The effect of a prostaglandin E1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Background

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).

Methods

QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).

Results

Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.

Conclusion

According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.     

Ultrafast-charging and long cycle-life anode materials of TiO2-bronze/nitrogen-doped graphene nanocomposites for high-performance lithium-ion batteries

Emerging technologies demand a new generation of lithium-ion batteries that are high in power density, fast-charging, safe to use, and have long cycle lives. This work reports charging rates and specific capacities of TiO₂(B)/N-doped graphene (TNG) composites. The TNG composites were prepared by the hydrothermal method in various reaction times (3, 6, 9, 12, and 24 h), while the N-doped graphene was synthesized using the modified Hummer''s method followed by a heat-treatment process. The different morphologies of TiO₂ dispersed on the N-doped graphene sheet were confirmed as anatase-nanoparticles (3, 6 h), TiO₂(B)-nanotubes (9 h), and TiO₂(B)-nanorods (12, 24 h) by XRD, TEM, and EELS. In electrochemical studies, the best battery performance was obtained with the nanorods TiO₂(B)/N-doped graphene (TNG-24h) electrode, with a relatively high specific capacity of 500 mA h g⁻¹ at 1C (539.5 mA g⁻¹). In long-term cycling, excellent stability was observed. The capacity retention of 150 mA h g⁻¹ was observed after 7000 cycles, at an ultrahigh current of 50C (27.0 A g⁻¹). The synthesized composites have the potential for fast-charging and have high stability, showing potential as an anode material in advanced power batteries for next-generation applications.

The TiO₂-bronze/nitrogen-doped graphene nanocomposites have the potential for fast-charging and have high stability, showing potential as an anode material in advanced power batteries for next-generation applications.     

Amphipathic helical peptide-based fluorogenic probes for a marker-free analysis of exosomes based on membrane-curvature sensing

With increasing knowledge about the diverse roles of exosomes in the biological process, much attention has been paid to develop analytical methods for detection and quantification of exosomes. Immunoassays based on the recognition of exosomal protein markers by antibodies were widely used. However, considering that exosomal protein composition varies with the cell type, the protein markers should be carefully selected for a sensitive and selective analysis of target exosomes. Herein, we developed a new class of exosome-binding fluorogenic probes based on membrane curvature (MC) sensing of amphipathic helical (AH) peptides for exosome analysis without the need to use protein markers on the exosomal membranes. The C-terminal region of apolipoprotein A-I labeled with Nile red (ApoC-NR) exhibited a significant fluorescence enhancement upon selective binding to the highly curved membranes of synthetic vesicles. Circular dichroism (CD) measurements involving 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1-2-dioleoyl-sn-glycerol (DOG) vesicles suggested that ApoC-NR recognizes the lipid packing defects in the surface of highly curved membranes via the hydrophobic insertion of the α-helix structure of the ApoC unit. ApoC-NR exhibited a stronger binding affinity for exosome-sized vesicles and a higher MC selectivity compared to all other previously reported peptide probes. ApoC-NR can be used in a simple and rapid “mix and read” analysis of various kinds of exosomes derived from different cell types (limit of detection: –10⁵ particles/μL) without being influenced by the variation in the expression of the surface proteins of the exosomes, which stands in sharp contrast to immunoassays.

Fluorogenic probes based on membrane curvature sensing-amphipathic helical peptides have been developed for a marker-free exosome analysis.     

Functional changes are associated with tracheal structural abnormalities in patients with acromegaly

Introduction

Although impaired pulmonary function and respiratory sleep disorders are described as responsible for increased mortality in acromegalic patients, little is known about the tracheal abnormalities in this group of patients. Thus, the objectives of this study were to describe the tracheal structural abnormalities and correlate these changes with the respiratory function and clinical data of acromegalic patients.

Material and methods

This is a cross-sectional study that was carried out at two university hospitals. Twenty acromegalic patients underwent spirometry, forced oscillation technique, and computed tomography (CT) assessments. Dyspnea and daytime sleepiness were assessed using the Modified Medical Research Council (MMRC) scale and the Epworth Sleepiness Scale (ESS), respectively. Forty matched subjects served as controls.

Results

The acromegalic patients exhibited larger median ratios between forced expiratory flow and forced inspiratory flow at 50% of the forced vital capacity (FEF_50%/FIF_50%) (2.05 vs. 1.06, p = 0.0001) compared with healthy volunteers. In the CT analysis, acromegalic patients exhibited larger median differences between their cervical and thoracic tracheal diameters (Δ tracheal diameters) (3 vs. 1 mm; p = 0.003). An association was found between FEF_50%/FIF_50% and the following variables: mean resistance (Rm), cervical tracheal diameter, and Δ tracheal diameters. Rm also exhibited a negative correlation with cervical tracheal diameter. Neither the MMRC scale nor the ESS exhibited any significant correlation with large airway obstruction (LAO) indices or with the measured tracheal diameters.

