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1.
Internet Interv ; 26: 100449, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34504779

RESUMEN

PURPOSE: Evaluate the feasibility, acceptability and potential efficacy of a form of online therapy for clinical depression and/or anxiety in people living with advanced cancer. METHODS: A single-arm open trial of a six-lesson clinician-supervised, internet-delivered cognitive behavioural therapy (iCBT) transdiagnostic intervention (iCanADAPT Advanced) was undertaken. Qualitative (semi-structured telephone interview conducted at 3-months) and quantitative data (questionnaires collected at pre-, post-, and 3-month follow-up) were analysed. RESULTS: 27 participants partook (26 women, 56% breast cancer, mean age 56yo; average number of mental health diagnoses 1.8, with majority (81%) meeting criteria for generalised anxiety disorder). Feasibility - Unanticipated numbers (48%) of participants had physical health deterioration (cancer progression or death). iCBT had high adherence overall (completion rates: 37% did 6 lessons; 70% did 4 lessons) but adherence was higher for those whose cancer remained stable (completion rates: 43% did 6 lessons; 85% did 4 lessons). Acceptability - the intervention was acceptable to the majority of participants, with high treatment satisfaction. Advisory data was achieved regarding future versions. Potential efficacy - regardless of physical health status, participants who completed the iCBT showed a significant decrease over time in anxiety and depression symptoms. CONCLUSIONS: Online therapies may be useful in assisting those living with advanced cancer dealing with clinical depression and anxiety disorders. The specific modality of clinician supervised iCBT has significant potential to be a suitable modality of online therapy.

2.
Psychooncology ; 29(1): 76-85, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31659822

RESUMEN

PURPOSE: To evaluate internet-delivered cognitive behavioural therapy (iCBT) on clinical depression and/or anxiety, distress, fear of cancer recurrence, and quality of life in cancer survivors. METHODS: Random assignation of 114 participants to iCBT or treatment-as-usual (TAU). The clinician-supervised iCBT program (iCanADAPT Early) consisted of eight lessons over 16 weeks. Self-report questionnaires occurred at baseline, midpoint, and posttreatment for both groups with 3-month follow-up for iCBT participants. A mixed modelling approach to compare groups occurred. RESULTS: iCBT was superior to TAU on all outcome measures at posttreatment. Compared with TAU, the iCBT group showed a significant decrease over time in anxiety and depression symptoms (primary outcome, Hospital Anxiety and Depression Scale, Hedges g = 1.51). Additionally the iCBT group had significantly lower general distress (Kessler-10, g = 1.56), fear of cancer recurrence (Fear of Cancer Recurrence Inventory, g = 0.39), and significantly higher quality of life (Functional Assessment of Cancer Therapy-General, g = 0.74) at posttreatment compared with the TAU group. High adherence and satisfaction were found for iCBT with low clinician time. CONCLUSION: Clinician-supervised iCBT has significant benefits for cancer survivors with clinical depression and anxiety disorders.


Asunto(s)
Ansiedad/terapia , Supervivientes de Cáncer/psicología , Terapia Cognitivo-Conductual , Depresión/terapia , Intervención basada en la Internet , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
3.
Nature ; 573(7773): 235-237, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31511683

RESUMEN

The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.

