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1.
Aust J Rural Health ; 29(3): 464-472, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34148278

RESUMO

OBJECTIVES: In this study, we aimed to determine the prevalence and risk factors of alcohol use among a cohort of population in Sabah. DESIGN: This is a prospective, cohort study involving rural community residents. SETTING: Rural community resident at Bingkor, Keningau, Sabah. PARTICIPANTS: 363 individuals aged 13 years old and above. INTERVENTION: Community-based participatory research to determine the prevalence and risk factors associated with alcohol use. MAIN OUTCOME MEASURES: Measurement of alcohol use using Alcohol Use Disorders Identification Test (AUDIT) and assessment of psychiatric morbidity using Mini International Neuropsychiatric Interview (MINI) questionnaires. RESULTS: Most alcohol drinkers aged between 36-45 years old, followed by 26-35 years old and 46-55 years old. Interestingly, there are almost similar female to male ratio. Most were Kadazan-Dusun ethnic, non-Muslims, and married. Although only less than a third of the participants received tertiary education, the majority were working. Based on the findings, being a male, non-Muslim and having an obsessive-compulsive disorder (OCD) (current) posed a significantly higher risk of alcohol consumption. CONCLUSION: A worryingly high prevalence of hazardous alcohol consumption among the locals is reported. There is a need for population-wide intervention towards preventive measures based on the identified risk factors for hazardous alcohol use.


Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo , Povos Indígenas , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Bornéu/epidemiologia , Pesquisa Participativa Baseada na Comunidade , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
2.
Drug Des Devel Ther ; 15: 2721-2746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188450

RESUMO

Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.

3.
Int J Clin Pract ; 75(8): e14315, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33934480

RESUMO

BACKGROUND: Incidence of hypokalemia during the management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment. AIM: We aimed to find the role of pH-adjusted potassium (pHK ) in the development of hypokalemia, and their mutual impact on patient outcomes during DKA management. METHODOLOGY: Adult DKA patient's admission data of preceding 3 years (2015-2017) were retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (hours), severity of hypokalemia and hospitalisation length (days). Linear regression was used to determine significant associations/predictors. RESULTS: The study was concluded on 85 patients. Hypokalemia was observed in nearly 3/4th of all admissions and occurred by the time of ED care termination. Each 1 mmol/L increase in pHK significantly (a) reduced the degree of hypokalemia by 0.07 mmol/L, (b) delayed time to develop hypokalemia by 4.58 hours, (c) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each 1 mmol/L reduction in the degree of hypokalemia increased hospitalisation length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalisation length by 0.01 days. CONCLUSION: pH-adjusted potassium shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measured serum potassium in DKA. Utilising pHK will help to avoid hypokalemia, reduce its severity and shorten ED care which will subsequently reduce hospitalisation length. We expect pHK to improve pharmacoeconomics in the future.


Assuntos
Cetoacidose Diabética , Hipopotassemia , Adulto , Cetoacidose Diabética/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio , Hipopotassemia/tratamento farmacológico , Insulina , Potássio , Estudos Retrospectivos
4.
PLoS One ; 16(3): e0249091, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33784348

RESUMO

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

5.
Diabetes Metab Syndr ; 15(2): 573-580, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33706189

RESUMO

BACKGROUND AND AIMS: Diabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (SK) drops within normal range, and to withhold insulin if SK is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA. METHODS: Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia. RESULTS: Acidosis affects SK and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing SK level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated. CONCLUSION: In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.

6.
Pharmaceuticals (Basel) ; 14(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669084

RESUMO

Drug-related problems (DRPs) in the elderly include polypharmacy, potentially inappropriate medications, nonadherence, and drug-related falls. In this systematic review and meta-analysis, the prevalence of DRPs and complementary and alternative medicine (CAM) use among the Malaysian elderly was estimated. PubMed, Scopus, Web of Science, and Google Scholar databases were searched to identify studies published since their inception up to 24 August 2020. A random-effects model was used to generate the pooled prevalence of DRPs along with its corresponding 95% confidence interval (CI). The heterogeneity of the results was estimated using the I2 statistics, and Cochran's Q test and sensitivity analyses were performed to confirm the robustness of the results. We identified 526 studies, 23 of which were included in the meta-analysis. (n = 29,342). The pooled prevalence of DRPs among Malaysian elderly was as follows: (1) polypharmacy: 49.5% [95% CI: 20.5-78.6], (2) potentially inappropriate medications: 28.9% [95% CI: 25.4-32.3], (3) nonadherence to medications: 60.6% [95% CI: 50.2-70.9], and (4) medication-related falls 39.3% [95% CI: 0.0-80.8]. Approximately one in two Malaysian elderly used CAM. The prevalence of polypharmacy and potentially inappropriate medications among the Malaysian elderly population was high, calling for measures and evidence-based guidelines to ensure the safe medication use.

