Experimental models of dermal fibrosis and systemic sclerosis

Vasculopathy, immunological abnormalities, and fibrosis are the key features in the pathogenesis of systemic sclerosis (SSc). Expression of each of the three pathologic features varies among SSc patients leading to disease heterogeneity and variable organ manifestations. Although the etiology of SSc has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interplay between endothelial cells, immune cells and fibroblasts through cell–cell and cell–matrix interactions and communications. Relevant animal models are essential tools to in-depth investigate pathogenesis of SSc. Several murine and avian models are available; however, some models display inflammation followed by fibrosis, whether some others primarily mimic autonomous fibroblast activation. In addition, typical microvascular changes of SSc are only observed in few models. Therefore, none of these animal models encompasses all features of the human disease and a critical selection is mandatory for successful in vivo studies. Hence, we will provide an overview of the most important experimental models of dermal fibrosis and SSc and discuss their respective contribution to the better understanding of SSc pathogenesis.     

Intraoperative neurophysiologic monitoring and neurologic outcomes in patients with epidural spine tumors

Purpose

Multimodal intraoperative neurophysiologic monitoring (IOM) provides assessment of spinal cord pathways during neurosurgery. Despite widespread use, few data exist regarding sensitivity and specificity of IOM in predicting neurologic outcome during decompression and instrumentation for epidural spine tumors.

Methods

Retrospective analysis evaluated consecutive spine procedures involving IOM modalities (somatosensory evoked potentials [SSEP], motor evoked potentials [MEP], and electromyography [(EMG]) from 2007 to 2009. Demographic and surgical information, intraoperative neurophysiologic data, and pre- and postoperative neurologic status were collected. All cases involved neoplastic epidural spinal cord compression by a primary or metastatic tumor and included posterolateral decompression and instrumented fusion.

Results

Two-hundred and eight consecutive patients had spine surgery during this time period and one hundred and fifty-two met inclusion criteria. All patients had SSEP monitoring, with 4 having transient changes and 7 persistent changes. One hundred and twenty-two patients had combined SSEP and MEP monitoring, with 3 having transient changes and 4 persistent changes in MEP signals. Two patients had neurophysiologic changes associated with hypotension and correction led to normalization. One developed new neurologic deficits after surgery. Two from the total cohort had new postoperative neurologic deficits. One had a transient decrease in MEP amplitude while the other had no intraoperative changes.

Discussion

These cases are often long with significant blood loss, and stability of multiple IOM modalities provides reassurance that spinal cord function remains intact. Signal changes should result in scrutiny of blood pressure, surgical technique and anesthesia. Preserved IOM signals are suggestive of preserved neurologic outcome.     

Taurine, an inducer for tau polymerization and a weak inhibitor for amyloid-beta-peptide aggregation

Taurine is an abundant aminoacid present in brain. Its concentration is decreased in the brain of Alzheimer's disease (AD) patients. The chemical structure of taurine is similar to 3-amino-1-propanesulfonic acid, a known compound which interferes with beta-amyloid peptide aggregation. Here, we have tested if taurine show similar properties. Taurine slightly decreases beta-amyloid peptide aggregation at a milimolar concentration. At that concentration, taurine favours the assembly of tau protein into fibrillars polymers. Thus, it is proposed that the negative charge present in taurine may be involved in the binding to tau protein, facilitating its assembly. In addition, the possible role of taurine in Alzheimer disease is commented.     

Evaluation of two 13-loci STR multiplex system regarding identification and origin discrimination of Brazilian Cannabis sativa samples

International Journal of Legal Medicine - According to the Brazilian Federal Police (BFP), the Brazilian Cannabis sativa illicit market is mainly supplied by drugs originated from Paraguay and...     

Precise evaluation of liver histology by computerized morphometry shows that steatosis influences liver stiffness measured by transient elastography in chronic hepatitis C

Background

Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology.

Methods

650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis.

Results

The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic.

Conclusion

A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.