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1.
Phys Rev E ; 106(2-2): 025205, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36109929

RESUMO

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

2.
Osteoarthritis Cartilage ; 29(8): 1181-1192, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33915295

RESUMO

OBJECTIVE: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA). DESIGN: Three-month-old inducible biglycan (BgniKO) and decorin/biglycan compound (Dcn/BgniKO) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (DcniKO) knockout mice. RESULTS: In the DMM model, BgniKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in DcniKO mice (1.38 [0.91 1.85] difference). Dcn/BgniKO mice exhibited similar histological OA phenotype as DcniKO mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/BgniKO mice showed further cartilage thinning than DcniKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. BgniKO and Dcn/BgniKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while DcniKO and control mice did not. CONCLUSION: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.


Assuntos
Biglicano/deficiência , Decorina/deficiência , Progressão da Doença , Osteoartrite/patologia , Animais , Biglicano/genética , Osso Esponjoso/patologia , Cartilagem Articular , Decorina/genética , Modelos Animais de Doenças , Meniscos Tibiais/patologia , Camundongos Knockout , Ossificação Heterotópica/patologia , Osteoartrite/genética , Osteófito/patologia , Lesões do Menisco Tibial/patologia
3.
Sci Rep ; 11(1): 33, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420108

RESUMO

Perovskite solar cells (PSCs) expressed great potentials for offering a feasible alternative to conventional photovoltaic technologies. 2D/3D hybrid PSCs, where a 2D capping layer is used over the 3D film to avoid the instability issues associated with perovskite film, have been reported with improved stabilities and high power conversion efficiencies (PCE). However, the profound analysis of the PSCs with prolonged operational lifetime still needs to be described further. Heading towards efficient and long-life PSCs, in-depth insight into the complicated degradation processes and charge dynamics occurring at PSCs' interfaces is vital. In particular, the Au/HTM/perovskite interface got a substantial consideration due to the quest for better charge transfer; and this interface is debatably the trickiest to explain and analyze. In this study, multiple characterization techniques were put together to understand thoroughly the processes that occur at the Au/HTM/perovskite interface. Inquest analysis using current-voltage (I-V), electric field induced second harmonic generation (EFISHG), and impedance spectroscopy (IS) was performed. These techniques showed that the degradation at the Au/HTM/perovskite interface significantly contribute to the increase of charge accumulation and change in impedance value of the PSCs, hence resulting in efficiency fading. The 3D and 2D/3D hybrid cells, with PCEs of 18.87% and 20.21%, respectively, were used in this study, and the analysis was performed over the aging time of 5000 h. Our findings propose that the Au/HTM/perovskite interface engineering is exclusively essential for attaining a reliable performance of the PSCs and provides a new perspective towards the stability enhancement for the perovskite-based future emerging photovoltaic technology.

4.
J Hosp Infect ; 106(3): 594-599, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866631

RESUMO

BACKGROUND: Scabies is a contagious dermatosis. The risk factors for its transmission remain unclear. A scabies outbreak, involving patients who were receiving chemotherapy for haematological malignancies, occurred at our hospital. METHODS: The outbreak population was analysed to determine whether the incidence of scabies was higher among contact patients receiving chemotherapy for haematological malignancies. RESULTS: A patient with crusted scabies was the index case, and 18 of 78 contact healthcare workers (HCWs) and 22 of 135 contact patients were diagnosed with classical scabies. Ten of 17 contact patients with haematological malignancies and 12 of 118 contact patients with other diseases were infected with scabies. The incidence rate was significantly higher among the patients with haematological malignancies (P<0.001). The patients with haematological malignancies had a significantly lower mean minimum neutrophil count than those with other diseases (1159/µL vs 3761/µL, P=0.0012). Most haematological patients did not require special nursing assistance, suggesting that the higher incidence of scabies among these patients resulted from their immunodeficiency rather than greater skin-to-skin contact with infected HCWs. CONCLUSION: Our study suggests that patients receiving chemotherapy for haematological malignancies are more susceptible to scabies than patients with other diseases, and require stricter protection.