7.
ACS Chem Neurosci ; 12(3): 391-418, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33475334

RESUMO

Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.


Assuntos
Produtos Biológicos , Doença de Huntington , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Modelos Animais de Doenças , Doença de Huntington/tratamento farmacológico , Atividade Motora , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Nitrocompostos/farmacologia , Nitrocompostos/uso terapêutico , Propionatos/farmacologia , Propionatos/uso terapêutico , Ratos , Ratos Wistar
8.
Oxid Med Cell Longev ; 2020: 8878172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299532

RESUMO

Despite the availability of various antidiabetic drugs, diabetes mellitus (DM) remains one of the world's most prevalent chronic diseases and is a global burden. Hyperglycaemia, a characteristic of type 2 diabetes mellitus (T2DM), substantially leads to the generation of reactive oxygen species (ROS), triggering oxidative stress as well as numerous cellular and molecular modifications such as mitochondrial dysfunction affecting normal physiological functions in the body. In mitochondrial-mediated processes, oxidative pathways play an important role, although the responsible molecular mechanisms remain unclear. The impaired mitochondrial function is evidenced by insulin insensitivity in various cell types. In addition, the roles of master antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/antioxidant response elements (ARE) are being deciphered to explain various molecular pathways involved in diabetes. Dietary factors are known to influence diabetes, and many natural dietary factors have been studied to improve diabetes. Honey is primarily rich in carbohydrates and is also abundant in flavonoids and phenolic acids; thus, it is a promising therapeutic antioxidant for various disorders. Various research has indicated that honey has strong wound-healing properties and has antibacterial, anti-inflammatory, antifungal, and antiviral effects; thus, it is a promising antidiabetic agent. The potential antidiabetic mechanisms of honey were proposed based on its major constituents. This review focuses on the various prospects of using honey as an antidiabetic agent and the potential insights.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Mel , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Polifenóis/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
BMC Infect Dis ; 20(1): 874, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228562

RESUMO

BACKGROUND: Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH). METHODS: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire. RESULTS: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p < 0.0001). CONCLUSIONS: The findings support the improvement in ART adherence and HIV management. TRIAL REGISTRATION: The trial is registered with Australian New Zealand Clinical Trials Registry ( ACTRN12618001882213 ). Registered 20 November 2018.


Assuntos
Antirretrovirais/uso terapêutico , Aconselhamento/métodos , Infecções por HIV/tratamento farmacológico , HIV/imunologia , Adesão à Medicação/psicologia , Farmacêuticos/psicologia , Adulto , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Fatores de Risco , Autorrelato , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
11.
Antibiotics (Basel) ; 9(10)2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080862

RESUMO

Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5-57.1], 14.3% [95% CI: 11.4-17.2], 22.2% [95% CI: 18.8-25.7], 7.7% [95% CI: 5.6-9.7], and 0.3% [95% CI: 0.0-1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended.

