Doença de Charcot-Marie-Tooth: estudo da biópsia do nervo sural em 41 pacientes

São apresentados os resultados da biópsia do nervo sural à microscopia óptica e eletrônica (ME) em 41 pacientes com doença de Charcot-Marie-Tooth (CMT) Por estudos de neurocondução prévios nove eram do tipo I e 32 do tipo II. No tipo I, todos tinham grande diminuição do número de fibras, sendo os histogramas do tipo unimodal. Encontramos imagens de desmielinização, remielinização, formação de bulbos de cebola e de regeneração. Um paciente apresentava espessamento da bainha de mielina (atrofia axonal). No tipo II, sete pacientes não apresentavam anomalia à microscopia, com histograma normal. Nos restantes havia discreta a intensa perda de fibras mielínicas principalmente as de grande calibre. Em cinco enfermos havia aumento do número de fibras devido a grande regeneração. Alguns pacientes do tipo II apresentavam à ME imagens de pequenos bulbos de cebola e em um havia também atrofia axonal. Comparando com os dados clínicos e de neurocondução motora, no tipo I não encontramos relação entre a intensidade do quadro clínico e a perda de fibras mielínicas porém houve paralelismo da queda da neurocondução motora e a diminuição do número de fibras. No tipo II não houve relação entre o quadro clínico, a neurocondução e os achados da biópsia nervosa.We studied the pathological findings of sural nerve biopsy in 41 patients with Charcot-Marie-Tooth (CMT) disease. They were previously classified by the median motor conduction velocity (MCV) in two types. Type I (demyelinating) with 9 patients and type II (axonal) with 32 cases. In type I we found loss of myelinated fibers (unimodal histogram), demyelinated and remyelinated axons with numerous onion bulb formations. In one case there was thickness of myelin with thin axons (axonal atrophy). In type II there were seven patients with normal sural nerve biopsy. In 25 cases there were mild to severe loss of myelinated fibers. In 5 patients the number of myelinated fibers was increased due to the great regeneration of the axons. The electron microscopic studies in type II showed in a few cases small onion bulbs and in one case axonal atrophy. In type I there was no correlation between clinical severity and the loss of myelinated fibers, but there was relationship between the low MCV and the intensity of myelinated fibers. In type II we did not found any correlation between clinical course, MCV and pathological findings

Allergen particle binding by human primary bronchial epithelial cells is modulated by surfactant protein D

<p>Abstract</p> <p>Background</p> <p>Allergen-containing subpollen particles (SPP) are released from whole plant pollen upon contact with water or even high humidity. Because of their size SPP can preferentially reach the lower airways where they come into contact with surfactant protein (SP)-D. Our previous work demonstrated that SP-D increases the uptake of SPP by alveolar macrophages. In the present study, we investigated the uptake of SPP in human primary epithelial cells and the potential modulation by SP-D. The patho-physiological consequence was evaluated by measurement of pro-inflammatory mediators.</p> <p>Methods</p> <p>SPP were isolated from timothy grass and subsequently fluorescently labelled. Human primary bronchial epithelial cells were incubated with SPP or polystyrene particles (PP) in the presence and absence of surfactant protein D. In addition, different sizes and surface charges of the PP were studied. Particle uptake was evaluated by flow cytometry and confocal microscopy. Soluble mediators were measured by enzyme linked immunosorbent assay or bead array.</p> <p>Results</p> <p>SPP were taken up by primary epithelial cells in a dose dependent manner. This uptake was coincided with secretion of Interleukin (IL)-8. SP-D increased the fraction of bronchial epithelial cells that bound SPP but not the fraction of cells that internalized SPP. SPP-induced secretion of IL-8 was further increased by SP-D. PP were bound and internalized by epithelial cells but this was not modulated by SP-D.</p> <p>Conclusions</p> <p>Epithelial cells bind and internalize SPP and PP which leads to increased IL-8 secretion. SP-D promotes attachment of SPP to epithelial cells and may thus be involved in the inflammatory response to inhaled allergen.</p

