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1.
Phys Rev Lett ; 126(8): 086802, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33709762

RESUMO

Mesoscopic conductance fluctuations are a ubiquitous signature of phase-coherent transport in small conductors, exhibiting universal character independent of system details. In this Letter, however, we demonstrate a pronounced breakdown of this universality, due to the interplay of local and remote phenomena in transport. Our experiments are performed in a graphene-based interaction-detection geometry, in which an artificial magnetic texture is induced in the graphene layer by covering a portion of it with a micromagnet. When probing conduction at some distance from this region, the strong influence of remote factors is manifested through the appearance of giant conductance fluctuations, with amplitude much larger than e^{2}/h. This violation of one of the fundamental tenets of mesoscopic physics dramatically demonstrates how local considerations can be overwhelmed by remote signatures in phase-coherent conductors.

2.
BMC Complement Altern Med ; 18(1): 174, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29866088

RESUMO

BACKGROUND: In the view of endemic avian influenza H9N2 infection in poultry, its zoonotic potential and emergence of antiviral resistance, two herbal plants, Ocimum sanctum and Acacia arabica, which are easily available throughout various geographical locations in India were taken up to study their antiviral activity against H9N2 virus. We evaluated antiviral efficacy of three different extracts each from leaves of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) against H9N2 virus using in ovo model. METHODS: The antiviral efficacy of different leaves extracts was systematically studied in three experimental protocols viz. virucidal (dose-dependent), therapeutic (time-dependent) and prophylactic (dose-dependent) activity employing in ovo model. The maximum non-toxic concentration of each herbal extracts of O. sanctum and A. arabica in the specific pathogen free embryonated chicken eggs was estimated and their antiviral efficacy was determined in terms of reduction in viral titres, measured by Haemagglutination (HA) and real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. RESULTS: All the extracts of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) showed significant virucidal activity, however, crude extract ocimum and terpenoid ocimum showed highly significant to significant (p < 0.001-0.01) decrease in virus genome copy numbers with lowest dose tested. Similarly, therapeutic effect was observed in all three extracts of O. sanctum in comparison to the virus control, nevertheless, crude extract ocimum and terpenoid ocimum maintained this effect for longer period of time (up to 72 h post-incubation). None of the leaves extracts of A. arabica had therapeutic effect at 24 and 48 h post-incubation, however, only the crude extract acacia and polyphenol acacia showed delayed therapeutic effect (72 h post-inoculation). Prophylactic potential was observed in polyphenol acacia with highly significant antiviral activity compared to virus control (p < 0.001). CONCLUSIONS: The crude extract and terpenoid isolated from the leaves of O. sanctum and polyphenol from A. arabica has shown promising antiviral properties against H9N2 virus. Future investigations are necessary to formulate combinations of these compounds for the broader antiviral activity against H9N2 viruses and evaluate them in chickens.


Assuntos
Acacia/química , Antivirais , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Ocimum sanctum/química , Extratos Vegetais , Animais , Antivirais/química , Antivirais/farmacologia , Antivirais/toxicidade , Embrião de Galinha , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Folhas de Planta/química , Reação em Cadeia da Polimerase em Tempo Real , Replicação Viral/efeitos dos fármacos
3.
Scand J Immunol ; 85(2): 130-137, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28256060

RESUMO

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition involving the airways and characterized by airflow limitation. Gaseous and noxious particles play an important role in this process. Antioxidants are the substances that may protect cells from the damage caused by unstable molecules known as free radicals. The increased oxidative stress in patients with COPD is the result of an increased burden of inhaled oxidants, as well as increased amounts of reactive oxygen species (ROS) generated by various inflammatory, immune and epithelial cells of the airways. A total of 150 subjects with COPD and 100 healthy controls subjects were enrolled in this study from the period October 2015 to January 2016. The investigation included measurements of plasma superoxide dismutase activity (SOD), catalase activity (CAT), glutathione content (GSH) reduced form, (GPx) glutathione peroxidase, glutathione reductase (GR) and lipid peroxidation (LPO). Absorbance was measured by UV spectrophotometer. The estimated values of SOD, catalase, GPx, GSH and GR were found to be significantly (P = 0.0001) lower among the cases compared with controls. But, the levels of MDA were higher (P = 0.0001) in cases as compared to control group and there was significant difference in the oxidative stress parameters among the various stages of COPD. The post hoc analysis revealed that SOD was significantly (P < 0.01) lower among the mild, moderate and severe patients compared with very severe patients. The catalase was also observed to be significantly (P = 0.01) lower among mild, moderate and severe patients than very severe patients. The GPx was found to be significantly (P = 0.002) lower among the mild, moderate and severe patients compared with very severe patients. MDA was observed to be significantly higher in mild, moderate and severe patients compared with very severe (P = 0.001). GR was significantly (P = 0.003) lower among mild, moderate and severe patients than very severe patients. However, there was no significant difference in GSH among severity of COPD patients. This study suggests that oxidant and antioxidant imbalance plays an important role in various stages of severity of COPD. These results revealed the presence of an oxidative stress in subjects with COPD, and it is proportionate to the severity of disease.


