Una nueva mutación de la enfermedad de Dent en un niño de 11 años con nefrolitiasis y nefrocalcinosis / A novel mutation of Dent's disease in an 11-year-old male with nephrolithiasis and nephrocalcinosis

La enfermedad de Dent es una tubulopatía recesiva ligada al cromosoma X caracterizada por proteinuria de bajo peso molecular (bpm), hipercalciuria, nefrocalcinosis o nefrolitiasis, disfunción tubular proximal e insuficiencia renal en la adultez. Las mujeres son portadoras y, en general, padecen una forma leve de la enfermedad. La progresión hacia la insuficiencia renal en estadio terminal se da entre los 30 y los 50 años de edad en el 30-80% de los varones afectados. A falta de un tratamiento dirigido al defecto molecular, en la actualidad, los pacientes con enfermedad de Dent reciben tratamientos complementarios orientados a prevenir la nefrolitiasis y la nefrocalcinosis. El caso que presentamos es el de un niño de 11 años con nefrocalcinosis y nefrolitiasis, en quien se detectó una nueva mutación en el gen CLCN5.

Dent's disease is a rare X-linked recessive tubulopathy characterized by low molecular weight (LMW) proteinuria, hypercalciuria, nephrolcalcinosis or nephrolithiasis, proximal tubular dysfunction and renal failure in adulthood. Females are carriers and usually mildly affected. Progression to endstage renal failure are at the 3rd-5th decades of life in 30-80% of affected males. In the absence of therapy targeting for the molecular defect, the current care of patients with Dent's disease is supportive, focusing on the prevention of nephrolithiasis and nephrocalcinosis. We present an 11-year-old child with nephrocalcinosis and nephrolithiasis caused by a new mutation at CLCN5 gene.

Evaluación del comportamiento del sistema de ajuste locator asociado con una prótesis parcial removible, análisis de elementos finitos / Evaluation of the behavior system locator associated with a removable partial denture, finite element analysis

Objetivo: El propósito de esta investigación fue evaluar el comportamiento del sistema de ajuste locator asociado con una prótesis parcial removible (PPR) con extensión distal inferior por medio del método de análisis de elementos finitos (MEF). Materiales y Métodos: Se diseñó un modelo clase II Kennedy tridimensional utilizando un Software CAD de Solid Works 2010 (SolidWorks Corp., Concord, MA, USA), y posteriormente se procesó y analizó a través Software ANSYS versión 14. Se modelo un (1) implante Tapered Screw-Vent® (ref. TSVB10 Zimmer Dental-Carlsbad, CA, USA) de 10mm de longitud x 3.7mm de diámetro con una plataforma de 3.5mm, de hexágono interno con su respectivo tornillo de fijación; este se ubicó en el diente 37 como pilar posterior de una PPR, cuyo conector mayor fue una barra lingual colada (aleación cromo cobalto), con base combinada (metal/acrílico), con dientes a reemplazar (37, 36 y 35). Se evaluaron los esfuerzos von Mises en una carga 400N. Este análisis permitió valorar el comportamiento de las diferentes estructuras protésicas modeladas y los efectos generados en las interfases hueso-implante. Resultados: Se observaron diferencias entre los valores von Mises en todas las estructuras y ante las cargas no hubo deformaciones permanentes en ninguna de ellas. Estructuras como el hueso mostraron microdeformaciones en valores normales. Conclusiones: El comportamiento de la conexión PPR-implante, mostró una distribución de esfuerzos favorable al utilizar una PPR, sometiéndola a carga en dirección vertical.

Aim: The purpose of this research was to evaluate the behavior of the system locator settings associated with distal extension removable partial denture lower (PPR) by finite element analysis (FEA). Materials and Methods: A Class II Kennedy 3D model using a CAD software Solid Works 2010 (SolidWorks Corp., Concord, MA, USA), and subsequently processed and analyzed by ANSYS Software version Model 14. One (1) was designed implant Tapered Screw -Vent® (ref TSVB10 Zimmer Dental-Carlsbad,CA,USA.) length x 10mm diameter 3.7mm with a 3.5mm platform, internal hexagon with its respective screw fixation; this was located at the tooth 37 as a rear pillar of a PPR, whose major connector was a lingual bar casting (alloy cobalt chromium), based combined (metal/ acrylic) with teeth to replace (37, 36 and 35). Efforts were evaluated von Mises in a 400N load. This analysis allowed assessing the performance of various prosthetic structures modeled and generated effects on bone-implant interface. Results: Differences between the values von Mises in all structures and loads were observed before there was no permanent deformation in any of them. Structures such as bone showed in normal values microstrain Conclusions: The behavior of the PPRimplant connection, showed a favorable distribution efforts by using a PPR, subjecting it to load in the vertical direction

Origin of Proteinuria as Observed from Qualitative and Quantitative Analysis of Serum and Urinary Proteins