4.
J Eur Acad Dermatol Venereol ; 33(11): 2179-2187, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31166045

RESUMEN

BACKGROUND: Our suggested 'modern' concepts of 'neutrophilic dermatoses' (ND) and 'neutrophilic disease' were based on observations in adult patients and have not been studied in paediatric patients. Only a minority of ND occurs in children, and little is known about age-specific characteristics. OBJECTIVES: To describe age-specific characteristics of ND in children and to study whether our suggested 'modern' classification of ND may be applied to children. METHODS: We conducted a retrospective multicentre study in a French cohort of 27 paediatric patients diagnosed with pyoderma gangrenosum (PG) or Sweet's syndrome (SS). RESULTS: Demographics and distribution of typical/atypical forms were similar in patients diagnosed with PG and SS. Atypical ND were more frequent in infants (90%), when compared to young children (60%) and adolescents (33%). Neutrophilic disease was observed in 17/27 patients and was most frequent in infants. Neutrophilic disease of the upper respiratory tract, as well as cardiac neutrophilic disease, was only observed in infants, whereas other locations were similarly found in infants, young children and adolescents. In infants and young children, ND were associated with a large spectrum of general diseases, whereas in adolescents associations were limited to inflammatory bowel disease and Behçet's disease. CONCLUSIONS: Our study describes the concept of ND in paediatric patients and shows that they have some characteristics different from ND occurring in adults. ND occurring in infants can be associated with a large spectrum of general diseases. Occurrence of neutrophilic disease is frequent in children. Thus, ND occurring in young paediatric patients should incite clinicians to schedule complementary explorations in order to search for involvement of other organs and to rule out monogenetic autoinflammatory syndromes.


Asunto(s)
Trastornos Leucocíticos/diagnóstico , Neutrófilos , Enfermedades de la Piel/diagnóstico , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Enfermedades de la Piel/clasificación , Enfermedades de la Piel/inmunología
5.
Indoor Air ; 27(3): 529-538, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-27564375

RESUMEN

This study aimed to demonstrate that particles, especially those associated with fungi, could be released from fibrous filters used in the air-handling unit (AHU) of heating, ventilation and air-conditioning (HVAC) systems during ventilation restarts. Quantification of the water retention capacity and SEM pictures of the filters was used to show the potential for fungal proliferation in unused or preloaded filters. Five fibrous filters with various particle collection efficiencies were studied: classes G4, M5, M6, F7, and combined F7 according to European standard EN779:2012. Filters were clogged with micronized rice particles containing the fungus Penicillium chrysogenum and then incubated for three weeks at 25°C and 90% relative humidity. The results indicated that the five clogged tested filters had various fungal growth capacities depending on their water retention capacity. Preloaded filters were subjected to a simulated ventilation restart in a controlled filtration device to quantify that the fraction of particles released was around 1% for the G4, 0.1% for the M5 and the M6, and 0.001% for the F7 and the combined F7 filter. The results indicate that the likelihood of fungal particle release by low efficiency filters is significantly higher than by high efficiency filters.


Asunto(s)
Microbiología del Aire , Contaminación del Aire Interior/análisis , Filtración , Penicillium chrysogenum/aislamiento & purificación , Contaminantes Atmosféricos/análisis , Análisis de Varianza , Ambiente Controlado , Filtración/métodos , Filtración/normas , Hongos/aislamiento & purificación , Humanos , Microscopía Electrónica de Rastreo , Ventilación
6.
Pharmazie ; 72(8): 447-448, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29441902

RESUMEN

Water and water vapor are the bane of amorphous drug stability, both in storage and after administration. As is to be expected, crystallization of amorphous azithromycin did occur when exposed to water as dissolution medium. However, experimental results showed that, although solution-mediated phase transformation had occurred, it was not a rapid process for this drug. It is considered to be an advantageous characteristic of amorphous azithromycin and likely due to the high molecular mass (748.984 g/mol) and complex structure necessitating more energy for transformations to occur. A high apparent solubility is maintained for a considerable period of time, potentially rendering a higher percentage of this BCS Class II drug available for absorption when administered orally.


