RESUMEN
Cyclosporine A, a potent immunosuppressive agent extensively used to prevent allograft rejections, is under scrutiny due to severe toxic effects. CsA therapy is often continued during pregnancy in conditions such as organ transplantations and autoimmune diseases. Herein, we investigated the effects of CsA on early morphogenesis of zebrafish and identified a spectrum of proteins whose expression was altered in the drug treated embryos. Time-lapse fluorescence imaging of germ-line double transgenic zebrafish embryos treated with CsA revealed severe blood regurgitation in heart chambers, absence of blood circulation in vessels, pericardial and yolk sac edema. We also observed lack of mature blood vessels and down-regulation of endothelial markers in CsA treated embryos. Proteomic analysis using 2D-DIGE followed by mass-spectrometry led to the identification of 37 proteins whose expression was significantly modulated in presence of the drug. These proteins were mostly associated with cytoskeletal/structural assembly, lipid-binding, stress response and metabolism. Furthermore, mRNA expression analysis of eight proteins and Western blotting of actin revealed consistency between the changes observed in protein expression and its corresponding mRNA levels. Our findings demonstrate that CsA administration during early morphogenesis in zebrafish modulates the expression of some proteins which are known to be involved in important physiological processes.
Asunto(s)
Ciclosporina/efectos adversos , Embrión no Mamífero/embriología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Inmunosupresores/efectos adversos , Morfogénesis/efectos de los fármacos , Proteoma/biosíntesis , Proteínas de Pez Cebra/biosíntesis , Pez Cebra/embriología , Anomalías Múltiples/inducido químicamente , Anomalías Múltiples/embriología , Anomalías Múltiples/metabolismo , Animales , Ciclosporina/farmacología , Embrión no Mamífero/metabolismo , Femenino , Humanos , Inmunosupresores/farmacología , Embarazo , Proteómica/métodos , Pez Cebra/metabolismoRESUMEN
BACKGROUND: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet therapy reduces clot formation. We have studied the risk of venous thrombosis with use of statins, other lipid-lowering medication, and antiplatelet therapy. MATERIALS AND METHODS: Patients with a first episode of deep vein thrombosis in the leg or pulmonary embolism between March 1999 and September 2004 were included in a large population-based case-control study (MEGA study). Control subjects were partners of patients (53%) or recruited via a random-digit-dialing method (47%). Participants reported different all-medication use in a questionnaire. RESULTS: Of 4538 patients, 154 used statins (3.3%), as did 354 of 5914 control subjects (5.7%). The use of statins [odds ratio (OR) 0.45; 95% confidence interval (CI) 0.36-0.56] but not other lipid-lowering medications (OR 1.22; 95% CI 0.62-2.43), was associated with a reduced venous thrombosis risk as compared with individuals who did not use any lipid-lowering medication, after adjustment for age, sex, body mass index, atherosclerotic disease, antiplatelet therapy and use of vitamin K antagonists. Different types and various durations of statin therapy were all associated with a decreased venous thrombosis risk. Antiplatelet therapy also reduced venous thrombosis risk (OR 0.56; 95% CI 0.42-0.74). However, sensitivity analyses suggested that this effect is most likely explained by a so-called 'healthy user effect'. Simultaneous use of medication most strongly reduced venous thrombosis risk. CONCLUSION: These results suggest that the use of various types of statins is associated with a reduced risk of venous thrombosis, whereas antiplatelet therapy and other lipid-lowering medications are not.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipolipemiantes/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Trombosis de la Vena/tratamiento farmacológico , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo , Encuestas y Cuestionarios , Resultado del Tratamiento , Trombosis de la Vena/epidemiología , Vitamina K/antagonistas & inhibidores , Adulto JovenRESUMEN
Spillage of gallstones during laparoscopic cholecystectomy is not a rare event. We present a patient with spilled calculi causing an incarcerated hernia.
Asunto(s)
Colecistectomía Laparoscópica/efectos adversos , Hernia Inguinal/etiología , Hernia Inguinal/cirugía , Complicaciones Intraoperatorias , Colecistectomía Laparoscópica/métodos , Colelitiasis/cirugía , Estudios de Seguimiento , Hernia Inguinal/patología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
We report a secretory paraganglioma in an eleven-year-old Trinidadian girl of East Indian descent who presented with malignant hypertension, proteinuria and modest elevation of urinary vanillylmandelic acid levels. The extra-adrenal mass was surgically removed without complications. The patient has been normotensive without evidence of recurrence of disease but with persistent visual sequel two years later. This case reinforces the observation that extraadrenal retroperitoneal paragangliomas can be functionally very active and early computed tomography or other imaging procedure is necessary for rapid noninvasive evaluation, timely surgery and prevention of permanent morbidity.
Asunto(s)
Hipertensión Maligna/etiología , Paraganglioma/complicaciones , Neoplasias Retroperitoneales/complicaciones , Trastornos de la Visión/etiología , Niño , Femenino , Humanos , Hipertensión Maligna/cirugía , Paraganglioma/cirugía , Neoplasias Retroperitoneales/cirugía , Ácido Vanilmandélico/orina , Agudeza VisualRESUMEN
We report a secretory paraganglioma in an eleven-year-old Trinidadian girl of East Indian descent who presented with malignant hypertension, proteinuria and modest elevation of urinary vanillylmandelic acid levels. The extraadrenal mass was surgically removed without complications. The patient has been normotensive without evidence of recurrence of disease but with persistent visual sequel two years later. This case reinforces the observation that extraadrenal retroperitoneal paragangliomas can be functionally very active and early computed tomography or other imaging procedure is necessary for rapid noninvasive evaluation, timely surgery and prevention of permanent morbidity.(Au)
Asunto(s)
Niño , Informes de Casos , Femenino , Humanos , Paraganglioma/complicaciones , Hipertensión Maligna/etiología , Neoplasias Retroperitoneales/complicaciones , Trastornos de la Visión/etiología , Trinidad y Tobago , Hipertensión Maligna/cirugía , Paraganglioma/cirugía , Neoplasias Retroperitoneales/cirugía , Ácido Vanilmandélico/orina , Agudeza VisualRESUMEN
We report a secretory paraganglioma in an eleven-year-old Trinidadian girl of East Indian descent who presented with malignant hypertension, proteinuria and modest elevation of urinary vanillylmandelic acid levels. The extraadrenal mass was surgically removed without complications. The patient has been normotensive without evidence of recurrence of disease but with persistent visual sequel two years later. This case reinforces the observation that extraadrenal retroperitoneal paragangliomas can be functionally very active and early computed tomography or other imaging procedure is necessary for rapid noninvasive evaluation, timely surgery and prevention of permanent morbidity.