Neuropatía femoral: hematoma en músculo ilíaco y fractura vertebral lumbar

75-year-old patient with a history of acenocumarol anticoagulated atrial fibrillation, which shows pain, functional impotence and right lower limb paresthesias after fall. Studies evidenc evertebral fracture L5 and haematoma on right iliac muscle, proceeding to surgical drainage, suspension of acenocumarol, and onset of apixaban. After treatment persisted femoral neuropathy, which not allowed complete functional recovery.DiscussionFemoral neuropathy as possible cause of compressive hematoma over iliopsoas muscle or secundary to lumbar canal stenosis and contact with L4 root. In both of the misit posible to observe weakness of proximal lower limb musculature. Haematoma was suspected due to lower back pain, flank mass and hypovolemia. Handlingis based on the severity of the symptomatology, from conservative to surgical drainage to reduce sequelae and bleeding complications. Apixaban has shown a higher safety profile. Stabilization of lumbar fracture allowed partial functional recovery.     

Modulating TRPV4 channels with paclitaxel and lithium

Transient receptor potential V4 (TRPV4), a plasma membrane calcium channel, is implicated as a contributor to the initiation of chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel (PTX) is a commonly used anticancer drug that causes CIPN and lithium has been shown to prevent CIPN. However, the direct effect of PTX and lithium on TRPV4 is not clear. This study investigated these actions using biochemical, pharmacological, and electrophysiological approaches using a neuronal cell line (SH-SY5Y). The addition of pharmacologically appropriate levels of PTX increased the expression of TRPV4, TRPV4 currents, and TRPV4-dependent calcium fluxes. Prolonged exposure to PTX amplified the acute effects of TRPV4 expression, currents, and calcium fluxes. Pretreatment with lithium (1 mM) decreased TRPV4 currents and calcium fluxes in the absence and presence of PTX. These findings enhance our understanding of the properties and regulation of TRPV4, the cellular mechanisms of PTX-induced neuropathy, and the mechanism of lithium for prevention of CIPN.     

Correction

The Schwann cell myelin sheath is a multilamellar structure with distinct structural domains in which different proteins are localized. Intracellular dye injection and video microscopy were used to show that functional gap junctions are present within the myelin sheath that allow small molecules to diffuse between the adaxonal and perinuclear Schwann cell cytoplasm. Gap junctions are localized to periodic interruptions in the compact myelin called Schmidt–Lanterman incisures and to paranodes; these regions contain at least one gap junction protein, connexin32 (Cx32). The radial diffusion of low molecular weight dyes across the myelin sheath was not interrupted in myelinating Schwann cells from cx32-null mice, indicating that other connexins participate in forming gap junctions in these cells. Owing to the unique geometry of myelinating Schwann cells, a gap junction-mediated radial pathway may be essential for rapid diffusion between the adaxonal and perinuclear cytoplasm, since this radial pathway is approximately one million times faster than the circumferential pathway.     

Decreased myo-lnositol Uptake Is Associated with Reduced Bradykinin-Stimulated Phosphatidylinositol Synthesis and Diacylglycerol Content in Cultured Neuroblastoma Cells Exposed to L-Fucose

Abstract: L-Fucose is a potent, competitive inhibitor of myo-inositol transport by cultured mammalian cells. Chronic exposure of neuroblastoma cells to L-fucose causes a concentration-dependent decrease in myo-inositol content, accumulation, and incorporation into phosphoinositides. In these studies, L-fucose supplementation of culture medium was used to assess the effect of decreased myo-inositol metabolism and content on bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol production. Chronic exposure of cells to 30 mML-fucose caused a sustained decrease in bradykinin-stimulated, but not basal, ³H-inositol phosphate release and ³²P incorporation into phosphatidylinositol in cells incubated in serum-free, unsupplemented medium. In addition, ³²P incorporation into phosphatidylinositol 4-phosphate and phosphatidylinositol 4, 5-bisphosphate was not altered in L-fucose-conditioned cells. Acute exposure of cells to serum-free medium containing 30 mM L-fucose did not affect either basal or bradykinin-stimulated ³²P incorporation into phosphatidylinositol. Basal diacylglycerol content was decreased by 20% in cells chronically exposed to 30 mM L-fucose, although analysis of the molecular species profile revealed no compositional change. Bradykinin stimulated diacylglycerol production in neuroblastoma cells by increasing the hydrolysis of both phosphoinositides and phosphatidylcholine. Bradykinin-stimulated production of total diacylglycerol was similar for control and L-fucose-conditioned cells. However, there was a decrease in the bradykinin-induced generation of the 1 -stearoyl-2-arachidonoyl diacylglycerol molecular species in the cells chronically exposed to 30 mM L-fucose. This molecular species accounts for about 70% of the composition of phosphoinositides, but only 10% of phosphatidylcholine. The results suggest that a decrease in myo-inositol uptake results in diminished agonist-induced phosphatidylinositol synthesis and phosphoinositide hydrolysis in cultured neuroblastoma cells grown in L-fucose-containing medium.     

