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1.
Langmuir ; 38(47): 14465-14474, 2022 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-36383640

RESUMEN

Cyclohexane is a representative of volatile organic compounds (VOCs). VOCs can cause serious health problems in case of continuous exposure; therefore, it is essential to develop efficient personal protective equipment. Historically, activated carbons are used as VOC adsorbents. However, the emergence of promising novel adsorbents, such as metal-organic frameworks, has pushed the research to study their behavior under the same conditions. In this work, the use of the well-known HKUST-1 MOF of different particle sizes (20 µm, 300-600 µm, and 1-1.18 mm) for the adsorption of low-grade (5000 ppm) cyclohexane combined with different water concentrations (dry, 27 and 80% RH) in a fixed bed is proposed. The results were compared under the same conditions for a typically used activated carbon, PICACTIF TA 60. HKUST-1 has higher affinity to cyclohexane than PICACTIF for the whole pressure range studied, especially at low partial pressures. It begins to adsorb much earlier (0.0025 kPa) than the activated carbon (0.01 kPa). However, a different adsorption behavior is evidenced for both materials in the presence of water vapor since HKUST-1 is very hydrophilic in the zone near to the copper open metal sites, whereas PICACTIF is hydrophobic. After three consecutive cycles, good stability results were obtained for the MOF, comparable to activated carbon, even in the presence of water. As the main finding, although the unstability of HKUST-1 is well established under high humid conditions, the kinetic of degradation has not been established so far. Here, it is shown that the time usage of HKUST-1 as the adsorbent for respiratory mask (single pass) is not affected by the degradation of the structure, which may occur on a longer time scale. Finally, shaping by tableting provides good results since it is possible to increase the MOF density by around 69% with minor loss of adsorption capacity. The best fraction is 300-600 µm, reaching cyclohexane breakthrough times around 85 min/cm3 at 80% RH, comparable with PICACTIF-activated carbon and promising for practical applications.


Asunto(s)
Estructuras Metalorgánicas , Compuestos Orgánicos Volátiles , Compuestos Orgánicos Volátiles/química , Carbón Orgánico/química , Adsorción , Ciclohexanos
2.
J Neurooncol ; 155(1): 35-43, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34546498

RESUMEN

PURPOSE: The outcomes of five fraction stereotactic radiotherapy (hfSRT) following brain metastasectomy were evaluated and compared with published series. METHODS: 30 Gy in 5 fractions HfSRT prescribed to the surgical cavity was reduced to 25 Gy if the volume of 'brain-GTV' receiving 20 Gy exceeded 20 cm3. Endpoints were local recurrence, nodular leptomeningeal recurrence, new brain metastases and radionecrosis. The literature was searched for reports of clinical and dosimetric outcomes following postoperative hfSRT in 3-5 fractions. RESULTS: 39 patients with 40 surgical cavities were analyzed. Cavity local control rate at 1 year was 33/40 (82.5%). 3 local failures followed 30 Gy/5 fractions and 4 with 25 Gy/5 fractions. The incidence of leptomeningeal disease (LMD) was 7/40 (17.5%). No grade 3-4 toxicities, particularly no radionecrosis, were reported. The incidence of distant brain metastases was 15/40 (37.5%). The median overall survival was 15 months. Across 13 published series, the weighted mean local control was 83.1% (adjusted for sample size), the mean incidence of LMD was 14.9% (7-34%) and the mean rate of radionecrosis was 10.3% (0-20.6%). CONCLUSION: Postoperative hfSRT can be delivered with 25-30 Gy in 5 fractions with efficacy in excess of 82% and no significant toxicity when the dose to 'brain-GTV' does not exceed 20 cm3.


