RESUMO
PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.
Assuntos
Síndrome de Cornélia de Lange/complicações , Papiloma do Plexo Corióideo/complicações , Araquidonato 15-Lipoxigenase/genética , Hibridização Genômica Comparativa , Proteínas de Ligação a DNA , Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/cirurgia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Proteínas Nucleares/genética , Proteínas de Transporte Nucleocitoplasmático/genética , Papiloma do Plexo Corióideo/genética , Papiloma do Plexo Corióideo/cirurgia , Proto-Oncogene Mas , Proteínas de Ligação a RNA , Fatores de TranscriçãoRESUMO
Introducción: La prueba Evaluación del Desarrollo Infantil (EDI) es un instrumento de tamizaje de problemas en el desarrollo diseñado y validado en México. La calificación obtenida se expresa como semáforo. Se consideran positivos tanto el resultado amarillo como el rojo, aunque se plantea una intervención diferente para cada uno. El objetivo de este trabajo fue evaluar la capacidad de la prueba EDI para discriminar entre los niños identificados con semáforo amarillo y los identificados con rojo al compararse con el Inventario de Desarrollo de Battelle 2.ª edición (IDB-2) en cuanto al cociente de desarrollo del dominio (CDD). Métodos: El análisis se llevó a cabo utilizando la información obtenida para el estudio de la validación. Se excluyeron los pacientes con resultado normal (verde) en EDI. Se utilizaron 2 puntos de CDD (IDB-2) por dominio: < 90 para incluir normal-bajo y < 80 para diagnóstico de retraso. Se analizó el resultado con base en la correlación del resultado del semáforo de EDI (amarillo o rojo) y el IDB-2, total y por subgrupos de edad. Resultados: Al considerar un CDD < 90 en amarillo, el 86.8% tuvo al menos un dominio afectado, y el 50%, 3 o más dominios, en comparación con el 93.8% y el 78.8% para el resultado en rojo, respectivamente. Hubo diferencias en todos los dominios entre amarillos y rojos (p < 0.001) para el porcentaje de niños con un CDD < 80: cognitivo (36.1 vs. 61.9%); comunicación (27.8 vs. 50.4%); motor (18.1 vs. 39.9%); personal-social (20.1 vs. 28.9%); y adaptativo (6.9 vs. 20.4%). Conclusiones: Los resultados de semáforo (amarillo o rojo) permiten identificar diferente magnitud de los problemas en el desarrollo y apoyan intervenciones diferenciadas.
Background: The Child Development Evaluation (CDE) is a screening tool designed and validated in Mexico for detecting developmental problems. The result is expressed through a semaphore. In the CDE test, both yellow and red results are considered positive, although a different intervention is proposed for each. The aim of this work was to evaluate the reliability of the CDE test to discriminate between children with yellow/red result based on the developmental domain quotient (DDQ) obtained through the Battelle Development Inventory, 2nd edition (in Spanish) (BDI-2). Methods: The information was obtained for the study from the validation. Children with a normal (green) result in the CDE were excluded. Two different cut-off points of the DDQ were used (BDI-2): < 90 to include low average, and developmental delay was considered with a cut-off < 80 per domain. Results were analyzed based on the correlation of the CDE test and each domain from the BDI-2 and by subgroups of age. Results: With a cut-off DDQ <90, 86.8% of tests with yellow result (CDE) indicated at least one domain affected and 50% 3 or more compared with 93.8% and 78.8% for red result, respectively. There were differences in every domain (P < 0.001) for the percent of children with DDQ < 80 between yellow and red result (CDE): cognitive 36.1% vs. 61.9%; communication: 27.8% vs. 50.4%, motor: 18.1% vs. 39.9%; personal-social: 20.1% vs. 28.9%; and adaptive: 6.9% vs. 20.4%. Conclusions: The semaphore result yellow/red allows identifying different magnitudes of delay in developmental domains or subdomains, supporting the recommendation of different interventions for each one.
RESUMO
The febrile cholestatic disease as a presentation of Hodgkin's lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.
