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1.
J Endocrinol Invest ; 46(5): 855-867, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36624224

RESUMO

BACKGROUND AND AIM: There are efficacy and safety concerns related to teneligliptin treatment. A systematic review of randomized controlled trials (RCTs) was undertaken to comprehensively profile the efficacy and safety of teneligliptin in the treatment of type 2 diabetes mellitus (T2DM). METHODS: Thirteen studies were chosen from a search of scientific databases for RCTs using teneligliptin as a monotherapy or as an adjunct to other glycemic agents with pre-specified inclusion criteria. We calculated weighted mean differences (WMDs) and 95% confidence intervals (CIs) in each included trial and pooled the data using a random-effects model. RESULTS: Thirteen studies enrolled 2853 patients were identified. Teneligliptin treatment was associated with weight gain (vs. placebo, weighted mean difference (WMD) 0.28 kg; 95% CI - 0.20-0.77 kg; I2 = 86%; P = 0.25). Compared to monotherapy, add on therapy with teneligliptin showed significant improvement in FPG mg/dl levels (WMD - 16.75 mg/dl; 95% CI - 19.38 to - 14.13 mg/dl), HOMA-ß (WMD 7.91; 95% CI 5.38-10.45) and HOMA-IR (WMD - 0.27; 95% CI - 0.46 to - 0.07). The improvement in HbA1c was greater with monotherapy (WMD - 8.88 mmol/mol; 95% CI - 9.59 to - 8.08 mmol/mol). There was no significant risk of any hypoglycemia with teneligliptin compared to placebo (OR 0.84; 95% CI 0.44-1.60; I2 = 0%; P = 0.60). However, the risk was 1.84 times high when combined with other glycemic agents. The risk of cardiovascular events was comparable, regardless of treatment duration when compared to placebo or any other active comparator (OR 0.79; 95% CI 0.40-1.57; I2 = 0%; P = 0.50). [PROSPERO, CRD42022360785]. CONCLUSIONS: Teneligliptin is an effective and safe therapeutic option for patients with T2DM, both as monotherapy and as add-on therapy. However, additional large-scale, high-quality, long-term follow-up clinical trials with diverse ethnic populations are required to confirm its long-term efficacy and safety.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Humanos , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Pirazóis/efeitos adversos
2.
Arch Microbiol ; 202(6): 1301-1315, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32130434

RESUMO

Antimicrobial resistance is a serious public health threat worldwide today. Escherichia coli is known to resist low doses of antibiotics in the presence of sodium salicylate and related compounds by mounting non-heritable transient phenotypic antibiotic resistance (PAR). In the present study, we demonstrate that Bgl+ bacterial strains harboring a functional copy of the ß-glucoside (bgl) operon and are actively hydrolyzing plant-derived aromatic ß-glucosides such as salicin show PAR to low doses of antibiotics. The aglycone released during metabolism of aromatic ß-glucosides is responsible for conferring this phenotype by de-repressing the multiple antibiotics resistance (mar) operon. We also show that prolonged exposure of Bgl+ bacteria to aromatic ß-glucosides in the presence of sub-lethal doses of antibiotics can lead to a significant increase in the frequency of mutants that show heritable resistance to higher doses of antibiotics. Although heritable drug resistance in many cases is known to reduce the fitness of the carrier strain, we did not see a cost associated with resistance in the mutants, most of which carry clinically relevant mutations. These findings indicate that the presence of the activated form of the bgl operon in the genome facilitates the survival of bacteria in environments in which both aromatic ß-glucosides and antibiotics are present.


Assuntos
Resistência Microbiana a Medicamentos/genética , Glucosídeos/metabolismo , Óperon/genética , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Álcoois Benzílicos/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Mutação , Fenótipo
3.
Microbiology (Reading) ; 165(6): 683-696, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31063124