COMP-Angiopoietin-1 Recovers Molecular Biomarkers of Neuropathy and Improves Vascularisation in Sciatic Nerve of ob/ob Mice

mice. mice displayed regeneration of small-diameter endoneural microvessels. Effects of COMP-Ang-1 corresponded to increased phosphorylation of Akt and p38 MAPK upon Tie-2 receptor. mice suggesting COMP-Ang-1 as novel treatment option to improve morphologic and protein expression changes associated with diabetic neuropathy

Hybrid Shell Engineering of Animal Cells for Immune Protections and Regulation of Drug Delivery: Towards the Design of “Artificial Organs”

BACKGROUND: With the progress in medicine, the average human life expectancy is continuously increasing. At the same time, the number of patients who require full organ transplantations is augmenting. Consequently, new strategies for cell transplantation are the subject of great interest. METHODOLOGY/PRINCIPAL FINDINGS: This work reports the design, the synthesis and the characterisation of robust and biocompatible mineralised beads composed of two layers: an alginate-silica composite core and a Ca-alginate layer. The adequate choice of materials was achieved through cytotoxicity LDH release measurement and in vitro inflammatory assay (IL-8) to meet the biocompatibility requirements for medical purpose. The results obtained following this strategy provide a direct proof of the total innocuity of silica and alginate networks for human cells as underscored by the non-activation of immune defenders (THP-1 monocytes). The accessible pore size diameter of the mineralised beads synthesized was estimated between 22 and 30 nm, as required for efficient immuno-isolation without preventing the diffusion of nutrients and metabolites. The model human cells, HepG2, entrapped within these hybrid beads display a high survival rate over more than six weeks according to the measurements of intracellular enzymatic activity, respiration rate, as well as the "de novo" biosynthesis and secretion of albumin out of the beads. CONCLUSIONS/SIGNIFICANCE: The current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system. The functionality of the cell strain can be maintained. Consequently, cells coated with an artificial and a biocompatible mineral shell could respond physiologically within the human body in order to deliver therapeutic agents in a controlled fashion (i.e. insulin), substituting the declining organ functions of the patient

The Neuropathology Of Chronic Relapsing Experimental Allergic Encephalomyelitis Induced In The Lewis Rat By Inoculation With Whole Spinal Cord And Treatment With Cyclosporin A

Chronic relapsing experimental allergic encephalomyelitis was induced in Lewis rats by inoculation with guinea-pig spinal cord and complete Freund's adjuvant followed by treatment with low-dose cyclosporin A. In most animals, tail and limb weakness developed in a relapsing remitting pattern but in some these signs were persistent or progressive from onset. Histological studies during the early stages of clinically active disease ( 28 days after inoculation) had extensive spinal cord demyelination but minimal PNS demyelination. In these animals, large plaques of demyelination with gliosis and prominent plasma cells occurred particularly in the thoracic spinal cord, and lesions of different ages were present within the spinal cord. CNS and PNS remyelination with oligodendocytes and Schwann cells respectively was present in all animals studied later than 18 days after inoculation (the time of the first remission, if it occurred). In both early and late clinically active disease electron microscopy revealed macrophages invading and destroying CNS myelin sheaths. Active demyelination was sometimes found in regions of CNS remyelination, suggesting that remyelinated fibres were being attacked. Axonal degeneration occurred in the spinal cord. During clinical remission there was CNS and PNS remyelination and much less inflammation; however active demyelination still occurred to a limited degree

Increased Susceptibility to Ischemic Damage in Steptozocin-Diabetic Nerve

Nerve ischemia, both acute and chronic, may contribute to diabetic neuropathies, but the pathogenesis remains obscure. The vulnerability of diabetic nerve to ischemia was assessed by ligating arteries of supply of rat sciatic nerve after 20 wk of streptozocin-induced diabetes. In the first 24 h after the arterial ligations, severe and more rapidly occurring clinicopathological abnormalities were invariably seen in diabetic nerves, but these findings were less severe in nondiabetic nerves. The results imply that peripheral nerve in diabetes mellitus is more subject to ischemia than normal nerve. This phenomenon may ensue from endoneurial hypoxia and play an important role in the development of diabetic neuropathies.</jats:p