Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the core kinase components of the ERK cascade, Raf, MEK, ERK to provide spatial and temporal regulation of Ras-dependent ERK cascade signaling. Interruption of this mechanism can have a high influence in inhibiting the downstream signaling of the mutated tyrosine kinase receptor kinase upon ligand binding. Still none of the studies targeted to prevent the binding of Raf, MEK binding on kinase suppressor of RAS. In that perspective the cysteine rich C1 domain of scaffold proteins kinase suppressor of Ras-1 was targeted rather than its ATP binding site with small ligand molecules like flavones and anthocyanidins and analyzed through insilico docking studies. The binding energy evaluation shows the importance of hydroxyl groups at various positions on the flavone and anthocyanidin nucleus. Over all binding interaction shows these ligands occupied the potential sites of cysteine rich C1 domain of scaffold protein KSR.
Vascular remodelling is an adaptive mechanism, which counteracts pressure changes in blood circulation. Nicotine content in cigarette increases the risk of hypertension. The exact relationship between nicotine and vascular remodelling still remain unknown. Current study was aimed to determine the effect of clinically relevant dosage of nicotine (equivalent to light smoker) on aortic reactivity, oxidative stress markers and histomorphological changes. Twelve age-matched male Sprague-Dawley rats were randomly divided into two groups, i.e.: normal saline as control or 0.6 mg/kg nicotine for 28 days (i.p., n=6 per group). On day-29, the rats were sacrificed and the thoracic aorta was dissected immediately for further studies. Mean arterial pressure (MAP) and pulse pressure (PP) of nicotine-treated vs. control were significantly increased (p<0.05). Nicotine-treated group showed significant (p<0.05) increase tunica media thickness, and decrease in lumen diameter, suggesting vascular remodelling which lead to prior hypertension state. The phenylephrine (PE)-induced contractile response in nicotine group was significantly higher than control group (ED50=1.44×10(5) M vs. 4.9×10(6) M) (p<0.05~0.001). However, nicotine-treated rat showed significantly lower endothelium-dependent relaxation response to acetylcholine (ACh) than in control group (ED50=6.17×10(7) M vs. 2.82×10(7) M) (p<0.05), indicating loss of primary vascular function. Malondialdehyde (MDA), a lipid peroxidation marker was significantly higher in nicotine group. Superoxide dismutase (SOD) enzymatic activity and glutathione (GSH) were all reduced in nicotine group (p<0.05) vs. control, suggesting nicotine induces oxidative imbalance. In short, chronic nicotine administration impaired aortic reactivity, probably via redox imbalance and vascular remodelling mechanism.
To supply the increasing demand of natural high potency sweeteners to reduce the calories in food and beverages, we have looked to steviol glycosides. In this work we report the bioconversion of rebaudioside A to rebaudioside I using a glucosyltransferase enzyme. This bioconversion reaction adds one sugar unit with a 1→3 linkage. We utilized 1D and 2D NMR spectroscopy (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY and NOESY) and mass spectral data to fully characterize rebaudioside I.
MeSH terms: Beverages; Food; Glucosides/metabolism; Glucosyltransferases/metabolism; Magnetic Resonance Spectroscopy/methods; Mass Spectrometry/methods; Sweetening Agents/metabolism; Diterpenes, Kaurane/metabolism*
Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model.
MeSH terms: Aged; Aged, 80 and over; Europe; Female; Hospitalization*; Humans; Male; Models, Theoretical*; Risk Factors; Reproducibility of Results; Comorbidity; Multivariate Analysis; Databases as Topic; Drug-Related Side Effects and Adverse Reactions/diagnosis*
Conference abstract:
OBJECTIVES.. To evaluate doctors’ adherence to Malaysian Clinical Practice Guideline (CPG) 2009 in the management of diabetes mellitus with co-morbidities in Malaysia.