Assuntos
Febre/etiologia , Doença de Hodgkin/complicações , Icterícia Obstrutiva/etiologia , Biópsia , Evolução Fatal , Feminino , Humanos , Fígado/patologia , Pessoa de Meia-IdadeRESUMO
La ictericia febril colestásica como forma de presentación de los linfomas de Hodgkin es un cuadro muy infrecuente. Describimos aquí un caso de síndrome febril prolongado asociado a ictericia progresiva, en el que el diagnóstico de la enfermedad se realiza a través de la biopsia hepática, dada la ausencia de afectación ganglionar que caracteriza a esta enfermedad. Destacamos asimismo el cuadro clínico avanzado y el compromiso multisistémico de una enfermedad rápidamente evolutiva.
The febrile cholestatic disease as a presentation of Hodgkin's lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Febre/etiologia , Doença de Hodgkin/complicações , Icterícia Obstrutiva/etiologia , Biópsia , Evolução Fatal , Fígado/patologiaRESUMO
La ictericia febril colestásica como forma de presentación de los linfomas de Hodgkin es un cuadro muy infrecuente. Describimos aquí un caso de síndrome febril prolongado asociado a ictericia progresiva, en el que el diagnóstico de la enfermedad se realiza a través de la biopsia hepática, dada la ausencia de afectación ganglionar que caracteriza a esta enfermedad. Destacamos asimismo el cuadro clínico avanzado y el compromiso multisistémico de una enfermedad rápidamente evolutiva.(AU)
The febrile cholestatic disease as a presentation of Hodgkins lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.(AU)
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Febre/etiologia , Doença de Hodgkin/complicações , Icterícia Obstrutiva/etiologia , Biópsia , Evolução Fatal , Fígado/patologiaRESUMO
BACKGROUND: The Child Development Evaluation (CDE) is a screening tool designed and validated in Mexico for detecting developmental problems. The result is expressed through a semaphore. In the CDE test, both yellow and red results are considered positive, although a different intervention is proposed for each. The aim of this work was to evaluate the reliability of the CDE test to discriminate between children with yellow/red result based on the developmental domain quotient (DDQ) obtained through the Battelle Development Inventory, 2nd edition (in Spanish) (BDI-2). METHODS: The information was obtained for the study from the validation. Children with a normal (green) result in the CDE were excluded. Two different cut-off points of the DDQ were used (BDI-2): <90 to include low average, and developmental delay was considered with a cut-off<80 per domain. Results were analyzed based on the correlation of the CDE test and each domain from the BDI-2 and by subgroups of age. RESULTS: With a cut-off DDQ<90, 86.8% of tests with yellow result (CDE) indicated at least one domain affected and 50% 3 or more compared with 93.8% and 78.8% for red result, respectively. There were differences in every domain (P<0.001) for the percent of children with DDQ<80 between yellow and red result (CDE): cognitive 36.1% vs. 61.9%; communication: 27.8% vs. 50.4%, motor: 18.1% vs. 39.9%; personal-social: 20.1% vs. 28.9%; and adaptive: 6.9% vs. 20.4%. CONCLUSIONS: The semaphore result yellow/red allows identifying different magnitudes of delay in developmental domains or subdomains, supporting the recommendation of different interventions for each one.
RESUMO
The febrile cholestatic disease as a presentation of Hodgkins lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.
