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.     

Assessment of lifestyle effect on oxidative stress biomarkers in free‐living elderly in rural Japan

Background: Oxidative stress is believed to play a crucial role in aging and age‐related diseases, and is widely thought to increase morbidity and mortality in the elderly. Assessment of biomarkers of oxidative stress, such as 8‐isoprostane and 8‐hydroxy‐2‐deoxyguanosine, are considered to be useful in predicting disease risks at the population level. Objective: The aim of the present study was to assess the health status of the elderly by comparing their lifestyles and levels of oxidative stress biomarkers. Methods: We carried out a cross‐sectional study where urine samples from a total of 100 elderly men and women were assayed for 8‐isoprostane, 8‐hydroxy‐2‐deoxyguanosine, selenium, cadmium and creatinine. They were asked to answer a questionnaire that included questions about their lifestyle. Results: Most of the participants were prehypertensive, non‐alcohol users and on a rich plant‐based diet. There were no differences in any biomarkers of oxidative stress between men and women. 8‐Isoprostane was found to correlate positively with systolic blood pressure in women, but not in men. There was a slight increase of 8‐isoprostane in participants with a poor intake of vegetables, and a decrease of 8‐hydroxy‐2‐deoxyguanosine in participants who consumed fish. Multiple regression analysis showed that oxidative stress biomarkers were positively associated with cadmium, and negatively associated with selenium and fish intake in all participants, 89% of which were non‐smokers. Conclusion: Results from the present study show that fish intake has the potential of decreasing oxidative stress among elderly persons. Geriatr Gerontol Int 2012; 12: 547–554.     

Detailed magnetic analysis and successful deep-neural-network-based conformational prediction for [VO(dmso)5][BPh4]2

Pentakis(dimethylsulfoxide-κO)oxidovanadium(iv) bis(tetraphenylborate), [VO(dmso)₅][BPh₄]₂ (dmso: dimethylsulfoxide), was synthesized, and its pseudo-C₄ VO₆ coordination geometry was revealed by a single-crystal X-ray method. A novel equation set was obtained for magnetic susceptibility and magnetization of the d¹ complexes, considering the axial distortion and the spin–orbit coupling for the ²D free-ion term. The equation set enabled magnetic simulation for significantly symmetry-lowered d¹ complexes to obtain the anisotropic g-values and also the excitation energies. In addition, conformational prediction was conducted, using the enumeration results on the basis of the group theory. The dominant conformers were predicted on the basis of the density functional theory (DFT) method, and especially, the conformer in the crystal was successfully predicted by a deep neural network method.

The conformer in the crystal was successfully predicted by a deep neural network method.     

Large Na+ influx and high Na+, K+–ATPase activity in mitochondria-rich epithelial cells of the inner ear endolymphatic sac

Fluid in the mammalian endolymphatic sac (ES) is connected to the endolymph in the cochlea and the vestibule. Since the dominant ion in the ES is Na(+), it has been postulated that Na(+) transport is essential for regulating the endolymph pressure. This study focused on the cellular mechanism of Na(+) transport in ES epithelial cells. To evaluate the Na(+) transport capability of the ES epithelial cells, changes in intracellular Na(+) concentration ([Na(+)](i)) of individual ES cells were measured with sodium-binding benzofurzan isophthalate in a freshly dissected ES sheet and in dissociated ES cells in response to either the K(+)-free or ouabain-containing solution. Analysis of the [Na(+)](i) changes by the Na(+) load and mitochondrial staining with rhodamine 123 showed that the ES cells were classified into two groups; one exhibited an intensive [Na(+)](i) increase, higher Na(+), K(+)-ATPase activity, and intensive mitochondrial staining (mitochondria-rich cells), and the other exhibited a moderate [Na(+)](i) increase, lower Na(+), K(+)-ATPase activity, and moderate mitochondrial staining (filament-rich cells). These results suggest that mitochondria-rich ES epithelial cells (ca. 30% of ES cells) endowed with high Na(+) permeability and Na(+), K(+)-ATPase activity potentially contribute to the transport of Na(+) outside of the endolymphatic sac.     

Evaluation of QOL After Proximal Gastrectomy Using a Newly Developed Assessment Scale (PGSAS-45)

Background

Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG.

Methods

In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach.

Results

The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had.

Conclusion

These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.     

Usefulness of dobutamine stress echocardiography in a patient with aortic valve stenosis and left ventricular dysfunction: a case report

A 76-year-old man with previous antero-septal myocardial infarction and aorto-coronary bypass surgery developed exertional dyspnea. Echocardiography revealed diffuse left ventricular hypokinesis and aortic stenosis with a mean pressure gradient of 29 mmHg. Coronary angiography showed no significant lesions in the bypass grafts and total occlusions of the proximal left anterior descending artery and mid circumflex artery. Dobutamine stress echocardiography was performed to evaluate the severity of aortic stenosis and left ventricular functional reversibility. Administration of dobutamine increased the mean pressure gradients to 48 mmHg and increased the stroke volume by 28% without change in aortic valve area of about 0.5 cm2. We considered that our patient had severe aortic stenosis with contractile reserve. After aortic valve replacement, he improved with better left ventricular function.