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BACKGROUND: Despite decades of use, the magnitude of efficacy of narrowband ultraviolet B (NB-UVB) phototherapy for atopic dermatitis (AD) beyond industry-sponsored trials remains unclear. AIM: To evaluate the clinical efficacy of NB-UVB in AD under real-world conditions. METHODS: We conducted a historical inception cohort study using automated recording of dispensed drugs to provide an objective treatment outcome in a large population catchment of 420 000 people over 15 years. We analysed clinical treatment outcomes, recorded multicentre and prospectively over 15 years, of a large AD treatment cohort (n = 844), along with the drugs dispensed to this cohort. RESULTS: The majority (70%) of patients with AD received significantly fewer topical corticosteroids (TCS) during the 12-month window after finishing NB-UVB compared with the 12-month window before starting the treatment (median reduction from 37.5 to 19.7 g/month). The number of patients dispensed with oral corticosteroids and antihistamines also dropped significantly (from 20% to 10% and from 69% to 31%, respectively), while all AD-unrelated drugs dispensed remained unchanged. Clinically, NB-UVB treatment achieved a 'clear' or 'almost clear' status in 48.7% of patients, while 20.4% achieved 'moderate clearance'. Treatment outcomes scores were validated by a strong correlation with reduction in AD-specific drug treatment. CONCLUSION: Our data confirm the significant efficacy of NB-UVB for AD under conditions of routine care.
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Corticoesteroides/administración & dosificación , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/radioterapia , Fármacos Dermatológicos/administración & dosificación , Terapia Ultravioleta , Administración Cutánea , Administración Oral , Adolescente , Adulto , Niño , Preescolar , Femenino , Antagonistas de los Receptores Histamínicos/administración & dosificación , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
AIM: To investigate the prognostic significance of bone marrow (BM) 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) uptake in relation to posterior iliac crest BM biopsy (BMB) results in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Pretreatment integrated positron-emission tomography(PET)/computed tomography (CT) images of 512 DLBCL patients who underwent BMB and received rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy were analysed retrospectively. BM uptake was assessed visually and by maximum standard uptake value (SUVmax). Associations with lymphoma-specific survival (LSS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: FDG(+) BM was observed in 64 cases (41 focal, 12 heterogeneous, 11 diffuse). This finding distinguished iliac crest involvement (positive in 59 and negative in 453) with 89.6% accuracy (459/512) and 93.6% specificity (424/453). In BMB(+) patients, BM-to-liver SUVmax ratio >1.8 concurred perfectly with FDG(+) BM. During 52 months of follow-up, there were 156 lymphoma-related deaths. In the entire population, multivariate analysis revealed high International Prognostic Index (IPI; p<0.001), old age (p=0.003), bulky disease (p=0.011), BMB(+) (p=0.028), and FDG(+) BM (p=0.019) as independent predictors of worse LSS. In the BMB(+) subgroup, high National Comprehensive Cancer Network-revised IPI (NCCN-IPI; p=0.029) and FDG(+) BM (p=0.008) were significant independent predictors. Among BMB(+) patients with low to low-intermediate NCCN-IPI, FDG(+) BM was associated with significantly worse 2-year LSS (33.3% versus 100%; p=0.017). The same was true among those with high-intermediate NCCN-IPI (34.7% versus 76.9%.; p=0.026). CONCLUSION: Increased BM FDG in DLBCL is a predictor of worse LSS independent of BMB results and other prognostic variables including IPI/NCCN-IPI.
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Médula Ósea/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Fluorodesoxiglucosa F18 , Humanos , Ilion/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Pronóstico , Radiofármacos , Estudios Retrospectivos , Rituximab/uso terapéutico , Tasa de Supervivencia , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients. AIM: To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy. METHODS: Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription-polymerase chain reaction (rRT-PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT-PCR. FINDINGS: Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT-PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room. CONCLUSION: Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.