RESUMO

Regulators encoded by the beta-glucoside (bgl) operon of Escherichia coli are known to influence the expression of downstream target genes that confer a fitness advantage in stationary phase. We have examined the role of bglG in the regulation of ridA that encodes an enamine/imine deaminase essential for the elimination of reactive intermediates generated during the catabolism of amino acids such as serine. We report here that ridA is positively regulated by leucine responsive regulatory protein (Lrp) and leucine antagonizes the activation by Lrp. We also show that Lrp itself is under the indirect regulation of BglG, which brings about the overexpression of ridA in Bgl+ strains during stationary phase. Loss of ridA function in a Bgl+ background results in a significant growth retardation in serine-containing media compared to that in a Bgl- background. We propose that overexpression of ridA in Bgl+ background during stationary phase is physiologically relevant to eliminate toxic metabolites generated by the catabolism of serine-containing peptides as a result of elevated levels of their uptake.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/genética , Proteína Reguladora de Resposta a Leucina/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Bactérias/genética , Sítios de Ligação , Meios de Cultura/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/antagonistas & inibidores , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Leucina/farmacologia , Proteína Reguladora de Resposta a Leucina/antagonistas & inibidores , Proteína Reguladora de Resposta a Leucina/genética , Mutação , Óperon/genética , Regiões Promotoras Genéticas , Proteínas de Ligação a RNA/genética , Serina/análise , Serina/metabolismo
4.
J Viral Hepat ; 25(6): 631-639, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29274193

RESUMO

The phase 2, open-label ACCORDION (ClinicalTrials.gov: NCT02349048) study investigated the efficacy, safety and pharmacokinetics of a 6- or 8-week regimen of simeprevir, daclatasvir and sofosbuvir in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (GT) 1 infection and either early-stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early-stage fibrosis: simeprevir 150 mg, daclatasvir 60 mg, sofosbuvir 400 mg once daily for 6 weeks; compensated cirrhosis: same regimen for 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty-eight patients were treated (6-week group: n = 59; 8-week group: n = 9). SVR12 was achieved by 86.4% (51/59) of patients with early-stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR12 in the 6-week group was viral relapse (11.9%; 7/59). One patient had on-treatment failure due to an early withdrawal (lost to follow-up due to incarceration). One patient with SVR12 in the 6-week group had a late viral relapse at post-treatment week 24. No clinically significant drug-drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct-acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment-naïve, HCV GT1-infected patients with early-stage fibrosis or compensated cirrhosis.


Assuntos
Antivirais/administração & dosagem , Genótipo , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/farmacocinética , Carbamatos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Imidazóis/efeitos adversos , Imidazóis/farmacocinética , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Simeprevir/efeitos adversos , Simeprevir/farmacocinética , Sofosbuvir/efeitos adversos , Sofosbuvir/farmacocinética , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Valina/análogos & derivados , Adulto Jovem
5.
Microb Pathog ; 116: 44-48, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29330059

RESUMO

Biosynthesized nanoparticles have an incredible application in biomedicine owing to its simplicity, eco-friendly properties and low cost. The present study aims to determine the green synthesized zinc oxide nanoparticles from methanolic leaf extract of Glycosmis pentaphylla. The synthesized nanoparticles were characterized using UV-VIS Spectroscopy, Fluorescence spectrometer, FT-IR, XRD, SEM with EDAX and TEM. The confirmations of synthesized nanoparticles were characterized by peak at 351 and 410 nm in the UV-VIS spectrum and photoluminescence spectrum respectively. FT-IR studies revealed the functional group of the nanoparticles. The XRD data showed the crystalline nature of the nanoparticles and EDAX measurements indicated the 20.70% of highly pure zinc oxide metal. The morphological characterization of synthesized zinc oxide nanoparticles was analyzed by SEM and TEM and size of the particles were ranging from 32 to 36 nm. The synthesized zinc oxide nanoparticles exhibited interesting antimicrobial activity against pathogenic organisms. In addition, this is the first report on leaf mediated synthesis of zinc oxide (ZnO) nanoparticles from Glycosmis pentaphylla.