METHODS. Cross-sectional study was done at a tertiary-care hospital in Malaysia. Total 51 physicians and 1020 patients’ prescriptions written by same physicians (20 prescriptions per physician) were analyzed. All patients had diabetes mellitus with co-morbidities. Depending on the recommendations of CPG 2009, the prescriptions were clustered as adherent and non-adherent prescriptions. All obtained data were analyzed using descriptive and inferential statistics.
RESULTS. A statistically significant negative association (Ф= 0.094, p-value=0.003) was observed between diabetes mellitus control and co-morbidities. CPG adherent had statistically weak negative association (Ф= - 0.081, p-value=0.010) with patients having co-morbidities (41.6%). No statistically significant association was observed between CPG adherence and any other co-morbidity. Majority of the patients received guidelines-compliant pharmacotherapy. The overall good level of physician adherence with CPG 2009 was observed in the management of diabetes mellitus with co-morbidities.
CONCLUSIONS. The study explored several features of prescription pattern of the physicians involved in the management of diabetes mellitus with co-morbidities and recognized the need for improvement in their prescription pattern for treating the diabetes mellitus.
OBJECTIVES. Osteoporotic fractures are common in older adults and are often associated with high morbidity and mortality. As the incidence increases with age, it is natural that osteoporotic fractures have become a major health problem worldwide. Increasing number of patients with osteoporotic fracture will have a serious economic impact on the patient themselves and the society. The objective of this study is to study the cost-effectiveness of strontium ranelate compared to alendronate for patients with post-menopausal osteoporotic fractures in Malaysia.
METHODS. A Markov model was developed to project clinical and economic benefits of strontium in a hypothetical cohort of patients (N=1,000) over a 5-year time horizon. This study was conducted from a payer perspective. Model parameters including transition probabilities and costs of treating fracture at various sites were Malaysia-specific. Drug costs were obtained from a public teaching hospital in Kuala Lumpur. Utilities were derived from previous literatures and efficacy data were derived from two pivotal trials, i. e. SOTI and TROPOS trials. Outcomes were presented as cost per quality-adjusted life year (QALY) gained. A discount rate of 3% was applied. Both 1-way and multivariate probabilistic sensitivity analyses were undertaken to evaluate robustness of results.
RESULTS. Compared to alendronate, strontium could prevent 328 wrist, 192 hip, 7 vertebra and 115 multiple fractures respectively over 5 years, which was translated into 27.9 QALYs gained. Using strontium can lead to cost reduction of MYR1,416,595 (USD442,685), MYR478,257 (USD149,455), MYR22,784 (USD7,120) and MYR61,883 (USD113,088) due to reduced episodes of fractures at wrist/hip/vertebra/multiple sites respectively. The total reduction of direct medical costs of MYR2,279,519 (USD712,349) was larger than the extra drug cost, hence making strontium a cost-saving therapy.
CONCLUSIONS. It was shown that strontium appeared to be more cost-effective compared to alendronate and hence should be recommended in the public sector in Malaysia.
Conference abstract;
Objectives: Warfarin use in atrial fibrillation has been established for preventing occurrence of stroke in patients with atrial fibrillation. However, safety and clinical monitoring of warfarin use is crucial due to its risk of bleeding complications. This study aims to compare and establish relation of time in therapeutic range (TTR) of warfarin in patients with atrial fibrillation in the first 6 months and 6 month thereafter of anticoagulation therapy.
Methods: This is a retrospective study carried out at a tertiary-care hospital with anticoagulation clinic in the state of Selangor, Malaysia. Data collected included patients’ demographics, co-morbidities, and international normalized ratio (INR). TTR were determined using Rosendaal method based on records found in database (INR Desk 4.0 system) and patients’ hemorrhage events were also recorded. Samples of the study were patient who started warfarin from January 2009 until March 2013.
