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1.
Bioprocess Biosyst Eng ; 47(8): 1259-1269, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38526617

RESUMO

This study emphasized on the synthesis of zinc oxide nanoparticles (ZnO NPs) in an environmentally friendly manner from the extract of Catharanthus roseus leaves and its antibacterial assessment against the pneumonia-causing pathogen Klebsiella pneumoniae. This simple and convenient phytosynthesis approach is found to be beneficial over conventional methods, wherein plants serve as excellent reducing, capping, and stabilizing agents that enables the formation of ZnO NPs without the use of harmful chemicals. The formation of ZnO NPs was confirmed through several characterization techniques such as UV-visible spectroscopy, XRD, FT-IR, SEM, HR-TEM, and EDX. XRD analysis revealed high polycrystallinity with crystallite size of approximately 13 nm. SEM and HR-TEM revealed the hexagonal structure of ZnO NPs with the particle size range of 20-50 nm. The EDX shows the elemental purity without any impurity. Furthermore, the antibacterial efficacy by the technique of disc diffusion exhibited clear inhibition zones in ZnO NPs-treated discs. In addition, 125 µg/mL of ZnO NP concentration showed minimum inhibition by the microbroth dilution method. The potent inhibitory activity was further validated with trypan blue dye exclusion and fluorescence microscopy. Finally, SEM examination confirmed the efficient antibacterial potential of ZnO NPs through disruption of the intact morphology of Klebsiella pneumoniae.


Assuntos
Antibacterianos , Catharanthus , Klebsiella pneumoniae , Nanopartículas Metálicas , Óxido de Zinco , Klebsiella pneumoniae/efeitos dos fármacos , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Catharanthus/química , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Difração de Raios X
2.
Saudi Pharm J ; 32(2): 101939, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38261891

RESUMO

Many Ruellia species have been utilized in traditional medicine and despite the prevalent use of Ruellia tweediana in folk medicine, its antioxidant potential and polyphenol content have not been investigated. Therefore, the present study aimed to explore the medicinal value of R. tweediana by evaluating its total phenolic (TPC) and flavonoid contents (TFC), GC-MS analysis, antioxidant, antibacterial, and enzyme inhibition activities. The TPC and TFC of the extract/fractions were assessed using the Folin-Ciocalteu and aluminum trichloride methods, respectively. To determine the antioxidant capacity, five different assays were used: DPPH, ABTS, CUPRAC, FRAP, and metal chelating assays. The inhibition activity against α-glucosidase, α-amylase, cholinesterases, and lipoxygenase enzymes was also analyzed. Furthermore, GC-MS was performed for chemical screening of non-polar fraction. The methanol extract showed the maximum TPC (167.34 ± 2.23 mg GAE/g) and TFC (120.43 ± 1.71 mg RE/g) values among all the tested samples. GC-MS screening of the n-hexane fraction showed the presence of 40 different phytoconstituents. The results demonstrated the highest scavenging potential of the methanol extract against DPPH (167.79 ± 2.75 mg TE/g) and ABTS (255.32 ± 2.91 mg TE/g) radicals, as well as the metal-reducing capacity measured by CUPRAC (321.34 ± 3.09 mg TE/g), FRAP (311.32 ± 2.91 mg TE/g), and metal chelating assay (246.78 ± 10.34 mg EDTAE/g). Notably, the n-hexane fraction revealed the highest α-glucosidase and α-amylase inhibition activity (186.8 ± 2.84 and 179.7 ± 4.32 mg ACAE/g, respectively) while methanol extract showed highest acetylcholinesterase and butyrylcholinesterase inhibition activity (198.6 ± 3.31 and 184.3 ± 2.92 mg GALE/g, respectively). The GC-MS identified Lupeol showed best binding affinity with all docked enzymes as compared to standard compounds. The presence of bioactive phytoconstituents showed by GC-MS underscores the medicinal importance of R. tweediana, making it a promising candidate for natural medicine.

3.
Molecules ; 27(6)2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35335393

RESUMO

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.


