RESUMEN
AIMS: To compare the effectiveness and safety of polypropylene (PP) and polyvinylidene fluoride (PVDF) transobturator tapes (TOT) for the treatment of female stress urinary incontinence (SUI). METHODS: This is a multicentre randomized trial. Women with SUI or stress-predominant mixed urinary incontinence and scheduled for a TOT procedure were randomized to PP or PVDF slings. The primary outcome was 1-year cure or improvement rate using composite criteria. Complications were also compared. Relationships with outcomes were analyzed using multivariable logistic regressions models. RESULTS: From April 2016 to January 2018 285 participants were randomized. PP and PVDF slings showed similar high cure or improvement rate (91.0% vs. 95.6%, p = .138). Improvement in validated questionnaires was also similar. PVDF slings were associated with a lower rate of de novo urgency incontinence (adjusted odds ratio = 0.35; 95% confidence interval = 0.15-0.80). We found no statistical differences in complications rates, although a higher incidence of long-term pain events were observed in the PP group. The study is underpowered to find differences in specific complications owing to the low number of events. CONCLUSION: PP and PVDF TOTs are equally effective, although PVDF is associated with fewer cases of de novo urgency incontinence. Further studies are needed to give robust conclusions on safety profiles.
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Polipropilenos/uso terapéutico , Polivinilos/uso terapéutico , Incontinencia Urinaria/tratamiento farmacológico , Incontinencia Urinaria/terapia , Procedimientos Quirúrgicos Urológicos/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polipropilenos/farmacología , Polivinilos/farmacología , Encuestas y Cuestionarios , Resultado del Tratamiento , Incontinencia Urinaria de EsfuerzoRESUMEN
Studies carried out in nonclinical samples have found an association between cyberbullying victimization and eating disorder (ED) psychopathology (negative emotions, low self-esteem, unhealthy eating behaviors, and body dissatisfaction); however, these previous studies were carried out with participants without an ED diagnosis. To extend the knowledge in this area of research, we aim to confirm these associations in two different samples: on the one hand, a sample composed of participants with ED diagnoses and, on the other hand, a sample composed of participants at high risk of ED. In study 1, the sample was composed of 80 participants diagnosed with EDs: 41.2 percent, n = 33, matched bulimia nervosa criteria; 33.8 percent, n = 27, matched anorexia nervosa restrictive criteria; and 25 percent, n = 20, matched eating disorder not otherwise specified. In study 2, the sample was composed of 156 participants at high risk of ED (elite athletes, both men and women). In both samples, the results indicated that cyberbullying victimization was positively correlated with ED psychopathology and depression. The model consisting of gender, body mass index, appearance evaluation, depression, and cyberbullying victimization was a significant predictor of ED psychopathology. This study suggests that cyberbullying victimization is a predictor of eating behaviors, attitudes, and symptoms associated with ED.
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Imagen Corporal/psicología , Víctimas de Crimen/psicología , Ciberacoso/psicología , Depresión/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Adolescente , Adulto , Índice de Masa Corporal , Emociones , Conducta Alimentaria/psicología , Femenino , Humanos , Masculino , Satisfacción Personal , Autoimagen , Factores Sexuales , Adulto JovenRESUMEN
Chondrodermatitis nodularis chronica helicis is a rare non-neoplastic inflammatory and degenerative process of the external ear, characterized by necrobiotic changes in the dermis that extend down to the perichondrium. This condition has been occasionally reported in patients with limited cutaneous systemic sclerosis but not in those with concomitant primary biliary cirrhosis; this association is known as Reynolds syndrome. We report a 70-year-old woman diagnosed with primary biliary cirrhosis at age 47 and with limited cutaneous systemic sclerosis at age 54 who developed a painful ulcerated nodule on the helical rim of the left ear shortly after the last diagnosis. The lesion was excised because of the suspicion of malignancy, but the histopathology was consistent with chondrodermatitis nodularis chronica helicis. Although this condition is infrequent, it is necessary to know, because it may occur in patients with systemic sclerosis and be mistaken for neoplasms, such as basal cell and squamous cell carcinoma, and these patients have an increased risk for the development of skin malignancies.