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Infecciones por Coronavirus/terapia , Descontaminación/normas , Contaminación Ambiental/análisis , Oxigenoterapia Hiperbárica/normas , Habitaciones de Pacientes/normas , Neumonía Viral/terapia , Neumonía/terapia , Guías de Práctica Clínica como Asunto , Respiración Artificial/normas , Microbiología del Aire , COVID-19 , Humanos , PandemiasRESUMEN
We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. It shows great potential for the treatment of a broad range of cancers.
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Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Doxorrubicina/administración & dosificación , Lecitinas/química , Membrana Dobles de Lípidos/química , Nanopartículas/química , Polímeros/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Camptotecina/administración & dosificación , Camptotecina/química , Camptotecina/farmacología , Camptotecina/uso terapéutico , Línea Celular , Proliferación Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Combinación de Medicamentos , Células HeLa , Humanos , Irinotecán , Células MCF-7 , Ratones , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
The surface-flow constructed wetland (CW) located in Nonsan City, South Korea, and constructed as the final stage of a piggery wastewater treatment plant that aims to treat high nutrient content effluent during dry days and stormwater runoff during wet days was monitored from October 2008 to November 2011. This research investigated the seasonal nutrient uptake of plant biomass in the CW and nutrient concentration changes in each treatment region under monsoon and temperate climate conditions. Results showed that the mean total nitrogen removal during summer (June to August) was higher by 13% than in spring (March to May), while total phosphorus removal was higher by 22% in fall (September to November) than in winter (December to February). All plants in the CW reached their maximum biomass coverage and weight in summer and minimum growth in winter. The highest N and P content in plants occurred in September with 583.2 g/m(2) and August with 62.0 g/m(2), respectively. Based on the results, it is recommended that the harvesting of plants should be conducted during the time of the peak nutrient uptake and before the plants release the nutrient content back to the CW. The dependence of nutrient removal efficiency on plants is not so significant. In order to increase the nutrient removal rate by plant uptake, it is suggested that the treatment regions in the CW be covered by plants.
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Biomasa , Estaciones del Año , Typhaceae/metabolismo , Purificación del Agua , Humedales , Animales , Vivienda para Animales , Porcinos , Movimientos del Agua , Calidad del AguaRESUMEN
This research was conducted to investigate the phosphorus forms present in water, soil and sediment and to estimate the phosphorus mass balance in a surface flow constructed wetland (CW). Water quality and sediment samples were collected from each cell along the hydrologic path in the CW from October 2008 to December 2010. At the same time, three dominant plant species (e.g. common reed and cattails) were observed through the measurement of the weight, height and phosphorus content. Based on the results, the orthophosphate constituted 24-34% of total phosphorus in water for each cell. The overall average phosphorus removal efficiency of the CW was approximately 38%. The average inflow and outflow phosphorus loads during the monitoring period were 1,167 kg/yr and 408 kg/yr, respectively. The average phosphorus retention rate was 65%, was mainly contributed by the settling of TP into the bottom sediments (30%). The phosphorus uptake of plants was less than 1%. The estimated phosphorus mass balance was effective in predicting the phosphorus retention and release in the CW treating wastewater. Continuous monitoring is underway to support further assessment of the CW system and design.
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Magnoliopsida/metabolismo , Fósforo/análisis , Eliminación de Residuos Líquidos/métodos , Contaminantes Químicos del Agua/análisis , Humedales , Adsorción , Crianza de Animales Domésticos , Animales , Sedimentos Geológicos/análisis , Magnoliopsida/química , Fósforo/química , Fósforo/metabolismo , Porcinos , Movimientos del Agua , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/metabolismoRESUMEN
BACKGROUND: It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM: To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS: We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS: Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS: Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.
