Asunto(s)
Desprendimiento de Retina/diagnóstico , Perforaciones de la Retina/diagnóstico , Adulto , Terapia Combinada , Crioterapia , Femenino , Francia , Humanos , Edema Macular/complicaciones , Edema Macular/diagnóstico , Edema Macular/terapia , Desprendimiento de Retina/complicaciones , Desprendimiento de Retina/terapia , Perforaciones de la Retina/complicaciones , Perforaciones de la Retina/terapia , Tomografía de Coherencia Óptica , VitrectomíaRESUMEN
INTRODUCTION: Laparoscopy has become the gold-standard approach for excision of benign adrenal tumors but the question of its safety for malignant lesions is still controversial. Our aim was to evaluate the oncologic outcome of laparoscopic adrenalectomy for adrenal metastasis and to look for predictors of a negative surgical outcome. PATIENTS AND METHODS: We retrospectively reviewed the charts of all patients who underwent laparoscopic adrenalectomy for suspicion of adrenal metastasis between 2007 and 2013 at a single academic institution. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Univariate analysis was performed to determine risk factors of negative surgical outcome (positive surgical margins, complications, conversion, significant blood loss) and predictors of RFS and CSS. RESULTS: Thirteen patients underwent 14 laparoscopic adrenalectomies. All patients were operated by a single highly experienced surgeon. Complications occurred in 2 patients (15%): 2 blood transfusions (Clavien-score=2). There were 3 positive surgical margins (21%). Mean length of hospital stay was 4.3 days. Unadjusted RFS and CSS were respectively 48.4% and 83.3% at 1 year, 39.5% and 66.7% at 5 years. In univariate analysis, tumor size was the only risk factor of complication (P=.009) and conversion (P=0.009). Capsule invasion and tumor size were risk factors of positive surgical margins (P=0.01 and P<0.0001). One hundred percent of complications, conversion and positive surgical margins occurred in tumor>7.5 cm on preoperative CT-scan. No predictors of RFS and CSS was found in univariate analysis. CONCLUSION: Laparoscopic adrenalectomy for adrenal metastasis achieves good surgical and oncologic outcomes. When performed by highly experienced surgeon, complications and positive surgical margins occur only in tumors>7.5 cm. These patients may benefit from an open surgical approach.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/efectos adversos , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/mortalidad , Adrenalectomía/efectos adversos , Anciano , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/estadística & datos numéricos , Conversión a Cirugía Abierta , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Registros Médicos , Persona de Mediana Edad , Invasividad Neoplásica , Cintigrafía , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
CONTEXT: The placenta plays an essential role in the fetomaternal exchanges of iodine and thyroid hormones. Propylthiouracil (PTU) is presently considered to be the treatment of choice for hyperthyroidism during the first trimester of pregnancy. Little is known on the expression of iodide transporters in invasive human trophoblast and the possible effect of PTU on this early phase of human placental development. OBJECTIVE: To analyze during early pregnancy expression of sodium/iodide symporter (NIS) and pendrin at the feto-maternal interface in situ in first trimester placentas, in vitro during human trophoblastic cell differentiation in presence or not of PTU. DESIGN: NIS and pendrin immunodetection were performed on 8-10 WG placental tissue sections and in primary cultures of first trimester placenta trophoblastic cells, which differentiate in vitro into syncytiotrophoblast or invasive extravillous cytotrophoblasts (EVCT). The effect of PTU (1 mM) was tested in EVCT on iodide transporters expression, cell invasion, and hCG secretion. RESULTS: NIS and pendrin were present in early human trophoblast at the maternofetal interface. Their expression was modulated with in vitro trophoblast differentiation. Early invasive EVCT were characterized by higher expression of NIS than pendrin. In vitro PTU did modify significantly neither EVCT iodide transporters expression nor EVCT biological functions: i.e. invasive properties and hCG secretion. CONCLUSION: This study reveals that NIS is highly expressed in early human trophoblast at the feto-maternal interface. PTU has no effect on early human trophoblast invasion.
