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BACKGROUND: Metformin has been added in the Malaysian clinical practice guideline (CPG) as one of the first-line options in the management of gestational diabetes mellitus (GDM); however, the uptake on this practice among healthcare professionals is unknown. OBJECTIVE: The objective of the study is to determine the awareness, attitude, and practice and their predictors on the use of metformin for GDM among healthcare professionals in Malaysia. MATERIALS AND METHODS: This was a multicenter, cross-sectional study in three tertiary hospitals in Malaysia. Medical doctors and pharmacists working in several departments were invited to participate in a survey using self-administered questionnaires. RESULTS: From 350 questionnaires distributed, 225 were completed by medical doctors (43.1%), pharmacists (40.4%), and specialists (7.5%). Less than 30% of them were aware on the option of using metformin as one of the first-line agents in GDM. Education level, department, and profession were found to be associated with the awareness level (P = 0.016, P = 0.004, and P = 0.001, respectively). 70.2% of the respondents showed a positive attitude toward metformin use in GDM. Only 64 (28.4%) of the respondents have prescribed/dispensed metformin for GDM before, although more than half will consider doing so in the future. Having postgraduate qualifications increased the likelihood of having a good awareness (odds ratio [OR]: 2.44, 95% confidence interval [CI] 1.23-4.85) and to consider prescribing/dispensing metformin for GDM patients (OR: 2.27, 95% CI 1.08-4.78). CONCLUSION: Despite a positive attitude toward metformin use in GDM among healthcare professionals in Malaysia, their awareness level on this practice was low as they currently prefer the use of insulin over metformin.
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This study aims to investigate the potential of bioactive secondary metabolites contained in Sphagneticola trilobata (L.) J.F Pruski leaves as novel plant-derived anticancer agent. Qualitative bioactive compound contents in the methanolic extract of S. trilobata leaves were screened using phytochemical method. Antioxidant evaluation was carried out using 2,2-diphenyl-1-picrylhydrazyl assay; antibacterial - using well diffusion method on Escherichia coli and Salmonella typhi; and cytotoxicity - using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on MCF-7 cell line and Vero Cell. It was found that the methanolic extract exhibited antioxidant activity with an IC50 value of 124.34 µg/mL. The inhibition zone values against E. coli and S. thypi (at extract concentration of 100 mg/mL) were 34.33 and 36 mm, respectively. In vitro MTT assay showed that our extract successfully reached 96% mortality with LC50 = 189.287 µg/mL, where the selective index of 2.5 suggest its selectivity against MCF-7 breast cancer cell line. In conclusion, the data of biological activities suggest the potential development of methanolic extract from S. trilobata leaves as a phytomedicine for breast cancer treatment.
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Objectives. The current health technology assessment used to evaluate respiratory inhalers is associated with limitations that have necessitated the development of an explicit formulary decision-making framework to ensure balance between the accessibility, value, and affordability of medicines. This study aimed to develop a multiple-criteria decision analysis (MCDA) framework, apply the framework to potential and currently listed respiratory inhalers in the Ministry of Health Medicines Formulary (MOHMF), and analyze the impacts of applying the outputs, from the perspective of listing and delisting medicines in the formulary. Methods. The overall methodology of the framework development adhered to the recommendations of the ISPOR MCDA Emerging Good Practices Task Force. The MCDA framework was developed using Microsoft Excel 2010 and involved all relevant stakeholders. The framework was then applied to 27 medicines, based on data gathered from the highest levels of available published evidence, pharmaceutical companies, and professional opinions. The performance scores were analyzed using the additive model. The end values were then deliberated by an expert committee. Results. A total of eight main criteria and seven subcriteria were determined by the stakeholders. The economic criterion was weighted at 30%. Among the noneconomic criteria, "patient suitability" was weighted the highest. Based on the MCDA outputs, the expert committee recommended one potential medicine (out of three; 33%) be added to the MOHMF and one existing medicine (out of 24; 4%) be removed/delisted from the MOHMF. The other existing medicines remained unchanged. Conclusions. Although this framework was useful for deciding to add new medicines to the formulary, it appears to be less functional and impactful for the removal/delisting existing medicines from the MOHMF. The generalizability of this conclusion to other formulations remains to be confirmed.