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Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Aceite Etiodizado/administración & dosificación , Aceite Yodado/administración & dosificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The efficiency of a free water surface flow constructed wetland (CW) in treating agricultural discharges from stream was investigated during storm and non-storm events between April and December, 2009. Physico-chemical and water quality constituents were monitored at five sampling locations along the flow path of the CW. The greatest reduction in pollutant concentration was observed after passing the sedimentation zone at approximately 4% fractional distance from the inflow. The inflow hydraulic loading, flow rates and pollutant concentrations were significantly higher and variable during storm events than non-storm (baseflow) condition (p <0.001) that resulted to an increase in the average pollutant removal efficiencies by 10 to 35%. The highest removal percentages were attained for phosphate (51 ± 22%), ammonium (44 ± 21%) and phosphorus (38 ± 19%) while nitrate was least effectively retained by the system with only 25 ± 17% removal during non-storm events. The efficiency of the system was most favorable when the temperature was above 15 °C (i.e., almost year-round except the winter months) and during storm events. Overall, the outflow water quality was better than the inflow water quality signifying the potential of the constructed wetland as a treatment system and capability of improving the stream water quality.
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Eliminación de Residuos Líquidos/métodos , Contaminantes del Agua/análisis , Purificación del Agua/métodos , Humedales , Agricultura , Análisis de la Demanda Biológica de Oxígeno , Carbono/análisis , Concentración de Iones de Hidrógeno , Corea (Geográfico) , Nitratos/análisis , Nitrógeno/análisis , Oxígeno/análisis , Fosfatos/análisis , Fósforo/análisis , Compuestos de Amonio Cuaternario/análisis , Lluvia , Ríos , Calidad del Agua , Abastecimiento de AguaRESUMEN
A total of 240 d-old male Ross chicks (average BW 37·15 ± 0·49 g) were fed on an iron (Fe)-deficient semi-synthetic diet (45 mg Fe/kg) from d 1-7 post hatching. At d 7, all 240 chicks (average BW 140·15 ± 1·4 g) with depleted Fe-stores were randomly assigned to three treatments on the basis of BW to study the efficiency of dietary inorganic and organic iron (Fe) utilisation. Each treatment had 4 replicates with 20 birds in each. Dietary treatments were: maize-soyabean meal-based basal diet, containing 103 to 106 mg Fe/kg (control); and basal diets supplemented with an additional 80 mg/kg Fe either from an inorganic (FeSO4 · H2O, 28% Fe) or organic (ferrous methionine chelate, 10% Fe) source. The starter and finisher diets were fed from d 7 to 21 and d 21 to 35, respectively. Improved body weight gain and FCR during finisher phase and overall study period; and greater DM and CP retention, and excreta Fe excretion, at d 20 to 21 and d 34 to 35; were observed in birds fed on Fe supplemented diets when compared with birds fed on control diet. At d 35, the RBC, Hb, haematocrit, and Fe concentration in plasma, tibia and liver were higher in birds fed on Fe supplemented diets than birds fed on the control diet. Supplementation of Fe in organic form resulted in greater Fe concentration in the tibia and liver and less Fe excretion at d 34 to 35, when compared with birds receiving inorganic Fe. These results indicate the necessity to supplement Fe in the commercial diets of broilers; however, organic and inorganic sources of Fe supplementation at 80 mg/kg were equally effective in improving performance, nutrient retention and haematological indices. In addition, Fe supplementation through an organic source seems to be more efficient in depositing Fe in the haemopoietic organs (liver and tibia) of birds under Fe depleted conditions.