Assuntos
Antioxidantes/metabolismo , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/patologia , Adulto , Idoso , Catalase/sangue , Catalase/metabolismo , Estudos Transversais , Feminino , Glutationa/sangue , Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Glutationa Redutase/sangue , Glutationa Redutase/metabolismo , Humanos , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Espectrofotometria Ultravioleta , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
4.
Clin Radiol ; 71(9): 869-75, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27177853

RESUMO

AIM: To evaluate the clinical feasibility and accuracy of acoustic radiation force impulse (ARFI) elastography for the detection of liver fibrosis in patients with chronic viral hepatitis. MATERIALS AND METHODS: ARFI-based ultrasound elastography was performed in 69 patients with chronic liver disease (CLD) of viral aetiology and 36 healthy volunteers. Fifty-eight patients with CLD also underwent liver biopsy. RESULTS: ARFI was feasible in all 36 healthy volunteers and all 69 CLD patients, while valid measurements were obtained in 65 patients (95.6%) and all healthy volunteers. The mean shear-wave velocity (SWV) in healthy volunteers was 1.12±0.2 m/s. A gradual increase in mean SWV was noted from fibrosis of Grade F0 to F6 (Ishak's score) and a high positive correlation was found between the mean SWV on ARFI and fibrosis scores at liver biopsy (rho=0.789). The difference between the mild (F1 and F2) versus significant fibrosis (F3 and F4) was also statistically significant (p<0.001). The difference in the SWV measurements obtained from consecutive groups (i.e., F1 versus F2, F2 versus F3, and F3 versus F4) was not statistically significant. Using the area under the receiver operating characteristic curve (AUROC), the best calculated cut-off SWVs for the presence of fibrosis (≥F1), significant fibrosis (≥F3), severe fibrosis (≥F4), and cirrhosis (F6) were found to be 1.207, 1.347, 1.513, and 1.92 m/s, respectively. ARFI values were significantly higher in cirrhotic patients than in other patients (p<0.001). CONCLUSIONS: ARFI elastography allows valid non-invasive evaluation of liver stiffness and may help to distinguish between no/mild fibrosis and significant fibrosis and guide management decisions.


Assuntos
Biópsia/métodos , Técnicas de Imagem por Elasticidade/métodos , Hepatite Viral Humana/diagnóstico por imagem , Hepatite Viral Humana/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Adulto , Doença Crônica , Estudos de Viabilidade , Feminino , Hepatite Viral Humana/complicações , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
J Obstet Gynaecol ; 33(8): 810-3, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24219719

RESUMO

The aim of this study was to evaluate scar thickness in cases of pregnancy with previous caesarean section, by trans-vaginal sonography (TVS) and magnetic resonance imaging (MRI), and to correlate precision of radiologically-measured scar thickness with actual measurement of scar thickness. A total of 35 pregnant patients with previous caesarean section planned for elective caesarean section, were evaluated prospectively. Their scar thickness was measured by TVS and MRI on the day of elective repeat caesarean section. These measurements were correlated with each other and with scar thickness measured during elective repeat caesarean section by using a caliper. The correlation coefficients between scar thickness measured by TVS and MRI with peroperative evaluation with a caliper, were +0.72 and +0.59, respectively. The study concluded that as MRI is a costlier modality and TVS has better correlation coefficient with actual scar thickness, TVS can be considered to be the better modality for antenatal scar thickness measurement.


