Silencing of hepsin and inosine 5-monophosphate dehydrogenase 2 by siRNA reduces prostate cancer cells proliferation.

Prostate cancer (PCa) is a multifactorial disease, which arises from the activation of genes related to cell proliferation and DNA synthesis. Two important genes namely hepsin (HPN) and inosine 5-monophosphate dehydrogenase type 2 (IMPDH2) were studied to understand the pathogenesis of this disease. This study aimed to determine the transcript level of PCa-related genes, HPN and IMPDH2, in archived tissues. Their functional roles were further determined using an in vitro model of PCa. Total RNA extraction was done from formalin-fixed paraffin-embedded PCa tissues, and benign prostatic hyperplasia (BPH) tissues acted as the control. Quantitative real-time polymerase chain reaction (qPCR) was performed to measure HPN and IMPDH2 expression. The functional assay was performed in a prostate cancer cell line (DU145) on these two genes by silencing their RNA. We discovered a significantly higher expression of IMPDH2 in PCa samples compared to non-cancerous tissues (P < 0.001). While HPN expression level showed a downward trend in PCa but the result was not statistically significant compared to the control. SiRNA-mediated knockdown of IMPDH2 expression in the cell line significantly decreased cell proliferation. The silencing of IMPDH2, however, did not affect cell migration, invasion, and apoptosis of the DU145 cell line. Our study demonstrated that IMPDH2 plays an essential role in clinical samples as well as in vitro models of this cancer. Inhibition of this gene through siRNA causes retardation of cell proliferation suggesting that IMPDH2 plays an essential role in prostate cancer.

Hedgehog signalling molecule, SMO is a poor prognostic marker in bladder cancer.

INTRODUCTION: Hedgehog (HH) pathway is an important signalling cascade for growth and patterning during embryonic development. Constitutive activation of Hedgehog pathway can be found in various types of malignancies including medulloblastoma, basal cell carcinoma, gastrointestinal, breast, pancreatic, prostate cancer and leukaemia. Little is known about the expression and role of Hedgehog signalling in bladder cancer. MATERIALS AND METHODS: The purpose of this study was to investigate the immunohistochemical expression of SMO in 112 bladder cancer cases and determine their association with demographic and clinicopathological parameters. Bladder cancer tissues were obtained from the Hospital Kuala Lumpur. RESULTS: SMO was expressed in the cytoplasm of all cases of bladder cancer. 6 cases (5.4%) showed low expression, while 106 cases (94.6%) showed high expression. Positive expression of SMO protein was correlated with a few variables which include grade and stage of tumour, lymph node metastasis and distant metastasis. SMO expression showed statistically significant association with higher grade (p=0.001) and higher stage (p=0.042) of bladder cancer. SMO expression also showed borderline association with lymph node metastasis (p=0.056). CONCLUSION: These findings indicate that SMO expression may be a poor prognostic marker in bladder cancer.

Towards Higher Oil Yield and Quality of Essential Oil Extracted from Aquilaria malaccensis Wood via the Subcritical Technique.

A method that delivers a high yield and excellent quality of essential oil, which retains most of its value-added compounds, and undergoes least change after the extraction process, is greatly sought after. Although chemical free methods are acceptable, they call for an extensive processing time, while the yield and quality from these methods are often disappointing. This work utilizes subcritical water technology to address these issues. In this undertaking, essential oil was extracted from Aquilaria malaccensis wood by way of subcritical conditions, and characterized through gas chromatography/mass spectroscopy (GC/MS). Optimization through response surface methodology revealed temperature to be the most critical factor for the extraction process, while the optimum conditions for temperature, sample-to-solvent ratio, and time for subcritical water extraction was revealed as 225 °C, 0.2 gr/mL, and 17 min, respectively. The subcritical water extraction technique involves two simultaneous processes, which are based on good fitting to the two-site kinetic and second order model. In comparison to the hydrodistillation method, GC/MS results indicated that the quality of A. malaccensis' wood oils, derived through the subcritical water technique, are of significantly better quality, while containing many constructive value-added compounds, such as furfural and guaiacol, which are useful for the production of pesticides and medicines. Pore size, functional groups, and morphology analysis revealed the occurrence of substantial damage to the samples, which facilitated an improved extraction of bio-products. In comparison to conventional methods, the use of the subcritical method not only involves a shorter processing time, but also delivers a higher oil yield and quality.

