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Introduction: Though complex injuries like CarpoMetacarpal (CMC) Joint dislocations represent only 1% of all hand injuries, they have disabling impact on the functional status of patient. There are no reports in the literature classifying disabling complex injuries like CMC joint dislocations presumably because of low incidence. We propose a new classification through retrospective analysis of patients, along with literature search. Materials and Methods: A new classification system has been proposed and designed at our clinical unit and applied to eight patients with CMC joint dislocations. All patients were treated with open reduction with Kirschner wire fixation. At follow-up all these patients were analysed for radiographic assessments and functional scores. Results: The proposed classification identifies three types of dislocations and an additional complex category to supplement any basic type. The direction of dislocation describes the types as Type A: Dorsal, Type B: Volar and Type C: Divergent. Among the eight patients in our study, we had two of Type A, two Type B, three Type B.1, one Type C. 1. These patients had average follow-up of 18 months. The quick DASH score improved from 75.76 at 6 weeks to 1.9 at 18 months. We also did intra-observer and inter-observer reliability which scored 1. Conclusion: Our proposal is a reproducible, simple, comprehensive and practical classification, easily remembered and communicated among colleagues. It is clinically relevant as it helps us in planning surgical management and prognostic evaluation.
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BACKGROUND: Although expander-based breast reconstruction is the most commonly used method of reconstruction worldwide, it continues to be plagued with complication rates as high as 60% when radiotherapy is implemented. We hypothesized that quantitative measures of radiotherapy-induced vascular injury can be mitigated by utilizing amifostine in a murine model of expander-based breast reconstruction. METHODS: 30 rats were divided into three groups: expander placement (Control), expander placement followed by radiotherapy (XRT), and expander placement followed by radiotherapy with amifostine (AMF/XRT). All groups underwent placement of a sub-latissimus tissue expander. After a 45 day recovery period, all groups underwent vascular perfusion and micro-CT analysis. RESULTS: Micro-CT analysis was used to calculate vessel volume fraction (VVF), vessel number (VN), and vessel separation (VSp). A significant increase in VN was seen in the XRT group as compared to the Control (p = 0.021) and the AMF/XRT (p = 0.027). There was no difference between Control and AMF/XRT (p = 0.862). VVF was significantly higher in XRT than either Control (p = 0.043) and AMF/XRT (p = 0.040), however no difference was seen between Control and AMF/XRT (p = 0.980). VSp of XRT was smaller when compared to both Control and AMF/XRT specimens (p = 0.05 and p = 0.048, respectively), and no difference was seen between Control and AMF/XRT (p = 0.339). CONCLUSIONS: Amifostine administered prior to radiotherapy preserved vascular metrics similar to those of non-radiated specimens. Elevated vascularity demonstrated within the XRT group was not seen in either the Control or AMF/XRT groups. These results indicate that amifostine protects soft tissue in our model from a radiotherapy-induced pathologic vascular response.
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Amifostina/administración & dosificación , Neoplasias de la Mama/radioterapia , Mamoplastia/métodos , Arterias Mamarias/patología , Neoplasias Experimentales , Traumatismos Experimentales por Radiación/prevención & control , Dispositivos de Expansión Tisular , Angiografía , Animales , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/cirugía , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Imagenología Tridimensional , Masculino , Arterias Mamarias/efectos de los fármacos , Arterias Mamarias/efectos de la radiación , Traumatismos Experimentales por Radiación/diagnóstico , Protectores contra Radiación/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
Head and neck malignancies constitute a major cause of morbidity and mortality all over the world. Radiotherapy plays a pivotal role in the management of these tumours; however, it has associated complications, with mandibular osteoradionecrosis (ORN) being one of the gravest orofacial complications. Early diagnosis, extent evaluation, and detection of complications of ORN are imperative for instituting an appropriate management protocol. ORN can closely mimic tumour recurrence, the differentiation of which has obvious clinical implications. The purpose of the present review is to acquaint the radiologist with the imaging features of mandibular ORN and the ways to differentiate ORN from tumour recurrence.