Assuntos
Anemarrhena , Espirostanos , Anemarrhena/química , Desenho de Fármacos , Espirostanos/química , Espirostanos/farmacologia
4.
Molecules ; 27(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35458770

RESUMO

Bisphenol A (BPA), a well-known xenoestrogen, is commonly utilised in the production of polycarbonate plastics. Based on the existing evidence, BPA is known to induce neurotoxicity and behavioural issues. Flavonoids such as silibinin and naringenin have been shown to have biological activity against a variety of illnesses. The current research evaluates the neuropharmacological effects of silibinin and naringenin in a zebrafish model against neurotoxicity and oxidative stress caused by Bisphenol A. In this study, a novel tank diving test (NTDT) and light−dark preference test (LDPT) were used in neurobehavioural investigations. The experimental protocol was planned to last 21 days. The neuroprotective effects of silibinin (10 µM) and naringenin (10 µM) in zebrafish (Danio rerio) induced by BPA (17.52 µM) were investigated. In the brine shrimp lethality assay, the 50% fatal concentrations (LC50) were 34.10 µg/mL (silibinin) and 91.33 µg/mL (naringenin) compared to the standard potassium dichromate (13.15 µg/mL). The acute toxicity investigation found no mortality or visible abnormalities in the silibinin- and naringenin-treated groups (LC50 > 100 mg/L). The altered scototaxis behaviour in LDPT caused by BPA was reversed by co-supplementation with silibinin and naringenin, as shown by decreases in the number of transitions to the light zone and the duration spent in the light zone. Our findings point to BPA's neurotoxic potential in causing altered scototaxis and bottom-dwelling behaviour in zebrafish, as well as the usage of silibinin and naringenin as potential neuroprotectants.


Assuntos
Fármacos Neuroprotetores , Síndromes Neurotóxicas , Animais , Compostos Benzidrílicos/toxicidade , Desenho de Fármacos , Flavanonas , Flavonoides , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Fenóis , Silibina/farmacologia , Peixe-Zebra
5.
Molecules ; 27(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35566187

RESUMO

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski's drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer's animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Doença de Alzheimer/tratamento farmacológico , Animais , Benzopiranos , Desenho de Fármacos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Doença de Parkinson/tratamento farmacológico
6.
Molecules ; 27(15)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35956923

RESUMO

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.


Assuntos
Bacopa , Infecções Urinárias , Antibacterianos/farmacologia , Bacopa/química , Etanol , Klebsiella pneumoniae , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteus mirabilis , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
7.
Molecules ; 27(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36014304

RESUMO

Viniferin is a resveratrol derivative. Resveratrol is the most prominent stilbenoid synthesized by plants as a defense mechanism in response to microbial attack, toxins, infections or UV radiation. Different forms of viniferin exist, including alpha-viniferin (α-viniferin), beta-viniferin (ß-viniferin), delta-viniferin (δ-viniferin), epsilon-viniferin (ε-viniferin), gamma-viniferin (γ-viniferin), R-viniferin (vitisin A), and R2-viniferin (vitisin B). All of these forms exhibit a range of important biological activities and, therefore, have several possible applications in clinical research and future drug development. In this review, we present a comprehensive literature search on the chemistry and biosynthesis of and the diverse studies conducted on viniferin, especially with regards to its anti-inflammatory, antipsoriasis, antidiabetic, antiplasmodic, anticancer, anti-angiogenic, antioxidant, anti-melanogenic, neurodegenerative effects, antiviral, antimicrobial, antifungal, antidiarrhea, anti-obesity and anthelminthic activities. In addition to highlighting its important chemical and biological activities, coherent and environmentally acceptable methods for establishing vinferin on a large scale are highlighted to allow the development of further research that can help to exploit its properties and develop new phyto-pharmaceuticals. Overall, viniferin and its derivatives have the potential to be the most effective nutritional supplement and supplementary medication, especially as a therapeutic approach. More researchers will be aware of viniferin as a pharmaceutical drug as a consequence of this review, and they will be encouraged to investigate viniferin and its derivatives as pharmaceutical drugs to prevent future health catastrophes caused by a variety of serious illnesses.


Assuntos
Estilbenos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antivirais , Descoberta de Drogas , Preparações Farmacêuticas , Resveratrol/farmacologia , Estilbenos/química , Estilbenos/farmacologia , Estilbenos/uso terapêutico
8.
Molecules ; 27(3)2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35163934

RESUMO

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.