Assuntos
Cesárea/efeitos adversos , Cicatriz/diagnóstico por imagem , Adulto , Cicatriz/etiologia , Cicatriz/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Gravidez , Ultrassonografia , Útero/diagnóstico por imagem , Útero/patologia , Adulto Jovem
6.
J Infect Dis ; 206(2): 148-57, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22561367

RESUMO

BACKGROUND: Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. METHODS: Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. RESULTS: Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. CONCLUSIONS: This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.


Assuntos
Antivirais/farmacologia , Surtos de Doenças , Farmacorresistência Viral , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/virologia , Oseltamivir/farmacologia , Adolescente , Adulto , Austrália/epidemiologia , Sequência de Bases , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , DNA Viral/química , Feminino , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Neuraminidase/genética , Filogenia , Alinhamento de Sequência , Adulto Jovem
7.
Hernia ; 27(2): 245-257, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36607459

RESUMO

BACKGROUND: Patient-Reported Outcome Measures (PROM's) are increasingly used to assess surgical outcomes in low-risk surgeries such as minimally invasive primary ventral and incisional hernia repair. The purpose of this meta-analysis was to systematically summarize the available evidence for the effect of laparoscopic versus robotic primary ventral and incisional hernia repair on PROM's. METHODS: A systematic review and meta-analysis were performed in accordance with PRISMA guidelines. Randomised control trials, retrospective and prospective studies were included. Medline, Embase, SCOPUS, Web of Science, and Cochrane CENTRAL, and two trial registers were searched. Pooled effect sizes and 95% confidence intervals were calculated using the Mantel-Haenszel method. The overall quality of evidence was assessed using GRADE. RESULTS: Of the 2728 titles screened, eight studies involving 41,205 participants were included. Return to activities of daily living, return to work day and recurrence rate were statistically better in the robotic group. Length of stay, readmission, postoperative pain, quality of life, body image, and patient satisfaction were similar in both groups. The GRADE rating of the quality of evidence was moderate for postoperative pain and low to very low for the quality of life, length of stay, recurrence and readmission. CONCLUSION: The available data of PROM's of laparoscopic and robotic primary ventral and incisional hernia repair is scarce and highly heterogeneous, thus making it difficult to assess the superiority of the laparoscopic technique over the robotic technique. Further studies with uniform reporting of PROM's in laparoscopic and robotic primary ventral and incisional hernia repair are needed.


Assuntos
Hérnia Ventral , Hérnia Incisional , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Hérnia Incisional/cirurgia , Atividades Cotidianas , Qualidade de Vida , Estudos Retrospectivos , Estudos Prospectivos , Herniorrafia/métodos , Hérnia Ventral/cirurgia , Dor Pós-Operatória/cirurgia , Laparoscopia/métodos , Telas Cirúrgicas , Medidas de Resultados Relatados pelo Paciente
8.
Euro Surveill ; 17(27)2012 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-22790606

RESUMO

Although oseltamivir-resistant pandemic influenza A(H1N1)pdm09 is uncommon in immunocompetent individuals, a recent report from Newcastle, Australia, showed the first sustained community spread, from June to August 2011, of oseltamivir-resistant influenza A(H1N1)pdm09 virus carrying the H275Y neuraminidase (NA) mutation. To determine the frequency and the extent of this viral variant spread in the nearest major city to Newcastle, we performed a sequencebased genotypic assessment on samples from 143 oseltamivir untreated and 23 oseltamivir post-treatment individuals with influenza collected contemporaneously in Sydney, 120 km southwest of Newcastle. The detection of two of 143 (1.4%) community-derived samples containing H275Y suggests a low prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 virus in the general community and no convincing evidence of spread of the NA H275Y-bearing influenza A(H1N1)pdm09 virus. In oseltamivir treated patients, oseltamivir-resistant influenza A(H1N1)pdm09 virus continue to emerge with three of 23 (13%) post-treatment samples containing the H275Y mutation. The observation of signature mutations and distinct phylogenetic relationship in full-length sequences of haemagglutinin and neuraminidase genes derived from 2011 strains against 2009 strains indicates continued genetic evolution and antigenic drift of the influenza A(H1N1)pdm09 viruses circulating in Australia.


