RESUMEN
In Israel, Krabbe disease is frequent in two Moslem Arab villages in the Jerusalem area. In this paper we present our experience of almost four decades with diagnosis of Krabbe disease, carrier screening and prenatal diagnosis. The screening program is well accepted by the community, and there is a clear trend towards premarital testing. The screening program and prenatal diagnosis have led to a decrease in the incidence of Krabbe disease from 1.6 per 1,000 live births to 0.82 per 1,000.
Asunto(s)
Pruebas Genéticas , Leucodistrofia de Células Globoides/genética , Preescolar , Familia , Encuestas Epidemiológicas , Heterocigoto , Humanos , Aprendizaje , Diagnóstico PrenatalRESUMEN
High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2 degrees C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality.
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Electricidad , Enfermedades Pulmonares/terapia , Infecciones por Pseudomonas/terapia , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/efectos de la radiación , Animales , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Recuento de Colonia Microbiana , Modelos Animales de Enfermedad , Electrodos , Femenino , Calor , Humanos , Pulmón/microbiología , Pulmón/patología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/patología , Ratones , Ratones Endogámicos ICR , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields--TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. METHODS: Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line EmtR1; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. RESULTS: TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. CONCLUSIONS: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Estimulación Eléctrica , Proteínas de Neoplasias/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2 , Transportadoras de Casetes de Unión a ATP/genética , Animales , Antineoplásicos/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Células CHO , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Emetina/farmacología , Femenino , Humanos , Concentración 50 Inhibidora , Mitoxantrona/farmacología , Proteínas de Neoplasias/genética , Paclitaxel/farmacología , Factores de Tiempo , Regulación hacia ArribaRESUMEN
BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. METHODS: Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients. RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index