Gleason scores in prostate needle biopsy and prostatectomy specimens in prostatic adenocarcinoma: A correlation study.

INTRODUCTION: Gleason scoring (GS) categorised prostatic adenocarcinoma into five prognostic grade groups (PGGs); associated with different prognosis and treatment. This study aims to correlate between Gleason scores of needle biopsies with the corresponding total prostatectomy specimens, and to assess the relationship between the percentage of Gleason 4 tumour pattern (GP4) within Gleason score 7 (GS7) needle biopsy groups with the pathological staging. MATERIALS AND METHODS: Seventy-eight specimens of needle prostate biopsy and its subsequent radical prostatectomy were retrospectively studied. The GSs of the needle biopsy were compared with the corresponding prostatectomy specimens. The percentage of GP4 in GS7 needle biopsy groups was calculated and correlated with the pathological staging. RESULTS: More than half (60%) of GS 6 needle biopsy cases (PGG 1) were upgraded in the prostatectomy specimen, while the majority (80%) of the GS7 needle biopsy groups (PGG 2 and 3) remain unchanged. Cohen's Kappa shows fair agreement in the Gleason scoring between needle biopsies and prostatectomy specimens, K = 0.324 (95% CI, 6.94 to 7.29), p <0.0005 and in the percentage of GP4 in GS7 needle biopsy groups and their corresponding radical prostatectomy specimens, K = 0.399 (95% CI 34.2 - 49.2), p<0.0005. A significant relationship was seen between the percentage of GP4 in GS7 needle biopsy with the pT and pN stage of its radical prostatectomy (p = 0.008 and p=0.001 respectively). CONCLUSION: A higher percentage of GP4 in GS7 tumour is associated with worse tumour behaviour, therefore it is crucial for clinicians to realise this in deciding the optimal treatment.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate.

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.

Dental students' perceptions on the contribution and impact role of a clinical teacher.

OBJECTIVES: This study was conducted in University of Malaya to evaluate student perceptions on the contribution and role of an effective clinical teacher based on the cognitive apprenticeship model in clinical practice. METHODS: Self-administered questionnaires were distributed to 233 undergraduate dental students involved with clinical teaching. This modified and validated questionnaire focusing on students' learning environment was used in order to gain relevant information related to dental clinical teaching. Six domains with different criteria applicable to clinical teaching in dentistry were selected consisting of modelling (four criteria), coaching (four criteria), scaffolding (four criteria), articulation (four criteria), reflection (two criteria) and general learning environment (six criteria). Data analyses were performed using IBM SPSS Statistics 20. RESULTS: Majority of the students expressed positive perceptions on their clinical learning experience towards the clinical teachers in the Faculty of Dentistry, University of Malaya, in all criteria of the domains. Few negative feedbacks concerning the general learning environment were reported. CONCLUSION: Further improvement in the delivery of clinical teaching preferably by using wide variety of teaching-learning activities can be taken into account through students' feedback on their learning experience.

Meta-analysis and systematic review of laparoscopic versus open mesh repair for elective incisional hernia.