Assuntos
Antivirais/uso terapêutico , Surtos de Doenças , Farmacorresistência Viral , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Influenza Humana/genética , Oseltamivir/uso terapêutico , Adulto , Austrália/epidemiologia , Sequência de Bases , Infecções Comunitárias Adquiridas/epidemiologia , Vírus de DNA/efeitos dos fármacos , Vírus de DNA/genética , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/virologia , Masculino , Mutação/efeitos dos fármacos , Neuraminidase/genética , Reação em Cadeia da Polimerase , Prevalência , RNA Viral/análise , RNA Viral/genética , Análise de Sequência de DNA
9.
Environ Technol ; 33(7-9): 751-60, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22720398

RESUMO

The present work describes the biofiltration of mixture of n-propanol (as a model hydrophilic volatile organic compound (VOC)) and toluene (as a model hydrophobic VOC) in a biofilter packed with a compost-woodchip mixture. Initially, the biofilter was fed with toluene vapours at loadings up to 175 g m(-3) h(-1) and removal efficiencies of 70%-99% were observed. The biofilter performance when removing mixtures of toluene and n-propanol reached elimination capacities of up to 67g(toluene) m(-3) h(-1) and 85 g(n-propanol) m(-3) h(-1) with removal efficiencies of 70%-100% for toluene and essentially 100% for n-propanol. The presence of high n-propanol loading negatively affected the toluene removal; however, n-propanol removal was not affected by the presence of toluene and was effectively removed in the biofilter despite high toluene loadings. A model for toluene and n-propanol biofiltration could predict the cross-inhibition effect of n-propanol on toluene removal.


Assuntos
1-Propanol/química , Poluição do Ar/prevenção & controle , Tolueno/química , Compostos Orgânicos Voláteis/química , Gerenciamento de Resíduos/métodos , Poluentes Atmosféricos/química , Simulação por Computador , Filtração/métodos , Modelos Químicos
10.
Infection ; 39(6): 579-82, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21713429

RESUMO

We describe an unusual presentation of Q fever with associated haemophagocytic syndrome, confirmed by bone marrow aspirate, Q fever polymerase chain reaction (PCR) and serological testing. Clinical recovery was observed after the commencement of doxycycline with normalisation of the patient's full blood count and serum biochemistry. Serial monitoring of the Q fever serology revealed the subsequent development of sustained high phase 1 IgG antibodies, suggestive of chronic Q fever. Although many infectious aetiologies have been associated with haemophagocytosis, Q fever has only rarely been described in this context. The diagnosis of Q fever is often overlooked, especially when the presentation is atypical. We describe how the use of PCR testing significantly shortened the interval to definitive diagnosis and helped elucidate the underlying cause of the patient's haematological disorder.


Assuntos
Coxiella burnetii/isolamento & purificação , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/microbiologia , Febre Q/complicações , Febre Q/diagnóstico , Anticorpos Antibacterianos/sangue , Medula Óssea/patologia , Coxiella burnetii/genética , Coxiella burnetii/imunologia , Histocitoquímica , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Testes Sorológicos
12.
Science ; 276(5318): 1564-6, 1997 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-9171060

RESUMO

Self-incompatibility in Brassica refers to the rejection of self-related pollen and is mediated by a receptor protein kinase localized to the plasma membrane of the stigma epidermis in the flower. The recessive mutation mod eliminates self-incompatibility in the stigma. In mod mutants, self-compatibility was shown to be associated with the absence of transcripts encoded by an aquaporin-related gene. This observation suggests that a water channel is required for the self-incompatibility response of Brassica, which is consistent with the concept that regulation of water transfer from the stigma to pollen is a checkpoint in the early events of pollination in the crucifer family.


Assuntos
Brassica/fisiologia , Genes de Plantas , Canais Iônicos/fisiologia , Proteínas de Plantas/fisiologia , Sequência de Aminoácidos , Brassica/genética , Canais Iônicos/genética , Dados de Sequência Molecular , Proteínas de Plantas/genética , Pólen , Reprodução , Água/fisiologia
13.
Eur J Pharm Sci ; 35(3): 183-92, 2008 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-18652892

RESUMO

Self-nanoemulsifying granules (SNGs) were formulated with the objective of enhancing the bioavailability of the ezetimibe. Various modified oils, surfactant and cosurfactant mixtures were used and composition of self-nanoemulsifying system (SNS) was optimized. SNS diluted and resultant emulsion was characterized for mean globule size and stability. The self-nanoemulsifying systems were formulated into free flowing self-nanoemulsifying granules using varying proportions of hydrophilic colloidal silicon dioxide as an adsorbing agent. Self-nanoemulsifying granules were characterized by X-ray diffraction pattern, differential scanning calorimetry, dissolution profile and for in vivo performance in rats. X-ray diffraction studies indicated loss of crystallinity and/or solubilisation of ezetimibe in the self-nanoemulsifying granules. It was supported by SEM studies, which did not show evidence of precipitation of the drug on the surface of the carrier. Dissolution studies revealed remarkable increase in dissolution of the drug as compared to plain drug. In vivo evaluation in rats showed significant decrease in the total cholesterol levels as compared to positive control. The SNGs filled into hard gelatin capsules showed two to threefold increase in the dissolution rate as compared to plain drug filled capsules signifying its potential in improved delivery of lipophilic drugs.