Assuntos
Produtos Biológicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Desenho de Fármacos , Desenvolvimento de Medicamentos , Flavonoides/farmacologia , Glicosídeos/farmacologia , Animais , Humanos
9.
Molecules ; 27(3)2022 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-35163999

RESUMO

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol's anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Desenho de Fármacos , Desenvolvimento de Medicamentos , Inflamação/tratamento farmacológico , Animais , Citocinas/metabolismo , Humanos
10.
Molecules ; 26(11)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073527

RESUMO

This article studies the solubility, Hansen solubility parameters (HSPs), and thermodynamic behavior of a naturally-derived bioactive thymoquinone (TQ) in different binary combinations of isopropanol (IPA) and water (H2O). The mole fraction solubilities (x3) of TQ in various (IPA + H2O) compositions are measured at 298.2-318.2 K and 0.1 MPa. The HSPs of TQ, neat IPA, neat H2O, and binary (IPA + H2O) compositions free of TQ are also determined. The x3 data of TQ are regressed by van't Hoff, Apelblat, Yalkowsky-Roseman, Buchowski-Ksiazczak λh, Jouyban-Acree, and Jouyban-Acree-van't Hoff models. The maximum and minimum x3 values of TQ are recorded in neat IPA (7.63 × 10-2 at 318.2 K) and neat H2O (8.25 × 10-5 at 298.2 K), respectively. The solubility of TQ is recorded as increasing with the rise in temperature and IPA mass fraction in all (IPA + H2O) mixtures, including pure IPA and pure H2O. The HSP of TQ is similar to that of pure IPA, suggesting the great potential of IPA in TQ solubilization. The maximum molecular solute-solvent interactions are found in TQ-IPA compared to TQ-H2O. A thermodynamic study indicates an endothermic and entropy-driven dissolution of TQ in all (IPA + H2O) mixtures, including pure IPA and pure H2O.


Assuntos
2-Propanol/química , Benzoquinonas/química , Química Farmacêutica/métodos , Água/química , Técnicas de Química Analítica , Desenho de Fármacos , Análise de Regressão , Reprodutibilidade dos Testes , Solubilidade , Solventes , Temperatura , Termodinâmica
11.
Diabet Med ; 36(12): 1686-1693, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31498920

RESUMO

AIM: A hypothesized mechanism for increased type 1 diabetes risk among caesarean births is lack of exposure to the vaginal microbiota. Children born by prelabour caesarean are not exposed to the vaginal microbiota, whereas caesarean births during labour (intrapartum) may be exposed. The aim of this study was to estimate type 1 diabetes risk among children born by caesarean compared with normal vaginal delivery. METHODS: This whole-of-population study linked routinely collected, de-identified administrative data from the South Australian Early Childhood Data Project for all births from 1999 to 2013. Type 1 diabetes cases were identified using inpatient hospitalizations from 2001 to 2014 (ICD-10-AM codes E10-E109). Type 1 diabetes risk for caesarean was assessed by Cox regression using two models: (i) caesarean vs. vaginal and (ii) prelabour or intrapartum caesarean vs. vaginal. Analyses were adjusted for confounding and multiple imputation was used to address missing data. RESULTS: A total of 286 058 children born between 1999 and 2013 contributed to 2 200 252 person-years, of which 557 had type 1 diabetes. Of all births, 90 546 (31.7%) were caesarean, and of these 53.1% were prelabour and 46.9% intrapartum caesarean. Compared with vaginal delivery, the adjusted hazard ratio for type 1 diabetes was 1.05 [95% confidence interval (CI) 0.86-1.28) for caesarean, 1.02 (95% CI 0.79-1.32) for prelabour caesarean and 1.08 (95% CI 0.82-1.41) for intrapartum caesarean. CONCLUSION: There may be a small increased type 1 diabetes risk following caesarean, but confidence intervals included the null. The lower estimate for prelabour compared with intrapartum caesarean, and the potential for unmeasured confounding suggest that neonatal vaginal microbiota might not be involved in type 1 diabetes.


Assuntos
Cesárea/efeitos adversos , Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Adulto , Austrália/epidemiologia , Cesárea/estatística & dados numéricos , Criança , Estudos de Coortes , Parto Obstétrico/métodos , Feminino , Seguimentos , Humanos , Saúde Materna , Microbiota/fisiologia , Gravidez , Fatores de Risco , Vagina/microbiologia
12.
Nanomedicine ; 17: 150-187, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30716419

RESUMO

Micro RNAs (miRNAs) are small non-coding RNAs which bind to the 3'-untranslated region of a mature mRNA to induce degradation; thereby regulating gene expression. It is reported that dysregulated miRNAs involved in neurodegenerative diseases including Parkinson's disease, could play a significant role as prognostic markers and therapeutic targets. Neuroprotective effect of delta opioid receptors (DOR) and its known miRNA regulation against endoplasmic reticulum (ER) stress have been reported previously by our lab. Current study focuses on understanding the regulation of novel miRNAs by DOR under ER stress. Novel miRNAs were identified for three different samples; control, tunicamycin (ER stress inducer), and tunicamycin+DADLE (DOR agonist). Differentially regulated miRNAs between the different samples were identified and pathway/target genes analysis was carried out. The results suggest that following DOR activation novel miRNAs like xxx-m0073-3p, xxx-m0225-3p, xxx-m0088-3p, xxx-m0098-5p etc. could regulate cell survival mechanisms in neuronal cells (SH-SY5Y) under ER stress.