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Alimentación Animal , Pollos/crecimiento & desarrollo , Suplementos Dietéticos , Hierro/metabolismo , Animales , Análisis Químico de la Sangre/veterinaria , Pollos/sangre , Pollos/metabolismo , Dieta/veterinaria , Hierro/análisis , Hierro/sangre , Hierro de la Dieta/análisis , Hierro de la Dieta/sangre , Hierro de la Dieta/metabolismo , Hígado/metabolismo , Masculino , Bazo/metabolismo , Tibia/metabolismo , Aumento de PesoRESUMEN
Four experiments were conducted to determine the effects of dietary supplementation of corn distillers dried grain with solubles (DDGS) diets with mannanase on performance, apparent total tract digestibility (ATTD) of energy and nutrients, blood metabolites, and carcass characteristics of grower-finisher pigs. In Exp. 1, 96 grower pigs (initial BW, 57.6 kg), 6 pigs per pen and 4 pens per treatment, were fed corn-soybean meal-based diets containing 10% DDGS and 0, 200, 400, or 600 units (U) of mannanase/kg. The ADG and blood glucose increased (linear, P < 0.05) with increasing concentrations of dietary mannanase. Pigs fed diets containing increasing levels of mannanase had improved ATTD of DM and CP (quadratic, P < 0.05). In Exp. 2, 64 finisher pigs (initial BW, 92.7 kg) were allotted to 4 treatment groups with 4 pigs per pen and 4 pens per treatment. Pigs were fed corn-soybean meal-based diets containing 15% DDGS and 0, 200, 400, or 600 U of mannanase/kg. Linear increases (P < 0.05) in ADG, blood glucose, and ATTD of DM, GE, and CP were observed with increasing levels of dietary mannanase supplementation. In Exp. 3, 208 grower pigs (initial BW, 60.5 kg) were allotted to 4 treatment groups with 13 pigs per pen and 4 pens per treatment. Pigs were fed diets containing 0 or 10% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. An increase (P < 0.05) in ADG and blood glucose for pigs fed diets containing mannanase was observed. The ATTD of DM and CP (P < 0.05) was decreased with the inclusion of DDGS, whereas pigs fed the mannanase-supplemented diets had an increased (P < 0.05) ATTD of CP. In Exp. 4, 208 finisher pigs (initial BW, 86.5 kg), with 13 pigs per pen and 4 pens per treatment, were fed diets containing 0 or 15% DDGS and 0 or 400 U of mannanase/kg in a 2 x 2 factorial arrangement. The ADG and blood glucose increased (P < 0.05) when mannanase was included in the diets. The ATTD of DM (P < 0.05), GE (P < 0.10), and CP (P < 0.05) increased by the supplementation with mannanase in the diets of finisher pigs. The carcass characteristics and meat quality were not affected by the DDGS or mannanase inclusion. These results indicated that including 10 and 15% DDGS in conventional swine grower and finisher diets had no detrimental effects on growth performance or carcass characteristics. In addition, supplementation with 400 U of mannanase/kg to diets containing 10 and 15% DDGS fed to grower and finisher pigs may improve growth performance and the ATTD of CP.
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Alimentación Animal/análisis , Composición Corporal/efectos de los fármacos , Dieta/veterinaria , Digestión/fisiología , Grano Comestible/química , Manosidasas/farmacología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Glucemia , Colesterol/sangre , Suplementos Dietéticos , Mananos/metabolismo , Manosidasas/química , Manosidasas/metabolismo , Carne/normas , Triglicéridos/sangreRESUMEN
Two experiments were conducted to evaluate potato protein (PP, experiment 1) and refined PP (RPP, experiment 2) obtained from Gogu valley tubers as an antimicrobial agent in broiler diets. In both the experiments, 1-d-old male Ross 308 chicks were allotted to 5 treatments and performance, nutrient retention, and microbial populations in excreta and cecum were studied. Dietary treatments were as follows: basal diet (negative control, NC), basal diet with antibiotic (positive control, PC, 10 mg/kg of avilamycin), and low, medium, or high levels of PP (0.25, 0.50, and 0.75%, respectively, in experiment 1) or RPP (200, 400, and 600 mg/kg, respectively, in experiment 2). The overall gain and retention of DM (d 20 to 21) and CP (d 20 to 21 and d 41 to 42) were greater in birds fed PC and high PP diets than birds fed the NC diet. Population of total aerobic bacteria and coliforms was lowest in the cecum and excreta of birds fed the PC diet and highest in birds fed the NC diet. An increase in dietary PP linearly improved BW gain, feed intake, and feed conversion ratio during starter phase and overall BW gain. Also, there was linear improvement in retention of DM (d 20 to 21) and CP (d 20 to 21 and d 41 to 42) and reduced populations of total aerobic bacteria and coliforms in the cecum (d 42) and excreta (d 28 and 42) due to an increase in dietary PP. In the second experiment, the PC diet and diets with increasing levels of RPP had no effect on performance and nutrient retention. Birds fed the PC diet had the lowest microbial population in excreta and cecum, whereas the population of total aerobic bacteria and coliforms in excreta and cecum decreased (linear, P < 0.05) as the level of RPP was increased in the diet. These results suggest that both PP and RPP obtained from Gogu valley potato tubers have in vivo antimicrobial activity.