Assuntos
Anti-Infecciosos/metabolismo , Nanopartículas/metabolismo , Rutaceae/metabolismo , Óxido de Zinco/metabolismo , Aspergillus/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Nanopartículas/química , Extratos Vegetais/metabolismo , Espectrometria por Raios X , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
6.
J Viral Hepat ; 24(4): 287-294, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27878906

RESUMO

Approximately three million individuals in the United States are chronically infected with hepatitis C virus (HCV). Chronic HCV infection may lead to the development of compensated as well as decompensated liver cirrhosis. The Phase II IMPACT study was conducted in HCV genotype 1- or 4-infected cirrhotic patients with portal hypertension or decompensated liver disease and assessed for the first time the combination of the three direct-acting antivirals simeprevir, daclatasvir and sofosbuvir. Treatment-naïve or treatment-experienced adults with Child-Pugh (CP) score <7 (CP A) and evidence of portal hypertension, or CP score 7-9 (CP B), received 12 weeks of simeprevir 150 mg, daclatasvir 60 mg and sofosbuvir 400 mg, once daily. The primary efficacy endpoint was sustained virologic response 12 weeks after end of treatment (SVR12). Pharmacokinetics and safety were also assessed. Overall, 40 patients were enrolled (CP A: 19; CP B: 21). All 40 patients achieved SVR12. At week 8, the mean pharmacokinetic exposure to simeprevir, sofosbuvir, daclatasvir and GS-331007 (sofosbuvir metabolite) was 2.2-, 1.5-, 1.2- and 1.2-fold higher in patients with CP B than CP A, respectively. Grade 1/2 adverse events (AEs) occurred in 26 of 40 (65%) patients. One CP B patient had a Grade 3 AE (gastrointestinal haemorrhage), which was reported as a serious AE but not considered related to study drugs. Treatment for 12 weeks with simeprevir, daclatasvir and sofosbuvir was generally safe and well tolerated, and resulted in 100% of cirrhotic patients with portal hypertension or decompensated liver disease achieving SVR12.


Assuntos
Antivirais/administração & dosagem , Insuficiência Hepática/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Imidazóis/administração & dosagem , Simeprevir/administração & dosagem , Sofosbuvir/administração & dosagem , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/farmacocinética , Carbamatos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/farmacocinética , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Simeprevir/efeitos adversos , Simeprevir/farmacocinética , Sofosbuvir/efeitos adversos , Sofosbuvir/farmacocinética , Resultado do Tratamento , Estados Unidos , Valina/análogos & derivados
7.
Microb Pathog ; 113: 445-450, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29170043

RESUMO

In the present study deals with the green synthesis of silver nano particles from methanolic leaf extracts of Atalantia monophylla. The synthesized nano-particles are characterized by UV-vis spectroscopy, PL, FTIR, XRD, SEM with EDAX and TEM. The nano-particles are indicated in absorption peak at 404 nm in the absorption spectrum. Further micro graphical analysis confirmed the average size was estimated about 35 nm and SEAD pattern authorized well crystalline materials. The FTIR studies help to confirm the functional group of synthesized silver nano particles. The XRD data shown the crystalline nature of nano particles and EDAX measurement indicates the purity of silver metal. The antimicrobial effect of silver nanoparticles was tested on pathogenic organisms using agar well diffusion method. Minimum inhibitory concentration (MIC) and Minimum bactericidal/fungicidal concentration (MBC/MFC) were also investigated in different concentrations of leaf extract. The results indicated that synthesized silver nano particle of A. monophylla leaf extract has the potential of antimicrobial activity against pathogenic microorganism. In addition, this is the first report on leaf synthesized silver nano particles of A. monophylla. The antimicrobial activity against pathogenic microorganisms and the ability to detect hydrogen peroxide using the silver nanoparticles were confirmed which would find applications in the development of new antimicrobial drugs and new biosensors to detect the presence of hydrogen peroxide in various samples respectively.


Assuntos
Anti-Infecciosos/farmacologia , Química Verde/métodos , Peróxido de Hidrogênio/química , Nanopartículas Metálicas/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Rutaceae/química , Prata/química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
8.
Microbiology (Reading) ; 162(5): 764-776, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26944926