Assuntos
Anticolesterolemiantes/farmacologia , Azetidinas/farmacologia , Emulsões , Hipercolesterolemia/tratamento farmacológico , Nanopartículas , Animais , Anticolesterolemiantes/química , Anticolesterolemiantes/farmacocinética , Azetidinas/química , Azetidinas/farmacocinética , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Cápsulas , Química Farmacêutica , Colesterol/sangue , Cristalografia por Raios X , Modelos Animais de Doenças , Ezetimiba , Concentração de Íons de Hidrogênio , Hipercolesterolemia/sangue , Masculino , Microscopia Eletrônica de Varredura , Óleos/química , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/química , Solubilidade , Tensoativos/química
14.
Immunol Lett ; 196: 1-10, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29329680

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha (TNF-a). The present study was designed to assess the serum cytokines [Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)] levels in chronic obstructive pulmonary disease (COPD) patients and they were correlated with severity of disease by spirometric measurements. MATERIALS AND METHODS: A total of 384 COPD patients and 50 healthy controls were enrolled in this study. The COPD patients were divided according to gold stages ie: mild, moderate, severe and very severe. 5 ml of venous blood samples were taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min. Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL-6. Spirometry was performed according to the criteria set by the Gold 2012 RESULTS: Tnf-α (pg/ml), IL-6 (pg/ml), IL-1ß (pg/ml) serum levels in COPD patients and healthy controls subjects were measured. Tnf-α and IL-6 serum levels were significantly (<0.001) higher in COPD patients compared to healthy control subjects. Likewise, IL-1 beta levels were also significantly (p-value = 0.022) higher in COPD patients compared to healthy control subjects. The distribution of Tnf-α, IL-6, IL-1ß (pg/ml) serum levels in COPD patients in relation to GOLD grading. There was a significant (p < 0.001) difference in the level of TNF-α, IL-6 and IL-1ß (pg/ml) among the severity of COPD. The posthoc analysis revealed that the TNF-α was significantly (p < 0.05) higher among the than mild, moderate, severe and very severe COPD patients. A similar observation was also found for IL-6. However, IL-6 was significantly (p < 0.05) higher among mild, moderate, severe and very severe COPD patients. There was significant (p = < 0.0001) difference in the level of IL-1ß in the different severity of COPD. The posthoc comparison test showed that IL-1ß levels were significantly (p < 0.05) higher among the mild, moderate, severe and very severe COPD patients. CONCLUSION: The present study signifies that the levels of TNF-α, IL-1ß, and IL-6 are directly proportional to the post-bronchodilator FEV1 percentage. Results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Fator de Necrose Tumoral alfa/sangue
15.
Sci Rep ; 8(1): 16193, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385827

RESUMO

Falcipains are major haemoglobinases of Plasmodium falciparum required for parasite growth and development. They consist of pro- and mature domains that interact via 'hot-spot' interactions and maintain the structural integrity of enzyme in zymogen state. Upon sensing the acidic environment, these interactions dissociate and active enzyme is released. For inhibiting falcipains, several active site inhibitors exist, however, compounds that target via allosteric mechanism remains uncharacterized. Therefore, we designed and synthesized six azapeptide compounds, among which, NA-01 & NA-03 arrested parasite growth by specifically blocking the auto-processing of falcipains. Inhibitors showed high affinity for enzymes in presence of the prodomain without affecting the secondary structure. Binding of NA-03 at the interface induced rigidity in the prodomain preventing structural reorganization. We further reported a histidine-dependent activation of falcipain. Collectively, for the first time we provide a framework for blocking the allosteric site of crucial haemoglobinases of the human malaria parasite. Targeting the allosteric site could provide high selectivity and less vulnerable to drug resistance.