RESUMEN
Cutaneous plasmacytomas are monoclonal proliferations of plasma cells which can be classified into primary (with no other concomitant bony or extramedullary disease) or secondary (generally associated with multiple myeloma (MM), extramedullary plasmacytoma, or plasma cell leukemia). Cutaneous plasmacytomas can appear in some patients with MM and, rarely, the skin lesions suppose the first clinical manifestation of the disease. Their development is considered as a poor prognostic sign, associated with a life expectancy of less than 12 months after diagnosis. An unusual case of MM is described, in which the histopathological study of a skin nodule provided invaluable information for diagnosis.
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Mieloma Múltiple/patología , Neoplasias Cutáneas/patología , Piel/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Biopsia , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Mieloma Múltiple/química , Mieloma Múltiple/tratamiento farmacológico , Valor Predictivo de las Pruebas , Piel/química , Neoplasias Cutáneas/química , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
Spiny keratoderma is an infrequent dermatosis consisting of multiple projections located on the palms and soles, with the distinct histopathology feature of a parakeratotic column above a hypogranular epidermis. This entity has been reported under several different names, such as punctate porokeratotic keratoderma, punctate keratoderma, palmar filiform hyperkeratosis, and spiny keratoderma of the palms and soles. Most of the cases described are acquired, although there are also familial cases. Since this disease has been under-diagnosed and under-reported, it is important for dermatologists to keep spiny keratoderma of the palms and soles in mind. We present a familial case of spiny keratoderma and review the literature.
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Queratodermia Palmoplantar/genética , Queratodermia Palmoplantar/patología , Paraqueratosis/patología , Niño , Femenino , HumanosRESUMEN
We report the case of a 72-year-old man with history of ankylosing spondylitis, who, during the treatment with infliximab, developed painful, erythematous-violaceous plaques with later development of ulcers on his feet associated with cold exposure. Concomitantly with the appearance of these lesions, he presented increased antinuclear antibodies (ANA) titers, positivity for anti-DNA and IgM anticardiolipin antibodies, low complement levels, polyclonal hypergammaglobulinemia, and lymphopenia. He was diagnosed of chilblain lupus induced by infliximab, this agent was withdrawn and initiated treatment for chilblains with improvement of lesions. On reviewing of the literature, we found seven reported cases of tumor necrosis factor α (TNF-α) antagonists-induced chilblain lupus, all in rheumatoid arthritis patients and four of them with clinical and immunological characteristics available are presented and compared with our case. Although it is infrequent, chilblain lupus forms part of the spectrum of TNF-α antagonists-induced lupus erythematosus; usually is limited to skin without progression to systemic lupus erythematosus; presents ANA, anti-DNA, and antinucleosome antibodies positivity as more frequent immunological alterations; and responds appropriately to the specific treatment, TNF-α antagonists withdrawal being not necessary in almost all cases.
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Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Eritema Pernio/inducido químicamente , Lupus Eritematoso Cutáneo/inducido químicamente , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anciano , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Humanos , Infliximab , MasculinoRESUMEN
Orofacial granulomatosis, an uncommon immunologically mediated disorder, includes cheilitis granulomatosa and Melkersson-Rosenthal syndrome. It is clinically characterized by recurrent or persistent swelling of the orofacial tissues with a spectrum of other orofacial features and sometimes with neurological symptoms. The pathological findings are varied but are often characterized by the presence of noncaseating granuloma. We present a new case of orofacial granulomatosis with unusual histopathological findings, namely, intralymphatic granulomas. These may be the cause of the tissue edema. We demonstrated, by immunohistochemical studies, the lymphatic nature of the vessels affected by the granulomatous process.
Asunto(s)
Queilitis/patología , Granuloma/patología , Vasos Linfáticos/patología , Síndrome de Melkersson-Rosenthal/patología , Adulto , Biomarcadores/metabolismo , Queilitis/metabolismo , ADN/análisis , Reordenamiento Génico de Linfocito T , Granuloma/genética , Granuloma/metabolismo , Humanos , Inmunohistoquímica , Vasos Linfáticos/metabolismo , Masculino , Síndrome de Melkersson-Rosenthal/genética , Síndrome de Melkersson-Rosenthal/metabolismoRESUMEN
The quadrivalent human papillomavirus (qHPV) vaccine, the first vaccine for use in the prevention of cervical cancer and condyloma acuminatum, was approved in June 2006. In 2008, the mass media reported suspected links between the qHPV vaccine and serious adverse events; however, several studies have found that the vaccine is safe and the main adverse events are mild local reactions. Erythema multiforme (EM) is an acute self-limited cutaneous or mucocutaneous syndrome characterized by the abrupt onset of symmetric target lesions. The clinical manifestations and histological features of EM, Stevens-Johnson syndrome and toxic epidermal necrolysis show considerable overlap, and they are classically considered to represent a spectrum of skin disorders. We present a case of EM following qHPV vaccination to review the cutaneous side effects of this vaccine and the possibility of more serious side effects with the administration of booster doses.
