RESUMO
El síndrome renal-coloboma es una enfermedad autosómica dominante caracterizada por hipodisplasia renal y coloboma. Se presenta el caso de una niña de 12 años afecta de enfermedad renal crónica, colobomas papilares bilaterales y mutación excepcional del gen PAX-2. Con diagnóstico prenatal de hipoplasia renal bilateral, a los 5 días de vida, presentó clínica y datos analíticos compatibles con enfermedad renal crónica. En los controles posteriores, se apreció reflujo vesicoureteral grado ii bilateral, que se resolvió espontáneamente, proteinuria mantenida en rango no nefrótico controlada con enalapril y colobomas bilaterales con atrofia macular izquierda. La función renal se mantuvo estable. El estudio genético demostró mutación p.R104X de novo sin sentido en heterocigosis. Globalmente, existen documentados 80 casos de síndrome renal-coloboma asociado a mutaciones de este gen. Las evaluaciones oftalmológicas y genéticas son fundamentales en los casos de hipodisplasia renal. La función renal determinará el pronóstico. Se realizó una revisión bibliográfica de la etiopatogenia de la enfermedad.
Renal-coloboma syndrome is an autosomal dominant disease characterized by renal hypodysplasia and coloboma. A case of a 12-year-old girl with chronic kidney disease, bilateral optic nerve colobomas and an exceptional PAX-2 gene mutation is presented. Diagnosed in prenatal scans with bilateral renal hypoplasia, she presented clinical and laboratory findings of chronic kidney disease at 5 days of life. Following tests showed grade II bilateral vesicoureteral reflux spontaneously solved, maintained non nephrotic proteinuria controlled with enalapril and bilateral colobomas with left macular atrophy. Renal function remained stable. Genetic study showed de novo and non sense mutation p.R104X in heterocygosis. Currently there are 80 published cases of renal-coloboma syndrome associated with this gene mutations. Ophthalmologic and genetic evaluations are crucial in cases affected by renal hypodysplasia. Renal function will establish prognosis. We review the etiopathogenesis of this disease.
Assuntos
Humanos , Feminino , Criança , Refluxo Vesicoureteral/genética , Coloboma/genética , Insuficiência Renal/genética , MutaçãoRESUMO
Renal-coloboma syndrome is an autosomal dominant disease characterized by renal hypodysplasia and coloboma. A case of a 12-year-old girl with chronic kidney disease, bilateral optic nerve colobomas and an exceptional PAX-2 gene mutation is presented. Diagnosed in prenatal scans with bilateral renal hypoplasia, she presented clinical and laboratory findings of chronic kidney disease at 5 days of life. Following tests showed grade II bilateral vesicoureteral reflux spontaneously solved, maintained non nephrotic proteinuria controlled with enalapril and bilateral colobomas with left macular atrophy. Renal function remained stable. Genetic study showed de novo and non sense mutation p.R104X in heterocygosis. Currently there are 80 published cases of renal-coloboma syndrome associated with this gene mutations. Ophthalmologic and genetic evaluations are crucial in cases affected by renal hypodysplasia. Renal function will establish prognosis. We review the etiopathogenesis of this disease.
El síndrome renal-coloboma es una enfermedad autosómica dominante caracterizada por hipodisplasia renal y coloboma. Se presenta el caso de una niña de 12 años afecta de enfermedad renal crónica, colobomas papilares bilaterales y mutación excepcional del gen PAX-2. Con diagnóstico prenatal de hipoplasia renal bilateral, a los 5 días de vida, presentó clínica y datos analíticos compatibles con enfermedad renal crónica. En los controles posteriores, se apreció reflujo vesicoureteral grado ii bilateral, que se resolvió espontáneamente, proteinuria mantenida en rango no nefrótico controlada con enalapril y colobomas bilaterales con atrofia macular izquierda. La función renal se mantuvo estable. El estudio genético demostró mutación p.R104X de novo sin sentido en heterocigosis. Globalmente, existen documentados 80 casos de síndrome renal-coloboma asociado a mutaciones de este gen. Las evaluaciones oftalmológicas y genéticas son fundamentales en los casos de hipodisplasia renal. La función renal determinará el pronóstico. Se realizó una revisión bibliográfica de la etiopatogenia de la enfermedad.