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Enfermedades Mandibulares/diagnóstico , Osteorradionecrosis/diagnóstico , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética/métodos , Mandíbula/diagnóstico por imagen , Mandíbula/patología , Enfermedades Mandibulares/patología , Enfermedades Mandibulares/terapia , Osteorradionecrosis/patología , Osteorradionecrosis/terapia , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by a pentad consisting of thrombocytopenic, microangiopathic hemolytic anemia, renal dysfunction, neurological signs and fever. Coexistence of thrombotic thrombocytopenic purpura and Adult Onset Still's Disease (AOSD) is extremely rare. We report a case of 18 year old girl with AOSD who developed TTP. Neuroimaging of brain demonstrated white matter edema consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Complete recovery occurred with prompt anti-hypertensive treatment and high dose immunoglobulin infusions (IVIg). Plasma exchange is the standard of care and the first line treatment for patient with TTP. We used IVIg alone in our case and this showed a gratifying response. Use of IVIG before considering plasmapharesis is justifiable or not requires randomized control clinical trials. This should determine the optimal therapeutic strategies for TTP.
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Síndrome de Leucoencefalopatía Posterior/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Enfermedad de Still del Adulto/complicaciones , Adolescente , Corticoesteroides/uso terapéutico , Antihipertensivos/uso terapéutico , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Síndrome de Leucoencefalopatía Posterior/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Enfermedad de Still del Adulto/tratamiento farmacológicoRESUMEN
This paper deals with the textural, microstructural and interfacial properties of Au/TiO(2) nanocomposites, in relation to their photocatalytic activity for splitting of water. TiO(2) samples of two different morphologies were employed for dispersing different cocatalysts, such as: Au, Pt, Ag or Cu, for the sake of comparison. The samples were characterized using powder XRD, XPS, UV-visible, thermoluminescence, SEM, HRTEM and SAED techniques. Compared to other metal/TiO(2) photocatalysts, Au/TiO(2) with an optimum gold loading of 1 wt% was found to exhibit considerably higher activity for visible light induced production of H(2) from splitting water in the presence of methanol. Further, the sol-gel prepared TiO(2) (s.TiO(2)), having spherical grains of 10-15 nm size, displayed better photoactivity than a Degussa P25 catalyst. The electron microscopy investigations on s.TiO(2) revealed significant heterogeneity in grain morphology of individual TiO(2) particles, exposure of the lattice planes, metal dispersion, and the interfacial metal/TiO(2) contacts. The gold particles were found to be in a better dispersed state. O(2) TPD experiments revealed that the gold nanoparticles and Au/TiO(2) interfaces may serve as distinct binding sites for adsorbate molecules. At the same time, our thermoluminescence measurements provide an insight into Au-induced new defect states that may facilitate the semiconductor-to-metal charge transfer transition. In conclusion, the superior photocatalytic activity of Au/TiO(2) may relate to the grain morphology of TiO(2), dispersion of gold particles, and the peculiar architecture of metal/oxide heterojunctions; giving rise in turn to augmented adsorption of reactant molecules and their interaction with the photo-generated e(-)/h(+) pair. The role played by methanol as a sacrificial reagent in photocatalytic splitting of water is discussed.
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Acceptability and adherence in clinical trials of microbicides may possibly predict their acceptance by the community. In this study, we investigated the acceptability and adherence of Praneem polyherbal tablet, a candidate microbicide, among 100 HIV-uninfected participants of a Phase II randomised, double-blind, placebo-controlled trial in Pune, India, conducted between June 2004 and February 2006 involving 6 months of coitally-dependent product use. The relationship between five acceptability domains and adherence to product use during the study period was explored. Acceptability and adherence were assessed among 95 study participants completing all study follow-ups. One hundred percent adherence (product use during each sex act for the study period) was reported by 67 participants (70.5%). The majority of participants reported acceptability towards all product characteristics. Product odour was reported to be a concern both in the placebo and Praneem arms. Participants from the Praneem arm [adjusted odds ratio (AOR)=3.8; 95% CI 1.4-10.8] and participants reporting lower acceptability for experience of product use during the sex act (AOR=4.2; 95% CI 1.0-17.3) were more likely to have partial adherence. In conclusion, the study product was acceptable to the majority of participants. However, barriers to adherence attributable to undesirable sexual experiences need to be addressed.