Assuntos
Suscetibilidade a Doenças/induzido quimicamente , Tratamento Farmacológico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Escabiose/etiologia , Idoso , Idoso de 80 Anos ou mais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Suscetibilidade a Doenças/parasitologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Pessoal de Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Humanos , Controle de Infecções/métodos , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Escabiose/epidemiologia , Escabiose/transmissão
5.
Lupus ; 27(10): 1661-1669, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30028259

RESUMO

This study was performed to investigate the clinical characteristics of lupus enteritis in Japanese patients with systemic lupus erythematosus (SLE). A total of 481 patients with SLE admitted to our hospital between 2001 and 2015 were retrospectively reviewed. Diagnosis of lupus enteritis was based on the following three criteria: (1) abdominal symptoms, (2) diffuse long-segment bowel thickening and (3) a requirement for glucocorticoid therapy. Lupus enteritis was identified in 17 patients (3.5%) and there were two distinct types: small intestine-dominant and large intestine-dominant. Significant differences between the two types were noted with respect to the age, frequency of biopsy-proven lupus nephritis, frequency of rectal involvement, maximum bowel wall thickness, and requirement for steroid pulse therapy. Among patients with large intestine-dominant lupus enteritis, 60% had extra-intestinal symptoms (hydroureter, bladder wall thickening, and bile duct dilatation) that are known complications of intestinal pseudo-obstruction. Two patients with large intestine-dominant lupus enteritis developed intestinal pseudo-obstruction either before or after diagnosis of lupus enteritis. Five patients (29%) developed recurrence during a median observation period of 7.2 years (1.4-14.4 years). In conclusion, large intestine-dominant lupus enteritis resembles intestinal pseudo-obstruction and these two diseases may have a common pathogenesis.


Assuntos
Enterite/diagnóstico , Pseudo-Obstrução Intestinal/diagnóstico , Intestino Grosso/patologia , Intestino Delgado/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Povo Asiático , Biópsia , Enterite/tratamento farmacológico , Enterite/epidemiologia , Enterite/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Incidência , Pseudo-Obstrução Intestinal/tratamento farmacológico , Pseudo-Obstrução Intestinal/epidemiologia , Pseudo-Obstrução Intestinal/patologia , Intestino Grosso/diagnóstico por imagem , Intestino Grosso/efeitos dos fármacos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/efeitos dos fármacos , Japão/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
6.
AIDS Care ; 30(11): 1356-1359, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29920118

RESUMO

Transwomen of color are disproportionately impacted by HIV and may have worse health outcomes than other populations. This analysis was conducted to examine structural factors associated with poor health outcomes among transwomen of color living with HIV in the San Francisco Bay Area (N = 159). Univariate and multivariable analyses were conducted to determine if structural factors were associated with poor HIV-related health outcomes. A majority of participants were Black or African American (110/159, 69.2%), 32 (20.1%) identified their primary race/ethnicity as Hispanic or Latino/a or Spanish, and 17 (10.7%) identified as another race/ethnicity. Transwomen of color in our sample faced extreme structural barriers, including residential transience, extreme low income, high prevalence of running out of money in the last six months, high rates of food insecurity, high prevalence of income via entitlement programs, engagement in sex work and other illicit activities for income. Unstable housing was the structural factor most consistently associated with poor health outcomes along the HIV care continuum and may explain engagement in other sources of income generation. Interventions are needed that go beyond the individual and health care-level to address needs for housing and economic opportunities to improve HIV care outcomes among transwomen of color living with HIV in the San Francisco Bay Area.