Asunto(s)
Neoplasias Encefálicas , Metastasectomía , Traumatismos por Radiación , Radiocirugia , Encéfalo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Humanos , Neoplasias Meníngeas , Hipofraccionamiento de la Dosis de Radiación , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
3.
Av. odontoestomatol ; 37(2): 67-77, abr.-jun. 2021. ilus, tab
Artículo en Español | IBECS | ID: ibc-217499

RESUMEN

Los TMD son patologías que se presentan con frecuencia en nuestro medio, las causas van asociadas a factores como interferencias oclusales, problemas articulares, estrés y otras etiologías que provocan inestabilidad del sistema estomatognático; desencadenando una serie de problemas, con una manifestación común, encontrada a lo largo de esta revisión bibliográfica, el dolor. Objetivo: Analizar si las férulas oclusales controlan el dolor relacionado con trastornos temporomandibulares. Materiales y Métodos: Revisión sistemática, protocolo PRISMA, artículos científicos en plataforma electrónicas PUBLIMED, MEDLINE, WEB SCIENCE, SCOPUS, COCHRANE LIBRARY, 2009 a 2018, bases complementarias SCIELO, REDILYC, LATINDEX. Muestra total n = 59 artículos tamizaje, selección definitiva n= 13 artículos que cumplen los criterios de inclusión como palabras claves (Férulas, férulas oclusales, trastorno de la articulación temporomandibular, síndrome de disfunción de articulación temporomandibular); de los cuales 5 artículos son de estudio transversal y 8 caso y control. Resultados: n=13 artículos observacionales, casos y control, que indican en sus conclusiones que las férulas oclusales tienen un efecto positivo en los pacientes con trastornos temporomandibulares, disminuyendo considerablemente la sintomatología. Discusión: las férulas oclusales se consideran tratamientos placebos, que deben ser complementados con otras alternativas terapéuticas. Conclusión: Las férulas oclusales son dispositivos eficientes que cumplen con el objetivo de controlar la sintomatología en los pacientes que padecen trastornos temporomandibulares (AU)


The tempomandibular disorders are pathologies that occur frequently in our environment, the causes are associated with factors such as occlusal interference, joint problems, stress and other etiologies that cause instability of the stomatognathic system; triggering a series of problems, with a common manifestation, found throughout this bibliographic review, pain. Aims: To test whether occlusal splints control pain related to temporomandibular disorders. Methods: Systematic review, PRISMA protocol, scientific articles on electronic platforms PUBLIMED, MEDLINE, WEB SCIENCE, SCOPUS, COCHRANE LIBRARY, 2009 to 2018, complementary bases SCIELO, REDILYC, LATINDEX. Total sample no. 59 sieving items, definitive selection n=13 articles that meet the criteria of inclusion as keywords (splints, occlusal splints, temporomandibular joint disorder, joint dysfunction syndrome temporomandibular). Results: n=13 observational articles, cases and control, indicating in their conclusions that occlusal splints have a positive effect in patients with temporomandibular disorders, considerably decreasing symptomatology. Discussion: Occlusal splints are considered placebo treatments, which should be supplemented with other therapeutic alternatives. Conclusion.Occlusal splints are efficient devices that meet the goal of controlling symptomatology in patients with temporomandibular disorders (AU)


Asunto(s)
Humanos , Ferulas Oclusales/efectos adversos , Trastornos de la Articulación Temporomandibular , Aparatos Ortodóncicos , Síndrome de la Disfunción de Articulación Temporomandibular
4.
Clin Rheumatol ; 39(10): 2963-2971, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32285259

RESUMEN

OBJECTIVE: To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. METHODS: Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. RESULTS: Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and < 1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). CONCLUSIONS: UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.


Asunto(s)
Antirreumáticos , Artritis Psoriásica , Psoriasis , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Humanos , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , España , Resultado del Tratamiento , Ustekinumab/uso terapéutico
5.
Chemosphere ; 218: 128-137, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30471493