Assuntos
Febre/etiologia , Doença de Hodgkin/complicações , Icterícia Obstrutiva/etiologia , Biópsia , Evolução Fatal , Feminino , Humanos , Fígado/patologia , Pessoa de Meia-IdadeRESUMO
Introducción. En México, no se contaba con una prueba de evaluación del desarrollo infantil con propiedades psicométricas. La prueba de evaluación del desarrollo infantil (EDI) se desarrolló con este fin. El objetivo de este trabajo fue determinar las propiedades psicométricas de la EDI como prueba de tamizaje para los problemas de desarrollo infantil en menores de 5 años. Métodos. Se realizó un estudio transversal que incluyó pacientes menores de 5 años en tres entidades de la República Mexicana: Chihuahua, Yucatán y Distrito Federal. El espectro de la población incluyó niños con factores de riesgo biológico, ambiental y sin riesgo para retraso en el desarrollo. Se excluyeron los pacientes con alteraciones neurológicas evidentes. Se consideró, como prueba diagnóstica, el Inventario de Desarrollo de Battelle-2 en las tres entidades. En el Distrito Federal, adicionalmente, se aplicó Bayley-III. A cada participante se le aplicaron la prueba de tamizaje en dos versiones y la prueba diagnóstica, el mismo día o en un lapso no mayor a una semana. La persona que aplicó la prueba diagnóstica no conocía el resultado de la prueba de tamizaje. Se definió retraso cuando el cociente total de desarrollo resultó menor a 90. Resultados. Se incluyeron, en total, 438 niños menores de 5 años provenientes del Distrito Federal (n =152, 34.7%), Yucatán (n =151, 34.5%) y Chihuahua (n =135, 30.8%). Del total, 43.4% fueron del sexo femenino (n =190). La clasificación por tipo de riesgo fue biológico (n =197, 45%), ambiental (n =137, 31.3%) y sin riesgo (n =104, 23.7%). Se encontró una sensibilidad de 0.81 (IC 95%: 0.75-0.86), especificidad de 0.61 (IC 95%: 0.54-0.67), concordancia 0.70 (IC 95%: 0.66-0.74). La correlación parcial de las áreas del desarrollo entre la prueba de tamizaje y la prueba Bayley III (n =87) ajustada por grupo de edad del tamizaje fue la siguiente: área motor fino 0.468, motor grueso 0.441, lenguaje 0.508, social 0.336 y adaptativo 0.355 (p ≤0.001). Conclusiones. La prueba EDI posee propiedades adecuadas y similares a las pruebas más utilizadas en América.
Background. The ''Evaluación del Desarrollo Infantil'' (EDI) test was developed as an screening tool for the developmental evaluation of Mexican children younger than 5 years old. The objective of this study was to evaluate the psychometric properties of EDI as a screening tool for children with developmental problems. Methods. We carried out a cross-sectional study including patients from urban and rural areas in three locations: Mexico City, Yucatan and Chihuahua. The disease spectrum was defined according to biological risk, environmental risk or without risk for developmental problems. Patients with obvious neurological disabilities or genetic syndromes were excluded. The gold standards were the Battelle Developmental Inventory 2 (in Spanish) and Bayley-III. Each participant had two complete applications of the EDI test (all interrogated and all observed) and the gold standard (Bayley-III only in Mexico City). Developmental delay was defined as a total development quotient <90. Results. The study included 438 children <5 years old. Distribution by site includes Mexico City (n =152, 34.7%), Yucatan (n =151, 34.5%), Chihuahua (n =135, 30.8%); female gender (n =190, 43.4%). Classification by risk includes biological (n =197, 45%), environmental (n =137, 31.3%), without risk (n =104, 23.7%). With BDI-II as the gold standard, the modified version of EDI (interrogated plus observation) has a sensitivity of 0.81 (95% CI: 0.75-0.86), specificity 0.61 (95% CI: 0.54-0.67), and concordance 0.70 (95% CI: 0.66-0.74). The partial correlation between EDI areas and Bayley-III areas (n =87) was adjusted by test group: fine motor 0.468, gross motor 0.441, language 0.508, social 0.336 and adaptive 0.355 (p ≤0.001). Conclusions. The modified version of EDI has similar properties as the various developmental screening tools available in the U.S. or Latin America and could be a good screening tool in Spanish.