Assuntos
Negro ou Afro-Americano , Continuidade da Assistência ao Paciente , Infecções por HIV/epidemiologia , Hispânico ou Latino , Habitação , Renda , Pessoas Transgênero , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Pobreza , Prevalência , São Francisco/epidemiologia , Trabalho Sexual
7.
Clin Transl Sci ; 10(5): 360-365, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28625018

RESUMO

Use of agents to suppress gastric acid secretion is common among patients with hepatitis C virus (HCV) infection. The aims of this open-label, three-period, fixed-sequence study were to evaluate the effect of famotidine and pantoprazole on the pharmacokinetics and safety of elbasvir/grazoprevir fixed-dose combination (FDC) in 16 healthy subjects. Elbasvir and grazoprevir each exhibited similar pharmacokinetics following single-dose administration of elbasvir/grazoprevir with or without famotidine or pantoprazole. Geometric mean ratios (GMRs) of grazoprevir AUC(0,∞), Cmax , and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 0.89-1.17. Similarly, GMRs of elbasvir AUC(0,∞), Cmax , and C24 (elbasvir/grazoprevir + famotidine or elbasvir/grazoprevir + pantoprazole vs. elbasvir/grazoprevir) ranged from 1.02-1.11. These results indicate that gastric acid-reducing agents do not modify the pharmacokinetics of elbasvir or grazoprevir in a clinically relevant manner and may be coadministered with elbasvir/grazoprevir in HCV-infected patients without restriction.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/farmacocinética , Antivirais/farmacocinética , Benzofuranos/farmacocinética , Famotidina/farmacocinética , Hepacivirus/efeitos dos fármacos , Imidazóis/farmacocinética , Quinoxalinas/farmacocinética , 2-Piridinilmetilsulfinilbenzimidazóis/efeitos adversos , 2-Piridinilmetilsulfinilbenzimidazóis/farmacologia , Adulto , Amidas , Antivirais/efeitos adversos , Antivirais/farmacologia , Benzofuranos/efeitos adversos , Benzofuranos/sangue , Benzofuranos/farmacologia , Carbamatos , Ciclopropanos , Demografia , Interações Medicamentosas , Famotidina/efeitos adversos , Famotidina/farmacologia , Feminino , Humanos , Imidazóis/efeitos adversos , Imidazóis/sangue , Imidazóis/farmacologia , Masculino , Pessoa de Meia-Idade , Pantoprazol , Quinoxalinas/efeitos adversos , Quinoxalinas/sangue , Quinoxalinas/farmacologia , Sulfonamidas , Fatores de Tempo , Adulto Jovem
8.
Osteoarthritis Cartilage ; 25(1): 108-117, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27568574

RESUMO

OBJECTIVE: This study aims to demonstrate that cartilage nanoindentation modulus is a highly sensitive indicator of the onset and spatiotemporal progression of post-traumatic osteoarthritis (PTOA) in murine models. DESIGN: Destabilization of the medial meniscus (DMM) surgery was performed on the right knees of 12-week old male, wild-type C57BL/6 mice, with Sham control on contralateral left knees. Atomic force microscopy (AFM)-based nanoindentation was applied to quantify the nanoindentation modulus, Eind, of femoral condyle cartilage at 3 days to 12 weeks after surgery. The modulus changes were compared against the timeline of histological OA signs. Meanwhile, at 8 weeks after surgery, changes in meniscus, synovium and subchondral bone were evaluated to reveal the spatial progression of PTOA. RESULTS: The modulus of medial condyle cartilage was significantly reduced at 1 week after DMM, preceding the histological OA signs, which only became detectable at 4-8 weeks after. This reduction is likely due to concomitantly elevated proteolytic activities, as blocking enzymatic activities in mice can attenuate this modulus reduction. In later OA, lateral condyle cartilage and medial meniscus also started to be weakened, illustrating the whole-organ nature of PTOA. CONCLUSIONS: This study underscores the high sensitivity of nanoindentation in examining the initiation, attenuation and progression of PTOA in murine models. Meanwhile, modulus changes highlight concomitant changes in lateral cartilage and meniscus during the advancement of OA.