RESUMEN

This work analyzes the effect of nalidixic acid (NAL) on the kinetics of the heterotrophic and autotrophic biomass growth within a "NIPHO" activated sludge reactor treating municipal wastewater. Thus, the effect of this chemical in the degradation rates of carbon and nitrogen sources and net biomass growth rate is evaluated. Activated sludge samples were taken at three different operation conditions, changing the values of hydraulic retention time (2.8-3.8 h), biomass concentration (1400-1700 mgVSS L-1), temperature (12.6-14.8 °C), and sludge retention time (11.0-12.6 day). A respirometric method was applied to model the kinetic performance of heterotrophic and autotrophic biomass in absence and presence of NAL, and a multivariable statistical analysis was carried out to characterize the influence of the operation variables on the kinetic response of the system, which was finally optimized. The results showed that there was no inhibitory effect of NAL on heterotrophic biomass, with an increase of net heterotrophic biomass growth rate from 1.70 to 6.73 mgVSS L-1 h-1 at the most favorable period. By contrast, the autotrophic biomass was negatively affected by NAL, reducing the value of net autotrophic biomass growth rate from 25.37 to 10.29 mgVSS L-1 h-1 at the best operation conditions. In general, biomass concentration and temperature had the highest influence on the degradation rate of carbon and nitrogen sources, whereas hydraulic retention time and sludge retention time were the most influential on net heterotrophic and autotrophic biomass growth rates.


Asunto(s)
Biomasa , Reactores Biológicos/microbiología , Ácido Nalidíxico/farmacología , Aguas del Alcantarillado/química , Antibacterianos/farmacología , Procesos Autotróficos , Carbono , Procesos Heterotróficos , Cinética , Nitrógeno , Aguas del Alcantarillado/microbiología , Aguas Residuales/química
6.
Biomed Res Int ; 2017: 7830919, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28396871

RESUMEN

The innocuous transcutaneous stimulation of nerves supplying the outer ear has been demonstrated to be as effective as the invasive direct stimulation of the vagus nerve for the treatment of some neurological and nonneurological disturbances. Thus, the precise knowledge of external ear innervation is of maximal interest for the design of transcutaneous auricular nerve stimulation devices. We analyzed eleven outer ears, and the innervation was assessed by Masson's trichrome staining, immunohistochemistry, or immunofluorescence (neurofilaments, S100 protein, and myelin-basic protein). In both the cavum conchae and the auditory canal, nerve profiles were identified between the cartilage and the skin and out of the cartilage. The density of nerves and of myelinated nerve fibers was higher out of the cartilage and in the auditory canal with respect to the cavum conchae. Moreover, the nerves were more numerous in the superior and posterior-inferior than in the anterior-inferior segments of the auditory canal. The present study established a precise nerve map of the human cavum conchae and the cartilaginous segment of the auditory canal demonstrating regional differences in the pattern of innervation of the human outer ear. These results may provide additional neuroanatomical basis for the accurate design of auricular transcutaneous nerve stimulation devices.


Asunto(s)
Pabellón Auricular/inervación , Conducto Auditivo Externo/inervación , Oído Externo/inervación , Fibras Nerviosas Mielínicas , Anciano , Anciano de 80 o más Años , Pabellón Auricular/anatomía & histología , Conducto Auditivo Externo/anatomía & histología , Oído Externo/anatomía & histología , Femenino , Humanos , Masculino , Estimulación Eléctrica Transcutánea del Nervio , Cornetes Nasales/anatomía & histología , Cornetes Nasales/inervación , Nervio Vago/anatomía & histología
8.
Cancer Treat Rev ; 41(9): 742-53, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26051911

RESUMEN

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.


Asunto(s)
Hipertermia Inducida/métodos , Neoplasias/terapia , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia
9.
JIMD Rep ; 8: 91-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23430525

RESUMEN

The purpose of these analyses was to characterize demographic and baseline clinical characteristics of Latin American patients with Fabry disease compared to that of patients in the rest of the world. Observational data reported to the Fabry Registry were obtained from untreated patients or prior to treatment with enzyme replacement therapy. As of October 1, 2010, 3,752 patients were enrolled in the Fabry Registry worldwide, including 333 patients within Latin America. Latin American patients tended to be younger than Fabry Registry patients enrolled in the rest of the world: mean current age 35.5 years versus 39.2 years for men (p < 0.05 by t-test), mean age 37.8 years versus 43.6 years for women (p < 0.05 by t-test). A smaller percentage of Latin American patients have received enzyme replacement therapy, compared to patients in the rest of the world: 67% versus 80% for men, and 19% versus 39% of women, respectively. Thirty-one percent of men and 22% of women in Latin America reported experiencing a significant cardiovascular, renal, or cerebrovascular event, at a mean age of 35 ± 12.6 years in men and 44 ± 12.3 years in women. Cardiovascular events were the most common type of initial clinical event among men and women in Latin America. The medical community in Latin America should be aware of Fabry disease as a possible cause of renal or cardiac dysfunction. Increased awareness will facilitate prompt diagnosis and initiation of treatment.