RESUMO

The cellular proteolytic machinery orchestrates protein turnover and regulates several key biological processes. This study addresses the roles of Lon, a major ATP-dependent protease, in modulating the responses of Escherichia coli strain MG1655 to low and high amounts of sodium salicyclate (NaSal), a widely used clinically relevant analgesic. NaSal affects several bacterial responses, including growth and resistance to multiple antibiotics. The loss of lon reduces growth in response to high, but not low, amounts of NaSal. From amongst a panel of Lon substrates, MarA was identified to be the downstream target of Lon. Thus, stabilization of MarA in the absence of lon lowers growth of the strain in the presence of higher amounts of NaSal. The steady-state transcript levels of marA and its target genes, acrA, acrB and tolC, are higher in the Δlon strain compared with the WT strain. Consequently, the resistance to antibiotics, e.g. tetracycline and nalidixic acid, is enhanced in Δlon in a marA-dependent manner. Furthermore, the target genes of MarA, i.e. acrB and tolC, are responsible for NaSal-mediated antibiotic resistance. Studies using atomic force microscopy demonstrated that ciprofloxacin led to greater cell filamentation, which is lower in the Δlon strain due to higher levels of MarA. Overall, this study delineates the roles of Lon protease, its substrate MarA and downstream targets of MarA, e.g. acrB and tolC, during NaSal-mediated growth reduction and antibiotic resistance. The implications of these observations in the adaptation of E. coli under different environmental conditions are discussed.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Protease La/metabolismo , Salicilato de Sódio/farmacologia , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa/genética , Ciprofloxacina/farmacologia , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Lipoproteínas/genética , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Ácido Nalidíxico/farmacologia , Protease La/genética , Salicilato de Sódio/metabolismo , Tetraciclina/farmacologia , Resistência a Tetraciclina/genética
9.
Haemophilia ; 22(3): 342-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26987935

RESUMO

INTRODUCTION: Current factor prophylaxis strategy practised in developed countries is not feasible in resource constraint developing countries like India. AIM: The aim of this study was to investigate the efficacy and safety of very low-dose factor prophylaxis in India. METHODS: Children of 1-10 years of age with severe haemophilia were randomized to Prophylaxis group and Episodic (On demand) group. Children in prophylaxis group received very low-dose factor VIII (FVIII) concentrate, i.e. 10 units kg(-1) body weights on 2 days a week. Episodic group received factor concentrate in standard recommended doses. The study period was 11.5 months. RESULTS: In total 21 children were enrolled in this study, 11 assigned to prophylaxis and 10 to episodic group. Children on prophylaxis had 11 joint bleeds in comparison to 57 joint bleeds in episodic group. Mean number of haemarthrosis per patient per month were 0.08 (0.08 ± 0.13) in prophylaxis group compared to 0.48 (0.48 ± 0.34) in episodic group (P < 0.05). Total FVIII consumption was 87.51 and 56.32 units kg(-1) month(-1) in prophylaxis and episodic group respectively (P = ns). Overall median hospital emergency visits were 1 day in prophylaxis group and 9 days in episodic group (P ≤ 0.05). Median days of absenteeism from school were 25 days in episodic group and 3 days in prophylaxis group (P < 0.05). No significant complications were noted in prophylaxis group and compliance was 98%. CONCLUSION: To conclude, low-dose FVIII prophylaxis is cost effective, efficacious and a safe method of preventing joint bleeds and consequent joint damages.


Assuntos
Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Criança , Pré-Escolar , Países em Desenvolvimento , Relação Dose-Resposta a Droga , Fator VIII/isolamento & purificação , Seguimentos , Hemartrose/etiologia , Hemofilia A/patologia , Humanos , Índia , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Emerg Med J ; 33(10): 709-15, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27466347