Asunto(s)
Azitromicina/química , Química Farmacéutica/métodos , Agua/química , Azitromicina/administración & dosificación , Cristalización , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Soluciones Farmacéuticas , Solubilidad
7.
Environ Sci Technol ; 49(9): 5450-7, 2015 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-25760854

RESUMEN

Nanoclay-based nanocomposites have been widely studied and produced since the late 1990s, and frequently end up in waste disposal plants. This work investigates the behavior of PA6/HNTs nanocomposites (nylon-6 incorporating halloysite nanotubes) during incineration. Incineration tests were performed at lab-scale using a specific tubular furnace modified in order to control the key incineration parameters within both the combustion and postcombustion zones. The combustion residues and combustion aerosol (particulate matter and gas phase) collected downstream of the incinerator furnace were characterized using various aerosol analysis techniques. Time tracking of the gas and particle-number concentrations revealed two-step char formation during combustion. HNTs transformed into other mineral structures which were found in both the aerosol and the residues. During combustion of the polymer, it appears that HNTs contribute to the formation of a cohesive char layer that protects the residual material.


Asunto(s)
Silicatos de Aluminio/química , Incineración , Nanotubos/química , Caprolactama/análogos & derivados , Caprolactama/química , Arcilla , Nanocompuestos/química , Polímeros/química
8.
Comp Immunol Microbiol Infect Dis ; 37(3): 181-7, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24656063

RESUMEN

A 28-day study was conducted to assess the dynamic of blood feeding by Rhipicephalus sanguineus ticks on dogs treated or not with a novel topical combination of fipronil, amitraz and (S)-methoprene. Dogs were infested weekly through exposure to ticks in crates for 4h. Ticks were then counted in the crates at 2h and 4h post dog exposure. Ticks were also counted and removed from the dogs at 2h, 4h, 6h, 12h and 24h post tick exposure. The inhibition of blood feeding was assessed by both tick quantification and designing and performing a quantitative PCR (qPCR) to detect the canine hydroxymethylbilane synthase (HMBS) gene in ticks. The percentage of repellency sensu lato based on the ticks collected in crates at 2h varied from 4.7% at day 28 to 48.3% at day 7. The immediate mortality rate of the ticks expelled at 2h varied from 1.5% at day 21 to 31.7% at day 7. The efficacy calculation showed that the acaricidal combination started to kill ticks in as little as 2h. The average efficacy reached 90.0% at 12h post crate challenges and 100% at 24h post exposure in crates. The inclusion of an internal amplification control was used to ensure that no significant template-derived PCR inhibition (≤ 6.2%) affected the overall results. The reduction of blood feeding was significant at 4h (>80.0%) and >99.0% at 24h post tick exposure in the crate. The high repellency rate and the lethal efficacy of CERTIFECT(®) resulted in significantly fewer live attached ticks, consequently reducing blood intake and fluid exchanges.


Asunto(s)
Acaricidas/farmacología , Enfermedades de los Perros/tratamiento farmacológico , Conducta Alimentaria/efectos de los fármacos , Rhipicephalus sanguineus/efectos de los fármacos , Infestaciones por Garrapatas/tratamiento farmacológico , Infestaciones por Garrapatas/veterinaria , Animales , Enfermedades de los Perros/sangre , Enfermedades de los Perros/parasitología , Perros , Combinación de Medicamentos , Femenino , Hidroximetilbilano Sintasa/sangre , Hidroximetilbilano Sintasa/genética , Masculino , Metopreno/farmacología , Pirazoles/farmacología , Rhipicephalus sanguineus/fisiología , Infestaciones por Garrapatas/parasitología , Toluidinas/farmacología
9.
Environ Technol ; 34(5-8): 993-7, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23837350

RESUMEN

The aim of this study was to develop an experimental set-up and a methodology to uniformly contaminate several filter samples with high concentrations of cultivable bacteria and fungi. An experimental set-up allows contaminating simultaneously up to four filters for range of velocities representative of heating, ventilating and air-conditioning systems. The test aerosol was composed of a microbial consortium of one bacterium (Staphylococcus epidermidis) and one fungus (Penicillium oxalicum) and aerosol generation was performed in wet conditions. Firstly, the experimental set-up was validated in regards to homogeneity of the air flows. The bioaerosol was also characterized in terms of number and particle size distribution using two particle counters: optical particle counter Grimm 1.109 (optical diameters) and TSI APS 3321 (aerodynamic diameters). Moreover, stabilities of the number of particles generated were measured. Finally, concentrations of cultivable microorganisms were measured with BioSamplers (SKC) downstream of the four filters.