Assuntos
Menisco/lesões , Osteoartrite/etiologia , Animais , Modelos Animais de Doenças , Membro Posterior , Articulações/patologia , Masculino , Menisco/patologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite/patologia
9.
Langmuir ; 31(38): 10426-34, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26348460

RESUMO

The Langmuir-Blodgett method has always been traditionally utilized in the deposition of two-dimensional structures. In this work, however, we employed the method to deposit three-dimensional reduced graphene oxide layers using an unconventional protocol for the first time. This was achieved by carrying out the dipping process after the collapse pressure or breaking point, which results in the formation of a highly porous three-dimensional surface topography. By varying the number of deposition layers, the porosity could be optimized from nanometer to micrometer dimensions. Employed as bioelectrodes, these three-dimensional reduced graphene oxide layers may allow improved adhesion and biocompatibility compared to the conventional two-dimensional surfaces. A larger number of pores also improves the mass transport of materials and therefore increases the charge-sustaining capacity and sensitivity. This could ultimately improve the performance of biofuel cells and other electrode-based systems.


Assuntos
Grafite/química , Óxidos/química , Oxirredução , Tamanho da Partícula , Porosidade , Propriedades de Superfície
10.
Epidemiol Infect ; 143(2): 267-73, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24731294

RESUMO

US public health laboratories began reporting Escherichia coli O157 isolates to CDC in 1996. We describe temporal and geographical patterns of isolates reported from 1996 to 2011 and demographics of persons whose specimens yielded isolates. We calculated annual E. coli O157 isolation rates/100 000 persons by patient's state of residence, county of residence, age, and sex using census data. The average annual isolation rate was 0·84. The average isolation rate in northern states (1·52) was higher than in southern states (0·43). Counties with ⩾76% rural population had a lower isolation rate (0·67) than counties with ⩽25%, 26-50%, and 51-75% rural populations (0·81, 0·92, and 0·81, respectively). The highest isolation rate (3·19) was in children aged 1-4 years. Infections were seasonal with 49% of isolates collected during July to September. Research into reasons for higher incidence in northern states and for seasonality could guide strategies to prevent illnesses.


Assuntos
Infecções por Escherichia coli/epidemiologia , Escherichia coli O157 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estações do Ano , Estados Unidos/epidemiologia , Adulto Jovem
11.
Free Radic Res ; 48(12): 1409-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25179439

RESUMO

We here described the antioxidant effects of carnitine supplementation on 14-3-3 protein isoforms in the aged rat hippocampus detected using the fully automated two-dimensional chip gel electrophoresis system (Auto2D). This system was easy and convenient to use, and the resolution obtained was more sensitive and higher than that of conventional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). We separated and identified five isoforms of the 14-3-3 protein (beta/alpha, gamma, epsilon, zeta/delta, and eta) using the Auto2D system. We then examined the antioxidant effects of carnitine supplementation on the protein profiles of the cytosolic fraction in the aged rat hippocampus, demonstrating that carnitine supplementation suppressed the oxidation of methionine residues in these isoforms. Since methionine residues are easily oxidized to methionine sulfoxide, the convenient and high-resolution 2-D PAGE system can be available to analyze methionine oxidation avoiding artifactual oxidation. We showed here that the Auto2D system was a very useful tool for studying antioxidant effects through proteomic analysis of protein oxidation.


Assuntos
Proteínas 14-3-3/metabolismo , Envelhecimento , Antioxidantes/farmacologia , Carnitina/farmacologia , Hipocampo/metabolismo , Proteínas 14-3-3/química , Animais , Automação , Eletroforese em Gel Bidimensional , Masculino , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteômica , Ratos , Ratos Endogâmicos F344
12.
Epidemiol Infect ; 142(4): 878-81, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23842472

RESUMO

Vibrio vulnificus (Vv) can result in severe disease. Although pre-existing liver disease is a recognized risk factor for serious infection, the relative importance of other comorbidities has not been fully assessed. We analysed reports of Vv infections submitted to CDC from January 1988 to September 2006 in order to assess the role of pre-existing conditions contributing to severe outcomes. A total of 1212 patients with Vv infection were reported. Only patients with liver disease [adjusted odds ratio (aOR) 5.1)] were more likely to become septic when exposure was due to contaminated food. Patients with liver disease (aOR 4.1), a haematological disease (aOR 3.2), or malignancy (aOR 3.2) were more likely to become septic when infection was acquired via a non-foodborne exposure. As such, patients with these pre-existing medical conditions should be advised of the risk of life-threatening illness after eating undercooked contaminated seafood or exposing broken skin to warm seawater.