CONTEXT: The utility of laparoscopic repair in the treatment of incisional hernia repair is still contentious. OBJECTIVES: The aim was to conduct a meta-analysis of RCTs investigating the surgical and postsurgical outcomes of elective incisional hernia by open versus laparoscopic method. DATA SOURCES: A search of PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane Central Register of Controlled Trials published between January 1993 and September 2013 was performed using medical subject headings (MESH) "hernia," "incisional," "abdominal," "randomized/randomised controlled trial," "abdominal wall hernia," "laparoscopic repair," "open repair", "human" and "English". STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Prospective RCTs comparing surgical treatment of only incisional hernia (and not primary ventral hernias) using open and laparoscopic methods were selected. STUDY APPRAISAL AND SYNTHESIS METHODS: Data extraction and critical appraisal were carried out independently by two authors (AA and MAM) using predefined data fields. The outcome variables analyzed included (a) hernia diameter; (b) operative time; (c) length of hospital stay; (d) overall complication rate; (e) bowel complications; (f) reoperation; (g) wound infection; (h) wound hematoma or seroma; (i) time to oral intake; (j) back to work; (k) recurrence rate; and (l) postoperative neuralgia. These outcomes were unanimously decided to be important since they influence the practical and surgical approach towards hernia management within hospitals and institutions. The quality of RCTs was assessed using Jadad's scoring system. Random effects model was used to calculate the effect size of both binary and continuous data. Heterogeneity amongst the outcome variables of these trials was determined by the Cochran Q statistic and I (2) index. The meta-analysis was prepared in accordance with PRISMA guidelines. RESULTS: Sufficient data were available for the analysis of twelve clinically relevant outcomes. Statistically significant reduction in bowel complications was noted with open surgery compared to the laparoscopic repair in five studies (OR 2.56, 95 % CI 1.15, 5.72, p = 0.02). Comparable effects were noted for other variables which include hernia diameter (SMD -0.27, 95 % CI -0.77, 0.23, p = 0.29), operative time (SMD -0.08, 95 % CI -4.46, 4.30, p = 0.97), overall complications (OR -1.07, 95 % CI -0.33, 3.42, p = 0.91), wound infection (OR 0.49, 95 % CI 0.09, 2.67, p = 0.41), wound hematoma or seroma (OR 1.54, 95 % CI 0.58, 4.09, p = 0.38), reoperation rate (OR -0.32, 95 % CI 0.07, 1.43, p = 0.14), time to oral intake (SMD -0.16, 95 % CI -1.97, 2.28, p = 0.89), length of hospital stay (SMD -0.83, 95 % CI -2.22, 0.56, p = 0.24), back to work (SMD -3.14, 95 % CI -8.92, 2.64, p = 0.29), recurrence rate (OR 1.41, 95 % CI 0.81, 2.46, p = 0.23), and postoperative neuralgia (OR 0.48, 95 % CI 0.16, 1.46, p = 0.20). CONCLUSIONS: On the basis of our meta-analysis, we conclude that laparoscopic and open repair of incisional hernia is comparable. A larger randomized controlled multicenter trial with strict inclusion and exclusion criteria and standardized techniques for both repairs is required to demonstrate the superiority of one technique over the other.

Effect of storage of shelled Moringa oleifera seeds from reaping time on turbidity removal.

Moringa oleifera is an indigenous plant to Malaysia whose seeds are used for water purification. Many studies on Moringa oleifera have shown that it is highly effective as a natural coagulant for turbidity removal. In this study, two different methods for extraction of Moringa's active ingredient were investigated. Results of sodium chloride (NaCl) and distilled water extraction of Moringa oleifera seeds showed that salt solution extraction was more efficient than distilled water in extracting Moringa's active coagulant ingredient. The optimum dosage of shelled Moringa oleifera seeds extracted by the NaCl solution was comparable with that of the conventional chemical coagulant alum. Moreover, the turbidity removal efficiency was investigated for shelled Moringa oleifera seeds before drying in the oven under different storage conditions (i.e. open and closed containers at room temperature, 27 °C) and durations (fresh, and storage for 2, 4, 6 and 8 weeks from the time the seeds were picked from the trees). Our results indicate that there are no significant differences in coagulation efficiencies and, accordingly, turbidity removals between the examined storage conditions and periods.

A preliminary study on Jatropha curcas as coagulant in wastewater treatment.

Many coagulants, mainly inorganic, are widely used in conventional water and wastewater treatment. Recent studies reported the occurrence of some chronic diseases associated with residual coagulant in treated wastewater. The use of alternative coagulants which are biodegradable and environmentally friendly could alleviate the problem associated with these diseases. This work investigates the capability of Jatropha curcas seed and presscake (the residue left after oil extraction) to reduce the turbidity of wastewater through coagulation. The coagulant was prepared by dissolving Jatropha curcas seed and presscake powder into solution. Then jar tests were conducted on kaolin solution as the model wastewater. The Jatropha seed was found to be an effective coagulant with more than 96% of turbidity removal at pH 1-3 and pH 11-12. The highest turbidity removal was recorded at pH 3 using a dosage of 120 mg/L. The flocs formed using Jatropha were observed to be bigger and to sediment faster when compared with flocs formed using alum. The turbidity removal was high (>98%) at all turbidities (100 NTU to 8000 NTU), suggesting its suitability for a wide range of industrial wastewater. The performance of Jatropha presscake after extraction of oil was also comparable to the fresh seed and alum at highly acidic and highly alkaline conditions. The addition of Jatropha did not significantly affect the pH of the kaolin samples after treatment and the sludge volume produced was less in comparison to alum. These results strongly support the use of Jatropha curcas seed and presscake as a potential coagulant agent.