Assuntos
Estresse do Retículo Endoplasmático , MicroRNAs/genética , Receptores Opioides delta/genética , Linhagem Celular , Perfilação da Expressão Gênica , Humanos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Receptores Opioides delta/metabolismo , Transdução de Sinais
13.
BJOG ; 125(5): 556-564, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28755422

RESUMO

BACKGROUND: The development of clinical guidelines requires standardised methods informed by robust evidence synthesis. OBJECTIVES: We evaluated the methodological quality of endometriosis guidelines, mapped their recommendations, and explored the relationships between recommendations and research evidence. SEARCH STRATEGY: We searched EMBASE, MEDLINE, and PubMed from inception to February 2016. SELECTION CRITERIA: We included guidelines related to the diagnosis and management of endometriosis. DATA COLLECTION AND ANALYSIS: The search strategy identified 879 titles and abstracts. We include two international and five national guidelines. Four independent authors assessed the methodological quality of the included guidelines, using the Appraisal of Guidelines for Research & Evaluation (AGREE-II) instrument, and systematically extracted the guideline recommendations and supporting research evidence. MAIN RESULTS: One hundred and fifty-two different recommendations were made. Ten recommendations (7%) were comparable across guidelines. The European Society of Human Reproduction and Embryology was objectively evaluated as the highest quality guideline (methodological quality score: 88/100). There was substantial variation between the supporting evidence presented by individual guidelines for comparable recommendations. Forty-two recommendations (28%) were not supported by research evidence. No guideline followed the standardised guideline development methods (AGREE-II). CONCLUSIONS: There is substantial variation in the recommendations and methodological quality of endometriosis guidelines. Future guidelines should be developed with reference to high-quality methods in consultation with key stakeholders, including women with endometriosis, ensuring that their scope can truly inform clinical practice and eliminate unwarranted and unjustified variations in clinical practice. TWEETABLE ABSTRACT: #Endometriosis guidelines vary in recommendations and quality. @EndometriosisUK.


Assuntos
Endometriose/diagnóstico , Endometriose/terapia , Guias de Prática Clínica como Assunto/normas , Feminino , Humanos
14.
J Neurochem ; 142(5): 649-661, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28628196

RESUMO

Critical periods (CP) in early post-natal life are periods of plasticity during which the neuronal circuitry is most receptive to environmental stimuli. These early experiences translate to a more permanent and sophisticated neuronal connection in the adult brain systems. Multiple studies have pointed to the development of inhibitory circuitry as one of the central factors for the onset of critical periods. We discuss several molecular mechanisms regulating inhibitory circuit maturation and CP, from gene transcription level to protein signaling level. Also, beyond the level of gene sequences, we briefly consider recent information on dynamic epigenetic regulation of gene expression through histone methylation and acetylation and their implication on timed development of the inhibitory circuitry for the onset of CP.


Assuntos
Período Crítico Psicológico , Neurônios GABAérgicos/fisiologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Animais , Epigênese Genética/fisiologia , Humanos , Córtex Visual/fisiologia , Ácido gama-Aminobutírico/metabolismo
15.
Insect Mol Biol ; 26(4): 392-402, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28374513

RESUMO

The neutral sphingomyelinase (nSMase) 1 homologue gene LsSMase was cloned from Laodelphax striatellus, a direct sap-sucker and virus vector of gramineous plants, and expressed via a Bac to Bac baculovirus expression system. The LsSMase-enhanced green fluorescent protein fusion protein was located in the endoplasmic reticulum in a similar manner to mammalian nSMase 1. The biochemical properties of LsSMase were determined in detail. The optimal pH and temperature for recombinant LsSMase were 8 and 37 °C, respectively. LsSMase was an Mg2+ or Mn2+ dependent enzyme, but different concentration of each were needed. The activity of LsSMase was significantly stimulated by Ethylene glycol bis(2-aminoethyl ether)tetraacetic acid (EGTA), whereas it was inhibited by ethylenediaminetetraacetic acid. Millimolar concentrations of Zn2+ completely inhibited LsSMase. The reducing agents dithiothreitol and ß-mercaptoethanol varied in their effects on activity. Phospholipids were not found to stimulate LsSMase.