RESUMO

OBJECTIVES: To validate and assess reliability of a novel triage system, one-two-triage (OTT), that can be applied by inexperienced providers in low-resource settings. METHODS: This study was a two-phase prospective, comparative study conducted at three hospitals. Phase I assessed criterion validity of OTT on all patients arriving at an American university hospital by comparing agreement among three methods of triage: OTT, Emergency Severity Index (ESI) and physician-defined acuity (the gold standard). Agreement was reported in normalised and raw-weighted Cohen κ using two different scales for weighting, Expert-weighted and triage-weighted κ. Phase II tested reliability, reported in Fleiss κ, of OTT using standardised cases among three groups of providers at an urban and rural Cambodian hospital and the American university hospital. RESULTS: Normalised for prevalence of patients in each category, OTT and ESI performed similarly well for expert-weighted κ (OTT κ=0.58, 95% CI 0.52 to 0.65; ESI κ=0.47, 95% CI 0.40 to 0.53) and triage-weighted κ (κ=0.54, 95% CI 0.48 to 0.61; ESI κ=0.57, 95% CI 0.51 to 0.64). Without normalising, agreement with gold standard was less for both systems but performance of OTT and ESI remained similar, expert-weighted (OTT κ=0.57, 95% CI 0.52 to 0.62; ESI κ=0.6, 95% CI 0.58 to 0.66) and triage-weighted (OTT κ=0.31, 95% CI 0.25 to 0.38; ESI κ=0.41, 95% CI 0.35 to 0.4). In the reliability phase, all triagers showed fair inter-rater agreement, Fleiss κ (κ=0.308). CONCLUSIONS: OTT can be reliably applied and performs as well as ESI compared with gold standard, but requires fewer resources and less experience.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Triagem/métodos , California , Camboja , Feminino , Hospitais de Distrito , Hospitais Públicos , Hospitais Universitários , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
11.
J Viral Hepat ; 22(4): 366-75, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25363449

RESUMO

This pooled analysis of five Phase IIb and III studies evaluated the safety and tolerability of simeprevir, a once daily, oral hepatitis C virus (HCV) NS3/4A protease inhibitor. Data were summarised for patients who received simeprevir 150 mg once daily (n = 924) or placebo (n = 540) plus pegylated interferon-α/ribavirin for 12 weeks. During the first 12 weeks of treatment, few patients discontinued simeprevir or placebo due to adverse events (AEs) (both 2.2%). Pruritus (23.8% vs 17.4%), rash (any; 22.9% vs 16.7%) and photosensitivity (3.2% vs 0.6%) [Correction added on 16 January 2015, after first online publication: In the above sentence, the values in 'Photosensitivity' were previously incorrect and have now been changed to 3.2% vs 0.6%.] were more prevalent in the simeprevir vs the placebo groups. Most AEs were grade 1/2 (72.4% for simeprevir vs 71.3% for placebo). All grade 3/4 AEs occurred in <5.0% of patients, except neutropenia (9.8% vs 7.6%). Overall incidence of neutropenia was similar (17.3% vs 15.7%). Incidence of anaemia was 13.2% for simeprevir vs 10.9% for placebo, and incidence of increased bilirubin was 8.4% vs 2.8%. Bilirubin increases were mild-to-moderate and transient without concurrent transaminase increases or association with hepatic injury. Safety and tolerability did not vary with METAVIR score, although increased bilirubin and anaemia were more frequent in simeprevir-treated patients with METAVIR F4 (increased bilirubin, 13.0% vs 3.3%; anaemia, 19.0% vs 14.8%). Serious AEs were infrequent (2.1% for simeprevir vs 3.0% for placebo). No deaths were reported during the first 12 weeks of treatment. Patient-reported fatigue and other outcomes were comparable for both groups, but were of shorter duration for simeprevir due to the use of response-guided therapy. Simeprevir is well tolerated in HCV genotype 1-infected patients.


Assuntos
Antivirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Ribavirina/efeitos adversos , Simeprevir/efeitos adversos , Anemia/induzido quimicamente , Anemia/epidemiologia , Antivirais/administração & dosagem , Bilirrubina/sangue , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados como Assunto , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Exantema/induzido quimicamente , Exantema/epidemiologia , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon-alfa/administração & dosagem , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Prevalência , Prurido/induzido quimicamente , Prurido/epidemiologia , Ribavirina/administração & dosagem , Simeprevir/administração & dosagem
12.
Hum Reprod ; 30(1): 232-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25376457

RESUMO

STUDY QUESTION: Are mutations in NLRP2/7 (NACHT, LRR and PYD domains-containing protein 2/7) or KHDC3L (KH Domain Containing 3 Like) associated with recurrent pregnancy loss (RPL) or infertility? SUMMARY ANSWER: We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility. WHAT IS KNOWN ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS). STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT). MAIN RESULTS AND THE ROLE OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL. LIMITATIONS, REASONS FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations. WIDER IMPLICATIONS OF THE FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.