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INTRODUCTION: The National Pharmaceutical Regulatory Agency (NPRA) embarked on a regulatory-strengthening program and is evaluating its processes. Optimising Efficiencies in Regulatory Agencies (OpERA) is a regulatory-strengthening program that provides benchmarking data that can define performance targets and focus performance improvement. The objective of this study was to use OpERA methodology to determine where time is spent in the NPRA approval process and to form a baseline to measure the performance improvements. METHODS: The OpERA tool was used to collect specific milestone data that identify time periods, review stages, and data points for new active substances and biosimilars approved by NPRA in 2017. RESULTS: In 2017, 25 new active substances and 1 biosimilar were approved by NPRA in a median of 515 days, representing both agency and applicant time. The median time between dossier receipt and the initiation of NPRA scientific assessment was 135 days, but there was a wide variation in queuing time. The median total assessment time was 279 days (agency and applicant timing). NPRA took a median of 166 days; applicants took a median of 131 days to respond to deficiency questions, with up to 6 cycles of review required for approval and 65% of applications requiring 4-5 cycles to provide satisfactory responses. CONCLUSIONS: As a result of these data, NPRA proposes three improvements: target start for scientific assessment 100 days after file acceptance, a maximum of 5 review cycles, and applicant response time limited to 6 months. These results will serve as a baseline for further assessment.
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Medicamentos Biossimilares , Aprovação de Drogas , Órgãos Governamentais , MalásiaRESUMO
The authors have revised Figure 1. The revised figure is presented below.
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BACKGROUND: The genetic features indicate a crucial role in nephrolithiasis. The present study was aimed to investigate the role of Glutathione-S-transferase Mu (GSTM1), Glutathione-S- transferase Theta (GSTT1) and endothelial nitric oxide synthase (eNOs) gene polymorphism in nephrolithiasis. METHODS: We involved a case-control study in which 480 individuals were divided into 240 healthy control and 240 patients with nephrolithiasis. For each patient and control, we measured biochemical criteria, levels of glutathione S-transferase, eNOs, GSTM1, GSTT1genes and eNOS genes polymorphism by PCR-RFLP. RESULTS: GSTM1 and GSTT1 null genotypes are not a risk features for nephrolithiasis. The eNOS frequency GG, GT, and TT genotypes by using Ban II enzyme as restriction enzyme were found to be (48.33, 36.67, and 15.00) %. The eNOS frequency TT, GT, and GG genotypes by using the Ban II enzyme as restriction enzyme were found to be 15.84, 25.83, and 58.33%, respectively. The result showed an increase in serum eNOs levels were in the patient's group comparing to control. CONCLUSIONS: This work is the first in the literature to study the relation between eNOs genes polymorphisms and nephrolithiasis. The results conclude that TT genotypes in the eNOs genes are associated with an increase the oxidative stress in patients.
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Glutationa Transferase/genética , Nefrolitíase/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Fatores de RiscoRESUMO
OBJECTIVES: The aim of this study was to develop an EQ-5D-5L value set reflecting the health preferences of the Malaysian adult population. METHODS: Respondents were sampled with quotas for urbanicity, gender, age, and ethnicity to ensure representativeness of the Malaysian population. The study was conducted using a standardized protocol involving the EuroQol Valuation Technology (EQ-VT) computer-assisted interview system. Respondents were administered ten composite time trade-off (C-TTO) tasks and seven discrete choice experiment (DCE) tasks. Both linear main effects and constrained non-linear regression models of C-TTO-only data and hybrid models combining C-TTO and DCE data were explored to determine an efficient and informative model for value set prediction. RESULTS: Data from 1125 respondents representative of the Malaysian population were included in the analysis. Logical consistency was present in all models tested. Using cross-validation, eight-parameter models for C-TTO only and C-TTO + DCE hybrid data displayed greater out-of-sample predictive accuracy than their 20-parameter, main-effect counterparts. The hybrid eight-parameter model was chosen to represent the Malaysian value set, as it displayed greater out-of-sample predictive accuracy over C-TTO data than the C-TTO-only model, and produced more precise estimates. The estimated value set ranged from - 0.442 to 1. CONCLUSIONS: The constrained eight-parameter hybrid model demonstrated the best potential in representing the Malaysian value set. The presence of the Malaysian EQ-5D-5L value set will facilitate its application in research and health technology assessment activities.