Assuntos
Sepse/complicações , Sepse/epidemiologia , Vibrioses/complicações , Vibrioses/epidemiologia , Comorbidade , Feminino , Humanos , Hepatopatias/complicações , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Vibrio vulnificus
13.
Osteoporos Int ; 25(2): 485-95, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23794043

RESUMO

UNLABELLED: A 3-year follow-up study on 334 young Japanese females enrolled in a university at the age of 18 years revealed that discontinuation of leisure time impact-loading exercises performed in junior high and/or high school was associated with increased risk of reduction in calcaneus osteo-sono assessment index (OSI). INTRODUCTION: Bone strength rapidly increases during puberty and reaches its peak by the end of adolescence. The aim of this study was to determine the lifestyle factors that influence the maintenance of calcaneus OSI in young adult females around the time when peak bone mass is attained. METHODS: Annual health checkups including OSI measurements, anthropometrics, lifestyle analysis, and blood examination were performed 4 times on 334 Japanese females enrolled in a university at the age of 18 years. According to the slope of OSI change during the 3-year follow-up, the subjects were grouped into two categories: OSI loss (the lowest tertile) and OSI gain/stable (the second and third tertiles). RESULTS: At the baseline assessment, the OSI loss group had higher OSI and height and an earlier menarche age than the OSI gain/stable group. Performing leisure time impact-loading exercise in junior high and/or high school but discontinuing it at university was associated with increased risk of OSI loss, independent of OSI, height and weight at the age of 18 years, weight change during follow-up, age of menarche, energy-adjusted nutrient intake, and alcohol drinking; the odds ratios were 4.1-4.9 compared with those performing impact-loading exercise at university. In particular, duration, frequency, and subjective intensity of impact-loading exercise during high school were positively associated with OSI loss. CONCLUSION: Discontinuation of leisure time impact-loading exercises performed during late adolescence is associated with an increased risk of OSI loss in young adult females during the 3-year follow-up period.


Assuntos
Densidade Óssea/fisiologia , Calcâneo/fisiologia , Exercício Físico/fisiologia , Adolescente , Envelhecimento/fisiologia , Antropometria/métodos , Calcâneo/diagnóstico por imagem , Dieta/estatística & dados numéricos , Escolaridade , Comportamento Alimentar , Feminino , Seguimentos , Humanos , Atividades de Lazer , Estilo de Vida , Atividade Motora/fisiologia , Ultrassonografia , Adulto Jovem
14.
J Med Virol ; 85(10): 1852-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23861138

RESUMO

Human respiratory syncytial virus (HRSV) is an important cause of respiratory disease. The majority of studies addressing the importance of virus co-infections to the HRSV-disease have been based on the detection of HRSV by RT-PCR, which may not distinguish current replication from prolonged shedding of remnant RNA from previous HRSV infections. To assess whether co-detections of other common respiratory viruses are associated with increased severity of HRSV illnesses from patients who were shedding viable-HRSV, nasopharyngeal aspirates from children younger than 5 years who sought medical care for respiratory infections in Ribeirão Preto (Brazil) were tested for HRSV by immunofluorescence, RT-PCR and virus isolation in cell culture. All samples with viable-HRSV were tested further by PCR for other respiratory viruses. HRSV-disease severity was assessed by a clinical score scale. A total of 266 samples from 247 children were collected and 111 (42%) were HRSV-positive. HRSV was isolated from 70 (63%), and 52 (74%) of them were positive for at least one additional virus. HRSV-positive diseases were more severe than HRSV-negative ones, but there was no difference in disease severity between patients with viable-HRSV and those HRSV-positives by RT-PCR. Co-detection of other viruses did not correlate with increased disease severity. HRSV isolation in cell culture does not seem to be superior to RT-PCR to distinguish infections associated with HRSV replication in studies of clinical impact of HRSV. A high rate of co-detection of other respiratory viruses was found in samples with viable-HRSV, but this was not associated with more severe HRSV infection.