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Antiinfecciosos/administración & dosificación , Infecciones por VIH/prevención & control , Extractos Vegetales/administración & dosificación , Quinina/administración & dosificación , Cremas, Espumas y Geles Vaginales/administración & dosificación , Administración Intravaginal , Método Doble Ciego , Femenino , Humanos , India , Masculino , Aceptación de la Atención de Salud , Fitoterapia , Estadística como AsuntoRESUMEN
Low serum vitamin B(12) (V B(12)) and hyperhomocysteinemia have been reported in asymptomatic Asian Indian men. We studied the prevalence of V B(12) deficiency and hyperhomocysteinemia in 51 asymptomatic toddlers, from Pune, India. V B(12) levels were low and total serum homocysteine was high in 14% and homocysteine levels were significantly higher in boys. Programming for cardiovascular risk in adulthood possibly starts at a very young age through the homocysteine axis.
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Dieta Vegetariana/estadística & datos numéricos , Homocisteína/sangre , Hiperhomocisteinemia/epidemiología , Deficiencia de Vitamina B 12/epidemiología , Vitamina B 12/sangre , Estatura , Peso Corporal , Preescolar , Comorbilidad , Estudios Transversales , Femenino , Ácido Fólico/sangre , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/diagnóstico , India/epidemiología , Masculino , Prevalencia , Encuestas y Cuestionarios , Deficiencia de Vitamina B 12/sangre , Deficiencia de Vitamina B 12/diagnósticoRESUMEN
AIMS/HYPOTHESIS: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. METHODS: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. RESULTS: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.
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Ácido Fólico/sangre , Vitamina B 12/sangre , Tejido Adiposo/metabolismo , Antropometría , Composición Corporal , Índice de Masa Corporal , Niño , Femenino , Homocisteína/sangre , Humanos , Resistencia a la Insulina , Masculino , Ácido Metilmalónico/sangre , Embarazo , Complicaciones del EmbarazoRESUMEN
The liver X receptors alpha and beta are orphan nuclear receptors that are key regulators in maintaining cholesterol homeostasis. Originally they were found to play an important role in reverse cholesterol transport, a pathway for the removal of excess cellular cholesterol. However several groups have now shown that the liver X receptors also functions in lipid and carbohydrate metabolism, cellular differentiation, apoptosis and many immune responses. Tissue distribution of the two paralogues differs with liver X receptor beta ubiquitously expressed, while liver X receptor alpha is confined to the liver, kidney, intestine, spleen, adipose tissue, macrophages and skeletal muscle. The endogenous ligands for the liver X receptors are certain oxidized derivatives of cholesterol, the oxysterols. Upon activation by oxysterols, the receptors form obligate heterodimers with retinoid X receptors alpha, beta and gamma; and become competent to activate the transcription of target genes.
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Stereotactic radiosurgery (SRS) is a special radiotherapy technique used to irradiate intracranial lesions by 3-D arrangements of narrow photon beams eliminating the needs of invasive surgery. Three different tertiary collimators, namely BrainLab and Radionics circular cones and BrainLab micro multileaf collimator (mMLC), are used for linear accelerator-based SRS systems (X-Knife). Output factor (S(t)), tissue maximum ratio (TMR) and off axis ratio (OAR) of these three SRS systems were measured using CC01 (Scanditronix/ Welhofer) and Pinpoint (PTW) cylindrical and Markus plane parallel ionization chambers as well as TLD and radiochromic film. Measurement results of CC01 and Pinpoint chambers were very close to each other which indicate that further reduction in volume and physical dimensions of cylindrical ionization chamber is not necessary for SRS/SRT dosimetry. Output factors of BrainLab and Radionics SRS cones were very close to each other while output factors of equivalent diameter mMLC field were different from SRS circular cones. TMR of the three SRS systems compared were very close to one another. OAR of Radionics cone and BrainLab mMLC were very close to each other, within 2%. However, OARs of BrainLab cone were found comparable to OARs of Radionics cone and BrainLab mMLC within maximum variation of 4%. In addition, user-measured similar data of other three mMLC X-Knives were compared with the mMLC X-Knife data measured in this work and found comparable. The concept of switching over to mMLC-based SRS/SRT is thus validated from dosimetric characteristics as well.