Assuntos
Aborto Habitual/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Infertilidade Feminina/genética , Proteínas/genética , Proteínas Reguladoras de Apoptose , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Humanos , Mutação , Gravidez
13.
Proc Biol Sci ; 280(1762): 20130721, 2013 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-23677347

RESUMO

Bacteria present in natural environments such as soil have evolved multiple strategies to escape predation. We report that natural isolates of Enterobacteriaceae that actively hydrolyze plant-derived aromatic ß-glucosides such as salicin, arbutin and esculin, are able to avoid predation by the bacteriovorous amoeba Dictyostelium discoideum and nematodes of multiple genera belonging to the family Rhabditidae. This advantage can be observed under laboratory culture conditions as well as in the soil environment. The aglycone moiety released by the hydrolysis of ß-glucosides is toxic to predators and acts via the dopaminergic receptor Dop-1 in the case of Caenorhabditis elegans. While soil isolates of nematodes belonging to the family Rhabditidae are repelled by the aglycone, laboratory strains and natural isolates of Caenorhabditis sp. are attracted to the compound, mediated by receptors that are independent of Dop-1, leading to their death. The ß-glucosides-positive (Bgl(+)) bacteria that are otherwise non-pathogenic can obtain additional nutrients from the dead predators, thereby switching their role from prey to predator. This study also offers an evolutionary explanation for the retention by bacteria of 'cryptic' or 'silent' genetic systems such as the bgl operon.


Assuntos
Dictyostelium/fisiologia , Enterobacteriaceae/fisiologia , Cadeia Alimentar , Glucosídeos/metabolismo , Nematoides/fisiologia , Animais , Caenorhabditis elegans/fisiologia , Quimiotaxia , Hidrólise , Índia , Especificidade da Espécie
14.
Diabetes Res Clin Pract ; 202: 110810, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37391033

RESUMO

The ability of the Ipswich touch test (IpTT) and VibratipTM to detect loss of protective sensation (LOPS) was tested against a neurothesiometer in an outpatient diabetic population without a history for ulceration. Our results support the use of the IpTT as a screening tool for LOPS, but not of VibratipTM.


Assuntos
Diabetes Mellitus , Pé Diabético , Neuropatias Diabéticas , Humanos , Pé Diabético/prevenção & controle , Tato , Pacientes Ambulatoriais , Limiar Sensorial , Índia/epidemiologia , Neuropatias Diabéticas/diagnóstico
15.
J Bacteriol ; 194(1): 90-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22020646

RESUMO

We report that the bgl operon of Escherichia coli, encoding the functions necessary for the uptake and metabolism of aryl-ß-glucosides, is involved in the regulation of oligopeptide transport during stationary phase. Global analysis of intracellular proteins from Bgl-positive (Bgl(+)) and Bgl-negative (Bgl(-)) strains revealed that the operon exerts regulation on at least 12 downstream target genes. Of these, oppA, which encodes an oligopeptide transporter, was confirmed to be upregulated in the Bgl(+) strain. Loss of oppA function results in a partial loss of the growth advantage in stationary-phase (GASP) phenotype of Bgl(+) cells. The regulatory effect of the bgl operon on oppA expression is indirect and is mediated via gcvA, the activator of the glycine cleavage system, and gcvB, which regulates oppA at the posttranscriptional level. We show that BglG destabilizes the gcvA mRNA in vivo, leading to reduced expression of gcvA in the stationary phase. Deletion of gcvA results in the downregulation of gcvB and upregulation of oppA and can partially rescue the loss of the GASP phenotype seen in ΔbglG strains. A possible mechanism by which oppA confers a competitive advantage to Bgl(+) cells relative to Bgl(-) cells is discussed.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Lipoproteínas/metabolismo , Oligopeptídeos/metabolismo , Óperon/fisiologia , Proteínas de Ligação a RNA/metabolismo , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica/fisiologia , Lipoproteínas/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
16.
J Bacteriol ; 194(20): 5604-12, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22904288