Assuntos
Coinfecção/virologia , Vírus de RNA/isolamento & purificação , Infecções Respiratórias/virologia , Viroses/virologia , Brasil , Pré-Escolar , Coinfecção/patologia , Feminino , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringe/virologia , Infecções Respiratórias/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Índice de Gravidade de Doença , Cultura de Vírus , Viroses/patologia
16.
Clin Pharmacol Ther ; 92(1): 96-102, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22669291

RESUMO

MK-7246, an antagonist of the chemoattractant receptor on T helper type 2 (Th2) cells, is being developed for the treatment of respiratory diseases. In a first-in-human study, we investigated whether genetic polymorphisms contributed to the marked intersubject variability in the pharmacokinetics of MK-7246 and its glucuronide metabolite M3. Results from in vitro enzyme kinetic studies suggested that UGT2B17 is probably the major enzyme responsible for MK-7246 metabolism in both the liver and the intestine. As compared with those with the UGT2B17*1/*1 wild-type genotype, UGT2B17*2/*2 carriers, who possess no UGT2B17 protein, had 25- and 82-fold greater mean dose-normalized values of area under the plasma concentration-time curve (AUC) and peak concentration of MK-7246, respectively, and a 24-fold lower M3-to-MK-7246 AUC ratio. The apparent half-life of MK-7246 was not as variable between these two genotypes. Therefore, the highly variable pharmacokinetics of MK-7246 is attributable primarily to the impact of UGT2B17 genetic polymorphisms and extensive first-pass metabolism of MK-7246.


Assuntos
Carbolinas/farmacocinética , Glucuronosiltransferase/genética , Administração Oral , Adulto , Área Sob a Curva , Método Duplo-Cego , Monitoramento de Medicamentos , Genótipo , Glucuronídeos/metabolismo , Meia-Vida , Humanos , Masculino , Antígenos de Histocompatibilidade Menor , Farmacogenética/métodos , Polimorfismo Genético , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores
17.
Theriogenology ; 78(1): 225-31, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22460153

RESUMO

In livestock, parthenogenic embryos are simple to produce, but androgenetic embryos have been successfully produced only in sheep and cows. In the present study, matured porcine oocytes were enucleated by micromanipulation and then fertilized with sperm in vitro, thereby producing porcine androgenetic embryos. Porcine androgenetic embryos, which had only sperm genomes, were assessed for cleavage and for blastocyst formation 2 and 6 d after IVF, respectively. There was no difference in cleavage rate between androgenetic embryos and biparental IVF embryos (mean ± SD androgenetic: 65.5 ± 5.4%; biparental IVF: 63.2 ± 3.6%), but there was a difference in the rate of blastocyst formation (androgenetic: 4.5 ± 0.7%; biparental IVF: 30.2 ± 2.6%, P < 0.05). The average number of cells in Day 6 androgenetic blastocysts (34.3 ± 18.2) was lower (P < 0.05) than that in biparental IVF blastocysts (44.1 ± 19.5), but did not differ from that in parthenogenetic embryos (35.7 ± 16.7). The androgenetic embryos were transferred into recipient mothers to examine the competence of post-implantation development. Androgenetic fetuses were present on Days 21 and 25, but not on Days 28, 31, or 35. Of the six androgenetic fetuses recovered on Day 21, five had normal, translucent bodies, and two of these five had beating hearts. The four fetuses recovered on Day 25 were all non-viable. In conclusion, porcine androgenetic embryos initiated embryogenesis and had reached a viable fetal stage 21 days after IVF.


