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1.
Phys Rev E ; 106(2-2): 025205, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36109929

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-33915295

RESUMEN

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.


Asunto(s)
Biglicano/deficiencia , Decorina/deficiencia , Progresión de la Enfermedad , Osteoartritis/patología , Animales , Biglicano/genética , Hueso Esponjoso/patología , Cartílago Articular , Decorina/genética , Modelos Animales de Enfermedad , Meniscos Tibiales/patología , Ratones Noqueados , Osificación Heterotópica/patología , Osteoartritis/genética , Osteofito/patología , Lesiones de Menisco Tibial/patología
3.
Sci Rep ; 11(1): 33, 2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420108

RESUMEN

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.
Artículo en Inglés | MEDLINE | ID: mdl-32866631

RESUMEN

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.


Asunto(s)
Susceptibilidad a Enfermedades/inducido químicamente , Quimioterapia , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Escabiosis/etiología , Anciano , Anciano de 80 o más Años , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Susceptibilidad a Enfermedades/parasitología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Personal de Salud/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Humanos , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/estadística & datos numéricos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Escabiosis/epidemiología , Escabiosis/transmisión
5.
Lupus ; 27(10): 1661-1669, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30028259

RESUMEN

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.


Asunto(s)
Enteritis/diagnóstico , Seudoobstrucción Intestinal/diagnóstico , Intestino Grueso/patología , Intestino Delgado/patología , Lupus Eritematoso Sistémico/diagnóstico , Adolescente , Adulto , Pueblo Asiatico , Biopsia , Enteritis/tratamiento farmacológico , Enteritis/epidemiología , Enteritis/patología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Incidencia , Seudoobstrucción Intestinal/tratamiento farmacológico , Seudoobstrucción Intestinal/epidemiología , Seudoobstrucción Intestinal/patología , Intestino Grueso/diagnóstico por imagen , Intestino Grueso/efectos de los fármacos , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/efectos de los fármacos , Japón/epidemiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/patología , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto Joven
6.
AIDS Care ; 30(11): 1356-1359, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29920118

RESUMEN

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.


Asunto(s)
Negro o Afroamericano , Continuidad de la Atención al Paciente , Infecciones por VIH/epidemiología , Hispánicos o Latinos , Vivienda , Renta , Personas Transgénero , Adulto , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Pobreza , Prevalencia , San Francisco/epidemiología , Trabajo Sexual
7.
Clin Transl Sci ; 10(5): 360-365, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28625018

RESUMEN

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.


Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/farmacocinética , Antivirales/farmacocinética , Benzofuranos/farmacocinética , Famotidina/farmacocinética , Hepacivirus/efectos de los fármacos , Imidazoles/farmacocinética , Quinoxalinas/farmacocinética , 2-Piridinilmetilsulfinilbencimidazoles/efectos adversos , 2-Piridinilmetilsulfinilbencimidazoles/farmacología , Adulto , Amidas , Antivirales/efectos adversos , Antivirales/farmacología , Benzofuranos/efectos adversos , Benzofuranos/sangre , Benzofuranos/farmacología , Carbamatos , Ciclopropanos , Demografía , Interacciones Farmacológicas , Famotidina/efectos adversos , Famotidina/farmacología , Femenino , Humanos , Imidazoles/efectos adversos , Imidazoles/sangre , Imidazoles/farmacología , Masculino , Persona de Mediana Edad , Pantoprazol , Quinoxalinas/efectos adversos , Quinoxalinas/sangre , Quinoxalinas/farmacología , Sulfonamidas , Factores de Tiempo , Adulto Joven
8.
Osteoarthritis Cartilage ; 25(1): 108-117, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27568574

RESUMEN

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.


Asunto(s)
Menisco/lesiones , Osteoartritis/etiología , Animales , Modelos Animales de Enfermedad , Miembro Posterior , Articulaciones/patología , Masculino , Menisco/patología , Ratones , Ratones Endogámicos C57BL , Osteoartritis/patología
9.
Langmuir ; 31(38): 10426-34, 2015 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-26348460

RESUMEN

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.


Asunto(s)
Grafito/química , Óxidos/química , Oxidación-Reducción , Tamaño de la Partícula , Porosidad , Propiedades de Superficie
10.
Epidemiol Infect ; 143(2): 267-73, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24731294

RESUMEN

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.