Asunto(s)
Aire Acondicionado/instrumentación , Calefacción/instrumentación , Penicillium/aislamiento & purificación , Penicillium/fisiología , Staphylococcus epidermidis/aislamiento & purificación , Staphylococcus epidermidis/fisiología , Ultrafiltración/instrumentación , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Supervivencia Celular
10.
Aliment Pharmacol Ther ; 37(5): 537-45, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23289713

RESUMEN

BACKGROUND: Whether diffusion-weighted imaging (DWI)-MRI is of value in detecting and assessing inflammation of ileal Crohn's disease (CD) remains poorly investigated. AIM: To compare DWI-MR enterography (MRE) with conventional MRE in estimating inflammation in small bowel CD, to determine an apparent diffusion coefficient (ADC) threshold to differentiate active from non-active lesions and to assess inter-observer agreement. METHODS: Thirty-one CD patients from the Clermont-Ferrand IBD unit with ileal involvement were consecutively and prospectively included between April and June 2011. All patients underwent DWI-MRI to detect the digestive segment with the most severe lesions, which was then used to calculate the ADC. Qualitative and quantitative results were compared with conventional MRE including MaRIA (Magnetic Resonance Index of Activity) score calculation and independent activity predictors (wall thickening, oedema, ulcers). Each examination was interpreted independently by two radiologists blinded for clinical assessment. RESULTS: Seventeen patients (54.8%) had active CD as defined by the MaRIA score ≥7. DWI hyperintensity was highly correlated with disease activity evaluated using conventional MRE (P = 0.001). Qualitative analysis of DW sequences determined sensitivity, specificity, positive predictive value and negative predictive value as 100%, 92.9%, 94.4% and 100% respectively. Quantitative analysis using a cut-off of 1.6 × 10(-3) mm(2)/s for ADC yielded sensitivity and specificity values of, respectively, 82.4% and 100%. Inter-observer agreement was high with regard to DWI hyperintensity (κ = 0.69, accuracy rate = 85.7%) and ADC (correlation = 0.74, P < 0.001, and concordance = 0.71, P < 0.001). CONCLUSION: DWI-MR enterography is a well-tolerated, non-time-consuming and accurate tool for detecting and assessing inflammation in small bowel Crohn's disease.


Asunto(s)
Enfermedad de Crohn/diagnóstico , Imagen de Difusión por Resonancia Magnética/métodos , Ileítis/diagnóstico , Adolescente , Adulto , Niño , Reacciones Falso Positivas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Adulto Joven
11.
Ann Dermatol Venereol ; 139(10): 636-40, 2012 Oct.
Artículo en Francés | MEDLINE | ID: mdl-23122377

RESUMEN

BACKGROUND: Hypereosinophilic syndrome (HES) is defined as an eosinophil count equal to or greater than 1.5 G/L for more than 6 months with organ damage (heart, nervous system, lung, etc) after the exclusion of other common causes of eosinophilia. A myeloproliferative variant of HES with FIP1L1-PDGFRα fusion gene inducing constitutive activation of a tyrosine kinase receptor has been characterized. We report a case in which the diagnosis was revealed by mucosal erosions and ulcerations. PATIENTS AND METHODS: A 50-year-old man reported bipolar erosions. He presented with an erosion on the glans, an ulceration on the lower lip and mild dermographism. He had an eosinophil count of 7.5 G/L (n<0.7) and raised LDH at 520 IU/L (n<480). Screening for the usual causes of eosinophilia was negative. Histology of the labial ulceration showed a polymorphous inflammatory infiltrate containing eosinophils. A chest scan demonstrated a ground glass-like pulmonary infiltrate and broncho-alveolar lavage revealed eosinophilic alveolitis. The myelogram showed rich bone marrow with eosinophils. FIP1L1-PDGFRα fusion transcript was detected in the blood. Imatinib (Glivec(®)) was initiated and a favourable outcome was achieved within a few months and maintained after one year of treatment. DISCUSSION: Cutaneous signs are frequent features of HES. They are polymorphous and include pruritis, erythematous rash and urticaria. Mucosal ulcerations are uncommon and appear more frequently with the myeloproliferative FIP1L1-PDGFRα-associated variant of HES. Early diagnosis allows the onset of a targeted treatment with imatinib that may prevent the apparition of organ damage.