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Erupciones por Medicamentos/etiología , Eritema Multiforme/inducido químicamente , Vacunas contra Papillomavirus/efectos adversos , Vacunación/efectos adversos , Adolescente , Corticoesteroides/uso terapéutico , Eritema Multiforme/tratamiento farmacológico , Eritema Multiforme/patología , Eritema Multiforme/fisiopatología , Femenino , Antagonistas de los Receptores Histamínicos/uso terapéutico , Vacuna Tetravalente Recombinante contra el Virus del Papiloma Humano Tipos 6, 11 , 16, 18 , Humanos , Vacunas contra Papillomavirus/administración & dosificaciónAsunto(s)
Enfermedades de la Piel/patología , Xantomatosis/patología , Adulto , Nalgas , Humanos , Masculino , MusloRESUMEN
Downstream regulatory element antagonist modulator (DREAM)/potassium channel interacting protein (KChIP3) is a multifunctional protein of the neuronal calcium sensor subfamily of Ca2+-binding proteins with specific roles in different cell compartments. In the nucleus, DREAM acts as a Ca2+-dependent transcriptional repressor, and outside the nucleus DREAM interacts with Kv4 potassium channels, regulating their trafficking to the cell membrane and their gating properties. In this study we characterized the interaction of DREAM with GRK6 and GRK2, members of the G protein-coupled receptor kinase family of proteins, and their phosphorylation of DREAM. Ser-95 was identified as the site phosphorylated by GRK2. This phosphorylation did not modify the repressor activity of DREAM. Mutation of Ser-95 to aspartic acid, however, blocked DREAM-mediated membrane expression of the Kv4.2 potassium channel without affecting channel tetramerization. Treatment with the calcineurin inhibitors FK506 and cyclosporin A also blocked DREAM-mediated Kv4.2 channel trafficking and calcineurin de-phosphorylated GRK2-phosphorylated DREAM in vitro. Our results indicate that these two Ca2+-dependent posttranslational events regulate the activity of DREAM on Kv4.2 channel function.
Asunto(s)
Proteínas de Interacción con los Canales Kv/metabolismo , Transporte de Proteínas/fisiología , Proteínas Represoras/metabolismo , Canales de Potasio Shal/metabolismo , Quinasas de Receptores Adrenérgicos beta/metabolismo , Calcineurina/metabolismo , Calcio/metabolismo , Línea Celular , Membrana Celular/metabolismo , Quinasa 2 del Receptor Acoplado a Proteína-G , Quinasas de Receptores Acoplados a Proteína-G , Humanos , Riñón/citología , Leucina/metabolismo , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Estructura Cuaternaria de Proteína , Canales de Potasio Shal/química , Especificidad por Sustrato , Transcripción Genética/fisiología , Técnicas del Sistema de Dos HíbridosRESUMEN
Gefitinib (Iressa) is a new antineoplastic agent that acts by selectively inhibiting epidermal growth factor receptor tyrosine kinase (EGFR-TK). It has shown activity against several solid tumors. Because of their action mechanism, gefitinib and other tyrosine kinase inhibitors have been associated with multiple cutaneous effects, most of which are mild and well tolerated. We present a case of perforating dermatosis after treatment with gefitinib.
