab in the treatment of radiation-induced cystoid macular oedema among patients who underwent external beam radiotherapy for nasopharyngeal carcinoma.
In many workplaces, employment is conditional on a successful pre-employment medical examination. This examination is usually conducted by a general practitioner on the employers' panel of approved clinics or by an in-house company doctor.
MeSH terms: Adult; Ambulatory Care Facilities; Confidentiality/ethics; Employment*; Female; Humans; Malaysia; Personnel Selection/ethics*; Physical Examination; Physician-Patient Relations/ethics; Work Capacity Evaluation; Disclosure/ethics; General Practitioners/ethics*
To assess the knowledge, attitudes and practices of Imams (Islamic clerics) concerning fluoride toothpaste and fluoridated water to improve oral health in Kelantan.
MeSH terms: Adult; Cariostatic Agents/therapeutic use*; Fluoridation; Fluorides/therapeutic use*; Humans; Islam/psychology*; Health Knowledge, Attitudes, Practice*; Malaysia; Male; Middle Aged; Oral Health*; Oral Hygiene/psychology*; Surveys and Questionnaires; Religion and Medicine; Toothpastes/therapeutic use; Toothpastes/chemistry; Young Adult
Human chorion-derived stem cells (hCDSC) were previously shown to demonstrate multipotent properties with promising angiogenic characteristics in monolayer-cell culture system. In our study, we investigated the angiogenic capability of hCDSC in 3-dimensional (3D) in vitro and in vivo angiogenic models for the purpose of future application in the treatment of ischaemic diseases. Human CDSC were evaluated for angiogenic and endogenic genes expressions by quantitative PCR. Growth factors secretions were quantified using ELISA. In vitro and in vivo vascular formations were evaluated by histological analysis and confocal microscopic imaging. PECAM-1(+) and vWF(+) vascular-like structures were observed in both in vitro and in vivo angiogenesis models. High secretions of VEGF and bFGF by hCDSC with increased expressions of angiogenic and endogenic genes suggested the possible angiogenic promoting mechanisms by hCDSC. The cooperation of hCDSC with HUVECS to generate vessel-like structures in our systems is an indication that there will be positive interactions of hCDSC with existing endothelial cells when injected into ischaemic tissues. Hence, hCDSC is suggested as the novel approach in the future treatment of ischaemic diseases.
A method is described for the fabrication of a closed hollow bulb obturator prosthesis using a hard thermoforming splint material and heat-cured acrylic resin. The technique allowed the thickness of the thermoformed bulb to be optimized for weight reduction, while the autopolymerized seal area was covered in heat-cured acrylic resin, thus eliminating potential leakage and discoloration. This technique permits the obturator prosthesis to be processed to completion from the wax trial denture without additional laboratory investing, flasking, and processing.
This study aims to investigate potential diabetic retinopathy (DR) risk factors by evaluating the circulating levels of pentosidine, soluble receptor for advanced glycation end-product (sRAGE), advanced oxidation protein product (AOPP) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in DR patients. A total of 235 healthy controls, 171 type 2 diabetic without retinopathy (DNR) and 200 diabetic retinopathy (DR) patients were recruited. Plasma was extracted for the estimation of pentosidine, sRAGE, AOPP levels and GPx activity whereas peripheral blood mononuclear cells were disrupted for SOD activity measurement. DNR and DR patients showed significantly higher levels of plasma pentosidine, sRAGE and AOPP but lower GPx and SOD activities when compared to healthy controls. The sRAGE/pentosidine ratio in DR patients was significantly lower than the ratio detected in DNR patients. Proliferative DR patients had significantly higher levels of plasma pentosidine, sRAGE, AOPP and sRAGE/pentosidine ratio than non-proliferative DR patients. High HbA1c level, long duration of diabetes and low sRAGE/pentosidine ratio were determined as the risk factors for DR. This study suggests that sRAGE/pentosidine ratio could serve as a risk factor determinant for type 2 DR as it has a positive correlation with the severity of DR.
Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.
INTRODUCTION: Osteoporosis and osteopenia are well-recognized complications of inflammatory bowel disease. Previous studies have suggested that vitamin D deficiency is an important risk factor for the development of osteoporosis. We hypothesized that low vitamin D levels is the main reason for reduced bone mineral density in patients with inflammatory bowel disease. We aimed to study its potential role in Malaysia, which is a tropical country with 3 large ethnic groups. We also sought to examine the relationship between fracture risk and bone mineral density in this group.
METHODOLOGY: Relevant history as well as 25-hydroxycholecalciferol (vitamin D) levels and bone mineral density were obtained. Normal, inadequate, and low vitamin D levels were defined as 61-160 nmol/L (24-64 ng/mL), 30-60 nmol/L (12-24 ng/mL), and less than 30 nmol/L (<12 ng/mL), respectively.
RESULTS: Seventy-two patients were recruited. The prevalence of osteopenia and osteoporosis, respectively, were 58% and 17% in the spine and 51% and 14% in the hip. Mean vitamin D level in the group was low at 45.12 ± 17.4 nmol/L (18.05 ± 6.96 ng/mL), but there was no significant association between bone mineral density and vitamin D level. Twelve patients (16.7%) had a fragility fracture after the diagnosis of inflammatory bowel disease. The cumulative fracture incidence was 10% at 5 years and 35% at 10 years. There was a statistically significant association between osteoporosis of hip and a history of fracture (odds ratio 5.889; 95% confidence interval 1.41-24.53, P = .009).
CONCLUSION: Osteoporosis is prevalent among Malaysian patients with inflammatory bowel disease and is associated with a 6-fold increased risk of fractures. Most inflammatory bowel disease patients had inadequate or low vitamin D levels, but there was no association between vitamin D levels and BMD.