Asunto(s)
Infecciones por Escherichia coli/epidemiología , Escherichia coli O157 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estaciones del Año , Estados Unidos/epidemiología , Adulto Joven
11.
Free Radic Res ; 48(12): 1409-16, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25179439

RESUMEN

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.


Asunto(s)
Proteínas 14-3-3/metabolismo , Envejecimiento , Antioxidantes/farmacología , Carnitina/farmacología , Hipocampo/metabolismo , Proteínas 14-3-3/química , Animales , Automatización , Electroforesis en Gel Bidimensional , Masculino , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Proteómica , Ratas , Ratas Endogámicas F344
12.
Osteoporos Int ; 25(2): 485-95, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23794043

RESUMEN

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.


Asunto(s)
Densidad Ósea/fisiología , Calcáneo/fisiología , Ejercicio Físico/fisiología , Adolescente , Envejecimiento/fisiología , Antropometría/métodos , Calcáneo/diagnóstico por imagen , Dieta/estadística & datos numéricos , Escolaridad , Conducta Alimentaria , Femenino , Estudios de Seguimiento , Humanos , Actividades Recreativas , Estilo de Vida , Actividad Motora/fisiología , Ultrasonografía , Adulto Joven
13.
Epidemiol Infect ; 142(4): 878-81, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23842472

RESUMEN

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.


Asunto(s)
Sepsis/complicaciones , Sepsis/epidemiología , Vibriosis/complicaciones , Vibriosis/epidemiología , Comorbilidad , Femenino , Humanos , Hepatopatías/complicaciones , Hepatopatías/epidemiología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Vibrio vulnificus
14.
J Med Virol ; 85(10): 1852-9, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23861138

RESUMEN

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.


Asunto(s)
Coinfección/virología , Virus ARN/aislamiento & purificación , Infecciones del Sistema Respiratorio/virología , Virosis/virología , Brasil , Preescolar , Coinfección/patología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Recién Nacido , Masculino , Nasofaringe/virología , Infecciones del Sistema Respiratorio/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Cultivo de Virus , Virosis/patología
16.
Clin Pharmacol Ther ; 92(1): 96-102, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22669291

RESUMEN

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.


Asunto(s)
Carbolinas/farmacocinética , Glucuronosiltransferasa/genética , Administración Oral , Adulto , Área Bajo la Curva , Método Doble Ciego , Monitoreo de Drogas , Genotipo , Glucurónidos/metabolismo , Semivida , Humanos , Masculino , Antígenos de Histocompatibilidad Menor , Farmacogenética/métodos , Polimorfismo Genético , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores
17.
Theriogenology ; 78(1): 225-31, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22460153

RESUMEN

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.


Asunto(s)
Desarrollo Embrionario/fisiología , Fertilización In Vitro/métodos , Técnicas de Transferencia Nuclear , Partenogénesis/fisiología , Porcinos , Animales , Núcleo Celular/fisiología , Transferencia de Embrión/métodos , Transferencia de Embrión/veterinaria , Femenino , Fertilización In Vitro/veterinaria , Feto/fisiología , Edad Gestacional , Haploidia , Masculino , Oocitos/citología , Embarazo , Espermatozoides/fisiología , Porcinos/embriología , Porcinos/fisiología , Cromosoma Y
18.
Theriogenology ; 76(4): 598-606, 2011 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-21652062

RESUMEN

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.


Asunto(s)
Citocalasina B/farmacología , Técnicas de Cultivo de Embriones/veterinaria , Oocitos/fisiología , Partenogénesis/fisiología , Porcinos/fisiología , Tetraploidía , Animales , Distribución de Chi-Cuadrado , Estimulación Eléctrica/métodos , Técnicas de Cultivo de Embriones/métodos , Desarrollo Embrionario/fisiología , Femenino , Hibridación Fluorescente in Situ/veterinaria , Meiosis/fisiología , Oocitos/citología , Embarazo , Porcinos/embriología , Porcinos/genética
20.
Biomacromolecules ; 12(3): 540-7, 2011 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-21218766

RESUMEN

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).


Asunto(s)
Quitosano/química , ADN Bacteriano/análisis , Electroforesis/métodos , Nanocompuestos/química , Ácidos Nucleicos/análisis , Circonio/química , Sondas de ADN , Mycobacterium tuberculosis/aislamiento & purificación
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