Assuntos
Cisteína Endopeptidases/efeitos dos fármacos , Cisteína Proteases/efeitos dos fármacos , Malária/tratamento farmacológico , Peptídeos/farmacologia , Plasmodium falciparum/enzimologia , Sítio Alostérico/efeitos dos fármacos , Sequência de Aminoácidos/genética , Animais , Cisteína Endopeptidases/química , Cisteína Proteases/química , Cisteína Proteases/genética , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Precursores Enzimáticos/química , Precursores Enzimáticos/genética , Humanos , Malária/enzimologia , Malária/parasitologia , Peptídeos/síntese química , Peptídeos/química , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/patogenicidade , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estrutura Secundária de Proteína
16.
Curr Top Med Chem ; 17(19): 2221-2232, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28137230

RESUMO

INTRODUCTION: Mosquito borne diseases continue to propagate and cause millions of deaths annually. They are caused either by protozoan parasites such as Plasmodium, Toxoplasma or by flaviviruses including Dengue and Zika. Among the proteome of such parasitic organisms, proteases play essential roles in events such as host invasion, hemoglobin hydrolysis, replication and immune evasion. Plasmepsin V (PMV), an endoplasmic reticulum resident aspartic protease of Plasmodium spp., is involved in the export of ~400 proteins containing the conserved Plasmodium Export Element motif (PEXEL). Interactions and cleavage of PEXEL proteins by PM V is necessary for export to and across the parasitophorous vacuole membrane. Protease System: Similarly in flaviviruses, a two-component protease system consisting of nonstructural proteins, NS2B and NS3, interacts with other non-structural proteins and plays a major role in viral replication, polyprotein cleavage and virion particle assembly. Thus, proteases involved in indispensable roles in pathogen machinery can be considered as attractive drug targets. Inhibitors against proteases are being used in clinical trials for other communicable and non-communicable diseases. Currently, hydroxyethylamine based inhibitors targeting the catalytic site of PM V with picomolar inhibitory concentrations have been tested in vitro. CONCLUSION: For recently characterized disease such as Zika, no known treatments exist while compound such as Policresulen has high affinity for Dengue NS2B/NS3 complex. Understanding proteases structure-function relationship and protease-inhibitor interactions can provide new insights for novel chemotherapeutic strategies.


Assuntos
Desenho de Fármacos , Mosquitos Vetores , Peptídeo Hidrolases/metabolismo , Animais , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/enzimologia , Plasmodium/efeitos dos fármacos , Plasmodium/enzimologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Zika virus/efeitos dos fármacos , Zika virus/enzimologia
17.
Cancer Res ; 45(2): 608-15, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2981610

RESUMO

The cytochrome P-450 in hepatic microsomes prepared from rats pretreated with hematoporphyrin derivative was shown to be rapidly destroyed in the presence of long-wave ultraviolet light. The photocatalytic destruction of the heme-protein was dependent on both the dose of ultraviolet light and of hematoporphyrin derivative administered to the animals. The destructive reaction was accompanied by increased formation of cytochrome P-420, loss of microsomal heme content, and diminished catalytic activity of cytochrome P-450-dependent monooxygenases such as aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase. The specificity of the effect on cytochrome P-450 was confirmed by the observation that other heme-containing moieties such as myoglobin and cytochrome c were not susceptible to photocatalytic destruction. The destruction of cytochrome P-450 was a photodynamic process requiring oxygen since quenchers of singlet oxygen, including 2,5-dimethylfuran, histidine, and beta-carotene, each substantially diminished the reaction. Scavengers of superoxide anion such as superoxide dismutase and of H2O2 such as catalase did not protect against photodestruction of cytochrome P-450, whereas inhibitors of the hydroxyl radical, including benzoate, mannitol, and ethyl alcohol, did afford protection. These results indicate that lipid-rich microsomal membranes and the heme-protein cytochrome P-450 embedded therein are potential targets of injury in cells exposed to hematoporphyrin derivative photosensitization.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hematoporfirinas/farmacologia , Microssomos Hepáticos/enzimologia , Fotólise , Radiossensibilizantes/farmacologia , Animais , Grupo dos Citocromos c/metabolismo , Derivado da Hematoporfirina , Heme/metabolismo , Hemina/metabolismo , Peróxido de Hidrogênio/farmacologia , Hidróxidos/farmacologia , Radical Hidroxila , Masculino , Mioglobina/metabolismo , Oxigênio/metabolismo , Oxigenases/metabolismo , Ratos , Ratos Endogâmicos , Superóxidos/farmacologia , Raios Ultravioleta
18.
Cancer Res ; 45(7): 2951-6, 1985 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-4039974

