RESUMEN
Purpose: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied. Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats. Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway. Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway.
Asunto(s)
Hipertensión Pulmonar , Nanopartículas , Ratas , Animales , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Ratas Sprague-Dawley , Monocrotalina/efectos adversos , Fosfolipasas de Tipo C/efectos adversos , Fosfolipasas de Tipo C/metabolismo , Arteria Pulmonar , Transducción de SeñalRESUMEN
The purpose of the present study was to determine whether a correlation existed between chick mortality and the presence of Clostridium perfringens alpha-toxin and NetB-toxin genes (cpa and netB) in C. perfringens recovered from litter in commercial broiler houses. Because coccidiosis predisposes chickens to necrotic enteritis, the concentration of Eimeria oocysts in these samples was measured, and the numbers were used in similar correlation analyses. Litter samples were collected at 0, 2, and 4 wk growout from six broiler farms (18 houses total) during an anticoccidial drug (ACD) control program and from nine broiler farms (23 houses total) during an Eimeria vaccine (VAC) control program. Of these, litter samples were collected from five farms during both ACD and VAC programs. The litter samples were processed for Eimeria oocyst and C. perfringens spore enumerations by standard parasitologic and microbiologic techniques. DNA was also extracted for C. perfringens DNA for PCR detection of genes coding for alpha- and NetB-toxin. A general trend during the ACD programs was a transient decrease in both Eimeria maxima and non-E. maxima (Eamipt) numbers at 2 wk growout. The pattern was slightly different during VAC with E. maxima and Eamipt levels increasing over time. Average concentrations of C. perfringens in litter were highest at 2 wk (â¼105-106 spores/g) during ACD and at placement during VAC (â¼105-106 spores/g). During the ACD program, a strong correlation was observed between 0 and 3-wk chick mortality and the presence at placement (0 wk) of netB (r = 0.42-0.48) or cpa (r = 0.55-0.67). A very strong correlation was observed in 0-5-wk chick mortality and the presence of netB at 4 wk growout (0.73-0.95). During a VAC program, a strong correlation was only observed between the presence of netB at placement and 0-1-wk chick mortality (r = 0.67).
Asunto(s)
Toxinas Bacterianas/efectos adversos , Proteínas de Unión al Calcio/efectos adversos , Pollos , Infecciones por Clostridium/veterinaria , Clostridium perfringens/fisiología , Coccidiosis/veterinaria , Enfermedades de las Aves de Corral/mortalidad , Fosfolipasas de Tipo C/efectos adversos , Animales , Toxinas Bacterianas/genética , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/mortalidad , Coccidiosis/parasitología , Eimeria/aislamiento & purificación , Enterotoxinas/genética , Oocistos/aislamiento & purificación , Enfermedades de las Aves de Corral/microbiologíaRESUMEN
Clostridium perfringens causes gas gangrene with inflammatory myopathies and infrequently septicemia associated with massive intravascular hemolysis. The microorganism is known to produce a variety of toxins and enzymes that are responsible for severe myonecrotic lesions. Notably, alpha-toxin, which possesses hemolytic, necrotic and lethal activities, and phospholipase C and sphingomyelinase activities, is an important agent for the diseases. The cytokine storm induced by alpha-toxin, mainly the release of TNF-alpha, plays an important role in the death and massive hemolysis. The toxin-induced release of TNF-alpha from neutrophils and macrophages is dependent on the activation of ERK1/2 signal transduction via TrkA receptor. In addition, 14- and 15-membered macrolides specifically block the toxin-induced events through the activation of neutrophils and macrophages.
Asunto(s)
Toxinas Bacterianas , Proteínas de Unión al Calcio , Clostridium perfringens/patogenicidad , Gangrena Gaseosa/microbiología , Fosfolipasas de Tipo C , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Toxinas Bacterianas/efectos adversos , Toxinas Bacterianas/farmacología , Proteínas de Unión al Calcio/efectos adversos , Proteínas de Unión al Calcio/farmacología , Gangrena Gaseosa/tratamiento farmacológico , Hemólisis , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Macrólidos/farmacología , Macrólidos/uso terapéutico , Macrófagos/metabolismo , Neutrófilos/metabolismo , Fosforilación/efectos de los fármacos , Receptor trkA/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Fosfolipasas de Tipo C/efectos adversos , Fosfolipasas de Tipo C/farmacologíaRESUMEN
Necrotic enteritis is a potentially fatal multifactorial disease of chickens, which under commercial conditions is often associated with increased levels of mortality and reduced bird performance. The safety and efficacy of a Clostridium perfringens type A alpha-toxoid (Netvax™) formulated as an oil emulsion was investigated, following maternal immunization of broiler breeder hens, housed under commercial conditions, by the intramuscular route. A total of 11,234 hens were vaccinated across two integrated poultry sites. The vaccine was safe with no systemic reactions or adverse effects on bird performance detected. Vaccination resulted in a significant increase in anti-alpha toxin antibody in the hen that was maintained throughout the study, and subsequently transferred to their progeny throughout the laying period via egg yolk. Chicks hatched from eggs produced from vaccinated hens were shown to have reduced mortality specifically related to progeny flocks where gross gut lesions associated with necrotic enteritis were observed in control chicks. Further, whilst C. perfringens was isolated from control chicks with necrotic enteritis lesions, no such isolations were made at these time points from chicks from vaccinated hens. These results indicate that, under commercial conditions, maternal vaccination with Netvax™ can help to control losses related to necrotic enteritis.