Assuntos
Desenvolvimento Embrionário/fisiologia , Fertilização in vitro/métodos , Técnicas de Transferência Nuclear , Partenogênese/fisiologia , Suínos , Animais , Núcleo Celular/fisiologia , Transferência Embrionária/métodos , Transferência Embrionária/veterinária , Feminino , Fertilização in vitro/veterinária , Feto/fisiologia , Idade Gestacional , Haploidia , Masculino , Oócitos/citologia , Gravidez , Espermatozoides/fisiologia , Suínos/embriologia , Suínos/fisiologia , Cromossomo Y
18.
Theriogenology ; 76(4): 598-606, 2011 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-21652062

RESUMO

The objective was to produce porcine tetraploid parthenogenetic embryos using cytochalasin B, which inhibits polar body extrusion. Porcine cumulus-enclosed oocytes aspirated from antral follicles were cultured for 51 h, and treated with cytochalasin B from 35 h to 42 h after the start of culture. After maturation culture, 74.7% (2074/2775) of oocytes treated with cytochalasin B did not extrude a polar body (0PB oocytes). In contrast, 80.4% (1931/2403) of control oocytes extruded a polar body (1PB oocytes). The 0PB oocytes were electrically stimulated, treated with cytochalasin B again for 3 h, and then cultured without cytochalasin B. Six days after electrical stimulation, 49.8% (321/644) reached the blastocyst stage. The number of cells in these blastocysts derived from 0PB oocytes was significantly lower than that from 1PB oocytes (0PB: 24.9 ± 10.6; 1PB: 43.0 ± 17.1; mean ± SD). A porcine chromosome 1-specific sequence was detected in parthenogenetic 0PB embryos by fluorescence in situ hybridization (FISH) analysis. Typical pronucleus-stage samples derived from 0PB embryos had two pronuclei, each with two signals. In two-cell and blastocyst-stage embryos, four signals were detected in each nucleus derived from 0PB embryos. We inferred that 0PB oocytes, which had a tetraploid number of chromosomes, started to develop as tetraploid parthenotes after electrical stimulation, and that tetraploid status was stably maintained during early embryonic development, at least until the blastocyst stage.


Assuntos
Citocalasina B/farmacologia , Técnicas de Cultura Embrionária/veterinária , Oócitos/fisiologia , Partenogênese/fisiologia , Suínos/fisiologia , Tetraploidia , Animais , Distribuição de Qui-Quadrado , Estimulação Elétrica/métodos , Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/fisiologia , Feminino , Hibridização in Situ Fluorescente/veterinária , Meiose/fisiologia , Oócitos/citologia , Gravidez , Suínos/embriologia , Suínos/genética
20.
Biomacromolecules ; 12(3): 540-7, 2011 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-21218766

RESUMO

The present work describes electrophoretic fabrication of nanostructured chitosan-zirconium-oxide composite (CHIT-NanoZrO(2)) film (180 nm) onto indium-tin-oxide (ITO)-coated glass plate. This nanobiocomposite film has been explored as immobilization platform for probe DNA specific to M. Tuberculosis as model biomolecule to investigate its sensing characteristics. It is revealed that pH-responsive behavior of CHIT and its cationic skeleton is responsible for the movement of CHIT-NanoZrO(2) colloids toward cathode during electrophoretic deposition. The FT-IR, SEM, TEM, and EDX techniques have been employed for the structural, morphological, and composition analysis of the fabricated electrodes. The morphological studies clearly reveal uniform inter-linking and dispersion of hexagonal nanograins of ZrO(2) (30-50 nm) into the chitosan matrix, resulting in homogeneous nanobiocomposite formation. Electrochemical response measurements of DNA/CHIT-NanoZrO(2)/ITO bioelectrode, carried out using cyclic voltammetry and differential pulse voltammetry, reveal that this bioelectrode can specifically detect complementary target DNA up to 0.00078 µM with sensitivity of 6.38 × 10(-6) AµM(-1).


Assuntos
Quitosana/química , DNA Bacteriano/análise , Eletroforese/métodos , Nanocompostos/química , Ácidos Nucleicos/análise , Zircônio/química , Sondas de DNA , Mycobacterium tuberculosis/isolamento & purificação
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