Insulin-like growth factor binding protein-1 is pre-synaptic at mouse neuromuscular synapses and is transported in nerve

In a previous study, we localized insulin-like growth factor binding protein 1 (IGFBP-1) to mouse neuromuscular junctions, and intramuscular nerves. To determine if pre-synaptic accumulation of IGFBP-1 occurred, we used double ligation of sciatic nerve in adult mice at different time points. IGFBPs were deteced by Western ligand blot (WLB) with¹²⁵I-IGF-I. WLB and Western immunoblot (WIB) analysis of extracts from double-ligated nerves showed a delayed (6 days) increase of IGFBP-1 in the soluble fraction between the ligatures and distal to the distal ligature. For comparison we evaluated transport of neurofilament components, using WIB and confirmed the primarily anterograde transport of these intraaxonal proteins. These data suggest that expression of IGFBP-1 is both by activated Schwann cells as well as retrograde axonal transport with likely entry into the axon at the synapse.Special issue dedicated to Dr. Sidney Ochs.     

Acrylamide and Glycidamide Impair Neurite Outgrowth in Differentiating N1E.115 Neuroblastoma Without Disturbing Rapid Bidirectional Transport of Organelles Observed by Video Microscopy

Abstract: The nature of the pathogenic insult in acrylamide neuropathy is unknown, but axonal transport disturbances are suspected. Using N1E.115 neuroblastoma in vitro, we examined acrylamide and related compounds in terms of general cytotoxicity, ability to block neurite outgrowth, and effects on neurite integrity and fast axonal transport. Acrylamide, glycidamide, and methylene-bisacrylamide were weakly cytotoxic in a ⁵¹Cr-release assay, but only at ≥10 m M (order of efficacy: methylene-bis-acrylamide > glycidamide > acrylamide). Neurite outgrowth by differentiating cells was inhibited at 100-fold lower concentrations, with similar EC₅₀ values for all three toxicants, i.e., acrylamide, 70 ± 15 μ M ; methylene-bis-acrylamide, 92 ± 31 μ M ; glycidamide, 120 ± 30 μ M . Only glycidamide (1 m M ) caused degeneration of established neurites within a period of 48 h. Video-enhanced contrast differential interference contrast microscopy was used to test the effect of acrylamide and glycidamide on organelle transport in the neurites. In exposures of ≤48 h at 1 m M , neither toxicant altered bidirectional organelle flux, measured as organelles transported per minute per micrometer of neurite diameter. Anterograde and retrograde organelle speeds were also undisturbed. These results suggest that mechanisms other than direct inhibition of organellar motility are responsible for acrylamide's neurotoxicity in vivo.     

外伤性视神经病变最新治疗进展

外伤性视神经病(TON)最常见的原因是颅脑外伤,虽然其发病率不高,但是视力受损后果严重,特别是双侧视神经受损,大部分患者为青壮年,儿童患者占20%。其发病机制到目前为止仍未完全阐明,不同的医疗机构诊断和治疗不完全相同,临床疗效也千差万别。本文通过查阅近年最新文献,对外伤性视神经病变的最新研究进展从视神经解剖、发病机制、诊断、治疗(保守、手术)等方面分别进行综述。希望能够明确其发病机制,找到疗效确切的临床诊断和治疗方法。     

Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin

The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with Sprague-Dawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.