Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E₂ synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E₂-mediated pathway in astrocytes of the central nervous system.     

Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor.

BACKGROUND: In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction may occur due to loss of peritoneal mesothelial cells, peritoneal fibrosis and neovascularization. Lactate, long used as a buffer in peritoneal dialysates, has been substituted by bicarbonate in recent years. However, their effects on the peritoneum of CAPD patients are unknown. This study investigated the influence of lactate and bicarbonate on peritoneal dysfunction in CAPD patients. METHODS: The mitochondrial activity of human peritoneal mesothelial cells (HPMCs) and their expression of basic fibroblast growth factor (bFGF) were studied after culture under various conditions. We also assessed the mitochondrial-activating effect of the supernatant of those cultures on human peritoneal fibroblasts (HPFBs) and human umbilical vein endothelial cells (HUVECs) and the effect of recombinant human bFGF on the mitochondrial activity of HPFBs and HUVECs. We used the WST-1 assay to determine mitochondrial activity in HPMC. RESULTS: At pH 7.4, the mitochondrial activity of HPMCs was lowest in a medium containing 40 mM (Lac), intermediate in a lactate (15 mM) plus bicarbonate (25 mM) medium (Lac/Bic), and highest in a 40 mM bicarbonate medium (Bic). In culture supernatant, the increase of bFGF was: Lac > Lac/Bic > Bic. Mitochondrial activation of HPFBs and HUVECs was stimulated by HPMC culture supernatants in the following decreasing order: Lac > Lac/Bic > Bic. The effects of these supernatants were suppressed by a bFGF-neutralizing antibody, while recombinant bFGF caused concentration-dependent mitochondrial activation in HPFBs and HUVECs. CONCLUSIONS: The role of bFGF in peritoneal fibrosis and neovascularization may be important. A bicarbonate-containing medium is better than a lactate-containing medium for preserving cell viability in HPMCs and preventing bFGF expression by these cells.     

Surgical treatment for cervical myelopathy in patients aged > 80 years

The surgical outcomes of 13 patients who were diagnosed with cervical spondylotic myelopathy were reviewed retrospectively. Mean patient age at surgery was 83 years. The severity of cervical spondylotic myelopathy was evaluated using the Japanese Orthopaedic Association score. Daily activities were evaluated using the Barthel index. The preoperative JOA score and Barthel index were 7.8 and 63.5, respectively. The mean JOA score and Barthel index maximum recovery rate were 35% and 24%, respectively. The results of this study imply that surgery for patients with cervical spondylotic myelopathy aged > 80 years is warranted.     

Oculomotor nerve palsy evaluated by diffusion-tensor tractography

Introduction The aim of the study was to test the feasibility of the tractography technique based on diffusion-tensor imaging (DTI) for the assessment of small infarcts involving the brainstem.Methods A patient who presented with an isolated left third cranial nerve palsy underwent magnetic resonance examination. Images were obtained by use of a whole-body, 1.5-T imager. Data were transferred to an off-line workstation for fiber tracking.Results The conventional diffusion-weighted imaging (DWI) performed using a 5 mm slice thickness could only depict an equivocal hyperintensity lesion located at the left paramedian midbrain. An additional thin-slice DTI was performed immediately after the initial DWI using a 3 mm slice thickness and was able to delineate the lesion more clearly. Image postprocessing of thin-slice DTI data revealed that the lesion location involved the course of the third cranial nerve tract, corresponding with the patient’s clinical symptoms.Conclusion The tractography technique can be applied to assess fine neuronal structures of the brainstem, enabling direct clinicoradiological correlation of small infarcts involving this region.     

Evaluation of autonomic malfunction in idiopathic normal pressure hydrocephalus

OBJECTIVE: The autonomic nervous system plays an important role in urinary disturbance which is one of the main symptoms of idiopathic normal pressure hydrocephalus (iNPH); thus, the focus of the present study was to identify the autonomic function parameters that would be useful as clinical indicators of iNPH. METHODS: The subjects consisted of 18 iNPH patients (group N) and 31 normal controls (group C). Before and after a lumbar puncture test, they were examined for CVR-R and total heart rate. A power spectral analysis of R-R interval variability of their 24-hour Holter ECGs was also done. High frequency (HF) was an indicator of parasympathetic activity, while the low to high frequency ratio (L/H) was used as an indicator of sympathetic activity. Urinary incontinence was evaluated using the overactive bladder symptom score (OABSS) questionnaire and bladder capacity. Correlations between the above indicators and clinical indicators of iNPH, such as the mini-mental state examination and the Evans index, were examined. RESULTS: The HF values (ms(2)) were 190.3 in group C and 237.2 in group N; the difference was statistically significant. In group N, the HF value after the lumbar puncture test was lower (160.3) than the value before the lumbar puncture test, confirming that the increased parasympathetic state returned to a near normal level after CSF drainage. A significant positive correlation was noted only between the pre-lumbar puncture HF value and the OABSS. CONCLUSION: iNPH is associated with increased parasympathetic activity, and the lumbar puncture test and shunt surgery may correct this autonomic imbalance to near normal levels.     