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Nível de Saúde , Modelos Econométricos , Avaliação da Tecnologia Biomédica , Comportamento de Escolha , Humanos , Malásia , Preferência do Paciente , Anos de Vida Ajustados por Qualidade de Vida , Análise de Regressão , Projetos de Pesquisa , Inquéritos e Questionários , Avaliação da Tecnologia Biomédica/economia , Avaliação da Tecnologia Biomédica/métodosRESUMO
BACKGROUND: The pharmacy internship program is designed to provide comprehensive training for interns to perform various roles in pharmacy practice. In Malaysia, the current internship program has been in place since 2004 in public health facilities, but has never been extensively evaluated. AIM: To assess the level of job satisfaction and perception of Provisionally Registered Pharmacists (PRP) towards the internship training provided. METHODS: A cross-sectional nationwide survey was conducted amongst all PRPs undergoing training between December 2015 and February 2016 to assess their level of job satisfaction and perception towards the training requirements stipulated by the Pharmacy Board of Malaysia. RESULTS: A total of 733 PRPs participated in the survey and the response rate was 95.8%. On the basis of the response received, 92.5% (nâ¯=â¯678) felt that the one year training period was 'just nice', 30.5% (nâ¯=â¯223) felt that the logbooks were 'too complicated', and 33.2% (nâ¯=â¯241) said the targets set by the Pharmacy Board of Malaysia were 'too high'. On a scale of 1 to 5, respondents rated 3.32 (SD 0.54) for mean score of job satisfaction. Significant factors influencing mean score of job satisfaction were: perceived fairness at the work place; perceived self-competence after one year of training; preceptors' competence; and pharmacy as a chosen career pathway. CONCLUSION: Intern pharmacists were fairly satisfied with the internship training in government facilities in the Ministry of Health, Malaysia. A review of the internship logbooks and the practicality of targets set by the Pharmacy Board warrant further improvement.
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Percepção , Satisfação Pessoal , Farmacêuticos/psicologia , Residências em Farmácia/normas , Adulto , Estudos Transversais , Feminino , Humanos , Malásia , Masculino , Farmacêuticos/tendências , Inquéritos e QuestionáriosRESUMO
BACKGROUND: It is assumed that genetic factors play crucial role in nephrolithiasis. The present study was conducted to explore the role of Human Transcription Factor-7 like-2 (TCF7L2) ß-defensin (DEFB1) and CD14 gene polymorphism in development and progression of nephrolithiasis. METHODS: The genotypes of TCF7L2, DEFB1 and CD14 polymorphism were determined in 240 nephrolithiasis patients and 240 healthy controls by restriction digestion method of PCR. The levels of serum TCF7L2, DEFB1, CD14, uric acid and other biochemical parameters were measured both in nephrolithiasis patients and healthy control. RESULTS: The patients and control groups showed 30% and 50% 1654 AA DEFB1 genotype respectively. The Allele frequency in case of patient's group was 63.67% while in control group it was 36.33%. The mean serum DEFB1 levels of the patients and control groups attained were 115.66 and 239.43â¯pg/mL respectively. The allele frequency of TCF7L2 in patients and controls were 44.17% and 70.0% for C-allele, 55.83% and 30.00% for T-allele respectively. The mean of serum TCF7L2 levels were significantly decreased in patients compared to control group. CONCLUSIONS: The present findings are first of its class that validates a considerable connection of DEFB1 and TCF7L2 gene polymorphisms with nephrolithiasis and could probably act as indicators to estimate the risk associated to nephrolithiasis.
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Receptores de Lipopolissacarídeos/genética , Nefrolitíase/genética , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , beta-Defensinas/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The roles of multi-walled carbon nanotubes (MWNTs) and functionalised multiwalled carbon nanotubes (fMWNTs) in enhancing the efficacy of urea fertilizer (UF) as plant nutrition for local MR219 paddy variety was investigated. The MWNTs and fMWNTs were grafted onto UF to produce UF-MWNTs fertilizer with three different conditions, coded as FMU1 (0.6 wt. % fMWNTs), FMU2 (0.1 wt. % fMWNTs) and MU (0.6 wt. % MWNTs. The batches of MR219 paddy were systematically grown in accordance to the general practice performed by the Malaysian Agricultural Research and Development Institute (MARDI). The procedure was conducted using a pot under exposure to natural light at three different fertilization times; after a certain number of days of sowing (DAS) at 14, 35 and 55 days. Interestingly, it was found that the crop growth of plants treated with FMU1 and FMU2 significantly increased by 22.6% and 38.5% compared to plants with MU addition. Also, paddy treated with FMU1 produced 21.4% higher number of panicles and 35% more grain yield than MU while paddy treated with FMU2 gave 28.6% more number of panicles and 36% higher grain yield than MU, which implies the advantage of fMWNTs over MWNTs to be combined with UF as plant nutrition. The chemical composition and morphology of UF-MWNTs fertilizers which is further characterised by FTiR and FESEM confirmed the successful and homogeneous grafting of UF onto the fMWNTs.