Asunto(s)
Eosinofilia/diagnóstico , Trastornos Mieloproliferativos/genética , Antineoplásicos/uso terapéutico , Benzamidas , Biopsia , Médula Ósea/patología , Diagnóstico Diferencial , Eosinofilia/tratamiento farmacológico , Eosinofilia/genética , Eosinofilia/patología , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/patología , Proteínas de Fusión Oncogénica/sangre , Proteínas de Fusión Oncogénica/genética , Piperazinas/uso terapéutico , Eosinofilia Pulmonar/diagnóstico , Eosinofilia Pulmonar/tratamiento farmacológico , Eosinofilia Pulmonar/genética , Eosinofilia Pulmonar/patología , Pirimidinas/uso terapéutico , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/sangre , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/tratamiento farmacológico , Úlcera Cutánea/genética , Úlcera Cutánea/patología , Factores de Escisión y Poliadenilación de ARNm/sangre , Factores de Escisión y Poliadenilación de ARNm/genética
12.
J Mater Sci Mater Med ; 23(12): 3029-40, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22965382

RESUMEN

Successful long term bone replacement and repair remain a challenge today. Nanotechnology has made it possible to alter materials' characteristics and therefore possibly improve on the material itself. In this study, biphasic hydroxyapatite/ß-tricalcium phosphate nanobioceramic scaffolds were prepared by the electrospinning technique in order to mimic the extracellular matrix. Scaffolds were characterised by scanning electron microscopy (SEM) and attenuated total reflectance-fourier transform infrared. Osteoblasts as well as monocytes that were differentiated into osteoclast-like cells, were cultured separately on the biphasic bioceramic scaffolds for up to 6 days and the proliferation, adhesion and cellular response were determined using lactate dehydrogenase cytotoxicity assay, nucleus and cytoskeleton dynamics, analysis of the cell cycle progression, measurement of the mitochondrial membrane potential and the detection of phosphatidylserine expression. SEM analysis of the biphasic bioceramic scaffolds revealed nanofibers spun in a mesh-like scaffold. Results indicate that the biphasic bioceramic electrospun scaffolds are biocompatible and have no significant negative effects on either osteoblasts or osteoclast-like cells in vitro.


Asunto(s)
Huesos/fisiología , Fosfatos de Calcio/química , Osteoblastos/citología , Osteoclastos/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Materiales Biocompatibles/química , Regeneración Ósea , Adhesión Celular , Ciclo Celular , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Cerámica , Citoesqueleto/metabolismo , Humanos , L-Lactato Deshidrogenasa/metabolismo , Potenciales de la Membrana , Microscopía Electrónica de Rastreo/métodos , Mitocondrias/metabolismo
13.
Z Naturforsch C J Biosci ; 67(3-4): 163-71, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22624332

RESUMEN

The Sterculia striata ethanolic extract (Ss-EtOH) inhibited gastric lesions induced by ethanol, HCl/ethanol, and ischemia/reperfusion, but not those induced by indomethacin, and did not alter the gastric secretion. Ss-EtOH restored the catalase activity and content of nonprotein sulfhydryl groups in the stomach of mice treated with ethanol. The gastroprotection induced by Ss-EtOH in the ethanol-induced gastric lesion model was abolished by N(G)-nitroL-arginine methyl ester (L-NAME) pretreatment, suggesting the involvement of nitric oxide and antioxidant compounds, but not prostaglandins, in this activity. Lupeol obtained from Ss-EtOH promoted gastroprotection as well as the extract at the same dose, and it must therefore contribute to the observed effects.