Conclusions

Acromegalic patients have tracheal structural abnormalities which are associated with functional indicators of LAO but not with clinical data.     

A pediatric case of acute focal bacterial nephritis; comparison with the reports in Japanese child cases]

We report an 8-year-old boy with acute focal bacterial nephritis (AFBN). At the age of 3 months, he had a history of urinary tract infection and vesicoureteral reflux. He was admitted to our hospital because of high fever and costovertebral angle pain. Although acute pyelonephritis was suspected, neither pyuria nor cultures of blood and urine were positive. An initial ultrasonogram (US) of his kidneys was normal except for bilateral hydronephrosis. Two days later, however, a computed tomography (CT) revealed a poorly enhanced mass in the upper pole of the right kidney. Similar findings were also observed by US. Under the diagnosis of AFBN, he received antibiotics for 3 weeks. Voiding cystourethrogram showed both-sided vesicoureteral reflux and he underwent an operation. At present the mass of the kidney still remains, albeit its size tends to decrease. We suggest that an early examination of US or enhanced CT is necessary in cases with fever of unknown origin, considering the possibility of AFBN even if neither pyuria nor cultures of urine are positive.     

Evidence for an insulin receptor substrate 1 independent insulin signaling pathway that mediates insulin-responsive glucose transporter (GLUT4) translocation.

Interaction of the activated insulin receptor (IR) with its substrate, insulin receptor substrate 1 (IRS-1), via the phosphotyrosine binding domain of IRS-1 and the NPXY motif centered at phosphotyrosine 960 of the IR, is important for IRS-1 phosphorylation. We investigated the role of this interaction in the insulin signaling pathway that stimulates glucose transport. Utilizing microinjection of competitive inhibitory reagents in 3T3-L1 adipocytes, we have found that disruption of the IR/IRS-1 interaction has no effect upon translocation of the insulin-responsive glucose transporter (GLUT4). The activity of these reagents was demonstrated by their ability to block insulin stimulation of two distinct insulin bioeffects, membrane ruffling and mitogenesis, in 3T3-L1 adipocytes and insulin-responsive rat 1 fibroblasts. These data suggest that phosphorylated IRS-1 is not an essential component of the metabolic insulin signaling pathway that leads to GLUT4 translocation, yet it appears to be required for other insulin bioeffects.     

Right bundle branch block without overt heart disease predicts higher risk of pacemaker implantation: The study of atomic-bomb survivors

Background

We investigated the clinical course of complete right bundle branch block (RBBB) or RBBB with axis deviation (AD) in terms of subsequent pacemaker implantation for high-degree atrioventricular (AV) block or sick sinus syndrome (SSS).

Methods and results

Among the 16,170 atomic-bomb survivors in our biennial health examination between July 1967 and December 2010, we detected 520 newly-acquired RBBB subjects with no organic heart disease, and selected 1038 age- (at RBBB diagnosis) and sex-matched subjects without RBBB to serve as comparison subjects. Multivariate Cox regression analysis was used to estimate the hazard ratios (HRs) for the risk of pacemaker implantation due to all causes, AV block or SSS between RBBB and comparison subjects and between RBBB subjects with and without AD. The risk of pacemaker implantation for RBBB was 4.79 (95% confidence interval [CI] 1.89–12.58; P = 0.001), 3.77 (95% CI, 1.09–13.07; P = 0.036), and 6.28 (95% CI, 1.24–31.73, P = 0.026) when implantation was for all causes, AV block and SSS, respectively. RBBB subjects with AD had a higher risk for all-cause pacemaker implantation than subjects without AD (HR, 3.03; 95% CI, 1.00–9.13, P = 0.049). RBBB subjects with AD were younger than subjects without AD at the time of RBBB diagnosis (59.4 ± 7.6 vs 74.4 ± 3.1 years old, P = 0.019), and their progression from diagnosis to pacemaker implantation took longer (15.1 ± 6.6 vs 6.4 ± 3.0 years, P = 0.032).

Conclusions

RBBB, especially with AD, progresses to AV block and SSS that requires pacemaker implantation; the mechanisms by which the conduction defect progresses differ among patients with and without AD.     

Sphingosylphosphorylcholine is a novel messenger for Rho-kinase-mediated Ca2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C

Although recent investigations have suggested that a Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase-mediated Ca2+ sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+ sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 micromol/L) contraction, without [Ca2+]i elevation. In membrane-permeabilized MCA, SPC induced Ca2+ sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+ sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester-induced Ca2+ sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase-mediated Ca2+ sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.