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BACKGROUND: Nephrolithiasis is one of the causes which lead to chronic kidney disease (CKD). Matrix metalloproteinases (MMPs) are endopeptidases degrading extracellular matrix which correlate with the pathogenesis of atherosclerosis. The current study was designed to analyze the association of (R279Q, C1562T) polymorphism of MMP-9 with nephrolithiasis patients. METHODS: Genotyping of MMP-9/R279Q and of MMP-9/C1562T polymorphism were carried out by PCR-based restriction digestion method. Serum level of MMP-9, oxidative stress marker, MDA, and uric acid were measured in patients and control. RESULTS: Allele frequencies of the MMP-9/C1562T polymorphism for C and T allele were 71.25% and 28.75% in patients, 87.08% and 12.92% in control respectively. The homozygote TT was more frequent in the nephrolithiasis patients group, while T allele frequency was significantly higher in the nephrolithiasis patients group than in the control group. The patients with CT and TT genotype showed a significant increase in serum MMP-9, Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Malondialdehyde (MDA), and uric acid when compared to CC genotype in patients with nephrolithiasis. The R279Q polymorphism site with regard to the relationship with nephrolithiasis was not significant. CONCLUSION: The result indicates that patients with TT genotype had an increased risk of stones. Also, the results demonstrate that TT allele of the C1562T polymorphism in the MMP-9gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with TT genotype of MMP-9.
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Metaloproteinase 9 da Matriz/genética , Nefrolitíase/epidemiologia , Nefrolitíase/genética , Adulto , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Humanos , Malondialdeído/sangue , Metaloproteinase 9 da Matriz/sangue , Pessoa de Meia-Idade , Estresse Oxidativo , Polimorfismo GenéticoRESUMO
BACKGROUND: The intron 5 insertion/deletion polymorphism of Alpha-2-macroglobulin receptor-associated protein gene (Alpha-2-MRAP) has been implicated in numerous diseases. The current study was designed to analyze the association of intron 5 insertion/deletion polymorphism of Alpha-2-MRAP with nephrolithiasis patients. METHODS: PCR was conducted on genomic DNA of patients and control to look for Alpha-2-MRAP insertion/deletion polymorphism. Besides that, serum level of Alpha-2-MRAP, oxidative stress marker myeloperoxidase, Malondialdehyde (MDA), Advanced oxidation protein products (AOPP), and uric acid were determined. RESULTS: The D and I allele frequencies were 57.50% and 42.50% in patients, 77.50% and 22.50% in control, individually. The result showed that II genotype was associated with nephrolithiasis patients group. A significant decrease was observed in serum Alpha-2-MRAP,myeloperoxidase and TAS,while TOS,OSI,MDA,AOPP and uric acid were substantially increased in II and ID when compared to DD genotype in patients with nephrolithiasis. CONCLUSION: Our results demonstrate for the first time that patients with II genotype had an increased risk of stones. Also, the results demonstrate that I allele of the 5 insertion/deletion polymorphism in the Alpha-2-MRAP gene is related with an increase of oxidative stress in nephrolithiasis patients and may possibly impose a risk for cardiovascular diseases in patients with II genotype of Alpha-2-MRAP.
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Proteína Associada a Proteínas Relacionadas a Receptor de LDL/genética , Nefrolitíase/genética , Polimorfismo Genético , Feminino , Frequência do Gene , Genótipo , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Nefrolitíase/metabolismo , Estresse Oxidativo/genéticaRESUMO
Cancer is a complicated disease for which finding a cure presents challenges. In recent decades, new ways to treat cancer are being sought; one being nanomedicine, which manipulates nanoparticles to target a cancer and release drugs directly to the cancer cells. A number of cancer treatments based on nanomedicine are under way and mostly are in preclinical trials owing to challenges in administration, safety, and effectiveness. One alternative method for drug delivery is the use of photovoltaic nanoparticles, which has the potential to deliver drugs via light activation. The concepts are based on standard photovoltaic cell that holds opposite charges on its surfaces and releases drugs when charge intensity or polarity changes upon photo-stimulation such as from a laser source or sunlight. This review will cover some recent progress in cancer treatment using nanoparticles, including photovoltaic nanoparticles.