Assuntos
Coloboma/genética , Mutação , Insuficiência Renal/genética , Refluxo Vesicoureteral/genética , Criança , Feminino , HumanosRESUMO
Na+, K+-ATPase, or the Na+ pump, is a key component in the maintenance of the epithelial phenotype. In most epithelia, the pump is located in the basolateral domain. Studies from our laboratory have shown that the ß1 subunit of Na+, K+-ATPase plays an important role in this mechanism because homotypic ß1-ß1 interactions between neighboring cells stabilize the pump in the lateral membrane. However, in the retinal pigment epithelium (RPE), the Na+ pump is located in the apical domain. The mechanism of polarization in this epithelium is unclear. We hypothesized that the apical polarization of the pump in RPE cells depends on the expression of its ß2 subunit. ARPE-19 cells cultured for up to 8 weeks on inserts did not polarize, and Na+, K+-ATPase was expressed in the basolateral membrane. In the presence of insulin, transferrin and selenic acid (ITS), ARPE-19 cells cultured for 4 weeks acquired an RPE phenotype, and the Na+ pump was visible in the apical domain. Under these conditions, Western blot analysis was employed to detect the ß2 isoform and immunofluorescence analysis revealed an apparent apical distribution of the ß2 subunit. qPCR results showed a time-dependent increase in the level of ß2 isoform mRNA, suggesting regulation at the transcriptional level. Moreover, silencing the expression of the ß2 isoform in ARPE-19 cells resulted in a decrease in the apical localization of the pump, as assessed by the mislocalization of the α2 subunit in that domain. Our results demonstrate that the apical polarization of Na+, K+-ATPase in RPE cells depends on the expression of the ß2 subunit.
RESUMO
PURPOSE: In hypoxic tumoral tissues, vascular endothelial growth factor (VEGF) expression is positively regulated by histone deacetylase 1 (HDAC1) and negatively regulated by the tumour suppressor protein von Hippel-Lindau (VHL) via transforming growth factor-alpha (HIF-1alpha). It has been reported that VEGF, HDAC1 and LL-37, but not VHL, are over-expressed in psoriatic skin. Although HIF-1alpha is constitutively expressed in normal keratinocytes, it is not known if HDAC1 and VHL can regulate VEGF production in these cells. METHODS: The participation of HDAC1 and VHL in the regulation of VEGF expression in HDAC-, VHL- and LL-37-transfected HaCaT cells, and in HaCaT cells treated with HDAC1 inhibitors, was studied. RESULTS: The production of VEGF was increased in HDAC1- and LL-37-transfected HaCaT cells and maintained in VHL-transfected cells under hypoxic conditions; meanwhile, VEGF production decreased in HaCaT cells treated with TSA, in cells transfected with HDAC1-siRNA, in cells co-transfected with HIF-1alpha-siRNA and pHDAC-1 and in VHL-transfected HaCaT cells. The levels of cytoplasmic HIF-1alpha were high in pLL37-transfected cells and low in pVHL- and pHDAC1-transfected cells; however, HIF-1alpha was detected in the nucleus of the HDAC1-transfected cells. The expression of VEGF was high in cells co-transfected with pHDAC1- and pLL-37, and the expression decreased when pVHL was present. CONCLUSIONS: These data demonstrate that HDAC1, LL-37 and VHL can modulate the production of VEGF via HIF-1alpha in HaCaT cells.
Assuntos
Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Peptídeos Catiônicos Antimicrobianos , Catelicidinas/biossíntese , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Hipóxia , Queratinócitos/citologia , Microscopia de Fluorescência/métodos , Psoríase/metabolismo , Pele/metabolismo , TransfecçãoRESUMO
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasingly recognized as an important pathogen causing skin and soft tissue infections as well as necrotizing pneumonia. We describe a case of familial transmission of CA-MRSA between a 6-month-old boy and his mother in Santa Fe City, Argentina. Both isolates showed an identical antimicrobial susceptibility profile, carried type IV SCCmec and harboured the pvl and the lnu(A) genes. Isolates showed indistinguishable SmaI-PFGE patterns confirming their genetic relationship. These results corroborate the intrafamilial transmission of CA-MRSA and might associate this strain with the repetitive events of furunculosis within the family.
Assuntos
Proteínas de Bactérias/genética , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/transmissão , Argentina , Infecções Comunitárias Adquiridas , Humanos , Lactente , Masculino , Saúde da População UrbanaRESUMO
Cumulative evidence demonstrated effective downstream metabolism of pregnenolone in renal tissue. The aim of this study was to evaluate the expression and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1), which converts cholesterol into pregnenolone, in adult rat kidney. Immunohistochemical labeling for CYP11A1 was observed in renal cortex and medulla, on structures identified as distal convoluted tubule and thick ascending limb of Henle's loop, respectively. Immunoblotting analysis corroborated the renal expression of the protein in inner mitochondrial membrane fractions. The incubation of isolated mitochondria with the membrane-permeant cholesterol analogue 22R-hydroxycholesterol resulted in efficient formation of pregnenolone, the immediate precursor for the synthesis of all the steroid hormones. The low progesterone production rate observed in these experiments suggested a poor activity of 3ß-hydroxysteroid dehydrogenase enzyme in renal mitochondria. The steroidogenic acute regulatory protein (StAR), involved in the mitochondrial import of cholesterol, was detected in renal tissue at both mRNA and protein level. Immunostaining for StAR showed similar distribution to that observed for CYP11A1. The expression of StAR and CYP11A1 was found to be higher in medulla than in cortex. This enhanced expression of steroidogenesis-related proteins correlated with a greater pregnenolone synthesis rate and higher steroid hormones tissular content measured in medulla. In conclusion, we have established the expression and localization of StAR and CYP11A1 protein, the ability of synthesizing pregnenolone and a region-specific content of sex hormones in the adult rat kidney. These data clearly show that the kidney is a steroid hormones synthesizing organ. It is proposed that the existence in the kidney of complete steroidogenic machinery would respond to a physiological significance.
Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Rim/enzimologia , Animais , Proteínas de Transporte/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Rim/anatomia & histologia , Masculino , Membranas Mitocondriais/enzimologia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Pregnenolona/biossíntese , Progesterona/biossíntese , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Testosterona/metabolismoRESUMO
The very existence of higher metazoans depends on the vectorial transport of substances across epithelia. A crucial element of this transport is the membrane enzyme Na(+),K(+)-ATPase. Not only is this enzyme distributed in a polarized manner in a restricted domain of the plasma membrane but also it creates the ionic gradients that drive the net movement of glucose, amino acids, and ions across the entire epithelium. In a previous work, we have shown that Na(+),K(+)-ATPase polarity depends on interactions between the beta subunits of Na(+),K(+)-ATPases located on neighboring cells and that these interactions anchor the entire enzyme at the borders of the intercellular space. In the present study, we used fluorescence resonance energy transfer and coprecipitation methods to demonstrate that these beta subunits have sufficient proximity and affinity to permit a direct interaction, without requiring any additional extracellular molecules to span the distance.
Assuntos
Polaridade Celular , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Linhagem Celular , Cricetinae , Cricetulus , Cães , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Transferência Ressonante de Energia de Fluorescência , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/genética , Ratos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Hypochondriacal delusions may eventually appear in chronic psychosis. Some authors have proposed the existence of a chronic delusional disease named Hypochondriacal Paraphrenia in which these delusions constitute its main feature. In the present article we discuss the nosological validity of the Hypochondriacal Paraphrenia and its independence from other subtypes of Paraphrenias. With this aim, an historical review of the position of the hypochondriacal symptomatology was performed form the original definitions of Lasègue and Griesinger to the description of the Hypochondriacal Paraphrenia by Karl Leonhard. Then, three cases of patients with the diagnosis of Hypochondriacal Paraphrenia are presented. We conclude that the Hypochondriacal Paraphrenia is a valid and useful nosological construct.
Assuntos
Delusões/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Hipocondríase/diagnóstico , Delusões/etiologia , Transtorno Depressivo Maior/complicações , Feminino , França , Alemanha , Humanos , Hipocondríase/complicações , Pessoa de Meia-IdadeRESUMO
Cutaneous drug reactions are the most common type of adverse reaction observed with psychotropic medications. For this pharmacological group, the mood-stabilizing agents have the highest incidence of severe and life-threatening cutaneous drug reactions. The cutaneous drug reactions induced by psychotropic medications range from common and benign events (e.g., exanthematous reactions or urticaria) to severe and potentially life-threatening events (erythroderma, Stevens-Johnson syndrome, toxic epidermal necrolysis and anticonvulsant hypersensitivity syndrome). In this review we describe the clinical morphology and distribution of the cutaneous drug reactions, the associated systemic findings, and the treatments and drugs that most usually precipitate these reactions. Furthermore, we discuss the recommended interventions for diminishing the mortality of potentially life-threatening events.
Assuntos
Toxidermias/etiologia , Psicotrópicos/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Humanos , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/etiologia , SíndromeRESUMO
The geometry of iodotrimethylgermane has been determined by experimental and computational methods. Fourier transform infrared spectra have been recorded over a range of temperatures along with the Raman spectrum to obtain comprehensive vibrational data for the fundamental modes. The stretching, rocking, and deformation bands of the methyl groups have been resolved into their components with the aid of low-temperature infrared spectroscopy using Fourier self-deconvolution and curve-fitting methods. The optimized geometries and vibrational harmonic frequencies were calculated by density functional theory methods employing Pople-type basis sets, as well as those with descriptions for an effective core potential describing both germanium and iodine atoms. A scaled quantum mechanical analysis was carried out to yield the best set of harmonic force constants and obtain a transferable set of scale factors that can be applied to the (CH3)(3-)GeX (X = H, Cl, Br, I) series.