RESUMO

Diaminopropionate ammonia lyase (DAPAL) is a pyridoxal-5'phosphate (PLP)-dependent enzyme that catalyzes the conversion of diaminopropionate (DAP) to pyruvate and ammonia and plays an important role in cell metabolism. We have investigated the role of the ygeX gene of Escherichia coli K-12 and its ortholog, STM1002, in Salmonella enterica serovar Typhimurium LT2, presumed to encode DAPAL, in the growth kinetics of the bacteria. While Salmonella Typhimurium LT2 could grow on dl-DAP as a sole carbon source, the wild-type E. coli K-12 strain exhibited only marginal growth on dl-DAP, suggesting that DAPAL is functional in S. Typhimurium. The expression of ygeX in E. coli was low as detected by reverse transcriptase PCR (RT-PCR), consistent with the poor growth of E. coli on dl-DAP. Strains of S. Typhimurium and E. coli with STM1002 and ygeX, respectively, deleted showed loss of growth on dl-DAP, confirming that STM1002 (ygeX) is the locus encoding DAPAL. Interestingly, the presence of dl-DAP caused a growth inhibition of the wild-type E. coli strain as well as the knockout strains of S. Typhimurium and E. coli in minimal glucose/glycerol medium. Inhibition by dl-DAP was rescued by transforming the strains with plasmids containing the STM1002 (ygeX) gene encoding DAPAL or supplementing the medium with Casamino Acids. Growth restoration studies using media lacking specific amino acid supplements suggested that growth inhibition by dl-DAP in the absence of DAPAL is associated with auxotrophy related to the inhibition of the enzymes involved in the biosynthetic pathways of pyruvate and aspartate and the amino acids derived from them.


Assuntos
Amônia-Liases/genética , Escherichia coli K12/enzimologia , Escherichia coli K12/genética , Salmonella typhimurium/enzimologia , Salmonella typhimurium/genética , Ácido Aspártico/metabolismo , Carbono/metabolismo , Meios de Cultura/química , Escherichia coli K12/crescimento & desenvolvimento , Deleção de Genes , Perfilação da Expressão Gênica , Teste de Complementação Genética , Ácido Pirúvico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Salmonella typhimurium/crescimento & desenvolvimento , beta-Alanina/análogos & derivados , beta-Alanina/metabolismo
17.
J Emerg Med ; 43(2): 298-302, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22244286

RESUMO

BACKGROUND: The American Heart Association (AHA) Advanced Cardiovascular Life Support (ACLS) course is taught worldwide. The ACLS course is designed for consistency, regardless of location; to our knowledge, no previous study has compared the cognitive performance of international ACLS students to those in the United States (US). STUDY OBJECTIVES: As international health educational initiatives continue to expand, an assessment of their efficacy is essential. This study assesses the AHA ACLS curriculum in an international setting by comparing performance of a cohort of US and Indian paramedic students. METHODS: First-year paramedic students at the Emergency Management and Research Institute, Hyderabad, India, and a cohort of first-year paramedic students from the United States comprised the study population. All study participants had successfully completed the standard 2-day ACLS course, taught in English. Each student was given a 40-question standardized AHA multiple-choice examination. Examination performance was calculated and compared for statistical significance. RESULTS: There were 117 Indian paramedic students and 43 US paramedic students enrolled in the study. The average score was 86% (± 11%) for the Indian students and 87% (± 6%) for the US students. The difference between the average examination scores was not statistically significant in an independent means t-test (p=0.508) and a Wilcoxon test (p=0.242). CONCLUSION: Indian paramedic students demonstrated excellent ACLS cognitive comprehension and performed at a level equivalent to their US counterparts on an AHA ACLS written examination. Based on the study results, the AHA ACLS course proved effective in an international setting despite being taught in a non-native language.


Assuntos
Suporte Vital Cardíaco Avançado/educação , Pessoal Técnico de Saúde/educação , Estudantes , Adulto , Pessoal Técnico de Saúde/estatística & dados numéricos , Currículo , Avaliação Educacional , Feminino , Humanos , Índia , Masculino , Estatísticas não Paramétricas , Estudantes/estatística & dados numéricos , Estados Unidos , Adulto Jovem
18.
Telemed J E Health ; 18(9): 699-702, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23046243

RESUMO

We have used a telemedicine facility to conduct academic teaching/training sessions. The objective of this study was to examine the feasibility, advantages, and disadvantages of this method of e-learning sessions. The teaching/learning sessions were organized twice a week between the two teaching hospitals. The success of each academic session was analyzed in terms of satisfaction of the participating candidates, infrastructure difficulties (if any), and the overall outcome of the program. In total, 293 academic sessions were held from 2008 to 2010. Each session's presentation was 45 min long and was made using Microsoft(®) (Redmond, WA) PowerPoint. We have found that telemedicine proved to be effective in establishing communication not only between the patient and the physician, but also between the teacher and the student. Several candidates benefited from the application of this technology. Candidates expressed satisfaction and were content with the teaching methods adapted.