Assuntos
Hemípteros/enzimologia , Esfingomielina Fosfodiesterase/metabolismo , Sequência de Aminoácidos , Animais , Hemípteros/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Análise de Sequência de DNA , Esfingomielina Fosfodiesterase/genética
16.
Diabet Med ; 34(10): 1354-1360, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28636762

RESUMO

AIM: This study examined the outputs of research papers in diabetes from 31 European countries between 2002 and 2013, and their funding. METHODS: Diabetes research papers in the Web of Science were identified by means of a filter based on journals and title words. For 2009-2013 papers, the funders were coded to show their sector and nationality. RESULTS: Europe published 40 547 diabetes papers in the 12 years between 2002 and 2013. Denmark, Sweden and Finland published the most relative to their wealth, but the UK published the most absolutely despite an apparently low burden (as measured by disability-adjusted life years). The largest source of funding was government (30%), followed by the non-profit sector (18%) and industry (13%). The European Commission supported 2.7% of papers, but more in Latvia (33%) and Estonia (16%). Based on an estimated cost per paper of €260 000, the annual research expenditure in Europe was approximately €986 million in 2013. CONCLUSIONS: The European diabetes burden in disability-adjusted life years increased by one third between 2002 and 2012, but its output of research papers has decreased from 44% to 36% of the world total. This decrease needs to be reviewed in the context of European non-communicable disease research policy.


Assuntos
Pesquisa Biomédica/economia , Pesquisa Biomédica/estatística & dados numéricos , Diabetes Mellitus , Gastos em Saúde/estatística & dados numéricos , Pesquisa Biomédica/tendências , Diabetes Mellitus/economia , Diabetes Mellitus/epidemiologia , Europa (Continente)/epidemiologia , Financiamento Governamental/estatística & dados numéricos , Gastos em Saúde/tendências , Humanos , Publicações/estatística & dados numéricos , Anos de Vida Ajustados por Qualidade de Vida , Pesquisa/economia , Pesquisa/estatística & dados numéricos
17.
Int J Syst Evol Microbiol ; 67(11): 4435-4442, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28920841

RESUMO

Two Gram-stain-positive, rod-shaped and endospore-forming bacteria that represent a single species, designated strains KJ1-10-99T and KJ1-10-93, were isolated from a saline desert of Little Rann of Kutch, Gujarat, India. Analysis of 16S rRNA gene sequences revealed that the isolates belonged to the family Bacillaceae and were closely related to each other with 16S rRNA gene sequence similarity of 99.9 %. However, these two isolates formed a novel phylogenetic branch within this family. Both strains were aerobic, catalase and oxidase positive, and could grow optimally at 37 °C and pH 9. Further, strains KJ1-10-99T and KJ1-10-93 grew optimally at a NaCl concentration of 7.5 and 15 % (w/v), respectively. Both strains shared highest sequence similarity with Fermentibacillus polygoni IEB3T (96.90 %) followed by Bacillus nanhaiisediminis NH3T (96.3 %) and Bacillus alkalinitrilicus ANL-iso4T (96.3 %). The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17:0, C16 : 0, and iso-C15 : 0. The major polar lipids were diphosphatidylglycerol and phosphatidylglycerol in both strains. The predominant isoprenoid quinone was MK-7 in both the strains. The peptidoglycan contained meso-diaminopimelic acid (meso-DAP) as the diagnostic diamino acid. The DNA G+C content of strains KJ1-10-99T and KJ1-10-93 were 48.7 and 48.9 mol% respectively. Both strains could be distinguished from closest phylogenetic neighbours based on a number of phenotypic properties. On the basis of polyphasic taxonomic analysis and phylogenetic data, we conclude that the strains KJ1-10-99T (=LMG 29918T=KCTC 33878T) and KJ1-10-93 (=LMG 29919=KCTC 33877) represent a novel species of a new genus in the family Bacillaceae, order Bacillales, for which the name Desertibacillus haloalkaliphilus gen. nov., sp. nov. is proposed.