Asunto(s)
Antiulcerosos/farmacología , Malvaceae/química , Sterculia/química , Animales , Femenino , Masculino , Ratones , Ratas , Ratas Wistar
14.
Environ Technol ; 33(19-21): 2217-21, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23393961

RESUMEN

The aim of this study was to develop an experimental set-up and a methodology to uniformly contaminate several filter samples with high concentrations of cultivable bacteria and fungi. An experimental set-up allows contaminating simultaneously up to four filters for range of velocities representative of heating, ventilating and air-conditioning systems. The test aerosol was composed of a microbial consortium of one bacterium (Staphylococcus epidermidis) and one fungus (Penicillium oxalicum) and aerosol generation was performed in wet conditions. Firstly, the experimental set-up was validated in regards to homogeneity of the air flows. The bioaerosol was also characterized in terms of the number and particle size distribution using two particle counters: optical particle counter Grimm 1.109 (optical diameters) and TSI APS 3321 (aerodynamic diameters). Moreover, stabilities of the number of particles generated were measured. Finally, concentrations of cultivable microorganisms were measured with BioSamplers SKC downstream of the four filters.


Asunto(s)
Filtros de Aire/microbiología , Microbiología del Aire , Penicillium/fisiología , Staphylococcus epidermidis/fisiología , Biopelículas , Ambiente Controlado , Filtración
15.
Cell Prolif ; 44(6): 567-81, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21992416

RESUMEN

OBJECTIVES: To investigate anti-proliferative properties of a novel in silico-modelled 17ß-oestradiol derivative (C9), in combination with dichloroacetic acid (DCA), on MCF-7 and MCF-12A cells. MATERIALS AND METHODS: xCELLigence system was employed to determine optimal seeding number for cells, and crystal violet assay was used to assess cell number and to determine IC(50) value (24 h) for combination treatment. Light and fluorescent microscopy techniques were used to morphologically detect types of cell death. Flow cytometry was used to analyse cell cycle and apoptosis. RESULTS: Optimal seeding number for 96-well plates was determined to be 5000-10 000 cells/well for both MCF-7 and MCF-12A cells. IC(50) for MCF-7 cells of the combination treatment after 24 h was 130 nm of C9 in conjunction with 7.5 mm of DCA (P < 0.05). In contrast, the same concentration inhibited cell population growth by only 29.3% for MCF-12As after 24-h treatment (P < 0.05). Morphological studies revealed lower cell density of both types of combination-treated cells. Flow cytometric analyses demonstrated increase in sub-G(1) phase in combination-treated MCF-7 cells. CONCLUSIONS: These results demonstrate that the novel 17ß-oestradiol derivative C9, in combination with DCA is a potent anti-proliferation treatment, with properties of selectivity towards tumourigenic cells. Thus, this warrants further studies as a potential combination chemotherapeutic agent for further cancer cell lines.


Asunto(s)
Antineoplásicos/farmacología , Ácido Dicloroacético/farmacología , Estradiol/farmacología , Antineoplásicos/química , Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ácido Dicloroacético/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Estradiol/química , Humanos , Conformación Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas
16.
Mol Cell Biochem ; 357(1-2): 343-52, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21656128