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Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas , Neoplasias/tratamento farmacológico , HumanosRESUMO
Enzymatic reactions involving lipases as catalyst in transesterification can be an excellent alternative to produce environmental-friendly biodiesel. In this study, lipase extracted from Cocoa Pod Husk (CPH) and immobilized through cross linked enzyme aggregate (CLEA) technology catalysed the transesterification of Jatropha curcas oil successfully. Face centered central composite design (FCCCD) under response surface methodology (RSM) was used to get the optimal conditions of 3% (w/w) enzyme loading, 4h reaction time and 1:6 oil/ethanol ratio to achieve the highest conversion of free fatty acid and glycerides into biodiesel (93%). The reusability of CLEA-lipase was tested and after seven cycles, the conversion percentage reduced to 58%. The results revealed that CLEA lipase from CPH is a potential catalyst for biodiesel production.
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Biocombustíveis , Cacau/enzimologia , Jatropha/química , Lipase/metabolismo , Extratos Vegetais/química , Óleos de Plantas/metabolismo , Sementes/enzimologia , Proteínas de Plantas/metabolismoRESUMO
Cocoa pod husk (CPH) is a by-product of cocoa production obtained after removing the beans from the fruit. The analysis of CPH has shown that it contains high amounts of protein. This study is aimed to utilize this protein source in hydrolase enzyme production. In this study, seven hydrolase enzymes (amylase, fructosyltransferase, mannanase, glucosidase, glucanase, lipase and protease) were screened from CPH for the first time for feasible industrial production. Among these hydrolases, lipase was chosen for the next steps of experiments as it has a lot of applications in different industries. The extraction of high active lipase from CPH has been done under optimum conditions. The condition that was optimum for the three major factors was achieved using Face centered central composite design (FCCCD) with response surface methodology (RSM) to obtain the highest enzyme activity of crude lipase from CPH. The optimum condition of extraction is used for preparation of cross-linked enzyme aggregate (CLEA). For the production of immobilized biocatalyst, the technique of CLEA is considered as an effective technique for its industrially attractive advantages. Referring to the results of OFAT, CLEA-lipase was prepared in the best condition at the presence of 30 mM ammonium sulphate, 70 mM glutaraldehyde with 0.23 mM Bovine serum albumin as an additive. Immobilization effectively improved the stability of lipase against various organic solvents.
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Fungi are not classified as plants or animals. They resemble plants in many ways but do not produce chlorophyll or make their own food photosynthetically like plants. Fungi are useful for the production of beer, bread, medicine, etc. More complex than viruses or bacteria; fungi can be destructive human pathogens responsible for various diseases in humans. Most people have a strong natural immunity against fungal infection. However, fungi can cause diseases when this immunity breaks down. In the last few years, fungal infection has increased strikingly and has been accompanied by a rise in the number of deaths of cancer patients, transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients owing to fungal infections. The growth rate of fungi is very slow and quite difficult to identify. A series of molecules with antifungal activity against different strains of fungi have been found in insects, which can be of great importance to tackle human diseases. Insects secrete such compounds, which can be peptides, as a part of their immune defense reactions. Active antifungal peptides developed by insects to rapidly eliminate infectious pathogens are considered a component of the defense munitions. This review focuses on naturally occurring antifungal peptides from insects and their challenges to be used as armaments against human diseases.
