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.     

Criteria for the glucagon provocative test in the diagnosis of gastrinoma

Introduction

The glucagon provocative test is useful for the diagnosis of gastrinoma. The aim of this study was to determine the criteria for the glucagon provocative test.

Methods

This study reviewed 8 patients that underwent the glucagon provocative test preoperatively and in whom the diagnosis was confirmed as gastrinoma histologically. The glucagon provocative test was performed by administering glucagon (20 μg/kg) intravenously, followed by 20 μg/kg h for the next 30 min, and plasma gastrin levels were measured 3 and 1 min before and 3, 5, 7, 10, 15, 20, and 30 min after the administration of glucagon. This study evaluated the peak value of plasma gastrin and the time required to reach the peak.

Results

Two of the 8 patients had multiple endocrine neoplasm type 1. The basal plasma gastrin levels ranged from 524 to 10,300 pg/ml. The time required to reach the peak was 3–10 min for all patients. The increase in the peak from the basal value was 235–8,920 pg/ml, and the percentage of increase was 38–337 %.

Conclusions

These results suggest that a diagnosis of gastrinoma should thus be made when plasma gastrin levels peak within 10 min after glucagon administration, with an increase of greater than 200 pg/ml and greater than 35 % of the basal value.     

Locking versus non-locking neutralization plates for treatment of lateral malleolar fractures: a randomized controlled trial

Purpose

The reduction of periosteal compression through the use of a locking plate may minimize disturbances of bone blood supply and may improve the rate of bone union. A single-centre, assessor blinded randomized controlled trial was conducted to compare the clinical effectiveness of a locking plate and a non-locking plate.

Methods

A total of 52 patients with AO/OTA 44B lateral malleolar fractures were included in this study. All patients underwent surgical fixation using a lag screw and neutralization plate. An identical treatment protocol was used in all patients, with exception of plate selection. The rate of radiographic bone union, defined as the complete disappearance of fracture lines confirmed through anteroposterior, lateral, and internal oblique views was compared at three, six, and 12 months following surgery. In addition, the Medical Outcomes 36-Item Short-Form Health Survey (SF-36) score, the time required for resolution of tenderness at the fracture site and the complication rate were evaluated.

Results

Twenty-three patients were randomly assigned to undergo fixation using a locking plate, and 29 patients were assigned to undergo fixation using a non-locking plate. Intention-to-treat analysis showed no difference in the radiographic bone union rate of fibula, SF-36 score, the time for resolution of tenderness at the fracture site and complication rates.

Conclusion

No differences were observed in patients with AO/OTA 44B lateral malleolar fractures undergoing fixation with a locking versus non-locking neutralization plate.     

Pathogenesis, classification, diagnostic criteria for depression

There is the concern that adaptation range of depression is enlarged, because operation diagnosis methods of ICD-10 and DSM-IV-TR spread in a clinic of psychiatry. On the other hand, clinical condition of depressive state may diversify. This is a review of the pathogenesis, classification and diagnostic criteria of depression. In the pathogenesis, we discussed about the biological origin (a neurotransmitter-related model, a neuroendocrine model et al) and the psychosocial origin with focus on a historic flow and recent knowledge of the pathogenetic theory. In the classification and diagnostic criteria, we mainly explained the points to notice and the problems on ICD-10 and DSM-IV-TR. It is necessity to arise the problem such as clinical symptoms are inconsistent with the classification and diagnostic criteria of ICD-10 and DSM-IV-TR, because all the pathogenesis is not elucidated now. A development of the classification and criteria of depression is expected in future by scientific elucidation advancing.