It is well known that proteins present in the primary urine are reabsorbed in the renal proximal tubules, and that this reabsorption is mediated via the megalincubilin complex and the neonatal Fcgamma receptor. However, the reabsorption is also thought to be influenced by an electrostatic interaction between protein molecules and the microvilli of the renal proximal tubules. By analyzing the charge diversity of urinary IgG, we showed that this reabsorption process occurs in a cationic charge-preferential manner. The charge-selective molecular sieving function of the glomerular capillary walls has long been a target of research since Brenner et al. demonstrated the existence of this function by a differential clearance study by using the anionic dextran sulfate polymer. However, conclusive evidence was not obtained when the study was performed using differential clearance of serum proteins. We noted that immunoglobulin (Ig) A and IgG have similar molecular sizes but distinct molecular isoelectric points. Therefore, we studied the differential clearance of these serum proteins (clearance IgA/ clearance IgG) in podocyte diseases and glomerulonephritis. In addition, we studied this differential clearance in patients with Dent disease rather than in normal subjects because the glomerular sieving function is considered to be normal in subjects with Dent disease. Our results clearly showed that the charge-selective barrier is operational in Dent disease, impaired in podocyte disease, and lacking in glomerulonephritis.

Clinical and genetic analysis of Dent disease in 4 Chinese children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical features and gene mutations of 4 Chinese children with Dent disease.</p><p><b>METHODS</b>The clinical and laboratory data of 4 children with Dent disease were analyzed retrospectively. Genetic testing of the 4 cases was carried out.</p><p><b>RESULTS</b>All of 4 cases were boys. The first impression of Cases 1-3 was Fanconi syndrome. Proteinuria was presented as the first impression in Case 4. All 4 boys presented with low-molecular weight proteinuria (LMWP) and hypercalciuria, including 3 cases with hematuria, 1 case with kidney stones, 2 cases with nephrocalcinosis, 3 cases with hypophosphatemia, and 3 cases with rickets. Mutations of the CLCN5 gene were revealed in three patients (Cases 1, 2 and 4), including exon 6-7del, c.785_787de l(p.263del Leu) and c.1039 C>T (p.Arg347Term). The first two gene mutations had never reported before.</p><p><b>CONCLUSIONS</b>Urine protein electrophoresis should be carried out for patients with proteinuria. Dent disease should be taken into consideration when patients with Fanconi syndrome have hypercalciuria, nephrocalcinosis or kindey stones. Genetic analyses are needed for a definite diagnosis.</p>

Clinical and genetic analysis of Dent' s disease in 6 Chinese children with low molecular weight proteinuria / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and gene mutations of 6 Chinese children with Dent's disease.</p><p><b>METHOD</b>The clinical and laboratory data of 6 children with Dent's disease were summarized. CLCN5 gene was analyzed using PCR amplification and DNA sequencing.</p><p><b>RESULT</b>All the six patients presented with low molecular weight proteinuria and hypercalciuria, including 3/6 hematuria, 4/6 nephrocalcinosis, 3/6 hypophosphatemia, 1/6 rickets. Six mutations of the CLCN5 gene were revealed, including L594fsX595, R637X, R467X, IVS4-2A > G, S244L and V505G. The mutation L594fsX595, IVS4-2A > G and V505G was never reported before.</p><p><b>CONCLUSION</b>Low molecular weight proteinuria and hypercalciuria were the main clinical features of the six Chinese boys with Dent's disease. Dent's disease could be associated with a Bartter-like syndrome, which make the gene diagnosis more important.</p>

The properties of voltage-sensitive chloride channels / 한양의대학술지

Chloride (Cl) channels are probably found in every cell, from bacteria to mammals. Cl channels are distributed both in the plasma membrane and in intracellular organelles. Three well established structural classes of plasma membrane chloride channels now exist: the ligand-gated chloride channels, the cAMP-stimulated cystic fibrosis transmembrane conductance regulator channel, and the voltage-gated (or swelling-activated) members of the ClC chloride channel family. They have diverse functions, ranging from regulation of cell volume to transepithelial transport, homeostasis, and stabilization of membrane potential, signal transduction and acidification of intracellular organelles. These different functions require the presence of many distinct Cl channels, which are differentially expressed and regulated by various stimuli. A combination of mutagenesis and biophysical analysis has been used to correlate their structure with function. Also their physiological roles are explained by genetic defects leading to various inherited disease and knock-out mouse models. Thus, the loss of Cl channels leads to an impairment of transepithelial transport in Bartter's syndrome, to increased excitability in congenital myotonia, and to reduced endosomal acidification and impaired endocytosis in Dent's disease. Three major structural classes of chloride channels are known to date, but there may be others not yet identified at the molecular level. This review focuses on voltage-gated members of the ClC chloride channel family and their physiological roles.