Asunto(s)
Yodo/metabolismo , Proteínas de Transporte de Membrana/genética , Primer Trimestre del Embarazo/genética , Simportadores/genética , Trofoblastos/metabolismo , Trofoblastos/fisiología , Antitiroideos/farmacología , Adhesión Celular/efectos de los fármacos , Adhesión Celular/genética , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Células Cultivadas , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Proteínas de Transporte de Membrana/metabolismo , Modelos Biológicos , Embarazo , Primer Trimestre del Embarazo/metabolismo , Cultivo Primario de Células , Propiltiouracilo/farmacología , Transportadores de Sulfato , Simportadores/metabolismo , Trofoblastos/efectos de los fármacosRESUMEN
INTRODUCTION: During the past 15 years, therapeutic effects of repetitive Transcranial Magnetic Stimulation (rTMS) have been studied in psychiatric diseases, particularly in the treatment of depressive disorders. There are more and more data suggesting its efficacy in the treatment of depression in older patients. Thus, the authors found it useful to conduct an up-to-date review of studies that examined the efficacy and safety of rTMS to treat depressive disorders in the aged. METHOD: After an exhaustive consultation of databases (Medline/PubMed and the Avery-George-Holtzheimer Database of rTMS Depression Studies), supplemented by a manual research, the authors retained studies evaluating the therapeutic efficacy of rTMS on depressive disorders in the aged. RESULTS: Fifteen studies were retained. Four open studies using high frequency rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), demonstrated a decrease in the mean Hamilton Depression Rating Scale (HDRS) scores; however, only a quarter of the aged patients studied experienced a significant remission of depression. Five parallel arm double-blind versus placebo studies concluded in contradicting results: two studies confirmed a significantly greater efficacy of rTMS compared to placebo, whereas three studies did not; but the sham procedure (positioning coil at 90 degrees from the scalp) was disputable in most studies. One study concluded in therapeutic efficacy by inhibiting the right DLPFC. Three controlled parallel arm studies compared rTMS and electroconvulsive-therapy (ECT); one study concluded in greater efficacy of ECT at end of treatment, but the number of ECT treatments depended on the patients' response, whereas a 15-day course of rTMS was systematically administered; additionally HDRS scores were similar in two groups of patients (rTMS and ECT) at 6 months. Lastly, three studies focused on aged patients with cerebrovascular disease. They showed the efficacy of rTMS, although older age and smaller frontal gray mater volumes were associated with a poorer response to rTMS. DISCUSSION: Thus, although some studies concluded contradicting results, literature data globally sustain an efficacy of rTMS for depression in the elderly. Several parameters might be associated with greater antidepressant efficacy (higher intensity pulses of rTMS of the left DLPFC; higher number of stimulations or higher number of rTMS sessions). Poorer responsiveness to rTMS may be related to several patients' factors including older age and smaller frontal gray matter volumes; lesions of the white matter pathways connecting the left DLPFC and the left anterior cingulate cortex might explain a poor response to rTMS. Literature data globally confirm that rTMS is safe and does not produce cognitive deficits, even among highly vulnerable patients with clinical evidence of cerebrovascular disease. CONCLUSION: Many questions remain concerning the optimal stimulation parameters, administration protocol, and privileged indications. Thus, the next rTMS studies should be carefully designed to clarify these questions.