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Antiinfecciosos/farmacología , Pollos/metabolismo , Pollos/microbiología , Proteínas de Vegetales Comestibles/farmacología , Solanum tuberosum , Animales , Peso Corporal/fisiología , Ciego/microbiología , Recuento de Colonia Microbiana/veterinaria , Heces/microbiología , Masculino , Distribución AleatoriaRESUMEN
A total of 280 weaned pigs (Landrace x Yorkshire x Duroc) were used in a 28-d growth study to investigate the effect of feeding different levels of potato proteins on growth performance, nutrient digestibility, immune response, small intestinal morphology, and bacterial populations in feces and large intestine. Pigs (initially 6.42 +/- 0.74 kg of BW and 23 +/- 3 d of age) were randomly allotted to 5 treatments on the basis of BW, each treatment composed of 4 pens, each pen having 14 pigs. Dietary treatments included positive control (PC; basal diet + 150 mg/kg apramycin and 10 mg/ kg colistin sulfate); and potato protein (PP), consisting of the basal diet with 0, 0.25, 0.50, or 0.75% of potato protein. Diets were fed in 2 phases: phase I (d 0 to 14 postweaning) and phase 2 (d 14 to 28 postweaning). Potato protein was extracted from a value-added type of the new potato variety, Solanum tuberosum L. cv. Gogu valley, and was shown to have a minimum inhibitory concentration of 300 to 500 mug/mL. Performance of PC was compared with 0.25 to 0.75% PP, whereas linear and quadratic trends of increasing PP (0 to 0.75% PP) were tested. Over the 28-d trial, pigs fed the PC diets showed improved overall ADG (P < 0.05) and G:F (P = 0.090) compared with pigs fed PP, whereas increasing levels of PP linearly improved ADG (P < 0.05), ADFI (P = 0.052), and G:F (P = 0.098). The digestibility of DM and CP in both the phases was greater in PC than PP, and feeding of PP linearly improved the DM digestibility (P < 0.05) in phase II. The bacterial populations in the feces of pigs fed PC and PP were comparable, except for total bacteria and coliform bacteria in the feces at d 14 and 28, which were decreased in PC; and feeding of PP was effective in linearly reducing the populations of microbes in feces and contents of cecum, colon, and rectum. There was linear increase (P < 0.10) in skin-fold thickness in response to phytohemagglutinin with an increase in PP levels. Haemagglutinin titers on d 21 were greater (P = 0.054) in PC, and at d 28 the haemagglutinin titers were quadratically affected in pigs fed PP (P = 0.070). There was a trend toward a decrease in crypt depth (P = 0.068) and a greater villus height:crypt depth ratio (P = 0.082) of ileum in PC compared with PP. These results suggest that PP may be an alternative to medicated feed with antibiotics because it showed antimicrobial activity by effectively reducing the population of coliform bacteria and also improved the performance of weanling pigs.