Assuntos
Educação a Distância/métodos , Educação Médica Continuada/métodos , Pessoal de Saúde/educação , Telemedicina , Estudos de Viabilidade , Feminino , Humanos , Índia , Masculino , Inquéritos e Questionários
19.
Curr Diabetes Rev ; 18(2): e050421192663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33820522

RESUMO

BACKGROUND: Diabetes mellitus has a significant impact on public health. Oxidative stress plays a major role in the pathophysiology of Type 2 Diabetes Mellitus (T2DM), leading to various complications of T2DM. Yoga is being widely used in the management of T2DM. The primary objective of this systematic review and meta-analysis is to understand the effects of yoga on oxidative stress parameters among adult patients diagnosed with T2DM. MATERIALS AND METHODS: Electronic databases such as PubMed, Scopus, Cochrane Library and Science Direct from start of the study till March 2020 were searched to obtain eligible studies. Study designs of all nature were included (except case studies and reviews). The primary outcome was Malondialdehyde (MDA) and secondary outcomes included fasting plasma glucose, HbA1C and Superoxide Dismutase (SOD) levels. RESULTS: A total of four trials with a total of 440 patients met the inclusion criteria. The results of meta-analysis indicated that yoga significantly reduced MDA (SMD: -1.4; 95% CI -2.66 to -0.13; P = 0.03; I2 = 97%), fasting plasma glucose levels (SMD: -1.87: 95% CI -3.83 to -0.09; P = 0.06; I2= 99%), and HbA1c (SMD: -1.92; 95% CI - 3.03 to -0.81; P = 0.0007; I2 = 92%) in patients with T2DM. No such effect was found for SOD (SMD: -1.01; 95% CI -4.41 to 2.38; P = 0.56; I2= 99%). CONCLUSION: The available evidence suggests that yoga reduces MDA, fasting plasma glucose and HbA1C, and thus would be beneficial in the management of T2DM as a complementary therapy. However, considering the limited number of studies and its heterogeneity, further robust studies are necessary to strengthen our findings and investigate the long-term benefits of yoga.


Assuntos
Diabetes Mellitus Tipo 2 , Yoga , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 2/terapia , Hemoglobinas Glicadas/análise , Humanos , Estresse Oxidativo , Superóxido Dismutase
20.
Diabetes Res Clin Pract ; 187: 109865, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35398144

RESUMO

AIMS: Literature indicates that altered plantar loading in people with diabetes could trigger changes in plantar soft tissue biomechanics which, in turn, could affect the risk for ulceration. To stimulate more research in this area, this study uses in vivo testing to investigate the link between plantar loading and tissue hardness. METHODS: Tissue hardness and plantar pressure distribution were measured for six plantar areas in 39 people with diabetes and peripheral neuropathy. RESULTS: Spearman correlation analysis revealed that increased pressure time integral at the 1st metatarsal-head region (r = -0.354, n = 39, P = 0.027) or at the heel (r = -0.378, n = 39, P = 0.018) was associated with reduced hardness in the same regions. After accounting for confounding parameters, generalised estimating equations analysis also showed that 10% increase in pressure time integral at the heel was associated with ≈ 1 unit reduction in hardness in the same region. CONCLUSIONS: For the first time, this study reveals that people with diabetes and neuropathy who tend to load their feet more heavily also tend to have plantar soft tissues with lower hardness. The observed difference in tissue hardness is likely to affect the tissue's vulnerability to overload injury. More research will be needed to explore the implications of the observed association for the risk of ulceration.


Assuntos
Diabetes Mellitus , Pé Diabético , Doenças do Sistema Nervoso Periférico , , Dureza , Calcanhar , Humanos
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