12.
Pharmaceutics ; 12(10)2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33080962

RESUMO

BACKGROUND: Paclitaxel (PTX) is a widely used anti-cancer drug for treating various types of solid malignant tumors including breast, ovarian and lung cancers. However, PTX has a low therapeutic response and is linked with acquired resistance, as well as a high incidence of adverse events, such as allergic reactions, neurotoxicity and myelosuppression. The situation is compounded when its complex chemical structure contributes towards hydrophobicity, shortening its circulation time in blood, causing off-target effects and limiting its therapeutic activity against cancer cells. Formulating a smart nano-carrier may overcome the solubility and toxicity issues of the drug and enable its more selective delivery to the cancerous cells. Among the nano-carriers, natural polymers are of great importance due to their excellent biodegradability, non-toxicity and good accessibility. The aim of the present research is to develop self-assembled sodium caseinate nanomicelles (NaCNs) with PTX loaded into the hydrophobic core of NaCNs for effective uptake of the drug in cancer cells and its subsequent intracellular release. METHODS: The PTX-loaded micelle was characterized with high-performance liquid chromatography (HPLC), Fourier Transform Infrared Spectra (FTIR), High Resolution-Transmission Electron Microscope (HR-TEM), Field Emission Scanning Electron Microscope (FESEM) and Energy Dispersive X-Ray (EDX). Following treatment with PTX-loaded NaCNs, cell viability, cellular uptake and morphological changes were analyzed using MCF-7 and MDA-MB 231 human breast cancer cell lines. RESULTS: We found that PTX-loaded NaCNs efficiently released PTX in an acidic tumor environment, while showing an enhanced cytotoxicity, cellular uptake and in-vivo anti-tumor efficacy in a mouse model of breast cancer when compared to free drug and blank micelles. Additionally, the nanomicelles also presented improved colloidal stability for three months at 4 °C and -20 °C and when placed at a temperature of 37 °C. CONCLUSIONS: We conclude that the newly developed NaCNs is a promising carrier of PTX to enhance tumor accumulation of the drug while addressing its toxicity issues as well.

13.
Biomed Res Int ; 2020: 6945730, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062692

RESUMO

Background: The 22q11.2 deletion syndrome (22q11.2DS) is the most common form of deletion disorder in humans. Low copy repeats flanking the 22q11.2 region confers a substrate for nonallelic homologous recombination (NAHR) events leading to rearrangements which have been reported to be associated with highly variable and expansive phenotypes. The 22q11.2DS is reported as the most common genetic cause of congenital heart defects (CHDs). Methods: A total of 42 patients with congenital heart defects, as confirmed by echocardiography, were recruited. Genetic molecular analysis using a fluorescence in situ hybridization (FISH) technique was conducted as part of routine 22q11.2DS screening, followed by multiplex ligation-dependent probe amplification (MLPA), which serves as a confirmatory test. Results: Two of the 42 CHD cases (4.76%) indicated the presence of 22q11.2DS, and interestingly, both cases have conotruncal heart defects. In terms of concordance of techniques used, MLPA is superior since it can detect deletions within the 22q11.2 locus and outside of the typically deleted region (TDR) as well as duplications. Conclusion: The incidence of 22q11.2DS among patients with CHD in the east coast of Malaysia is 0.047. MLPA is a scalable and affordable alternative molecular diagnostic method in the screening of 22q11.2DS and can be routinely applied for the diagnosis of deletion syndromes.


Assuntos
Síndrome de DiGeorge/diagnóstico , Síndrome de DiGeorge/genética , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Síndrome de DiGeorge/epidemiologia , Feminino , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Incidência , Recém-Nascido , Malásia , Masculino , Projetos Piloto
14.
Foods ; 9(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126433

RESUMO

Diabetes is a chronic metabolic disorder triggered by disturbances in carbohydrate, protein, and lipid metabolisms, where either reduced secretion or sensitivity of insulin is observed coupled with poor glucose control. Date palm fruits are one of the fruits reported to have good potential in diabetes treatment due to its presence of polyphenols exerting strong antioxidant activities. Other possible mechanisms of action include the polyphenolic compounds, which can inhibit enzymes like α-amylase and α-glucosidase. Flavonoids in dates can stimulate ß-cells by increasing the number of islets and ß-cells, recovering endocrine pancreatic tissues, reducing ß-cell apoptosis, activating insulin receptors following the increase in insulin secretion, in addition to improving diabetes-induced complications. In this review, the in vitro, in vivo, and human study-based evidence of date palm as an anti-diabetic fruit is summarised.

15.
BMC Nephrol ; 21(1): 388, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894076

RESUMO

BACKGROUND: New-onset diabetes after transplantation (NODAT) is associated with reduced patient and graft survival. This study examined the clinical and selected genetic factors associated with NODAT among renal-transplanted Malaysian patients. METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant. RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes. CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.

16.
Int J Mol Sci ; 21(18)2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32937817

RESUMO

Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5-6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.