Recurrent bilateral orbital myositis: case report and review of the literature.

Orbital myositis in children is uncommon. Recurrence is a major challenge in management. An 11-year-old Malay girl who presented with bilateral orbital myositis with recurrent attacks of diplopia is reported.

Effect of physical pretreatment on dilute acid hydrolysis of water hyacinth (Eichhornia crassipes).

Effects of different physical pretreatments on water hyacinth for dilute acid hydrolysis process (121 ± 3 °C, 5% H(2)SO(4), 60 min) were comparatively investigated. Untreated sample had produced 24.69 mg sugar/g dry matter. Steaming (121 ± 3 °C) and boiling (100 ± 3 °C) for 30 min had provided 35.9% and 52.4% higher sugar yield than untreated sample, respectively. The highest sugar yield (132.96 mg sugar/g dry matter) in ultrasonication was obtained at 20 min irradiation using 100% power. The highest sugar production (155.13 mg sugar/g dry matter) was obtained from pulverized samples. Hydrolysis time was reduced when using samples pretreated by drying, mechanical comminution and ultrasonication. In most methods, prolonging the pretreatment period was ineffective and led to sugar degradations. Morphology inspection and thermal analysis had provided evidences of structure disruption that led to higher sugar recovery in hydrolysis process.

A study of the factors related to intima-media thickness of the common carotid artery amongst rural middle age individuals in Hospital Universiti Sains Malaysia.

There is very little data regarding the factors related to intima-media thickness (IMT) of the common carotid artery in normal individuals in those with non-insulin diabetes mellitus and perimenopausal women in Southeast Asian countries. Ultrasound imaging evaluating the carotid artery IMT in those with diabetes and those on hormone replacement therapy (HRT) was performed beginning in August 2000 for a period of nearly two years at the Department of Radiology, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. A total of 153 participants were included. Significant differences between the women on HRT and not on HRT were IMT and systolic blood pressure. When comparing those with non-insulin dependent diabetes mellitus (NIDDM) and normal individuals, the significant differences were IMT, total cholesterol level, systolic blood pressure and diastolic blood pressure. IMT was high in those with NIDDM but not in those on HRT. Both those with NIDDM and those on HRT had associated dyslipidemia and systolic hypertension.

An empirical model on extractive lactic acid bioconversion.

The commercial production of lactic acid through fermentation process has always been in competition with its chemical synthesis process (Kirk Othmer, 1995). Lactic acid produced through the fermentation process has to cope with the problems of purification to meet the required quality standards. An attempt to improve the fermentative production is possible by proper design of an industrial process involving low capital cost for the plant. Also, the low energy costs both in its fermentation and purification, are required. In the commercial interest, the investment cost should be minimised, which is possible only when the cell density in fermenter is high. It means that the inhibitory effect of the product on process kinetics must be minimised. Based on these requirements, the extractive bioconversion technique is one of the approaches to achieve the commercially viable lactic acid production. Extractive lactic acid bioconversion using ion-exchange resin process has already been described in our earlier publications (Srivastava e al., 1992: Roychoudhury et al., 1995) It is always an advantage to develop a process model, thus opening an area of biotechnological improvements to the process. In the present paper, an empirical mathematical model has been described to explain this extractive bioconversion using ion-exchange resin process. It was based on generalised Monod's growth model and Leudeking and Piret equation. The system was defined with the assumption that the microbial growth can be represented as a single reaction; only a very little part of the substrate is utilised for the maintenance of the cells. The effect of end product inhibition on growth and product formation kinetics has also been considered in this model. A non-linear regression technique was used for evaluation of bioconversion kinetic parameters. The fourth order Runge Kutta method was used for solving the differential equations. The results of this process simulation are also discussed in the present paper. It indicates that the use of present technique has minimised the effect of lactic acid inhibition on process kinetics and hence higher productivity and least substrate utilisation for maintenance of cells. A statistical F-test has been performed for determining the validity of the model for a given set of experimental data with a level of significance alpha = 0.05 selected for this extractive batch recycle bioconversion process using ion-exchange resin.