11.
Cell Mol Biol (Noisy-le-grand) ; 48(8): 845-52, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12699242

RESUMEN

Erythrocyte uroporphyrinogen decarboxylase (UROD) activity was measured to classify 118 Spanish patients with porphyria cutanea tarda (PCT) into three subtypes: sporadic-, familial- and type III-PCT. Seventy-four patients (63%) had eythrocyte UROD activity within the normal range (74% to 126% of the mean activity of 43 healthy controls) and were classified as sporadic-PCT (47%) or as type III-PCT (16%) whenever a family history of PCT was documented. Forty-four patients (37%) had decreased UROD activity and were classified as familial-PCT. The frequency of both familial-PCT and type III-PCT was higher than reported in other countries. The clinical expression of PCT was associated with the coexistence of two or more risk factors in 80% of the sporadic-PCT patients and in 89% of the familial-PCT patients. Hepatitis C virus and alcohol abuse were risk factors frequently found in these patients, being unrelated to age of onset of skin lesions. A heavy alcohol intake was the main risk factor for type III-PCT. Estrogens appeared as a precipitating factor for women with familial-PCT. The H63D mutation in the hemochromatosis type 1 gene was more frequently found than the C282Y mutation. Both mutations appeared to play a role as precipitating factors in sporadic-PCT when associated with hepatitis C virus infection and alcohol abuse.


Asunto(s)
Porfiria Cutánea Tardía/diagnóstico , Porfiria Cutánea Tardía/genética , Adulto , Edad de Inicio , Consumo de Bebidas Alcohólicas , Alelos , Estrógenos/metabolismo , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad , Hemocromatosis/genética , Proteína de la Hemocromatosis , Hepatitis C/complicaciones , Antígenos de Histocompatibilidad Clase I/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Porfiria Cutánea Tardía/etiología , Porfiria Cutánea Tardía/virología , Factores de Riesgo , España , Uroporfirinógeno Descarboxilasa/sangre
12.
J Hazard Mater ; 81(1-2): 103-14, 2001 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-11118686

RESUMEN

Hydrodechlorination of tetrachloroethylene was investigated using red mud (RM, a by-product in the production of alumina by the Bayer process) as the catalyst. Use of RM as a hydrodechlorination catalyst is of interest from an industrial point of view because its cost is much lower than that of commercial catalysts. Hydrodechlorination reactions were carried out in a continuous fixed bed reactor. The influence of catalyst sulfiding, temperature (50-350 degrees C), pressure (2-10MPa), hydrogen flow rate and the presence of solvents (hexane, heptane, benzene and toluene) on the reaction was studied. Sulfided red mud is active as a hydrodechlorination catalyst, conversion of tetrachloroethylene increases as the pressure and temperature increase. The solvents did not influence the conversion, nor were side reactions involving the solvent observed. The kinetics of the reaction was studied at 350 degrees C and 10MPa, conditions for which mass transfer limitations were negligible. A good fit of a Langmuir-Hinselwood model to the experimental data was obtained.


Asunto(s)
Tetracloroetileno/química , Catálisis , Diseño de Equipo , Presión , Temperatura
13.
Ann N Y Acad Sci ; 914: 82-91, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11085311

RESUMEN

Methamphetamine (METH) has been shown to cause neurotoxic damage both in vitro and in vivo. The mechanisms of action are thought to involve the production of pathophysiologic concentration of free radicals. The present study was undertaken to assess the toxic effects of METH caused dose-dependent increased production of reactive oxygen species (ROS) and cell death. Cell death caused by METH was characterized by cytoplasmic vacuolar formation, shrinkage of cytoplasm and nuclear dissolution. Flow cytometric evaluation also revealed that this toxin causes changes similar to those observed in cells undergoing apoptosis. When taken together these observations suggest the METH can cause these cells to die via apoptosis. Further experiments indicated that growth of these cells in low (1%) serum or in the absence of serum markedly enhanced the apoptotic effects of METH. These data provide further support for the ideas that METH can cause ROS-mediated apoptosis.