Asunto(s)
Toxinas Bacterianas/efectos adversos , Vacunas Bacterianas/efectos adversos , Proteínas de Unión al Calcio/efectos adversos , Infecciones por Clostridium/veterinaria , Enteritis/veterinaria , Enfermedades de las Aves de Corral/prevención & control , Toxoides/efectos adversos , Fosfolipasas de Tipo C/efectos adversos , Animales , Anticuerpos Antibacterianos/inmunología , Toxinas Bacterianas/administración & dosificación , Vacunas Bacterianas/administración & dosificación , Proteínas de Unión al Calcio/administración & dosificación , Pollos , Infecciones por Clostridium/inmunología , Infecciones por Clostridium/prevención & control , Clostridium perfringens/fisiología , Enteritis/prevención & control , Inyecciones Intramusculares/veterinaria , Intestinos/microbiología , Intestinos/patología , Necrosis/prevención & control , Necrosis/veterinaria , Enfermedades de las Aves de Corral/inmunología , Toxoides/administración & dosificación , Resultado del Tratamiento , Fosfolipasas de Tipo C/administración & dosificación , Vacunación/métodos , Vacunación/veterinariaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most commonly occurring solid tumors worldwide and is the most frequent cause of cancer death in some parts of the world such as China and sub-Saharan Africa. HCC appears to be rising dramatically in incidence in developed western countries too. The most frequent underlying factors causing HCC are chronic viral hepatitis and cirrhosis. Early detection of HCC is a key factor in improving outcomes of therapies. There is growing evidence that HCC may be prevented with strategies aimed at preventing or treating viral hepatitis. Surgery, including liver transplantation, remains the most efficient treatment but only for 15-30% of patients. Recent developments suggest that other therapeutic modalities such as loco-regional (ablative) methods are also potentially curative.
Asunto(s)
Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Etanol/efectos adversos , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Humanos , Incidencia , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Estadificación de Neoplasias , Resultado del Tratamiento , Fosfolipasas de Tipo C/efectos adversosRESUMEN
OBJECTIVE: Clostridium perfringens is a classical agent of food-borne disease but because of the mildness and self-limiting nature of the illness, many cases are undiagnosed. This study describes the investigation of an outbreak of diarrhea due to C. perfringens in a public restaurant. METHODS: An epidemiological survey was performed and the restaurant was inspected. The specific attack rates for the items on the menu were calculated. Odds ratios were calculated to investigate the independent association between each item and the disease using a logistic regression model. Investigation of C. perfringens toxin in the feces of four symptomatic subjects and one exposed but asymptomatic subject was performed by the reverse passive latex agglutination test. RESULTS: The overall attack rate was 70.8%. The main symptoms were diarrhea (100%) and abdominal pain (94%). Significant differences were found in specific attack rates for consumption of different menu items. However, the independent contribution of each item was significant only for consumption of "ravioli with cheese sauce". Fecal detection of C. perfringens enterotoxin was positive in the four symptomatic subjects and negative in the exposed but asymptomatic subject. CONCLUSIONS: The overall attack rate in this outbreak was high. The clinical symptomatology was similar to previously published data. The epidemiological analysis revealed "ravioli with cheese sauce" to be responsible for transmission of the disease and clinical investigation together with the fecal enterotoxin detection established C. perfringens as the etiological agent.