Asunto(s)
Trastorno Depresivo Mayor/terapia , Estimulación Magnética Transcraneal , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Controlados como Asunto , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Dominancia Cerebral/fisiología , Método Doble Ciego , Terapia Electroconvulsiva , Estudios de Seguimiento , Humanos , Inventario de Personalidad , Corteza Prefrontal/fisiopatología , Resultado del TratamientoRESUMEN
INTRODUCTION: Prescription of anti-VEGF treatments have increased substantially over the past few years in treatment of wet age-related macular degeneration. We report the occurrence of macular hemorrhages after one year of use of anti-VEGF intravitreal injections, mainly for subfoveal choroidal neovascularization. MATERIAL AND METHODS: Four hundred forty five injections were given over one year (from 15 March 2007 to 15 March 2008), for age-related macular degeneration, retinal vascular occlusion, diabetic retinopathy, neovascular glaucoma, and idiopathic macular choroidal neovascularization; distributed as follows: 11.5% Bevacizumab, 18.6% Pegaptanib, 19.3% Triamcinolone, and 50.6% Ranibizumab. RESULTS: Six macular hemorrhages were observed, resulting in to a sharp decrease in visual acuity (20/400), with loss of five lines. All occurred after one injection of nonselective anti-VEGF (Ranibizumab) on already treated eyes (four previous injections on average, +/- photodynamic therapy). All were secondary to occult choroidal neovascularization or a large pigment epithelial detachment. Three patients presented a pigment epithelial tear. DISCUSSION: Anti-VEGF intravitreal injections can lead to pigment epithelial tears in case of large pigment epithelial detachment, especially with a small feeder vessel or with large occult choroidal neovascularization. The authors discuss the possible implications of anti-VEGF when macular hematoma occurs: retraction of choroidal neovascularization and alteration of physiological retinal vascularization. CONCLUSION: Macular hematoma affects visual prognosis in age-related macular degeneration. It may follow intravitreal anti-VEGF injection with large occult neovascularization, especially in previously treated eyes. Injection in large pigment epithelial detachment may cause a risk of epithelial tear. Other studies are necessary to evaluate the role of the nonselective anti-VEGF in the incidence of macular hematoma.
Asunto(s)
Degeneración Macular/tratamiento farmacológico , Hemorragia Retiniana/inducido químicamente , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Hemorragia Retiniana/epidemiología , Estudios RetrospectivosRESUMEN
AIMS/HYPOTHESIS: Islet cell death is a key initiating and perpetuating event in type 1 diabetes and involves both immune-mediated and endogenous mechanisms. The epithelial pantetheinase vanin-1 is proinflammatory and cytoprotective via cysteamine release in some tissues. We investigated the impact of a vanin-1 deficiency on islet death and type 1 diabetes incidence. METHODS: Vanin-1-deficient mice were produced and tested in drug-induced and autoimmune diabetes models. The contribution of vanin-1 to islet survival versus immune responses was evaluated using lymphocyte transfer and islet culture experiments. RESULTS: The vanin-1/cysteamine pathway contributes to the protection of islet beta cells from streptozotocin-induced death in vitro and in vivo. Furthermore, vanin-1-deficient NOD mice showed a significant aggravation of diabetes, which depended upon loss of vanin-1 expression by host tissues. This increased islet fragility was accompanied by greater CD4+ insulitis without impairment of regulatory cells. Addition of cystamine, the product of pantetheinase activity, protected islets in vitro and compensated for vanin-1 deficiency in vivo. CONCLUSIONS/INTERPRETATION: This study unravels a major cytoprotective role of cysteamine for islet cells and suggests that modulation of pantetheinase activity may offer alternative strategies to maintain islet cell homeostasis.