RESUMO
The administration of curcumin before and throughout the study attenuates oxidant stress and glomerular hemodynamic alterations induced by 5/6 nephrectomy (5/6NX). The purpose of this work was to study if curcumin is able to reverse established glomerular hemodynamic alterations (e.g. hyperfiltration and glomerular hypertension) and oxidant stress in rats with 5/6NX. Curcumin (120 mg/kg) was given to rats with established renal injury (30 days after surgery) and continued for 30 days (days 31-60 of the study). All rats were studied on day 60 after surgery. Curcumin was able (a) to reverse 5/6NX-induced glomerular hypertension and hyperfiltration, (b) to induce cell proliferation and nuclear translocation of Nrf2 and (c) to reverse 5/6NX-induced oxidant stress and decrease in antioxidant enzymes. These beneficial effects of curcumin were associated with the ability of this antioxidant to reverse renal structural alterations, proteinuria, hypertension, interstitial fibrosis, fibrotic glomeruli, tubular atrophy and mesangial expansion. It has been shown for the first time that curcumin is able to reverse established oxidants stress glomerular hypertension and hyperfiltration in rats with 5/6NX. These novel findings may play a key role in the attenuation of proteinuria and progression of renal damage in rats with 5/6NX. These data suggest that curcumin may be useful to reverse established hemodynamic alterations and renal injury in patients with chronic renal failure.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Nefropatias/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Núcleo Celular/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hemodinâmica/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Nefrectomia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Proteinúria/tratamento farmacológico , Ratos , Ratos WistarRESUMO
Introducción. La Academia Americana de Pediatría recomienda aplicar, sistemáticamente, pruebas de tamizaje del neurodesarrollo para el oportuno diagnóstico y tratamiento. Para lograr referir apropiadamente a los pacientes, es importante tener información bien fundamentada sobre estas herramientas. Métodos. Se realizó una revisión sistemática de estudios de validación de pruebas de tamizaje de neurodesarrollo para menores de 5 años en Estados Unidos y Latinoamérica, de 1980 a 2012. Resultados. Se encontraron 13 pruebas con diferentes características de evaluación y calificación. Obtuvieron la mejor sensibilidad y especificidad Battelle Developmental Inventory Screening (2nd Edition) (0.93 y 0.88) y PRUNAPE con VPP 0.94 y VPN 0.97. Conclusiones. De 1980 a 2012, se encontraron 13 pruebas de tamizaje del neurodesarrollo para menores de 5 años en Estados Unidos y Latinoamérica. La Battelle Developmental Inventory Screening obtuvo la mayor validez de criterio, y la PRUNAPE fue la más predictiva. No se encontraron estudios de validación en México. Por lo tanto, se consideró de vital importancia contar con una herramienta validada en nuestro país.
Background. The American Academy of Pediatrics recommends the application of neurodevelopmental screening tests for early intervention of neurodevelopmental disorders. In order to refer these tests appropriately, it is important to have well-founded information in regard to these tools. Methods. A systematic literature search targeted on validation studies of neurodevelopmental screening tests in children <5 years of age in the U.S. and Latin America from 1980 to 2012 was conducted. Results. We found 19 validation studies of 13 screening tests. Battelle Developmental Screening Inventory (2nd edition) reported the best sensitivity and specificity (0.93/0.88) and PRUNAPE with predictive positive and negative values (0.94/0.97). Conclusions. From 1980-2012we found 13 neurodevelopmental screening tests in the U.S. and Latin America for children <5 years of age. The best criterion and predictive validity was for Battelle Developmental Inventory Screening and PRUNAPE, respectively. No validation studies were found in Mexico; therefore, we consider it important to have a validated tool in our country.
RESUMO
Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8-10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.
