Effects of Jinmaitong serumon the expression of β-catenin, GSK-3β and myelin protein zeroin Schwann cells of rats cultured in high glucose medium / 基础医学与临床

Objective To investigate the effect of serum containing different concentrations of traditional Chinese medicine Jinmaitong on β-catenin, GSK-3β and P0 in Schwann cells cultured in high glucose medium.MethodsTwenty-five male Sprague-Dawley rats were randomly treated with 5, 10, 15 and 20 times of Jinmaitong and distilled water.Schwann cells were divided into six groups, which are control group, high glucose group, 5 times group, 10 times group, 15 times group, 20 times group.72 hours later, the proliferative activity of SCs cells were detected by CCK, the mRNA and protein expression of β-catenin, P0 and GSK-3β was detectived by rt-PCR and Western blot.Results High glucose medium could inhibit the proliferation of Schwann cells, down-regulate the expression of β-catenin and P0(P<0.01), and up-regulate the expression of GSK-3β(P<0.05) mRNA significantly.But Jinmaitong can invert the results (P<0.01, P<0.05).Conclusions High glucose medium will injure the proliferation of Schwann cells, but Jinmaitongcan increase the proliferation activity of Schwann cells, and promotes the secretion of P0 partially dependent on up-regulating the activity of β-catenin and down-regulating the activity of GSK-3β.

A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ) p.Thr124Met mutation shares the Belgian haplotype / Una familia costarricense afectada por la enfermedad de Charcot-Marie-Tooth, debido a la mutación p.thr124Met en la proteína mielina cero (MPZ) compartida con el haplotipo belga

The p.Thr124Met mutation in the myelin protein zero (MPZ) causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers´ sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch), the founder effect hypothesis for this allele migration is suggestive. Rev. Biol. Trop. 62 (4): 1285-1293. Epub 2014 December 01.

La mutación p.thr124Met en la proteína mielina cero (MPZ) causa la enfermedad de Charcot-Marie-Tooth tipo 2J, una neuropatía periférica con síntomas adicionales como alteraciones pupilares y sordera. Se ha observado en varias familias alrededor del mundo, originarias de Alemania, Bélgica, Japón, Italia y Norteamérica, entre otras. Aquí reportamos a pacientes centroamericanos provenientes de Costa Rica que acarrean esta mutación. Se realizaron análisis clínico, electrofisiológico y molecular de pacientes y controles, incluyendo secuenciación del gen y de marcadores ligados a éste. Estos pacientes comparten casi por completo el haplotipo con dos pacientes belgas no emparentados. Como resultado del análisis de los haplotipos, basado en diez marcadores (siete SNPs, dos microsatélites y un elemento poli-A intrónico), se sugiere que se ha dado un efecto fundador en la migración de este alelo.

Early-onset CMT1B due to the MPZ mutation c.320A>T associated with collateral inclusion body myopathy and Deafness.

Aims: To present the case of a patient with early-onset demyelinating neuropathy due to a MPZ-mutation, associated with deafness and inclusion-body-myopathy. Methods: Nerve conduction studies, electromyography, muscle biopsy, genetic testing. Results and Discussion: In a 46yo male with slowly progressive weakness and wasting since childhood initially of the lower and later also of the distal upper-limbs, ptosis, recurrent hyper-CK-emia, and progressive hearing impairment, nerve conduction studies revealed mixed demyelinating and axonal polyneuropathy and electromyography revealed neurogenic motor unit architecture. Nerve biopsy disclosed diffuse loss of myelinated fibers, reduced diameter of non-myelinated fibers, and fibers with hypomyelination and variable internodal myelination. Muscle biopsy revealed classical features of inclusion-body-myopathy. Upon genetic diagnostic work-up the MPZ-mutation c.320A>T, p.Glu107Val was detected. Since his son presented with a similar phenotype, inclusion-body-myopathy was interpreted as secondary to the neuropathy. Conclusions: CMT1B may show secondary axonal loss and mild clinical manifestations despite early onset. CMT1B may be associated with severe hearing impairment and collateral inclusion-body-myopathy.