Asunto(s)
Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Amidohidrolasas , Animales , Moléculas de Adhesión Celular/deficiencia , Muerte Celular/fisiología , Células Cultivadas , Cistamina/farmacología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Tipo 1/epidemiología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Proteínas Ligadas a GPI , Homeostasis/fisiología , Incidencia , Insulina/metabolismo , Estimación de Kaplan-Meier , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones Mutantes , Linfocitos T Reguladores/patología , Células TH1/patologíaRESUMEN
BACKGROUND: Bipolar mood disorders, after starting at adulthood, may remain active throughout life, but bipolar disorders may only be revealed in later life. Indeed, Yet few data on bipolar disorders in the elderly have been reported in the litterature. The influence of normal aging on the outcome of the disease as well as the specific prognosis of bipolar disorders in the elderly has occasionally been studied. Eventually Finally, and contrasting with adults, few studies comparing the various subtypes of mood disorders were have been performed in the elderly. OBJECTIVES: We therefore developed a study in patients aged 65 or above, in order to evaluate the course (recurrences) of bipolar disorders, compared to recurring depressions and single depressions, and to determine the influence of recurrences on the outcome of bipolar disorders. METHOD: Patients aged over 65 years were inpatients admitted to the department of psychiatry in 2000 for one of the three previously mentioned diagnoses according to DSM IV. Retrospective data were collected from medical reports. Prospectively, data were collected from the general practitioner of each patient (relying on telephone calls), before statistical analysis was performed. RESULTS: Our study demonstrates a more severe outcome for bipolar disorders compared to recurring depressions and single depressions. Patients with bipolar disorders have a higher prevalence of psychiatric recurrences. Furthermore, the greater the number of previous relapses (or the longer the duration and intensity of the disease), the higher the risk of future new future recurrences both in bipolar disorders and recurring depressions. An age of onset of bipolar disorders before 60 years and more than 5 in-hospital admissions increase the risk of recurrences. CONCLUSION: We originally compare the outcome of bipolar disorders in the elderly, to recurring depressions and single depressions. We confirm the fatal outcome of recurrences in bipolar disorders in old age. Bipolar disorders in the elderly should be considered as a real public health care problem: strategies to minimize the number of episodes experienced by patients with bipolar illness must be pursued aggressively throughout life.
Asunto(s)
Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Trastorno Depresivo/epidemiología , Trastorno Depresivo/psicología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
UNLABELLED: INTRODUCTION. We used high-field (3T) functional magnetic resonance imaging (fMRI) to map the retinotopic organization of human cortical areas. METHODS: Retinotopic maps were reconstructed using existing mapping techniques. Stimuli were made of a rotating wedge stimulus, which provided angular coordinate maps, and an expanding or contracting ring, which provided eccentricity coordinate maps. Stimuli consisted of a grey background alternating with a flickering checkerboard. A Brucker 3T scanner equipped with a head coil and a custom optical system was used to acquire sets of echoplanar images of 20 occipital coronal slices within a RT of 2.111 ms and an 8 mm3 voxel resolution. Surface models of each subject's occipital lobes were constructed using the Brainvisa software from a sagittal T1-weighted image with a 1 mm3 voxel resolution. The cortical models were then inflated to obtain unfolded surfaces. Statistical analyses of the functional data were made under SPM99, and the response amplitudes were finally assigned to the cortical reconstructed surfaces. RESULTS: We identified boundaries between different early visual areas (V1, V2, V3) using eccentricity and polar angle retinotopic maps and detection of reversals in the representation of the polar angle. Both complete maps and reversals corresponding to the V1/V2 borders were clearly visible with a single recording session. Also, we were able to compare data from subjects across various fMRI acquisitions and found that there was a strong correlation between maps acquired at different sessions for the same subject. CONCLUSIONS: We developed a quick (<40 min) retinotopic cortical area mapping method at 3T, which makes it possible to study the cortical remapping in patients with retinal scotomas.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Retina/anatomía & histología , Corteza Visual/anatomía & histología , Humanos , Procesamiento de Imagen Asistido por Computador , Escotoma/patologíaRESUMEN
INTRODUCTION: We report a case of a 66-year-old woman presenting a central retinal artery occlusion with no cardiovascular risk factor, with assessment using supra-aortic artery ultrasonography showing total internal carotid artery thrombosis. OBSERVATION: When vascular thrombosis risk factors are absent, more in-depth assessment such as a supra-aortic artery angioscan can provide the diagnosis of arterial dissection on arterial fibromuscular dysplasia. CONCLUSION: Central retinal artery occlusion is a rare but severe pathology. Therefore it is very important not to neglect the etiological assessment, because it can be the revealing element of a severe pathology.
Asunto(s)
Disección de la Arteria Carótida Interna/complicaciones , Displasia Fibromuscular/complicaciones , Oclusión de la Arteria Retiniana/etiología , Anciano , Femenino , HumanosRESUMEN
OBJECTIVE: In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. RESEARCH DESIGN AND METHODS: Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. RESULTS: Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P<0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1+/-4.7 vs. 24.0+/-5.8 U/mmol, P<0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. CONCLUSIONS: In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.