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The aim of our study was to determine the pattern of female reproductive organ growth in Indian girls from birth to 18 years of age and to correlate the uterine length, mean ovarian volume (MOV) and Fundo Cervical Ratio (FCR) with chronological age, bone age and pubertal breast staging. A cross sectional study was performed on 218 girls from birth to 18 years of age. Height, weight, stage of puberty, X-ray for bone age and transabdominal ultrasounds were performed on all girls. Higher chronological age, bone age and increase in breast stage significantly predicted higher MOV (P < 0.001) and higher uterine length (P < 0.001). The MOV, uterine length and FCR are positively correlated with chronological age, bone age, height, weight and breast staging. Data from present study may be useful in screening cases of precocious puberty and other disorders that may need further evaluation.
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Ovario/diagnóstico por imagen , Ovario/crecimiento & desarrollo , Útero/diagnóstico por imagen , Útero/crecimiento & desarrollo , Adolescente , Desarrollo del Adolescente/fisiología , Factores de Edad , Mama/crecimiento & desarrollo , Niño , Desarrollo Infantil/fisiología , Preescolar , Estudios Transversales , Femenino , Humanos , India , Lactante , Recién Nacido , Menarquia/fisiología , UltrasonografíaRESUMEN
The increase in the number of monitor units in sliding window intensity-modulated radiotherapy, compared with conventional techniques for the same target dose, may lead to an increase in peripheral dose (PD). PD from a linear accelerator was measured for 6 MV X-ray using 0.6 cm3 ionization chamber inserted at 5 cm depth into a 35 cm x 35 cm x 105 cm plastic water phantom. Measurements were made for field sizes of 6 cm x 6 cm, 10 cm x 10 cm and 14 cm x 14 cm, shaped in both static and dynamic multileaf collimation (DMLC) mode, employing strip fields of fixed width 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm, respectively. The effect of collimator rotation and depth of measurement on peripheral dose was investigated for 10 cm x 10 cm field. Dynamic fields require 2 to 14 times the number of monitor units than does a static open field for the same dose at the isocentre, depending on strip field width and field size. Peripheral dose resulting from dynamic fields manifests two distinct regions showing a crest and trough within 30 cm from the field edge and a steady exponential fall beyond 30 cm. All dynamic fields were found to deliver a higher PD compared with the corresponding static open fields, being highest for smallest strip field width and largest field size; also, the percentage increase observed was highest at the largest out-of-field distance. For 6 cm x 6 cm field, dynamic fields with 0.5 cm and 2 cm strip field width deliver PDs 8 and 2 times higher than that of the static open field. The corresponding factors for 14 cm x 14 cm field were 15 and 6, respectively. The factors by which PD for DMLC fields increase, relative to jaws-shaped static fields for out-of-field distance beyond 30 cm, are almost the same as the corresponding increases in the number of monitor units. Reductions of 20% and 40% in PD were observed when the measurements were done at a depth of 10 cm and 15 cm, respectively. When the multileaf collimator executes in-plane (collimator 90 degrees) motion, peripheral dose decreases by as much as a factor of 3 compared with cross-plane data. The knowledge of PD from DMLC field is necessary to estimate the increase in whole-body dose and the likelihood of radiation induced secondary malignancy.
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Planificación de la Radioterapia Asistida por Computador , Radioterapia de Alta Energía/métodos , Radioterapia de Intensidad Modulada/métodos , Humanos , Fantasmas de Imagen , Protección Radiológica , Dosificación Radioterapéutica , Radioterapia de Alta Energía/instrumentación , Radioterapia de Intensidad Modulada/instrumentación , Dispersión de RadiaciónAsunto(s)
Aneurisma Coronario/complicaciones , Trombosis Coronaria/complicaciones , Infarto del Miocardio/complicaciones , Adulto , Aneurisma Coronario/diagnóstico por imagen , Angiografía Coronaria , Trombosis Coronaria/diagnóstico por imagen , Trombosis Coronaria/tratamiento farmacológico , Humanos , Masculino , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
PURPOSE: To study the changing epidemiological pattern of micro-organisms as an aetiology of septic arthritis, and to correlate the pattern with the outcome of neonatal septic arthritis, in terms of joint function and morphology. METHODS: 15 consecutive cases of neonatal septic arthritis of hip admitted between 1999 and 2002 were studied. Diagnosis of septic arthritis was made on the basis of Morrey's criteria. All patients were treated by arthrotomy after aspiration of purulent fluid from the joint. Patients were followed up for a mean period of 2.4 years. Clinical and radiological examinations were performed at follow-up. RESULTS: The mean age of the 15 patients was 20.35 days. 13 (87%) patients had primary septic arthritis, while only 2 (13%) had associated osteomyelitis. Culture reports revealed that the spectrum consisted of 33% gram-negative organisms, 7% fungal, and only 20% gram-positive organisms-Staphylococcus aureus in 3 patients, Klebsiella in 2 patients, one each of Proteus, Candida, Escherichia coli, and Enterobactor. Six patients were pus-cell positive with negative culture. No organism was found in 6 (40%) cases. Investigations showed leukocytosis, raised C-reactive protein and erythrocyte sedimentation rate in all 15 patients. 12 patients had normal clinical and radiological parameters at follow-up. Three patients had delayed surgical drainage of more than 72 hours due to late presentation, and showed various radiological sequelae with terminal restriction of joint movements. CONCLUSION: There are more cases of primary septic arthritis than secondary septic arthritis. Clinicians should be alert of the aetiology shift to gram-negative organisms, in addition to fungal and gram-positive ones. Arthrotomy to drain pus from the joint should not be delayed. Better long-term results can be achieved by early surgical drainage and immediate antibiotic coverage.