RESUMEN

In anticancer research where the focus is on finding agents that induces cell death while leaving non-tumorigenic cells less affected, a novel 2-methoxyestradiol derivative has come forth. 2-Methoxyestradiol-bis-sulfamate (2-MeOE2bisMATE) is a 2-methoxyestradiol derivative produced by bis-sulphamoylation, which possesses increased antiproliferative activity and biological availability. Several questions remain regarding the type of cell death mechanisms and possible induction of autophagy by 2-MeOE2bisMATE. The aim of this in vitro study was to investigate the cell death mechanisms exerted by 2-MeOE2bisMATE in an adenocarcinoma cell line (MCF-7) by analyzing its influence on cell growth, morphology, and possible induction of cell death. Spectrophotometry (crystal violet staining), transmission electron microscopy (TEM), light microscopy (hematoxylin and eosin staining), and fluorescent microscopy (Hoechst 33342, propidium iodide and acridine orange) were employed. Spectrophotometrical studies indicated that 2-MeOE2bisMATE decreased cell numbers to 75% in MCF-7 cells after 24 h and to 47% after 48 h of exposure. TEM demonstrated membrane blebbing, nuclear fragmentation, and chromatin condensation indicating the hallmarks of apoptosis. Light microscopy revealed the presence of several cells blocked in metaphase, and apoptotic cells were also observed. Fluorescent microscopy demonstrated increased lysosomal staining; suggesting the induction of autophagy. 2-MeOE2bisMATE shows therapeutic potential, as an, anticancer agent, and the investigation of the cell death mechanisms used by 2-MeOE2bisMATE, thus, warrants further investigation.


Asunto(s)
Anticarcinógenos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Estriol/análogos & derivados , Línea Celular Tumoral , Células Epiteliales/efectos de los fármacos , Estriol/farmacología , Femenino , Humanos
17.
Cancer Radiother ; 15(5): 348-54, 2011 Aug.
Artículo en Francés | MEDLINE | ID: mdl-21683640

RESUMEN

At the beginning of the 21st century, radiation biology is at a major turning point in its history. It must meet the expectations of the radiation oncologists, radiologists and the general public, but its purpose remains the same: to understand the molecular, cellular and tissue levels of lethal and carcinogenic effects of ionizing radiation in order to better protect healthy tissues and to develop treatments more effective against tumours. Four major aspects of radiobiology that marked this decade will be discussed: technological developments, the importance of signalling and repair of radiation-induced deoxyribonucleic acid (DNA) damage, the impact of individual factor in the response to radiation and the contribution of radiobiology to better choose innovative therapies such as protontherapy or stereotactic body radiation therapy (SBRT). A translational radiobiology should emerge with the help of radiotherapists and radiation physicists and by facilitating access to the new radio and/or chemotherapy modalities.


Asunto(s)
Radiobiología/tendencias , Radioterapia/tendencias , ADN/efectos de la radiación , Roturas del ADN de Doble Cadena , Reparación del ADN , Predicción , Física Sanitaria , Humanos , Neoplasias/radioterapia , Neoplasias Inducidas por Radiación/etiología , Síndromes Neoplásicos Hereditarios/genética , Polimorfismo de Nucleótido Simple , Oncología por Radiación/tendencias , Tolerancia a Radiación/genética , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Radiocirugia , Radioterapia/métodos , Transducción de Señal/efectos de los fármacos , Tecnología Radiológica , Terapias en Investigación , Investigación Biomédica Traslacional
18.
Mol Microbiol ; 79(5): 1305-24, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21251090

RESUMEN

The unfolded protein response (UPR) is an important stress signalling pathway involved in the cellular development and environmental adaptation of fungi. We investigated the importance of the UPR pathway in the pathogenicity of the plant necrotrophic fungus Alternaria brassicicola, which causes black spot disease on a wide range of Brassicaceae. We identified the AbHacA gene encoding the major UPR transcription regulator in A. brassicicola. Deletion of AbHacA prevented induction of the UPR in response to endoplasmic reticulum stress. Loss of UPR in mutants resulted in a complete loss of virulence and was also associated with a cell wall defect and a reduced capacity for secretion. In addition, our results showed that the UPR was triggered by treatment of mycelia with camalexin, i.e. the major Arabidopsis thaliana phytoalexin, and that strains lacking functional AbHacA exhibited increased in vitro susceptibility to antimicrobial plant metabolites. We hypothesize that the UPR plays a major role in fungal virulence by altering cell protection against host metabolites and by reducing the ability of the fungus to assimilate nutrients required for growth in the host environment. This study suggests that targeting the UPR pathway would be an effective plant disease control strategy.