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Antifúngicos/farmacologia , Proteínas de Insetos/farmacologia , Micoses/tratamento farmacológico , Animais , Antifúngicos/química , Farmacorresistência Fúngica/efeitos dos fármacos , Fungos/citologia , Humanos , Proteínas de Insetos/química , Insetos/metabolismo , Insetos/microbiologia , Micoses/epidemiologia , Micoses/microbiologia , Peptídeos/química , Peptídeos/farmacologiaRESUMO
OBJECTIVE: Nephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase I/II activity and E3 SUMO-protein ligase NSE2 in the sera of nephrolithiasis patients to evaluate the possibility of a new biomarker for evaluating kidney damage. METHODS: Sixty nephrolithiasis patients and 50 control patients were enrolled in a case-control study. Their blood urea, creatinine, protein levels and DNase I/II activity levels were measured by spectrometry. Serum NSMCE2 levels were measured by ELISA. Blood was collected from patients of the government health clinics in Kuantan-Pahang and fulfilled the inclusion criteria. RESULTS: The result indicated that mean levels of sera NSMCE2 have a significantly increase (P<0.01) in patients compared to control group. Compared with control subjects, activities and specific activities of serum DNase I and II were significantly elevated in nephrolithiasis patients (P$lt;0.01). CONCLUSION: This study suggests that an increase in serum concentrations of DNase I/II and E3 SUMO-protein ligase NSE2 level can be used as indicators for the diagnosis of kidney injury in patients with nephrolithiasis.
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Desoxirribonuclease I/sangue , Endodesoxirribonucleases/sangue , Ligases/sangue , Nefrolitíase/enzimologia , Adulto , Proteínas Sanguíneas/análise , Estudos de Casos e Controles , Creatinina/sangue , Hemoglobinas/análise , Humanos , Malásia , Pessoa de Meia-Idade , Nefrolitíase/sangue , Ureia/sangueRESUMO
INTRODUCTION AND AIMS: It is necessary to ascertain current prescribing of antibiotics for upper respiratory tract infections (URTIs) to address potential overuse. A retrospective analysis was conducted of all prescriptions for URTIs among 10 public primary healthcare centers in Kedah, Malaysia, from 1 January to 31 March 2014. RESULTS: A total of 123,524 prescriptions were screened and analyzed. Of these, 7129 prescriptions were for URTI, with 31.8% (n = 2269) containing antibiotics. Macrolides were the most commonly prescribed antibiotic, constituting 61% (n = 1403) of total antibiotics prescribed. There was a statistically significant association between different prescribers and diagnoses (p = 0.001) and a weak positive trend suggesting family medicine specialists are more competent in antibiotic prescribing, followed by medical officers and assistant medical officers (τ = 0.122). CONCLUSIONS: Prescribing practices of some prescribers were inconsistent with current guidelines encouraging resistance development. National antimicrobial stewardship programs and further educational initiatives are ongoing in Malaysia to improve antibiotic use.
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Antibacterianos/uso terapêutico , Prescrições de Medicamentos/normas , Padrões de Prática Médica/normas , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/normas , Infecções Respiratórias/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Acute leukaemia is characterized by fast growth of abnormal clones of haemopoietic precursor cells inside bone marrow leading to undue accumulation in the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. MATERIALS AND METHODS: The study concerned 50 children diagnosed with ALL (mean age, 8.55±2.54) compared to 40 healthy controls (mean age, 8.00±1.85). The Hb, serum copper, ceruloplasmin oxidase, advanced oxidation protein products (AOPPs), total antioxidant activity (TAA) and protein were measured in all groups. One proteinous component was isolated by gel filtration chromatography from the precipitate produced by polyethylene glycol. RESULTS: Significantly higher levels of AOPP, copper and decrease in total antioxidant activity were noted in the cases. Statistical analysis also showed a significant increase (p<0.01) in the activity of serum ceruloplasmin oxidase in patients with ALL compared to normal subjects. The maximum velocity (Vmax) and Michaelis constant had values of 104.2 U/L and 11.7 mM, respectively. The ΔH* values for ceruloplasmin oxidase in ALL patients were positive, confirming the reaction to be endothermic. CONCLUSIONS: The results from this study showed a significant increase in AOPP, ceruloplasmine oxidase and decrease in total antioxidant activity .These parameters may play a role in development of DNA damage in childhood patients with acute lymphoblastic leukemia (ALL). The ΔS* and ΔG* values were negative, these refer that the reaction of ES formation is spontaneous, but needs energy in a so-called endergonic reaction. Also the negative ΔS* value of ceruloplasmin oxidase indicates that the complex [ES*] is further modulated through increasing structure arrangement.
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Biomarcadores/sangue , Ceruloplasmina/análise , Cobre/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Estudos de Casos e Controles , Criança , Seguimentos , Humanos , Estadiamento de Neoplasias , Oxirredução , PrognósticoRESUMO
BACKGROUND: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.