Asunto(s)
Toxinas Bacterianas/efectos adversos , Proteínas de Unión al Calcio , Clostridium perfringens/aislamiento & purificación , Contaminación de Alimentos , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Gastroenteritis/etiología , Fosfolipasas de Tipo C/efectos adversos , Adolescente , Adulto , Animales , Toxinas Bacterianas/aislamiento & purificación , Bovinos , Queso/microbiología , Niño , Brotes de Enfermedades , Heces/química , Femenino , Manipulación de Alimentos/métodos , Manipulación de Alimentos/normas , Enfermedades Transmitidas por los Alimentos/epidemiología , Gastroenteritis/inducido químicamente , Gastroenteritis/epidemiología , Humanos , Pruebas de Fijación de Látex , Carne/microbiología , Oportunidad Relativa , Restaurantes , España/epidemiología , Fosfolipasas de Tipo C/aislamiento & purificaciónRESUMEN
In skeletal muscle cells the steroid hormone 1alpha, 25-dihydroxy-vitamin-D3 (1,25(OH)2D3) nongenomically promotes Ca2+ release from intracellular stores and cation influx through both L-type and store-operated Ca2+ (SOC) channels. In the present work we evaluated the regulation and kinetics of the 1, 25(OH)2D3-stimulated SOC influx in chick muscle cells. Stimulation with 10(-9) M 1,25(OH)2D3 in Ca2+-free medium resulted in a rapid (40-60 s) but transient [Ca2+]i rise, which correlated with sterol-dependent inositol 1,4,5-trisphosphate production. The SOC influx stimulated by the hormone was insensitive to both L-type channel antagonists and polyphosphoinositide-specific phospholipase C (PPI-PLC) inhibitors but was fully inhibitable by La3+ and Ni2+. PPI-PLC blockade prior to 1,25(OH)2D3 stimulation suppressed both the [Ca2+]i transient and the SOC influx. 1,25(OH)2D3-induced SOC entry was markedly increased after 3 min of treatment (30% above basal) and then rapidly reached a steady-state level. The sterol-stimulated SOC influx was prevented by protein kinase C and tyrosine kinase inhibitors but unaffected by blockade of the protein kinase A pathway. None of these inhibitors altered the thapsigargin-induced SOC entry, suggesting the operation of a signaling mechanism different from that for sterol-dependent SOC influx. The present results indicate that 1,25(OH)2D3-induced activation of PPI-PLC is upstream to Ca2+ influx through SOC channels and point for a role of both protein kinase C and tyrosine kinases but not protein kinase A in the regulation of the sterol-dependent SOCE pathway.
Asunto(s)
Calcitriol/farmacología , Canales de Calcio/fisiología , Calcio/metabolismo , Músculo Esquelético/metabolismo , Proteína Quinasa C/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Fosfolipasas de Tipo C/metabolismo , Animales , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/efectos de los fármacos , Canales de Calcio Tipo L , Células Cultivadas , Embrión de Pollo , Inhibidores Enzimáticos/farmacología , Estrenos/farmacología , Inositol 1,4,5-Trifosfato/metabolismo , Cinética , Manganeso/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Neomicina/farmacología , Nifedipino/farmacología , Fosfatidilinositol Diacilglicerol-Liasa , Proteína Quinasa C/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirrolidinonas/farmacología , Tapsigargina/farmacología , Fosfolipasas de Tipo C/efectos adversos , Fosfolipasas de Tipo C/antagonistas & inhibidores , Verapamilo/farmacologíaRESUMEN
Este estudo mostra alguns aspectos da funçäo endotelial relacionados, diretamente, com a cirurgia cardíaca: 1) Após isquemia miocárdica global seguida de reperfusäo, o endotélio coronariano perde a habilidade de expressar vasodilataçäo endotélio-dependente mediada por receptores, ao passo que o relaxamento endotélio-dependente mediado pelo cálcio ionóforo A23187 e a fosfolipasec C, que näo dependem de estimulaçäo de receptores, encontra-se inalterada. O relaxamento produzido pelo fluoreto de sódio, o qual atua através de G-proteína(s), encontra-se comprometido. Estes experimentos indicam que o comprometimento da produçäo de EDRF/NO mediada por receptores após a lesäo de reperfusäo possa ser devido a uma disfunçäo de G-proteínas que liga os receptores da célula endotelial à via da sínese de EDRF/NO; 2) Quarenta e cinco minutos de parada cardioplégica de coraçöes de cäes, pela soluçäo St. Thomas näo comprometem a produçäo de EDRF/NO em artérias epicárdicas coronárias. Estudos farmacológicos in vitro semelhantes, testando-se os efeitos da soluçäo UW, suportaram o conceito de que ela näo lesa o endotélio coronariano, sendo segura para a preservaçäo cardíaca durantes transplantes cardíacos; 3) Em segmentos de artérias coronárias, renais, femorais, e em segmentos de artéria pulmonar, a protamina induziu vasodilataçäo endotélio-dependente, mediada pela estimulaçäo da liberaçäo de EDRF/NO. Nas circulaçöes coronariana e sistêmica, ao contrário do que se verificou nos experimentos envolvendo a circulaçäo pulmonar, este efeito foi independente da presença de heparina; 4) Em 83 por cento dos ensaios biológicos, o efluente da AMI esquerda induziu um relaxamento maior do anel coronariano bioensaiado do que o efluente da AMI direita, por liberaçäo basal de EDRF/NO. Este inibe a adesividade e a agregaçäo plaquetárias e a aterogêne, contribuindo para os resultados superiores obtidos quando se utiliza esta artéria para a revascularizaçäo do miocárdi. Quando expostos à hipoxia, as atividades vasodilatadoras da AMI e da veia safena foram maiores. Esta acentuaçäo da vasodilataçäo causada pela hipóxia foi inibida pelo tratamento com a indometacina, e, rapidamente, revertida, quando se restabeleceu a normóxia.