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Antiinfecciosos/farmacología , Intestinos/efectos de los fármacos , Proteínas de Plantas/farmacología , Solanum tuberosum/química , Porcinos/metabolismo , Animales , Anticuerpos/sangre , Recuento de Colonia Microbiana/veterinaria , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/aislamiento & purificación , Heces/microbiología , Femenino , Pruebas de Hemaglutinación/veterinaria , Histocitoquímica/veterinaria , Hipersensibilidad Inmediata/inmunología , Mucosa Intestinal/metabolismo , Intestinos/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Porcinos/crecimiento & desarrollo , Porcinos/inmunología , Porcinos/microbiologíaRESUMEN
Sulfotransferase 1E1 (SULT1E1) catalyze estrogen into sulfate conjugation and is involved in the metabolism of phytoestrogen. A community-based cross-sectional study was conducted on 397 Korean women, to evaluate the association between genetic polymorphisms of SULT1E1 and bone mineral density (BMD) and the combined effect of the genetic polymorphism and phytoestrogen intake for BMD in Korean women. BMDs of the distal radius and the calcaneus were measured by dual-energy X-ray absorptiometry. Genotypes of SULT1E1 IVS1-447 C>A, IVS4-1653 T>C, and *959 G>A were determined by the 5'-nuclease assay (TaqMan). Phytoestrogen intake was estimated by a food-frequency questionnaire validated against multiple 24-hour recalls. Women with the SULT1E1 *959 GG genotype had a 4.5% lower BMD at the distal radius (P (trend )= 0.05) and a 7.9% lower BMD at the calcaneus compared to those with AA genotype (P (trend) < 0.01), whereas the SULT1E1 IVS1-447 CC genotype and IVS4-1653 TT genotype were not associated with BMD. There was no significant trend of BMD with the numbers of CTG-containing haplotypes, but calcaneal BMDs significantly differed between SULT1E1 CTA-CTA haplotype and CTG-CCA haplotype (P < 0.05). When stratified by SULT1E1 genotype, the correlation between phytoestrogen consumption and BMD at the calcaneus was noteworthy in women with SULT1E1 *959 GG genotype (r = 0.25, P = 0.01) or SULT1E1 IVS 4-1653 TT genotype (r = 0.15, P = 0.02). This trend remained significant only in postmenopausal women (r = 0.36, P = 0.01) after multiple testing was corrected by the false discovery rate method. In conclusion, the genetic polymorphism of SULT1E1 *959 G > A was associated with BMD at the distal radius and calcaneus, and the association between phytoestrogen consumption and calcaneal BMD might be modified by this genetic polymorphism.
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Densidad Ósea/genética , Calcáneo/fisiología , Dieta , Fitoestrógenos/farmacología , Polimorfismo Genético , Sulfotransferasas/genética , Absorciometría de Fotón , Densidad Ósea/efectos de los fármacos , Femenino , Humanos , Corea (Geográfico) , Reacción en Cadena de la Polimerasa , Radio (Anatomía)/fisiologíaRESUMEN
The pharmacokinetic interaction between clozapine, an atypical antipsychotic with metabolic complications, including weight gain, and green tea consumption has not been evaluated, although green tea is responsible for beneficial effects, including weight reduction, and is widely consumed in the world. Commercial green tea extract (175 mg kg(-1)) or saline was administered orally for 4 days before the oral administration of clozapine (20 mg kg(-1) ) to rats. Plasma concentrations of clozapine were measured up to 5 h after clozapine administration, and then hepatic CYP1A2 expression and activity were determined. There was no significant difference in the elimination half-life of clozapine between the green tea extract and saline groups. However, the time to reach peak concentration (T(max)) was significantly increased by green tea extract. The mean total area under the plasma concentration-time curve (AUC(0-infinity)) and maximal peak plasma concentration (C(max)) of clozapine in the green tea extract group were significantly lower than those of controls. Green tea extract induced a approximately 2-fold increase in hepatic CYP1A2 levels, while the activity increased slightly (by 10% of control). Because of this reduction in AUC and T(max) of clozapine by green tea extract pretreatment, we suggest that both the rate and amount of absorption of clozapine may be reduced by green tea extract, although the hepatic elimination phase may not be significantly altered. Therefore, the clinical implications of the effects of green tea on the bioavailability of clozapine in patients should be further evaluated.