Asunto(s)
LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/uso terapéutico , Lipoproteínas LDL/sangre , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , HDL-Colesterol/sangre , Ensayo de Inmunoadsorción Enzimática , Estudios de Seguimiento , Humanos , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Peso Molecular , Valores de Referencia , Triglicéridos/sangreRESUMEN
Many studies have described the physiology of water immersion (WI), whereas few have focused on post WI physiology, which faces the global water loss of the large WI diuresis. Therefore, we compared hemodynamics and vasomotor tone in 10 trained supine divers before and after two 6h sessions in dry (DY) and head out WI environments. During each exposure (DY and WI) two exercise periods (each one hour 75W ergometer cycling) started after the 3rd and 5th hours. Weight losses were significant (-2.24 +/- 0.13 kg and -2.38 +/- 0.19 kg, after DY and WI, respectively), but not different between the two conditions. Plasma volume was reduced at the end of the two conditions (-9.7 +/- 1.6% and -14.7 +/- 1.6%, respectively; p < 0.05). This post-WI decrease was deeper than post DY (p < 0.05). Cardiac output (CO) and mean arterial blood pressure were maintained after the two exposures. Plasma levels of noradrenaline, antidiuretic hormone and ANP were twofold higher after WI than after DY (p < 0.05). After DY total peripheral resistances (TPR) were increased (p < 0.05) and heart rate (HR) was reduced (p < 0.05). After WI there was a trend for a decrease in stroke volume (p = 0.07) with unchanged TPR and HR, despite more sizeable increases in plasma noradrenaline and vasopressin than after DY. We hypothesized that the higher levels of plasma natriuretic peptides after WI were likely counteracting the dehydration-required vasomotor adjustments.
Asunto(s)
Deshidratación/fisiopatología , Inmersión/fisiopatología , Péptidos Natriuréticos/sangre , Adulto , Análisis de Varianza , Presión Sanguínea/fisiología , Deshidratación/sangre , Hemodinámica/fisiología , Humanos , Masculino , Volumen Plasmático/fisiología , Estadísticas no Paramétricas , Factores de Tiempo , Sistema Vasomotor/fisiologíaRESUMEN
BACKGROUND: In the context of HIV infection and antiretroviral therapy, adiponectin concentrations have been shown to be related to lipodystrophy, metabolic alterations and HIV-protease inhibitor (PI) use. The replacement of PI by nevirapine has improved the lipid profile of patients under antiretroviral therapy. The aim of the present study was to examine whether adiponectin concentration or insulin sensitivity level correlate with the modifications of lipid parameters after the switch of PI by nevirapine. MATERIAL AND METHODS: The evolution of metabolic parameters before and after 6 months of substitution of nevirapine for protease inhibitors was evaluated in a cohort of 55 HIV-1 infected patients. Adiponectin concentration, insulin sensitivity, lipid profile, cholesterol ester transfer protein (CETP) mass concentration and triglyceride enrichment of HDL were determined before and after the replacement of PI by nevirapine. Insulin sensitivity was evaluated by the HOMA model assessment. RESULTS: Twenty-four weeks of treatment with nevirapine improved significantly the lipid profile with a significant reduction of apoB (from 0.98 to 0.92 g L(-1); P = 0.005) and triglyceride (from 2.02 to 1.66 mmol L(-1); P = 0.02). HDL cholesterol and apoA1 increased significantly (from 0.99 to 1.19 mmol L(-1); P = 0.001 and from 1.40 to 1.57 g L(-1); P < 0.001, respectively). The triglyceride enrichment of HDL significantly decreased after the replacement of PI by nevirapine (from 0.248 +/- 0.092 to 0.213 +/- 0.093; P = 0.003). At baseline, and after 24 weeks of nevirapine treatment, we observed significant correlations between adiponectin level and lipid parameters [(HDL-cholesterol (r = 0.66, P = 0.001 and r = 0.69, P = 0.001); triglycerides (r = -0.42, P = 0.002 and r = -0.57, P = 0.001), and triglyceride enrichment of HDL (r = -0.43, P = 0.005 and r = -0.53, P = 0.005)]. Twenty-four weeks of