Assuntos
Núcleo Celular/metabolismo , Curcumina/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Hipertensão/prevenção & controle , Glomérulos Renais/enzimologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Nitrogênio da Ureia Sanguínea , Núcleo Celular/efeitos dos fármacos , Creatinina/sangue , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Glomérulos Renais/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nefrectomia , Oxidantes/toxicidade , Consumo de Oxigênio/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Proteinúria/sangue , Proteinúria/complicações , Proteinúria/fisiopatologia , Punções , Ratos , Ratos Wistar , Sístole/efeitos dos fármacosRESUMO
Deferoxamine (DFO) is a recognized iron chelator which has been shown to exert nephroprotection in models of toxic nephropathies. In the present work the potential protective effects of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress were evaluated. Rats were injected with a single injection (15mg/kg, s.c.) of potassium dichromate (K(2)Cr(2)O(7)). DFO was given as a single i.p. injection 30min before K(2)Cr(2)O(7) administration at three different doses (100, 200 and 400mg/kg). It was found that DFO pretreatment attenuated, in a dose-dependent way, K(2)Cr(2)O(7)-induced renal dysfunction and structural alterations evaluated by serum creatinine, blood urea nitrogen, creatinine clearance, proteinuria, plasma glutathione peroxidase activity, urinary excretion of N-acetyl-ß-d-glucosaminidase and histological analyses. Furthermore, DFO prevented the K(2)Cr(2)O(7)-induced renal oxidant stress and the decrease in the activity of the antioxidant enzymes superoxide dismutase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and catalase. Finally it was found that DFO, at 400mg/kg, decreases renal Cr(VI) content which prompted us to evaluate the potential Cr(VI) chelating properties of this compound. Indeed was found in an in vitro assay that DFO was an effective Cr(VI) chelator with an IC(50) of 800µg. In additional groups of rats was found that DFO posttreatment was ineffective to attenuate K(2)Cr(2)O(7)-induced nephrotoxicity and renal oxidant stress. Furthermore, DFO was unable to modify urinary excretion of total chromium. The nephroprotective effect of DFO against Cr(VI)-induced nephrotoxicity and oxidant stress may be explained, at least partially, by the ability of DFO to chelate Cr(VI) and to attenuate renal Cr(VI) content. However, it cannot be excluded that the ability of DFO to chelate iron may also be involved in the protection observed in our study.
Assuntos
Antídotos/farmacologia , Quelantes/farmacologia , Cromo/antagonistas & inibidores , Cromo/toxicidade , Desferroxamina/farmacologia , Nefropatias/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Dicromato de Potássio/antagonistas & inibidores , Dicromato de Potássio/toxicidade , Animais , Catalase/metabolismo , Quelantes/química , Cromo/urina , Desferroxamina/química , Glutationa/metabolismo , Técnicas In Vitro , Indicadores e Reagentes , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Nefropatias/prevenção & controle , Testes de Função Renal , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Dicromato de Potássio/farmacocinética , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium [Cr(VI)] compound potassium dichromate (K(2)Cr(2)O(7)) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400 mg/kg bw 10 days before and 2 days after K(2)Cr(2)O(7) injection), (2) pretreatment (400 mg/kg bw for 10 days before K(2)Cr(2)O(7) injection), and (3) posttreatment (400 mg/kg bw 2 days after K(2)Cr(2)O(7) injection). Rats were sacrificed 48 h later after a single K(2)Cr(2)O(7) injection (15 mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K(2)Cr(2)O(7)-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K(2)Cr(2)O(7)-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II-III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K(2)Cr(2)O(7)-induced renal dysfunction. In further experiments performed in curcumin (400 mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K(2)Cr(2)O(7) was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K(2)Cr(2)O(7)-induced renal oxidant damage.
