RESUMEN
Quantitative estimate of the response of ionization chamber based pocket dosimeters (DRDs) to various beta sources was performed. It has been established that the ionization chamber based pocket dosimeters do not respond to beta particles having energy (Emax)<1 MeV and same was verified using (147)Pm, (85)Kr and (204)Tl beta sources. However, for beta particles having energy >1 MeV, the DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively. As the energy of the beta particles increases, the response also increases. The response of DRDs to beta particles having energy>1 MeV arises due to the fact that the thickness of the chamber walls is less than the maximum range of beta particles. This may also be one of the reasons for disparity between doses measured with passive/legal dosimeters (TLDs) and DRDs in those situations in which radiation workers are exposed to mixed field of gamma photons and beta particles especially at uranium processing plants, nuclear (power and research) reactors, waste management facilities and fuel reprocessing plants etc. The paper provides the reason (technical) for disparity between the doses recorded by TLDs and DRDs in mixed field of photons and beta particles.
Asunto(s)
Partículas beta/efectos adversos , Monitoreo de Radiación/instrumentación , Radiometría/instrumentación , Rayos gamma/efectos adversos , Humanos , Exposición Profesional , Fotones/efectos adversos , Dosis de Radiación , Radioisótopos/efectos adversos , Dosimetría Termoluminiscente , Uranio/efectos adversosRESUMEN
CONTEXT: Butea frondosa (BF) Roxb. & Koen. (syn. B. monosperma Lam.) (Fabaceae) leaves have been used in folklore medicine for the treatment of diabetes, conjunctivitis, gastrointestinal tract, and central nervous system disorders such as anxiety, amnesia, etc. OBJECTIVE: To evaluate the effect of lyophilized hydroalcoholic extract of BF leaves (BFLE) at 100, 200 and 400 mg/kg, p.o., for its memory enhancing activity against scopolamine-induced amnesia in rats. MATERIALS AND METHODS: Antiamnesic effect of the BFLE was evaluated using Morris water maze and object recognition test models. The effect of BFLE on acetylcholinesterase activity and malondialdehyde and glutathione levels were also evaluated in brain homogenate. RESULT: BFLE ameliorates scopolamine-induced amnesia in both the models with maximum effect at 400 mg/kg. BFLE (400 mg/kg) decreased escape latency and increased time spent in target quadrant (24.2 and 42.5 s, respectively) in comparison to scopolamine (82 and 18.2 s, respectively) in the Morris water maze task. In the object recognition test, BFLE produced significant increase in ability to discriminate between novel and familiar objects. The highest investigated dose of BFLE (400 mg/kg), produced a significant decrease in acetylcholinesterase activity and malondialdehyde levels, and improves glutathione levels in comparison to scopolamine. Moreover, this effect of BFLE at 400 mg/kg was comparable to that of standard, donepezil. CONCLUSION: BFLE exhibited significant antiamnesic activity in rats thereby validating its folklore use.
Asunto(s)
Amnesia/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Butea/química , Liofilización , Memoria/efectos de los fármacos , Nootrópicos/farmacología , Extractos Vegetales/farmacología , Escopolamina , Acetilcolinesterasa/metabolismo , Administración Oral , Amnesia/inducido químicamente , Amnesia/metabolismo , Amnesia/psicología , Animales , Antioxidantes/farmacología , Encéfalo/metabolismo , Inhibidores de la Colinesterasa/farmacología , Discriminación en Psicología/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Reacción de Fuga/efectos de los fármacos , Femenino , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , Glutatión/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Nootrópicos/administración & dosificación , Nootrópicos/aislamiento & purificación , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Plantas Medicinales , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Reconocimiento en Psicología/efectos de los fármacos , Factores de TiempoRESUMEN
BACKGROUND/AIMS: Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart. METHODS: Heart failure was created by an arteriovenous fistula (AVF). Mice were divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was supplemented with drinking water for 6 weeks in the appropriate surgery groups after surgery. RESULTS: M-mode echocardiograms showed ventricular contractile dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9, and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase VI expression; however, STS supplementation reversed these effects in AVF mice. Among 2 enzymes that produce endogenous hydrogen sulfide (H(2)S), cystathionine-gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-beta-synthase (CBS) expression. In addition, reduced production of H(2)S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H(2)S when AVF mice were supplemented with STS compared to AVF alone. CONCLUSIONS: These results suggested that STS modulated cardiac dysfunction and the extracellular matrix, in part, by increasing ventricular H(2)S generation.
Asunto(s)
Cardiotónicos/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Sulfuro de Hidrógeno/metabolismo , Tiosulfatos/farmacología , Adenilil Ciclasas/genética , Adenilil Ciclasas/metabolismo , Animales , Aorta/fisiopatología , Fístula Arteriovenosa , Enfermedad Crónica , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Cistationina gamma-Liasa/efectos de los fármacos , Cistationina gamma-Liasa/metabolismo , Ecocardiografía , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/fisiopatología , Masculino , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Contracción Miocárdica/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-1/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
Hyperhomocysteinemia (HHcy) is associated with atherosclerotic events involving the modulation of arachidonic acid (AA) metabolism and the activation of matrix metalloproteinase-9 (MMP-9). Cytochrome P450 (CYP) epoxygenase-2J2 (CYP2J2) is abundant in the heart endothelium, and its AA metabolites epoxyeicosatrienoic acids (EETs) mitigates inflammation through NF-kappabeta. However, the underlying molecular mechanisms for MMP-9 regulation by CYP2J2 in HHcy remain obscure. We sought to determine the molecular mechanisms by which P450 epoxygenase gene transfection or EETs supplementation attenuate homocysteine (Hcy)-induced MMP-9 activation. CYP2J2 was over-expressed in mouse aortic endothelial cells (MAECs) by transfection with the pcDNA3.1/CYP2J2 vector. The effects of P450 epoxygenase transfection or exogenous supplementation of EETs on NF-kappabeta-mediated MMP-9 regulation were evaluated using Western blot, in-gel gelatin zymography, electromobility shift assay, immunocytochemistry. The result suggested that Hcy downregulated CYP2J2 protein expression and dephosphorylated PI3K-dependent AKT signal. Hcy induced the nuclear translocation of NF-kappabeta via downregulation of IKbetaalpha (endogenous cytoplasmic inhibitor of NF-kappabeta). Hcy induced MMP-9 activation by increasing NF-kappabeta-DNA binding. Moreover, P450 epoxygenase transfection or exogenous addition of 8,9-EET phosphorylated the AKT and attenuated Hcy-induced MMP-9 activation. This occurred, in part, by the inhibition of NF-kappabeta nuclear translocation, NF-kappabeta-DNA binding and activation of IKbetaalpha. The study unequivocally suggested the pivotal role of EETs in the modulation of Hcy/MMP-9 signal.