Asunto(s)
Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioterapia Adyuvante/efectos adversos , Erupciones por Medicamentos/etiología , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos , Úlcera Cutánea/inducido químicamente , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Erupciones por Medicamentos/patología , Receptores ErbB/antagonistas & inhibidores , Gefitinib , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/antagonistas & inhibidores , Neumonectomía , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinazolinas/uso terapéutico , Úlcera Cutánea/patologíaRESUMEN
El gefitinib (Iressa®) es un nuevo agente antineoplásico que actúa inhibiendo selectivamente la tirosina cinasa del factor de crecimiento epidérmico (EGFR-TK). Ha demostrado actividad frente a varios tumores sólidos. Por su mecanismo de acción, el gefitinib y otros inhibidores de tirosina cinasa se han asociado a múltiples efectos cutáneos dermatológicos, la mayoría de ellos leves y bien tolerados. Se presenta un caso de dermatosis perforante tras tratamiento con gefitinib
Gefitinib (Iressa®) is a new antineoplastic agent that acts by selectively inhibiting epidermal growth factor receptor tyrosine kinase (EGFR-TK). It has shown activity against several solid tumors. Because of their action mechanism, gefitinib and other tyrosine kinase inhibitors have been associated with multiple cutaneous effects, most of which are mild and well tolerated. We present a case of perforating dermatosis after treatment with gefitinib
Asunto(s)
Masculino , Adulto , Humanos , Dermatosis Facial/diagnóstico , Dermatosis Facial/terapia , Antineoplásicos/efectos adversos , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Receptores ErbB/uso terapéutico , Hiperqueratosis Epidermolítica/complicaciones , Hiperqueratosis Epidermolítica/diagnóstico , Erupciones Acneiformes/complicaciones , Erupciones Acneiformes/diagnóstico , Dermatosis Facial/patología , Hiperqueratosis Epidermolítica/patología , Acantosis Nigricans/complicaciones , Erupciones Acneiformes/patología , Erupciones Acneiformes/fisiopatología , Erupciones Acneiformes/terapiaRESUMEN
The role of alpha-synuclein (alpha-Syn) has recently received considerable attention because it seems to play a role in Parkinson's disease (PD). Missense mutations in the alpha-Syn gene were found in autosomal dominant PD and alpha-Syn was shown to be a major constituent of protein aggregates in sporadic PD and other synucleinopathies. Under normal conditions, alpha-Syn protein is found exclusively in synaptic terminals. However, the potential participation of alpha-synuclein in maintaining and regulating synaptic efficacy is unknown. We have investigated the excitatory synaptic modulation of alpha-synuclein in CA1 pyramidal neurons, using the in vitro hippocampal slice technique. The 4-aminopyridine-induced increase of both spontaneous excitatory postsynaptic current (EPSC) frequency and amplitude was significantly higher in alpha-Syn wild-type than knockout mice, whereas basal spontaneous EPSC frequency and amplitude was similar in both animals. As the spontaneous synaptic activity was abolished by tetrodotoxin, which indicates that it was a result of action potential-mediated transmitter release from presynaptic terminals, spontaneous EPSC changes observed in alpha-Syn knockout mice suggest that these animals present a modification of synaptic transmission with a presynaptic origin. Presynaptic depression of evoked EPSCs by hypoxia or adenosine was significantly larger in alpha-Syn knockout than in wild-type mice, further supporting the hypothesis of regulation of synaptic transmission by alpha-Syn. Together, these observations indicate that the loss of alpha-Syn reduces synaptic efficacy when the probability of transmitter release is modified. We conclude that alpha-Syn might have important actions on the maintenance of the functional integrity of synaptic transmission and its regulation in hippocampus.
Asunto(s)
Hipocampo/citología , Hipoxia/fisiopatología , Proteínas del Tejido Nervioso/metabolismo , Neuronas/fisiología , Transmisión Sináptica/fisiología , Teofilina/análogos & derivados , 4-Aminopiridina/farmacología , Adenosina/farmacología , Analgésicos/farmacología , Anestésicos Locales/farmacología , Animales , Western Blotting/métodos , Interacciones Farmacológicas , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipoxia/genética , Hipoxia/prevención & control , Técnicas In Vitro , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Neuronas/efectos de los fármacos , Bloqueadores de los Canales de Potasio/farmacología , Transmisión Sináptica/efectos de los fármacos , Sinucleínas , Tetrodotoxina/farmacología , Teofilina/administración & dosificación , Factores de Tiempo , alfa-SinucleínaRESUMEN
Apoptosis is an active process that is regulated by different signalling pathways. One of the more important organelles involved in apoptosis regulation is the mitochondrion. Electron chain transport disruption increases free radical production leading to multiple conductance channel opening, release of cytochrome c and caspase activation. This death pathway can be blocked by anti-apoptotic members of the Bcl-2 protein family that might shift redox potential to a more reduced state, preventing free radical-mediated damage. 6-Hydroxydopamine (6-OHDA) has been widely used to generate Parkinson's disease-like models. It is able to generate free radicals and to induce catecholaminergic cell death. In this paper we have used the human neuroblastoma cell line SH-SY5Y overexpressing Bcl-x(L) as a model to gain insights into the mechanisms through which Bcl-x(L) blocks 6-OHDA-induced cell death and to identify the molecular targets for this action. Herein, we present evidence supporting that the Bcl-x(L)-anti-apoptotic signal pathway seems to prevent mitochondrial multiple conductance channel opening, cytochrome c release and caspase-3 like activity following 6-OHDA treatment in the human neuroblastoma cell line SH-SY5Y.