RESUMO

The effect of ellagic acid, a naturally occurring plant phenol, on the binding to DNA and metabolism of benzo(a)pyrene (BP) and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-DHD) in cultured explants of strain A mouse lung was investigated. The explants were cultured in a rocking organ culture chamber for 16 h in the presence or absence of 10, 25, 50, and 100 microM ellagic acid. These concentrations of ellagic acid were nontoxic as determined by biochemical and histological methods. The ellagic acid was then removed from the cultures, and the explants were incubated with either 1 microM [3H]BP or [3H]BP 7,8-DHD for 24 h. Explant DNA was isolated using hydroxylapatite chromatography, and the BP metabolites in the medium were analyzed by high-pressure liquid chromatography. Ellagic acid (50 microM) inhibited the binding of BP and BP 7,8-DHD to lung DNA by 46 to 50% and 60 to 70%, respectively. High-pressure liquid chromatography analysis showed that ellagic acid (100 microM) inhibited the metabolism of BP by 20 to 40% and of BP 7,8-DHD by 20%, as indicated by the increased amounts of unmetabolized substrates and decreased amounts of metabolites in the medium. The major BP:DNA adduct in the explants was 7R-N2-[10 beta-[7 beta, 8 beta, 9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene]yl: deoxyguanosine, and its formation was reduced by 60 to 65% in the presence of 100 microM ellagic acid. These data suggest that the reduction of BP and BP 7,8-DHD metabolite binding to DNA by ellagic acid may have been due to inhibition of the formation and/or removal of BP 7,8-diol-9,10-epoxide prior to its binding to DNA.


Assuntos
Benzo(a)pireno/metabolismo , Benzopiranos/farmacologia , Benzopirenos/metabolismo , DNA/metabolismo , Di-Hidroxi-Di-Hidrobenzopirenos , Ácido Elágico/farmacologia , Pulmão/metabolismo , Animais , Pulmão/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos
19.
Saudi J Anaesth ; 10(1): 29-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26955307

RESUMO

CONTEXT: Head down tilt is given to patients after sub arachnoid block for adjustment of height of block. However, the amount of tilt given is subjective and cannot be documented. AIMS: We used an android application named "clinometer" to measure exact degree of tilt given by anesthesiologists as their routine practice. SETTINGS AND DESIGN: This observational study, at a medical college hospital, was done in 130 patients given sub arachnoid block for lower abdominal surgeries. MATERIALS AND METHODS: We observed and documented vital data of patients and measured tilt given by application "clinometer." RESULTS: We observed that the application was easy to use and measured tilt each time. The result obtained can be documented, digitally saved and transferred. In 130 patients studied, we observed incidence of degree of tilt as follows: 6-8° tilt in 38 patients (29.23%), 8-10 in 36 patients (27.69%), 10-12 in 30 patients (23.08%), 12-14 in 12 patients (9.23%) and 14-16° tilt in 14 patients (10.77%). Use of application was received with enthusiasm by practicing anesthesiologists. Various possible uses of this application are discussed.

20.
J Cytol ; 33(4): 210-213, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28028336

RESUMO

BACKGROUND: Lung cancer is the leading cause of death in developed countries and is increasing at alarming rates in developing countries. Cytological techniques such as bronchoalveolar lavage (BAL), bronchial brushing (BB), and fine needle aspiration cytology (FNAC) can aid in the early diagnosis of lung malignancies. MATERIALS AND METHODS: A total of 67 cases, suspected of lung cancer between January 2010 and December 2012, were selected where samples of BAL, BB, FNAC, as well as biopsy were obtained and processed according to the standard procedures of cytology and histology. The aim of this study was to compare the diagnostic efficacy of the three modalities, i.e., BAL, BB, and FNAC in diagnosing malignant neoplasms of the lung. Biopsy was considered to be the gold standard diagnostic test. RESULTS: Sensitivity of BAL, BB, and FNAC was found to be 47.61, 65.07, and 88.88%, respectively, whereas specificity of BAL, BB, and FNAC was 75, 75, and 100%, respectively. CONCLUSIONS: FNAC is the best technique among the three for the diagnosis of lung cancers.

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