Assuntos
Osso e Ossos/química , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Antraciclinas/farmacologia , Materiais Biocompatíveis/química , Fosfatos de Cálcio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Permeabilidade/efeitos dos fármacos
17.
Medicine (Baltimore) ; 99(21): e20287, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481309

RESUMO

Unhealthy lifestyle contributes mainly to an increased prevalence of non-communicable diseases including hypertension and cardiovascular diseases tend to increase in Malaysia. These diseases lead to an increased risk of end organ damage and cardiovascular complications. In this study, the prevalence of prehypertension and its associated risk factors among a cohort of university students in Sabah was determined.This is a prospective, cross-sectional study conducted among 365 undergraduate students irrespective of faculties at Universiti Malaysia Sabah (UMS). Standardized and validated World Health Organization (WHO) STEPS questionnaires were used to collect sociodemographic data. Additionally, clinical and anthropometric data were measured and recorded by a trained staff, followed by descriptive and logistic regression analyses.A total of 365 UMS undergraduate students aged 18 years and above participated in the study. The prevalence of prehypertension among university students was high (31%) (95% CI [29.1%, 34.3%]). Well-known risk factors for hypertension including family history of hypertension, reduced sleep duration, reduced physical activity, smoking, being overweight or obese were significantly associated with the risk of developing prehypertension (P < .05) among UMS students. However, no association was observed between ethnicity, age, and gender with prehypertension.A worryingly high percentage of UMS students are prehypertensive, indicating the need of early preventive strategies aimed at increasing awareness, early screening, and lifestyle modification to reduce the rising burden of the disease and the associated complications in this age group.


Assuntos
Pré-Hipertensão/epidemiologia , Estudantes , Universidades , Adolescente , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Malásia/epidemiologia , Masculino , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
18.
PLoS One ; 15(4): e0230982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32315303

RESUMO

Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36-3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.


Assuntos
Proteínas do Citoesqueleto/genética , Comunicação Interatrial/genética , Mutação , Cadeias Pesadas de Miosina/genética , Miosina Tipo III/genética , Adolescente , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Estudos de Casos e Controles , Criança , Pré-Escolar , Sequência Conservada , Proteínas do Citoesqueleto/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Modelos Moleculares , Mutação de Sentido Incorreto , Cadeias Pesadas de Miosina/química , Miosina Tipo III/química , Polimorfismo de Nucleotídeo Único , Adulto Jovem
19.
Pathogens ; 9(3)2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197545

RESUMO

Epstein-Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.

20.
Arch Environ Contam Toxicol ; 78(3): 329-336, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31620805

RESUMO

The use of leaded gasoline adversely affects cardiovascular, nervous, and immune systems. Study projects to rule out different variables of prognostic importance in lead-exposed subjects. A total of 317 traffic wardens with 5 years of outdoor experience and Hb levels < 10 µg/dl, and 100 traffic wardens with indoor duties were substituted in two groups. Levels of vitamins, cytokines, lead, iron, minerals, oxidative stress, and lipid peroxidation were estimated with help of their standard ELISA and spectrophotometric methods respectively. The present study show increased levels of lead in subjects (29.8 ± 3.8 vs. 1.5 ± 0.2 µg/dl) that may be involved in increasing oxidative stress, i.e., levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and isoprostanes were increased in subjects (4.6 ± 0.5, 4.3 ± 0.6 and 37.2 ± 5.1). Moreover, levels of antioxidants, i.e., superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), were decreased. It also exhibits reduced levels of different enzymes in anemic traffic wardens. Current study concludes that wardens exposed to environmental lead are more susceptible to develop cardiovascular and neurological disorders. It shows that toxicity of lead maybe responsible for redox imbalance and production of proinflammatory cytokines. Thus, early detection of these biomarkers may help to reduce lead toxicity and it also may help to control the dilemma of uncontrolled environmental pollution by implicating strict actions against substandard gasoline.


Assuntos
Antioxidantes/metabolismo , Biomarcadores/sangue , Chumbo/toxicidade , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos dos fármacos , Emissões de Veículos/toxicidade , Hemoglobinas/análise , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Exposição Ocupacional/efeitos adversos , Polícia , Prognóstico
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