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Apoptosis/fisiología , Mitocondrias/metabolismo , Neuroblastoma/metabolismo , Oxidopamina/toxicidad , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Antioxidantes/metabolismo , Caspasa 3 , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Tumoral , Citocromos c/metabolismo , Citoprotección/efectos de los fármacos , Citoprotección/fisiología , Activación Enzimática/efectos de los fármacos , Humanos , Mitocondrias/efectos de los fármacos , Neuroblastoma/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Proteína bcl-XRESUMEN
Biochemical changes in rat brain acetylcholinesterase (AChE) activity and molecular isoform distribution were studied using the middle cerebral artery occlusion model. After 24 h of permanent focal ischemia, AChE specific activity from infarcted cortex was found to decrease compared with contralateral cortex. Also a decrease in the minor monomeric (G1) form of AChE is response to ischemia was observed. Ischemia-induced AChE decrease was partially diminished by pre-treatment with dizocilpine (MK-801), a neuroprotective NMDA receptor blocker.
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Acetilcolinesterasa/metabolismo , Isquemia Encefálica/enzimología , Isoformas de Proteínas/metabolismo , Animales , Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Química Encefálica , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Maleato de Dizocilpina/farmacología , Maleato de Dizocilpina/uso terapéutico , Lateralidad Funcional , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Endogámicas F344RESUMEN
Acetylcholinesterase (AChE) was analyzed in organotypic hippocampal slice cultures (OHSCs) during recovery from a brief period (20 min) of combined hypoxia and hypoglycemia. Simulated ischemia transiently increased AChE activity in OHSCs in a time-dependent manner reaching a 1.5 fold increase at 6 h post-ischemia. The ischemia-induced AChE increase was totally abolished by incubation with 10 microM dizocilpine (MK-801), a neuroprotective NMDA receptor blocker.
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Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Muerte Celular/fisiología , Infarto Cerebral/enzimología , Hipocampo/enzimología , Hipoxia-Isquemia Encefálica/enzimología , Animales , Animales Recién Nacidos , Muerte Celular/efectos de los fármacos , Infarto Cerebral/fisiopatología , Infarto Cerebral/prevención & control , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Hipoxia-Isquemia Encefálica/fisiopatología , Degeneración Nerviosa/enzimología , Degeneración Nerviosa/fisiopatología , Degeneración Nerviosa/prevención & control , Técnicas de Cultivo de Órganos , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
1 In this study, we have used isolated brain mitochondria to investigate the effects of superoxide anions (O(2)(-)) on mitochondrial parameters related to apoptosis, such as swelling, potential, enzymatic activity, NAD(P)H, cytochrome c release, and caspase activity. 2 Addition of the reactive oxygen species (ROS) generator KO(2) produced brain mitochondrial swelling, which was blocked by cyclosporin A (CSA), and which was Ca(2+) independent. 3 Calcium induced mitochondrial swelling only at high concentrations and in the presence of succinate. This correlated with the increase in O(2)(-) production detected with hydroethidine in mitochondrial preparations exposed to Ca(2+) and the fact that ROS were required for Ca(2+)-induced mitochondrial swelling. 4 Superoxide anions, but not Ca(2+), decreased citrate synthase and dehydrogenase enzymatic activities and dropped total mitochondrial NAD(P)H levels. 5 Calcium, but not O(2)(-), triggered a rapid loss of mitochondrial potential. Calcium-induced Deltapsi(m) dissipation was inhibited by Ruthenium Red, but not by CSA. 6 Calcium- and superoxide-induced mitochondrial swelling released cytochrome c and increased caspase activity from isolated mitochondria in a CS A-sensitive manner. 7 In summary, superoxide potently triggers mitochondrial swelling and the release of proteins involved in activation of postmitochondrial apoptotic pathways in the absence of mitochondrial depolarization.