treatment with nevirapine did not significantly change adiponectin concentrations (from 984 to 1086 micro g L(-1), P = 0.22), CETP mass and insulin sensitivity. CONCLUSION: This study shows that even though a strong correlation was found between adiponectin and some metabolic parameters at baseline and after 24 weeks of treatment by nevirapine, the improvement of lipid profile observed after the replacement of PI by nevirapine was not in relation to the change of plasma adiponectin concentration. The significant decrease of triglyceride enrichment of HDL after the replacement of PI by nevirapine probably leads to a decreased catabolism of HDL lipoprotein, and consequently explains the increase of plasma HDL concentration observed in this study.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , Péptidos y Proteínas de Señalización Intercelular , Lípidos/sangre , Nevirapina/uso terapéutico , Proteínas/metabolismo , Adiponectina , Adulto , Femenino , Infecciones por VIH/metabolismo , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , SueroRESUMEN
Vanin-1 is an epithelial ectoenzyme with pantetheinase activity and generating the amino-thiol cysteamine through the metabolism of pantothenic acid (vitamin B(5)). Here we show that Vanin-1(-/-) mice, which lack cysteamine in tissues, exhibit resistance to oxidative injury induced by whole-body gamma-irradiation or paraquat. This protection is correlated with reduced apoptosis and inflammation and is reversed by treating mutant animals with cystamine. The better tolerance of the Vanin-1(-/-) mice is associated with an enhanced gamma-glutamylcysteine synthetase activity in liver, probably due to the absence of cysteamine and leading to elevated stores of glutathione (GSH), the most potent cellular antioxidant. Consequently, Vanin-1(-/-) mice maintain a more reducing environment in tissue after exposure to irradiation. In normal mice, we found a stress-induced biphasic expression of Vanin-1 regulated via antioxidant response elements in its promoter region. This process should finely tune the redox environment and thus change an early inflammatory process into a late tissue repair process. We propose Vanin-1 as a key molecule to regulate the GSH-dependent response to oxidative injury in tissue at the epithelial level. Therefore, Vanin/pantetheinase inhibitors could be useful for treatment of damage due to irradiation and pro-oxidant inducers.
Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Glutatión/metabolismo , Estrés Oxidativo , Amidohidrolasas , Animales , Apoptosis/fisiología , Moléculas de Adhesión Celular/genética , Línea Celular , Cistamina/administración & dosificación , Cistamina/metabolismo , Cisteamina/metabolismo , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Proteínas Ligadas a GPI , Rayos gamma , Regulación Enzimológica de la Expresión Génica , Glutamato-Cisteína Ligasa/metabolismo , Herbicidas/administración & dosificación , Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Paraquat/administración & dosificación , Regiones Promotoras Genéticas , Protectores contra Radiación/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Timo/citología , Timo/fisiología , Timo/efectos de la radiaciónRESUMEN
We report a case of vitreal metastases from cutaneous melanoma. We describe the clinical findings and the histological aspects of the lesions, which allows us to discuss the diagnosis of masquerade syndrome and highlight the diagnostic importance of vitreous biopsy.
Asunto(s)
Neoplasias del Ojo/secundario , Melanoma/secundario , Neoplasias Cutáneas/patología , Cuerpo Vítreo , Neoplasias del Ojo/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We report a case of Penicillium chrysogenum endophthalmitis after penetrating ocular trauma in a 9-year-old child, describing the initial management and the therapeutic adaptation after biopsy culture. After a review of endophthalmitis treatment, we discuss mycotic endophthalmitis treatment and recommend the use of intravitreal antibiotics. In this case, we used amphotericin B to treat the fungal disorder with success.