Results: A total of 167 patients with atrial fibrillation were enrolled and only 6% (n=10) achieved TTR of more than 75% for the first 6 months of warfarin use as compared to 16.8% (n=28) of TTR more than 75% 6 months thereafter. As for bleeding incidences, 29% (n=45) of patients in the group of TTR less than 75% in the first 6 months had bleeding complications as compared to 18.7% (n=26) in patients of TTR less than 75% 6 months after.
Conclusions: A more regular follow up is necessary during the first 6 months of new warfarin users as they tend to be out of the TTR and have a higher bleeding risk.
Study site: anticoagulation clinic, tertiary hospital, Selangor, Malaysia
Objectives: Systematic anticoagulation management clinic is now recommended to manage warfarinized atrial fibrillation (AF) patient. In Malaysia, the service is recently introduced as pharmacist managed Warfarin Medication Therapy Adherence Clinic (WMTAC). The objective of the present study was to assess the cost effectiveness of anticoagulation clinic in comparison with usual medical in Kuala Lumpur Hospital.
Methods: A Markov model built using the provider perspective and 20 year time horizon was used to assess the cost effectiveness. The base case analysis assumed a cohort of patients with AF 57 years of age with comorbid illnesses. Data sources include a 6 month retrospective cohort analysis of the effectiveness of the clinics, the cost of drugs, cost of personnel and space of the clinics, cost of monitoring and cost of adverse events were obtained from the local source and publications. The transition probabilities of these clinics outcomes were obtained from a literature search. Future costs were discounted by 3% to convert to present values. All costs were in Ringgit Malaysia (RM) based on year 2012.
Results: The results of a 20-year period model showed that UMC was dominated by the WMTAC in the same time period. The mean cost of the WMTAC was RM 5864 whereas the UMC cost was RM 6550. The sensitivity analysis showed that clinic treatment costs and effectiveness influenced the cost-effectiveness. If the cost of WMTAC was increased by 50% of the current cost, the WMTAC would not be a dominant intervention. WMTAC was also cost effective for a willingness to pay of RM32000.
Conclusions: The anticoagulation management service appears to cost less and provide greater effectiveness than usual care. In conclusion, the Markov model suggests that from the provider perspective the anticoagulation clinic is a more cost effective option than the usual medical clinic in Kuala Lumpur Hospital.
Study site: Medication Therapy Adherence Clinic, Hospital Kuala Lumpur, Malaysia
Objectives: To assess the feasibility of a computer-based Standard Gamble (SG) visual prop whilst measuring utilities of different asthma health states at the same time.
Methods: Twenty adult asthma patients literate in either Malay or English language were conveniently sampled from a public hospital in Penang, Malaysia. They were interviewed by two trained interviewers using a bilingual script. Each patient was requested to value the given health states using Visual Analogue Scale (VAS) prior to SG exercise. There were three chronic health states (C1-C3) for 10 years, three temporary states (T1-T3) for 3 months, and two anchor states (healthy and dead). During the SG exercise, the visual prop was fully operated by the interviewers. The probability of being in a worse state was changed in a ‘ping-pong’ fashion until the indifference point was reached.
Results: All patients understood the SG exercise and rated SG easier than VAS. Around 85% (n=17) completed SG within 30 minutes. There was 90% (n=18) who ranked T3 as the worst temporary health state during VAS. Two patients provided logical inconsistency data in SG. The preferences by SG were higher than VAS. Preferences were also higher in temporary states measured by chained SG than other states by conventional SG. The mean utilities for C1=0.56 (SD 0.38), C2=0.47 (SD 0.33), C3=0.53 (SD 0.38), T1=0.65 (SD 0.31), T2=0.53 (SD 0.35), and T3=0.38 (SD 0.38).
Conclusions: The SG methods including the props are feasible for utilities measurement in asthma, based on the agreements achieved with other studies on the pattern of utilities measured in this preliminary study.
MeSH terms: Asthma; Cross-Sectional Studies; Hospitals, General; Humans; Malaysia