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Citocromos c/metabolismo , Potenciales de la Membrana/fisiología , Dilatación Mitocondrial/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Apoptosis , Encéfalo/citología , Calcio/metabolismo , Calcio/farmacocinética , Caspasas/biosíntesis , Caspasas/metabolismo , Citocromos c/efectos de los fármacos , Canales Iónicos/efectos de los fármacos , Canales Iónicos/fisiología , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial , Poro de Transición de la Permeabilidad Mitocondrial , Dilatación Mitocondrial/fisiología , NADP/análisis , NADP/metabolismo , Óxidos/farmacocinética , Consumo de Oxígeno/fisiología , Compuestos de Potasio/farmacocinética , Ratas , Ratas Sprague-Dawley , Superóxidos/farmacocinéticaRESUMEN
Our results provide evidence that 6-hydroxydopamine induced, after auto-oxidation, toxic levels of hydrogen peroxide (H2O2) that caused bovine chromaffin cell toxicity and death. 6-Hydroxydopamine (6-OHDA) treatment markedly reduced, in a dose-response fashion, chromaffin cell viability. Cell death was accompanied by cell shrinkage, nuclear condensation and DNA degradation. Under our experimental conditions, 6-OHDA auto-oxidation formed quinones and reactive oxygen species (ROS) that mainly contributed to 6-OHDA-induced cytotoxicity in bovine chromaffin cells. Accordingly, different antioxidants, including catalase, vitamin E, Mn(IIItetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) or ascorbic acid, provided protection against 6-OHDA-induced toxicity. Further evidence that 6-OHDA induces oxidative stress is provided by the fact that this compound decreased total mitochondrial reduced NAD(P)H levels. Our results also suggest that mitochondrial swelling and caspase activation do not play a direct role in 6-OHDA-induced death in bovine chromaffin cells.
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Caspasas/metabolismo , Células Cromafines/efectos de los fármacos , Células Cromafines/enzimología , Mitocondrias/efectos de los fármacos , Oxidopamina/toxicidad , Animales , Antioxidantes/farmacología , Bovinos , Células Cultivadas , Células Cromafines/citología , Relación Dosis-Respuesta a Droga , Peróxido de Hidrógeno/metabolismo , Mitocondrias/metabolismo , NAD/metabolismo , NADP/metabolismo , Oxidación-Reducción/efectos de los fármacos , Oxidopamina/metabolismo , Quinonas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
1. Mitochondrial mechanisms involved in veratridine-induced chromaffin cell death have been explored. 2. Exposure to veratridine (30 micro M, 1 h) produces cytochrome c release to the cytoplasm that seems to be mediated by superoxide anions and that is blocked by cyclosporin A (10 micro M), MnTBAP (10 nM), catalase (100 IU ml(-1)) and vitamin E (50 micro M). 3. Following veratridine treatment, there is an increase in caspase-like activity, blocked by vitamin E (50 micro M) and the mitochondrial permeability transition pore blocker cyclosporin A (10 micro M). 4. Superoxide anions open the mitochondrial permeability transition pore in isolated mitochondria, an effect that is blocked by vitamin E (50 micro M) and cyclosporin A (10 micro M), but not by the Ca2+ uniporter blocker ruthenium red (5 micro M). 5. These results strongly suggest that under the stress situation caused by veratridine, superoxide anions become important regulators of mitochondrial function in chromaffin cells. 6. Exposure of isolated bovine chromaffin mitochondria to Ca2+ results in mitochondrial swelling. This effect was prevented by ruthenium red (5 micro M) and cyclosporin A (10 micro M), while it was not modified by vitamin E (50 micro M). 7. Veratridine (30 micro M, 1 h) markedly decreased total glutathione and GSH content in bovine chromaffin cells. 8. In conclusion, superoxide anions seem to mediate veratridine-induced cytochrome c release, decrease in total glutathione, caspase activation and cell death in bovine chromaffin cells.