Asunto(s)
Endoftalmitis/microbiología , Penicillium chrysogenum , Niño , Endoftalmitis/tratamiento farmacológico , Humanos , MasculinoRESUMEN
Thymic epithelium is organized in a highly connected three-dimensional network through which thymocytes differentiate. The molecular mechanisms underlying this organization are still unknown. In thymic medulla, a major site of tolerance induction, the development of the epithelial cell net is tightly regulated by the needs of thymocyte selection. These reticulated epithelial cells express high levels of the Ep-CAM molecule. Using different thymic epithelial cell lines as a model system, we found that transfection of Ep-CAM enhances cell growth and leads to a rapid reorganization of the actin cytoskeleton by inducing the formation of numerous stress fibers and long cell protrusions. Finally, the crosslinking of the extracellular domain of a chimeric CD25ec/Ep-CAMic molecule is sufficient to trigger the formation of protrusions. These results suggest that expression of Ep-CAM might balance the organizing capacity of cadherin molecules and may be participating in the formation of a dynamic stromal cell network in the thymus.
Asunto(s)
Actinas/metabolismo , Antígenos de Neoplasias , Moléculas de Adhesión Celular/fisiología , Células Epiteliales/metabolismo , Animales , Adhesión Celular/genética , Moléculas de Adhesión Celular/genética , División Celular/genética , Línea Celular , Movimiento Celular/genética , Molécula de Adhesión Celular Epitelial , Células Epiteliales/citología , Células Epiteliales/ultraestructura , Expresión Génica , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Microscopía de Contraste de Fase , Timo/citología , Timo/metabolismo , Factores de Tiempo , TransfecciónRESUMEN
The mouse Vanin-1 molecule plays a role in thymic reconstitution following damage by irradiation. We recently demonstrated that it is a membrane pantetheinase (EC 3.56.1.-). This molecule is the prototypic member of a larger Vanin family encoded by at least two mouse (Vanin-1 and Vanin-3) and three human (VNN1, VNN2, VNN3) orthologous genes. We now report (1) the structural characterization of the human and mouse Vanin genes and their organization in clusters on the 6q22-24 and 10A2B1 chromosomes, respectively; (2) identification of the human VNN3 gene and the demonstration that the mouse Vanin-3 molecule is secreted by cells, and (3) that the Vanin genes encode different isoforms of the mammalian pantetheinase activity. Thus, the Vanin family represents a novel class of secreted or membrane-associated ectoenzymes. We discuss here their possible role in processes pertaining to tissue repair in the context of oxidative stress.
Asunto(s)
Amidohidrolasas/genética , Moléculas de Adhesión Celular/genética , Cromosomas Humanos Par 6/genética , Proteínas de la Membrana/genética , Familia de Multigenes , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Secuencia Conservada , Proteínas Ligadas a GPI , Humanos , Ratones , Datos de Secuencia Molecular , Isoformas de Proteínas/genética , Homología de Secuencia de Aminoácido , Distribución TisularRESUMEN
Pantetheinase (EC 3.5.1.-) is an ubiquitous enzyme which in vitro has been shown to recycle pantothenic acid (vitamin B5) and to produce cysteamine, a potent anti-oxidant. We show that the Vanin-1 gene encodes pantetheinase widely expressed in mouse tissues: (1) a pantetheinase activity is specifically expressed by Vanin-1 transfectants and is immunodepleted by specific antibodies; (2) Vanin-1 is a GPI-anchored pantetheinase, and consequently an ectoenzyme; (3) Vanin-1 null mice are deficient in membrane-bound pantetheinase activity in kidney and liver; (4) in these organs, a major metabolic consequence is the absence of detectable free cysteamine; this demonstrates that membrane-bound pantetheinase is the main source of cysteamine in tissues under physiological conditions. Since the Vanin-1 molecule was previously shown to be involved in the control of thymus reconstitution following sublethal irradiation in vivo, this raises the possibility that Vanin/pantetheinase might be involved in the regulation of some immune functions maybe in the context of the response to oxidative stress.