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Antipsicóticos/farmacocinética , Clozapina/farmacocinética , Interacciones de Hierba-Droga , Extractos Vegetales/farmacología , Té , Animales , Antipsicóticos/sangre , Área Bajo la Curva , Camellia sinensis , Clozapina/sangre , Citocromo P-450 CYP1A2/biosíntesis , Semivida , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Treatment with unilateral left globus pallidus internus (GPi) deep brain stimulation is reported in a patient with severe delayed onset post-traumatic cervical dystonia. He had sustained severe head trauma at the age of 17 and had developed a mild right hemiparesis. Three years after the head injury, cervical dystonia with head turning to the left side developed. Magnetic resonance imaging (MRI) showed a discrete GPi lesion on the left side. At the age of 23, he underwent unilateral left GPi deep brain stimulation. He experienced immediate but short lasting benefit from the microlesioning effect of the electrode. With activation of deep brain stimulation, there was significant improvement of the cervical dystonia, persisting for 12 months of follow up. This case underlines the importance of the globus pallidus internus in the generation and amelioration of cervical dystonia.
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Ganglios Basales/patología , Terapia por Estimulación Eléctrica/métodos , Lateralidad Funcional/fisiología , Globo Pálido/fisiología , Tortícolis/patología , Tortícolis/terapia , Adulto , Lesiones Encefálicas/complicaciones , Electromiografía/métodos , Humanos , Imagen por Resonancia Magnética , Masculino , Radiografía , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/patología , Tortícolis/etiologíaRESUMEN
To investigate the molecular mechanism of the early-stage encapsulation reaction in insects, we purified a 47kDa protein from injected beads into Galleria mellonella larvae. When a cDNA clone was isolated, the 47kDa protein showed high homology with Drosophila and human calreticulin. Western blotting analysis showed that the 47kDa protein was present in the hemocytes, but not in the plasma. When the early-stage encapsulated beads were coated with 47kDa protein antibody and reinjected into G. mellonella larvae, any further encapsulation reaction was inhibited. These results suggest that calreticulin is involved in non-self recognition in invertebrate cellular defense reactions.
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Proteínas de Unión al Calcio/inmunología , Proteínas de Insectos/inmunología , Mariposas Nocturnas/inmunología , Ribonucleoproteínas/inmunología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/aislamiento & purificación , Calreticulina , Clonación Molecular , ADN Complementario/genética , Drosophila/genética , Hemocitos/inmunología , Humanos , Proteínas de Insectos/genética , Proteínas de Insectos/aislamiento & purificación , Larva/inmunología , Datos de Secuencia Molecular , Peso Molecular , Mariposas Nocturnas/genética , Ribonucleoproteínas/genética , Ribonucleoproteínas/aislamiento & purificación , Homología de Secuencia de AminoácidoRESUMEN
New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide of the phenyl ring, 9a-l, were prepared from the readily available starting compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme assays, it has been shown that all the target compounds 9a-l proved to be more potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38-fold. The effects on the IC(50) values were investigated by varying the alkoxy group (R) of the phenyl ring, the sulfonamide type (X), and the length of the methylene chain linking the carboxylic acid, and the results were discussed in detail. From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5 inhibitory activity and comparable to better selectivity over PDE isozymes in comparison with sildenafil, has been selected for more detailed biological investigations.
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Inhibidores de Fosfodiesterasa/síntesis química , Piperazinas/síntesis química , Piperazinas/farmacología , 3',5'-GMP Cíclico Fosfodiesterasas , Animales , Ácidos Carboxílicos/química , Bovinos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Evaluación Preclínica de Medicamentos , Disfunción Eréctil/tratamiento farmacológico , Humanos , Concentración 50 Inhibidora , Isoenzimas/efectos de los fármacos , Isoenzimas/metabolismo , Masculino , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/efectos de los fármacos , Hidrolasas Diéster Fosfóricas/metabolismo , Piperazinas/química , Purinas , Conejos , Citrato de Sildenafil , Relación Estructura-Actividad , Sulfonamidas/química , SulfonasRESUMEN
New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.