Assuntos
Bacillaceae/classificação , Clima Desértico , Filogenia , Microbiologia do Solo , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Índia , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Salinidade , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
18.
Mymensingh Med J ; 26(1): 61-67, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28260757

RESUMO

This cross sectional descriptive study was carried out in the Department of Cardiology, Mymensingh Medical College Hospital from July 2015 to December 2015, included 50 patients admitted with acute coronary syndrome diagnosed on the basis of history, typical anginal type of chest pain, characteristic electrocardiographic changes and increased cardiac biomarkers. Platelet count (PC), Mean platelet volume (MPV) and platelet distribution width (PDW) were measured using automated hematological analyzer and compared them with 50 age and sex matched healthy controls. All platelet parameter indices - platelet count (PC), mean platelet volume (MPV) & platelet distribution width (PDW) - were significantly raised in patients with ACS. In patients with ACS the mean values of platelet count, MPV & PDW were 352.2×109/L), 13.9fL & 15.6fL, respectively; while in normal healthy control the mean values of these indices were 256.2×109/L), 8.1fL & 10.5fL, respectively. Statistically significant difference in mean values of these indices was found (p value <0.05). Larger platelets are haemostatically more active and are a risk factor for developing coronary thrombosis and subsequent acute coronary events (myocardial infarction and unstable angina). Patients with larger platelets can easily be identified during routine hematological analysis and could possibly benefit from preventive treatment.


Assuntos
Síndrome Coronariana Aguda , Plaquetas , Volume Plaquetário Médio , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Estudos Transversais , Humanos , Contagem de Plaquetas
19.
Mymensingh Med J ; 26(2): 459-461, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28588188

RESUMO

L-Asparaginase is a critical component in the treatment of acute lymphoblastic leukemia in children. It is known to cause coagulation abnormalities, thrombosis and hemorrhage in the central nervous system in addition to vasculitis and hypersensitivity reactions. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Seizures are uncommon symptoms. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebrovascular events, completed in the department of Hematology of Bangabandhu Sheikh Mujib Medical University during March & April 2016.


Assuntos
Antineoplásicos , Asparaginase , Leucemia-Linfoma Linfoblástico de Células Precursoras , Convulsões , Doença Aguda , Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Criança , Hemorragia , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Convulsões/induzido quimicamente
20.
Mymensingh Med J ; 26(2): 223-229, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28588154

RESUMO

Breast cancer is the most common malignancy in women and the second most common cause of cancer-related mortality. The distinction by physical examination of physiologic nodularity from abnormal masses can be difficult, while the clinical differentiation of a malignant mass from a benign one is difficult; the medical as well as potential legal consequences of missing a palpable carcinoma are high. There are significant number of reported cases of false-negative findings on mammography and the great desire not to miss a malignant lesion in the early stage of disease lead to aggressive biopsy, but the biopsy rate for cancer is only 10.0% to 30.0%. This means that 70.0% to 90.0% of breast biopsies are performed for benign diseases, which induce unnecessary patients discomfort and anxiety in addition to increasing costs to the patient. Clearly, there is a great need for development of additional reliable methods to complement the existing diagnostic procedures to avoid unnecessary biopsy. This cross sectional study was carried out on 43 patients having palpable breast mass, attended in the Department of Radiology and Imaging Mymensingh Medical College Hospital, Mymensingh from 1st January 2012 to 31st December 2013 for the period of two year. These patients were evaluated by USG at the Department of Radiology and Imaging and histopathological examination at the Department of Pathology of the same College to confirm the diagnosis. In diagnosis of malignant mass by USG, 9(20.9%) cases were diagnosed as malignant and 34(79.1%) cases as other than malignant. Eight out of 9 were sonographically diagnosed as malignant lesions also proved as malignant lesion by histopathology and 1 other than malignant. Out of 34 sonographically diagnosed cases of other than malignant lesions 32 were proved histopathologically and 2 did not match with sonographic findings. USG, in diagnosis of malignant lesion, sensitivity was 80.0%, specificity 96.97%, positive predictive value (PPV) (88.89%), negative predictive value 94.12% and accuracy was 93.02% and comparable to other study. In diagnosis of benign lesion by USG, sensitivity was 96.97%, specificity 80.0%, positive predictive value (PPV) (94.12%), negative predictive value 88.89% and accuracy was 93.02%. So, USG is an appropriate imaging method for diagnosis & differential diagnosis of palpable breast mass.


Assuntos
Neoplasias da Mama , Mamografia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Sensibilidade e Especificidade
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