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Artritis Infecciosa/epidemiología , Artritis Infecciosa/microbiología , Antibacterianos , Artritis Infecciosa/terapia , Estudios de Cohortes , Terapia Combinada , Drenaje/métodos , Quimioterapia Combinada/uso terapéutico , Femenino , Estudios de Seguimiento , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Humanos , Incidencia , India/epidemiología , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.
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Tejido Adiposo/patología , Hiperinsulinismo/congénito , Hiperinsulinismo/patología , Parto , Población Blanca , Adulto , Antropometría , Peso al Nacer , Constitución Corporal , Femenino , Sangre Fetal , Humanos , Hiperinsulinismo/etnología , India , Recién Nacido , Insulina/sangre , Leptina/sangre , Londres , Madres , Concentración OsmolarRESUMEN
It is becoming increasingly evident that reactive oxygen species (ROS) act at different stages of carcinogenesis, and thus play multiple roles in oncogenesis. In addition to being mutagenic and initiating tumors, ROS or carcinogens that result in ROS generation may affect tumor promotion and progression through varied effects on growth promoting, growth inhibitory, or apoptotic signaling pathways.
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Neoplasias/inducido químicamente , Oxidantes/efectos adversos , Especies Reactivas de Oxígeno/efectos adversos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Carcinógenos/efectos adversosRESUMEN
The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We examined the role of ref-1 in vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1 translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced oxidative stress (H(2)O(2) production), NF-kappaB activation, and apoptosis, and also mitigated rac1-regulated H(2)O(2) production and NF-kappaB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.
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Apoptosis , Liasas de Carbono-Oxígeno/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa , Estrés Oxidativo , Adenoviridae , Liasas de Carbono-Oxígeno/biosíntesis , Liasas de Carbono-Oxígeno/genética , Hipoxia de la Célula , Línea Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Endotelio Vascular/citología , Expresión Génica , Vectores Genéticos , Humanos , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Vascular endothelial growth factor (VEGF) is a potent vascular endothelial cell-specific mitogen that modulates endothelial cell function. In the present study, we show that VEGF induces manganese-superoxide dismutase (MnSOD) mRNA and protein in human coronary artery endothelial cells (HCAEC) and pulmonary artery endothelial cells. VEGF-mediated induction of MnSOD mRNA was inhibited by pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI), and 4-(2-aminoethyl)-benzenesulfonyl fluoride, but not with the nitric oxide synthase inhibitor L-NAME (N-monomethyl-L-arginine) or the xanthine oxidase inhibitor allopurinol. VEGF stimulation of MnSOD was also inhibited by adenoviral-mediated overexpression of catalase Cu, Zn-SOD and a dominant-negative form of the small GTPase component of NADPH oxidase Rac1 (Rac1N17). Treatment of HCAEC with VEGF resulted in a transient increase in ROS production at 20 min, as measured by 2,7-dichlorodihydrofluorescein oxidation. This effect was abrogated by expression of Rac1N17. Taken together, these findings suggest that VEGF induces MnSOD by an NADPH oxidase-dependent mechanism and that VEGF signaling in the endothelium is coupled to the redox state of the cell.