Drosophila olfactory local interneurons and projection neurons derive from a common neuroblast lineage specified by the empty spiracles gene

Background

The skeletal neuromuscular junction is a useful model for elucidating mechanisms that regulate synaptogenesis. Developmentally important intercellular interactions at the neuromuscular junction are mediated by the synaptic portion of a basal lamina that completely ensheaths each muscle fiber. Basal laminas in general are composed of four main types of glycosylated proteins: laminins, collagens IV, heparan sulfate proteoglycans and nidogens (entactins). The portion of the muscle fiber basal lamina that passes between the motor nerve terminal and postsynaptic membrane has been shown to bear distinct isoforms of the first three of these. For laminins and collagens IV, the proteins are deposited by the muscle; a synaptic proteoglycan, z-agrin, is deposited by the nerve. In each case, the synaptic isoform plays key roles in organizing the neuromuscular junction. Here, we analyze the fourth family, composed of nidogen-1 and -2.

Results

In adult muscle, nidogen-1 is present throughout muscle fiber basal lamina, while nidogen-2 is concentrated at synapses. Nidogen-2 is initially present throughout muscle basal lamina, but is lost from extrasynaptic regions during the first three postnatal weeks. Neuromuscular junctions in mutant mice lacking nidogen-2 appear normal at birth, but become topologically abnormal as they mature. Synaptic laminins, collagens IV and heparan sulfate proteoglycans persist in the absence of nidogen-2, suggesting the phenotype is not secondary to a general defect in the integrity of synaptic basal lamina. Further genetic studies suggest that synaptic localization of each of the four families of synaptic basal lamina components is independent of the other three.

Conclusion

All four core components of the basal lamina have synaptically enriched isoforms. Together, they form a highly specialized synaptic cleft material. Individually, they play distinct roles in the formation, maturation and maintenance of the neuromuscular junction.     

中性粒细胞与淋巴细胞比值预测急性腔隙性脑梗死患者病情进展的临床价值

目的分析中性粒细胞与淋巴细胞比值(NLR)对急性腔隙性脑梗死患者病情进展的预测价值。方法根据病情进展与否将2012年2月～2017年1月收治的230例急性腔隙性脑梗死患者分为进展组(40例)与非进展组(190例),记录各组中性粒细胞绝对值、淋巴细胞绝对值等指标,计算NLR。受试者工作特征(ROC)曲线分析NLR等对急性腔隙性脑梗死患者病情进展预测的特异度、敏感度,Pearson相关性分析NLR等指标与mRS评分的关系。结果进展组NLR、白细胞计数、中性粒细胞绝对值均显著高于非进展组(P 0. 05);淋巴细胞绝对值显著低于非进展组(P 0. 05)。NLR对进展性腔隙性脑梗死(PLI)预测曲线下面积(AUC)为0. 800,最佳临界值3. 25,敏感度85. 06%,特异度70. 68%;白细胞计数、中性粒细胞绝对值、淋巴细胞绝对值对PLI预测AUC分别为0. 650、0. 745、0. 615。进展组预后良好率显著低于非进展组(P 0. 05)。NLR、中性粒细胞绝对值、白细胞计数与mRS评分正相关(P 0. 05)。结论 NLR值对急性腔隙性脑梗死患者病情进展有一定的预测价值,有可能作为患者预后评估的有效指标。     

Factors influencing the length of emergency room stay and hospital stay in nonfatal bicycle accidents: A retrospective analysis

Purpose: Lengthy hospitalization places a burden on patients and healthcare resources. However, the factors affecting the length of hospital stay (LHoS) and length of emergency room stay (LERS) in non-fatal bicycle accidents are currently unclear. We investigated these factors to inform efforts to minimize hospitalization. Methods: We performed a retrospective analysis of data from non-fatal injured bicyclists admitted to the Emergency and Critical Care Center at Kyoto Medical Center between January 2012 and December 2016. We measured LHoS, LERS, mechanism of injury, head injury prevalence, polytrauma, operations performed, injury severity score (ISS), abbreviated injury scale (AIS) score, maximum AIS score, and trauma and injury severity score probability of survival. We conducted multiple regression analysis to determine predictors of LHoS and LERS. Results: Within the study period, 82 victims met the inclusion and exclusion criteria and were included. Mean age was (46.0 ± 24.7) years. Overall mean LHoS was (16.8 ± 25.2) days, mean LERS was (10.6 ± 14.7) days, median ISS was 9 (interquartile range (IQR): 3-16), median maximum AIS was 3 (IQR: 1-4), and median trauma and injury severity score probability of survival was 98.0% (IQR: 95.5%-99.6%). Age, maximum AIS, ISS, and prevalence of surgery were significantly greater in long LHoS and LERS group compared with short LHoS and LERS group (p < 0.05). Performance of surgery independently explained LHoS (p = 0.0003) and ISS independently explained LERS (p = 0.0009). Conclusion: Surgery was associated with long hospital stays and ISS was associated with long emergency room stays. To improve the quality life of the bicyclists, preventive measures for reducing injury severity or avoiding injuries needing operation are required.