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Inhibidores de Fosfodiesterasa/química , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/efectos de los fármacos , Piperazinas/química , 3',5'-GMP Cíclico Fosfodiesterasas , Animales , Bovinos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5 , Evaluación Preclínica de Medicamentos , Concentración 50 Inhibidora , Modelos Moleculares , Estructura Molecular , Inhibidores de Fosfodiesterasa/síntesis química , Piperazinas/farmacología , Purinas , Conejos , Citrato de Sildenafil , Relación Estructura-Actividad , SulfonasRESUMEN
UNLABELLED: BACKGROUND AND OBJECTIVE To examine the biophysical effects of photothermal heating on herniated intervertebral discs during laser decompression surgery. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo bovine nucleus pulposus specimens were irradiated with a Nd: YAG laser (lambda = 1.32 microm, 100 seconds exposure time, 9-31 W/cm(2), 4.8 mm spot diameter), whereas changes in tissue thermal, mechanical, and optical properties were monitored by using, respectively, infrared radiometry, tissue tension measurements, and diffuse reflectance from a HeNe probe laser. Morphologic changes and mass reduction were monitored by recording shape changes on video and weighing specimens before and after laser exposure. RESULTS: At power densities below 20 W/cm(2), evaporation of water and specimen volume reduction (shrinking) were consistently observed on video during irradiation. In contrast, above 20 W/cm(2), vapor bubbles formed within the specimen matrix and subsequently ruptured (releasing heated vapors). When radiometric surface temperature approaches approximately 60 to 70 degrees C (denaturation threshold for tissue), tissue tension begins to increase, which is consistent with observations of specimen length reduction. The onset of this change in tissue tension is also reflected in characteristic alterations in diffuse reflectance. With cessation of laser irradiation, a sustained increase in tissue tension is observed, which is consistent with changes in specimen length and volume. Higher laser power results in a faster heating rate and subsequently an accelerated tension change. Specimen mass reduction increased with irradiance from 19 to 72% of the initial mass for 9--31 W/cm(2), respectively. Irradiated specimens did not return to their original shape after immersion in saline (48 hours) in contrast to air-dried specimens (24 hours), which returned to their original shape and size. CONCLUSION: These observations suggest that photothermal heating results in irreversible matrix alteration causing shape change and volume reduction (observed on video and evidenced by the increase in tissue tension) taking place at approximately 65 degrees C. Inasmuch as high laser power results in vapor bubble formation and specimen tearing, the heating process must be controlled. Diffuse reflectance measurements provide a noncontact, highly sensitive means to monitor dynamically changes in tension of nucleus purposus.
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Disco Intervertebral/fisiopatología , Disco Intervertebral/cirugía , Terapia por Láser , Fototerapia , Animales , Fenómenos Biomecánicos , Bovinos , Técnicas In Vitro , Disco Intervertebral/patología , Neodimio , Sensibilidad y Especificidad , Grabación en VideoRESUMEN
A human hepatoma cell line, Hep G2 cells, is a reliable system for the study of alcohol-induced hepatotoxicity. In this study, we investigated the effect of an aqueous extract of Asparagus cochinchinensis(MERRIL) (Liliaceae) roots (ACAE) on ethanol (EtOH)-induced cytotoxicity in Hep G2 cells. ACAE (1-100 microg/ml) dose-dependently inhibited the EtOH-induced tumor necrosis factor-alpha (TNF-alpha) secretion. ACAE (1-100 microg/ml) also inhibited the EtOH and TNF-alpha-induced cytotoxicity. Furthermore, we found that ACAE inhibited the TNF-alpha-induced apoptosis of Hep G2 cells. These results suggest that ACAE may prevent the EtOH-induced cytotoxicity through inhibition of the apoptosis of Hep G2 cells.