Asunto(s)
Estimulantes del Sistema Nervioso Central/toxicidad , Metanfetamina/toxicidad , Neuronas/efectos de los fármacos , Suero/metabolismo , Animales , Apoptosis/efectos de los fármacos , Recuento de Células , Línea Celular , Relación Dosis-Respuesta a Droga , Citometría de Flujo/métodos , Etiquetado Corte-Fin in Situ/métodos , Técnicas In Vitro , Mesencéfalo/citología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Factores de Tiempo
14.
Brain Res Mol Brain Res ; 80(2): 237-43, 2000 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-11038257

RESUMEN

Possible direct effects of methamphetamine (METH) on transcription factors AP-1 and cAMP response element-binding protein (CREB) in the nucleus were assessed by electrophoretic mobility-shift assay. In vitro addition of METH to nuclear extract from brain tissue increased DNA-binding activities of both transcription factors. In addition, injections of METH to mice induced increases in the binding of AP-1 and CREB, which were depleted by preincubating the nuclear extract with anti-METH antibody. We also examined the cellular distribution of METH in mesencephalic neuronal cells using an immunofluorescence experiment with anti-METH antibody. METH-like immunoreactivity was seen to accumulate in the cytosol 4-6 h after the METH treatment. Furthermore, METH-positive signals were also observed in the nuclei of the METH-treated cells. The present study is the first demonstration that METH can have direct effects on DNA-binding protein complex by redistributing not only in the cytosol but also into the nucleus.


Asunto(s)
Núcleo Celular/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Metanfetamina/farmacología , Neuronas/efectos de los fármacos , Animales , Línea Celular Transformada , Núcleo Celular/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Masculino , Ratones , Ratones Endogámicos , Microscopía Confocal , Neuronas/ultraestructura , Unión Proteica/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo
15.
Synapse ; 35(3): 228-33, 2000 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-10657030

RESUMEN

Parkinson's disease is a neurodegenerative disease that is consequent to the loss of brain dopamine (DA) cells. These abnormalities are thought, in part, to be a manifestation of increased free radical production during the metabolism of catecholamines. The antiapoptic agent, bcl-2, has been shown to protect cells against the toxic effects of reactive oxygen species (ROS). Thus, we tested whether bcl-2 could attenuate the toxic effects of DA on immortalized neural cells. Our results show that DA caused dose-dependent cell death. The use of confocal microscopy and flow cytometry demonstrated that DA caused cell death through an apoptotic process. Moreover, DA caused a marked increase in ROS in these cells. Furthermore, overexpression of bcl-2 caused significant protection against DA-induced apoptosis. These results are discussed in terms of their support for a role of bcl-2 in the development of Parkinson's disease.


Asunto(s)
Apoptosis/fisiología , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Cardiotónicos/farmacología , Dopamina/farmacología , Humanos , Neuronas/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos
16.
Brain Res Mol Brain Res ; 72(2): 158-65, 1999 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-10529474

RESUMEN

ApoI/Fas belongs to the tumor necrosis factor receptor (TNFR) superfamily and mediates cell death in various cell types. A dual mode of Fas-triggered cell death has been reported depending on cell types used in the experiments. The present study was carried out to test the possible role of reactive oxygen species in this dual mechanism in neuroglioma cells. Anti-Fas antibody caused dose-dependent and time-dependent increase in cell death measured by lactate dehydrogenase (LDH) release in control neuroglioma cells and in cells that were transfected with catalase cDNA. However, cells transfected with copper/zinc superoxide dismutase (Cu/ZnSOD) cDNA showed marked attenuation of Fas-induced LDH release. Moreover, flow cytometry and confocal microscopy revealed that Fas-induced cell death in control cells occur mostly through an apoptotic process. This process was also completely abrogated in cells overexpressing catalase or copper/zinc superoxide dismutase (Cu/ZnSOD). Further experiments revealed that Fas-induced cell death was associated with increased formation of superoxide anions in control neuroglioma cells and in cells overexpressing catalase. These increases were significantly suppressed by Cu/ZnSOD overexpression. These data indicate that Fas-mediated cell death in neuroglioma cells occur, in part, through the production of reactive oxygen species (ROS). These observations also suggest that Fas-induced cell death in these cells occur through apoptosis and necrosis. Thus overexpression of Cu/ZnSOD caused the suppression of both types of Fas-induced cell death whereas catalase prevented apoptotic but not necrotic cell death. These observations are discussed in terms of their support for a role for both peroxides and superoxide radicals in Fas-induced cell death.