Asunto(s)
Alternaria/metabolismo , Alternaria/patogenicidad , Arabidopsis/microbiología , Enfermedades de las Plantas/microbiología , Respuesta de Proteína Desplegada , Alternaria/química , Alternaria/genética , Secuencia de Aminoácidos , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Datos de Secuencia Molecular , Alineación de Secuencia , Virulencia
19.
S. Afr. j. sci. (Online) ; 107(9-10): 1-9, 2011.
Artículo en Inglés | AIM (África) | ID: biblio-1270898

RESUMEN

Mobile phone usage currently exceeds landline communication in Africa. The extent of this usage has raised concerns about the long-term health effects of the ongoing use of mobile phones. To assess the physiological effects of radiation from mobile phones in vitro; MCF-7 breast adenocarcinoma cells were exposed to 2W/kg non-thermal 900-MHz mobile phone radiation. The effects investigated were those on metabolic activity; cell morphology; cell cycle progression; phosphatidylserine (PS) externalisation and the generation of reactive oxygen species and nitrogen species. Statistically insignificant increases in mitochondrial dehydrogenase activity were observed in irradiated cells when compared to controls. Fluorescent detection of F-actin demonstrated an increase in F-actin stress fibre formation in irradiated MCF-7 cells. Cell cycle progression revealed no statistically significant variation. A small increase in early and late apoptotic events in irradiated MCF-7 cells was observed. No statistically significant changes were observed in reactive oxygen and reactive nitrogen species generation. In addition; quantitative and qualitative analyses of cell cycle activity and nuclear and cytosolic changes; respectively; revealed no significant changes. In conclusion; exposure to 1 h of 900-MHz irradiation induced an increase in PS externalisation and an increase in the formation of F-actin stress fibres in MCF-7 cells. Data obtained from this study; and their correlation with other studies; provides intriguing links between radio frequency radiation and cellular events and warrant further investigation


Asunto(s)
Adenocarcinoma , Teléfono Celular/estadística & datos numéricos , Efectos de la Radiación
20.
J Steroid Biochem Mol Biol ; 119(3-5): 149-60, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20193762

RESUMEN

In the present study, the antiproliferative mechanism of action of 1 microM 2-methoxyestradiol (2ME) was investigated in the MCF-7 cell line. Measurement of intracellular cyclin B and cytochrome c protein levels, reactive oxygen species formation, cell cycle progression and apoptosis induction were conducted by means of flow cytometry. Morphological changes were evaluated using transmission electron microscopy and fluorescent microscopy by employing Hoechst 33342 and acridine orange. Gene expression changes were conducted by means of microarrays. 2ME-treated cells demonstrated an increase in cyclin B protein levels, hydrogen peroxide formation, intracellular levels of cytochrome c, as well as an increase in early and late stages of apoptosis. In addition, morphological data revealed the presence of autophagic processes. Fluorescent microscopy showed an increase in acridine orange staining and electron microscopy revealed an increase in vacuolar formation in 2ME-treated cells. The gene expression of several genes associated with mRNA translation, autophagy-related processes and genes involved in microtubule dynamics were affected. The study contributes to the mechanistic understanding of 2ME's growth inhibition in MCF-7 cells and highlights the possibility of both apoptotic and autophagic processes being activated in response to 2ME treatment in this cell line.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/ultraestructura , Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Estradiol/análogos & derivados , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , 2-Metoxiestradiol , Adenocarcinoma/genética , Adenocarcinoma/ultraestructura , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias de la Mama/genética , Caspasa 3/deficiencia , Línea Celular Tumoral , Ciclina B1/metabolismo , Citocromos c/metabolismo , Estradiol/farmacología , Femenino , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Especies Reactivas de Oxígeno/metabolismo , Receptores de Estrógenos/metabolismo , Vacuolas/efectos de los fármacos , Vacuolas/ultraestructura
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