Assuntos
Antioxidantes/administração & dosagem , Curcumina/administração & dosagem , Rim/efeitos dos fármacos , Mitocôndrias/metabolismo , Insuficiência Renal/prevenção & controle , Animais , Antioxidantes/efeitos adversos , Carcinógenos Ambientais/administração & dosagem , Cromo/administração & dosagem , Curcumina/efeitos adversos , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologiaRESUMO
In the present work was analyzed whether sulforaphane (SFN) may protect against cisplatin (CIS)-induced hepatic damage, oxidant stress and mitochondrial dysfunction. Four groups of male Wistar rats were studied: control, CIS, CIS+SFN and SFN. SFN was given i.p. (500 µg/kg/d × 3 days) before CIS administration (single i.p. injection, 10mg/kg). Rats were sacrificed 3 days after CIS injection to evaluate hepatic damage (histological analysis, liver/body weight ratio and serum activity of aspartate aminotransferase and alanine aminotransferase), oxidant stress (lipid peroxidation and protein carbonyl and glutathione content), antioxidant enzymes (catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase and superoxide dismutase) in liver homogenates and isolated mitochondria and mitochondrial function (oxygen consumption using either malate/glutamate or succinate as substrates and the activity of mitochondrial complex I, II, II-III, IV and V). Furthermore it was evaluated if SFN is able to scavenge some reactive oxygen species in vitro. It was found that SFN prevents CIS-induced (a) hepatic damage, (b) oxidant stress and decreased activity of antioxidant enzymes in liver and mitochondria and (c) mitochondrial alterations in oxygen consumption and decreased activity of mitochondrial complex I. It was also found that the scavenging ability of SFN for peroxynitrite anion, superoxide anion, singlet oxygen, peroxyl radicals, hydrogen peroxide and hydroxyl radicals was very low or negligible. The hepatoprotective effect of SFN was associated to the preservation of mitochondrial function, antioxidant enzymes and prevention of liver and mitochondrial oxidant stress.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cisplatino/toxicidade , Tiocianatos/farmacologia , Animais , Antioxidantes/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Injeções Intraperitoneais , Isotiocianatos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/patologia , Estresse Oxidativo/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , SulfóxidosRESUMO
This work was designed to further study the mechanism by which sulforaphane (SFN) exerts a renoprotective effect against cisplatin (CIS)-induced damage. It was evaluated whether SFN attenuates the CIS-induced mitochondrial alterations and the impairment in the activity of the cytoprotective enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and γ glutamyl cysteine ligase (γGCL). Studies were performed in renal epithelial LLC-PK1 cells and in isolated renal mitochondria from CIS, SFN or CIS+SFN treated rats. SFN effectively prevented the CIS-induced increase in reactive oxygen species (ROS) production and the decrease in NQO1 and γGCL activities and in glutathione (GSH) content. The protective effect of SFN on ROS production and cell viability was prevented by buthionine sulfoximine (BSO), an inhibitor of γGCL, and by dicoumarol, an inhibitor of NQO1. SFN was also able to prevent the CIS-induced mitochondrial alterations both in LLC-PK1 cells (loss of membrane potential) and in isolated mitochondria (inhibition of mitochondrial calcium uptake, release of cytochrome c, and decrease in GSH content, aconitase activity, adenosine triphosphate (ATP) content and oxygen consumption). It is concluded that the protection exerted by SFN on mitochondrial alterations and NQO1 and γGCL enzymes may be involved in the renoprotection of SFN against CIS.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Glutamato-Cisteína Ligase/metabolismo , Rim/efeitos dos fármacos , Células LLC-PK1/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/prevenção & controle , NAD(P)H Desidrogenase (Quinona)/metabolismo , Tiocianatos/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Sinalização do Cálcio/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Inibidores Enzimáticos/farmacologia , Glutamato-Cisteína Ligase/antagonistas & inibidores , Glutationa/metabolismo , Isotiocianatos , Rim/metabolismo , Rim/patologia , Células LLC-PK1/metabolismo , Células LLC-PK1/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/enzimologia , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , Consumo de Oxigênio , Ratos , Sulfóxidos , SuínosRESUMO
Se evaluó la eficacia y la tolerancia del Florestor (Saccharomyces boulardii, dosis diaria oral 400 mg) en el síndrome de diarrea aguda, mediante un estudio clínico abierto y multicéntrico, donde se incluyeron 230 niños con edades comprendidas entre 3 meses y 5 años. La evaluación del total diario de puntos antes y después de tratamiento con Florestor mostró una diferencia estadísticamente significante (p<0,001). Esta cuantificación de la eficacia reflejó indirectamente porcentajes de curación de 91,7 por ciento a los tres días de tratamiento. Al tercer día de tratamiento, la eficacia clínica fue considerada como muy eficaz o eficaz en un 99,1 por ciento del total de pacientes. En un 96 por ciento del universo de los 230 pacientes, la tolerancia fue expresada como excelente o buena. Se concluye que florestor es un producto seguro y eficaz para el tratamiento de la diarrea aguda, no complicada, asociado a la rehidratación oral en niños ambulatorios con edades entre 3 meses y 5 años