Asunto(s)
Apoptosis/fisiología , Glioma/patología , Proteínas de Neoplasias/fisiología , Especies Reactivas de Oxígeno , Receptor fas/fisiología , Catalasa/genética , Catalasa/fisiología , Citometría de Flujo , Humanos , Microscopía Confocal , Peróxidos/metabolismo , Proteínas Recombinantes de Fusión/fisiología , Superóxido Dismutasa/genética , Superóxido Dismutasa/fisiología , Transfección
17.
Haemophilia ; 5(1): 73-5, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10215951

RESUMEN

We report the second confirmed case of the haemophilia B 'Brandenberg' phenotype. At the time of testing, patient HB530 was a 17-year-old post-puberty male with a persistent, clinically severe bleeding disorder and markedly reduced plasma procoagulant factor IX activity (< 1%). Sequencing studies revealed a G-->A transition at bp - 26 within the promoter region of the factor IX gene. This case report confirms the observation that not all patients with promoter mutations improve after puberty and supports the hypothesis that bp - 26 is a critical binding site within the factor IX gene promoter region for both constitutive as well as androgen-inducible transcription factors.


Asunto(s)
Hemofilia B/genética , Regiones Promotoras Genéticas , Adolescente , Humanos , Masculino , Mutación , Fenotipo
19.
Hum Mutat ; 11(5): 372-6, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9600455

RESUMEN

Exogenous (e.g., environmental) mutagens produce characteristic patterns of mutation. In contrast, endogenous mutation processes likely are associated with an invariant pattern of mutation. Analysis of factor IX gene mutations among large samples of hemophilia B patients from multiple, widely divergent geographic and ethnic populations reveals a remarkably constant mutational pattern, suggesting that the primary germline mutational process results from endogenous processes rather than environmental mutagens. To test this hypothesis further, we have initiated a study of hemophilia B patients from Peru because relatively large populations of AmerIndians can be found with low admixtures of other races. To determine if the factor IX (FIX) germline mutational pattern in AmerIndians differs from the common and putative endogenous pattern, FIX gene mutations were characterized in an initial sample of 10 AmerIndian Peruvian patients with hemophilia B. A minimum of 2.2 kb of the FIX gene was examined by PCR and direct sequencing of all eight exons, the splice junctions, and the promoter region. The pattern of germline mutation in AmerIndians was similar to the pattern of FIX germline mutations from larger U. S. Caucasian or Mexican Hispanic samples (P=0.55 and 0.63, respectively). The similar pattern in this initial sample of the Peru AmerIndian population provides additional support for the inference that the FIX germline mutational pattern results from predominantly endogenous processes rather than exogenous mutagens.


Asunto(s)
Mutación de Línea Germinal/genética , Hemofilia B/genética , Indígenas Norteamericanos/genética , Factor IX/genética , Hemofilia B/etnología , Hispánicos o Latinos/genética , Humanos , Americanos Mexicanos/genética , Perú , Población Blanca/genética
20.
Synapse ; 25(2): 176-84, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9021898

RESUMEN

Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are thought to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2 could protect against METH-induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation, and DNA laddering. All these changes were prevented by bcl-2 expression. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.


Asunto(s)
Apoptosis/efectos de los fármacos , Metanfetamina/farmacología , Neuronas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/farmacología , Análisis de Varianza , Animales , Citometría de Flujo , Ratas
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