Sulfatide accumulation in the dystrophic terminals of gracile axonal dystrophy mice: lipid analysis using matrix-assisted laser desorption/ionization imaging mass spectrometry

The gracile axonal dystrophy (gad) mutation in Uch-l1, the gene encoding the ubiquitin carboxy-terminal hydrolase isozyme L1 (UCH-L1), causes selective dying back degeneration of dorsal root ganglion neuron in the medulla oblongata along with progressive sensory-motor ataxia. Axonal spheroids are observed within degenerating axons, and their contents may illuminate the pathogenic mechanisms leading to neurodegeneration in gad mice. To analyze changes in negatively charged lipid molecules in dystrophic axons of gad mice, we performed matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS), electron microscopy, and fluorescence immunohistochemistry on tissue sections from gad and wild-type mouse medulla. MALDI-IMS revealed that m/z 806.68 and 822.68 molecules, assigned to sulfatide (ST) C18:0 and ST C18:0(OH), respectively, were concentrated in the dorsomedial medulla. This spatial distribution overlapped significantly with that of axonal spheroids. Immunostaining revealed that spheroids accumulated myelin and lymphocyte protein, a known ST binding protein. Sulfatides with short-chain fatty acids (C16–C20) are generally localized in intracellular vesicles; therefore, ST C18:0 accumulation may reflect intracellular vesicle aggregation within spheroids. Ubiquitin system disruption apparently alters lipid metabolism, membrane organization, protein turnover, and axonal transport. Changes in membrane organization, particularly STs within lipid rafts, may disrupt cellular signaling pathways necessary for neuronal viability.     

Mechanisms of Tumor Development and Anti-angiogenic Therapy in Glioblastoma Multiforme

Despite advances in surgical and medical therapy, glioblastoma multiforme (GBM) remains a fatal disease. There has been no significant increase in survival for patients with this disease over the last 20 years. Tumor vasculature formation and glioma cell invasion along the white matter tracts both play a pivotal role in glioma development. Angiogenesis and invasion are the major factors believed to be responsible for treatment resistance in tumors, and a better understanding of the glioma invasion and angiogenesis mechanisms will lead to the development of potential new treatments. In this review, we focus on the molecular characteristics of angiogenesis and invasion in human malignant glioma. We discuss bevacizumab and cilengitide, which are used to inhibit angiogenesis in GBM.     

Elevated levels of soluble fibrin in patients with venous thromboembolism

The fibrin-related markers (FRMs), including soluble fibrin (SF), d-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, d-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for d-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 μg/ml, FDP 2.1 μg/ml and d-dimer 4.8 μg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 μg/ml, FDP was less than 1.3 μg/ml, and d-dimer was less than 0.5 μg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.     

Incidence of Urolithiasis in Northeast Thailand

Background :
Urolithiasis is a major health problem in the northeast part of Thailand. In this study, we examined the prevalence of renal stone disease and differences of urinary components between stone formers and healthy control subjects in northeastern rural areas of Thailand.
Methods :
We selected 3 villages in the rural areas of Khon Kaen province in northeast Thailand. Three hundred and sixty-seven persons were asked questions relating to urolithiasis and were examined by abdominal ultrasound (US). We collected a spot urine sample from stone formers and healthy control subjects from each village.
Results :
Abnormal findings by US were detected in 39 individuals (10.6%), and included 31 individuals with renal calculi (8.4%), 16 with hydronephrosis (4.4%), and 1 individual with a renal cyst (0.3%). This yielded a disease rate of urinary stones in this study of 16.9%. The male/female ratio was 2/1 and the average age of the individuals examined was 40.3 + 13.9 years. However, there was no significant difference between the urinary parameters of stone formers and the healthy control subjects. Conclusion: There was a high incidence of renal stone disease in the northeast part of Thailand, but the tendency for hypocitraturia was only found in stone formers.