Involvement of calcium signaling in the fibronectin-stimulated macrophage recognition of oxidatively damaged erythrocytes

AbstractMacrophages recognize oxidatively damaged autologous erythrocytes, and cell surface fibronectin of macrophages enhances the recognition (Beppu et al., FEBS Lett. 295 (1991) 135–140). In the present study, mechanisms of enhanced macrophage recognition of oxidatively damaged erythrocytes by fibronectin were investigated. Monolayers of thioglycollate-induced mouse peritoneal macrophages with cell surface fibronectin recognized autologous erythrocytes oxidized with an iron catalyst ADP/Fe3+. The macrophage recognition of the oxidized erythrocytes was inhibited partially by pretreatment of the macrophage monolayers with a Ca2+ channel blocker (diltiazem), calmodulin inhibitors (W-7, trifluoperazine, chlorpromazine and dibucaine), an inhibitor of myosin light chain kinase (ML-9), a microfilament formation inhibitor (cytochalasin B), phospholipase A2 inhibitors (4-bromophenacyl bromide, mepacrine) and cyclooxygenase inhibitors (indomethacin and aspirin). Monolayers of macrophages depleted of fibronectin by trypsinization lost the ability of recognizing oxidized erythrocytes, but acquired the ability when stimulated with a fibronectin-coated coverslip. The recognition of fibronectin-stimulated trypsinized macrophages was also inhibited by the above inhibitors. On treatment with Ca ionophore A23187, trypsinized macrophages acquired the ability to recognize oxidized erythrocytes. The recognition of Ca ionophore-stimulated trypsinized macrophages was inhibited by the above inhibitors except the Ca2+ channel blocker. These results indicate that the Ca2+ signaling including Ca2+ influx, calmodulin activation and myosin light chain phosphorylation are involved in the fibronectin stimulation of the recognition of macrophages for oxidized erythrocytes. Involvement of microfilament formation and arachidonate cascade in the fibronectin stimulation was also suggested

Comparison of Sustained Hemodiafiltration with Acetate-Free Dialysate and Continuous Venovenous Hemodiafiltration for the Treatment of Critically Ill Patients with Acute Kidney Injury

We conducted a prospective, randomized study to compare conventional continuous venovenous hemodiafiltration (CVVHDF) with sustained hemodiafiltration (SHDF) using an acetate-free dialysate. Fifty critically ill patients with acute kidney injury (AKI) who required renal replacement therapy were treated with either CVVHDF or SHDF. CVVDHF was performed using a conventional dialysate with an effluent rate of 25 mL·kg−1 · h−1, and SHDF was performed using an acetate-free dialysate with a flow rate of 300−500 mL/min. The primary study outcome, 30 d survival rate was 76.0% in the CVVHDF arm and 88.0% in the SHDF arm (NS). Both the number of patients who showed renal recovery (40.0% and 68.0%, CVVHDF and SHDF, resp.; P < .05), and the hospital stay length (42.3 days and 33.7 days, CVVHDF and SHDF, resp.; P < .05), significantly differed between the two treatments. Although the total convective volumes did not significantly differ, the dialysate flow rate was higher and mean duration of daily treatment was shorter in the SHDF treatment arm. Our results suggest that compared with conventional CVVHDF, more intensive renal support in the form of post-dilution SHDF with acetate-free dialysate may accelerate renal recovery in critically ill patients with AKI

The Effect of a Portable Electrical Muscle Stimulation on Brain-Derived Neurotrophic Factor in Elderly People: Three Case Studies

金沢大学理工研究域フロンティア工学系Brain-derived neurotrophic factor (BDNF), which plays an important role in cognitive and nerve function, is released from skeletal muscle cells into the blood by muscle contractions and/or electrical muscle stimulation (EMS). However, the influence of EMS administered by a portable device on BDNF is unclear. The purpose of this case report was to quantify the influence of EMS administered by a portable device on BDNF and physical function. Three elderly people (age, 69.7 ± 1.5 years) were included in the present study. The participants used a portable EMS device to stimulate the bilateral quadriceps muscles for 8 weeks (23 min for 5 days/week). To determine the effects of EMS, the following parameters were assessed at baseline, 8 weeks, and 12 weeks (follow-up): knee extensor strength, muscle mass of the lower limb, Berg balance score, and blood BDNF level. All outcomes improved after the EMS intervention, but the improvements did not persist for 12 weeks. These findings suggest that portable EMS is potentially useful for improving the blood BDNF level and physical function

Laterality of the activation patterns of the vastus lateralis muscle in females with Parkinson\u27s disease during the medication state compared with healthy controls.

金沢大学理工研究域フロンティア工学系The aim of this study was to quantify the laterality of motor unit (MU) activation properties in people with Parkinson’s disease (PD) during force production (low- to high-intensity contraction) using high-density surface electromyography (HD-SEMG). Sixteen females with PD (age = 69.9 ± 7.6 years, disease duration = 4.9 ± 5.1 years) and 14 healthy female subjects (age = 68.6 ± 3.6 years) were enrolled in the study and performed submaximal ramp-up contractions during isometric knee extension. HD-SEMG signals were recorded from both vastus lateralis muscles. We calculated the level of heterogeneity in the spatial distribution patterns of the HD-SEMG signals and determined the modified entropy, coefficient of variation of the root mean square (RMS), and correlation coefficient to evaluate MU activation properties. Pearson’s correlation coefficients were calculated to examine the relationships between disease severity and the RMS and EMG variables. The RMS value and heterogeneity were significantly higher and lower on the more-affected side in people with PD than on the other side in people with PD or either side in control subjects (p 0.6, p < 0.001). We compared the laterality of MU activation properties between the people with PD and the control subjects. These findings suggest that people with PD have asymmetrical MU activation properties, regardless of the magnitude of force production

Association between the Degree of Pre-Synaptic Dopaminergic Pathway Degeneration and Motor Unit Firing Behavior in Parkinson’s Disease Patients

金沢大学理工研究域フロンティア工学系The relationship between motor unit (MU) firing behavior and the severity of neurodegeneration in Parkinson’s disease (PD) is not clear. This study aimed to elucidate the association between degeneration with dopaminergic pathways and MU firing behavior in people with PD. Fourteen females with PD (age, 72.6 ± 7.2 years, disease duration, 3.5 ± 2.1 years) were enrolled in this study. All participants performed a submaximal, isometric knee extension ramp-up contraction from 0% to 80% of their maximal voluntary contraction strength. We used high-density surface electromyography with 64 electrodes to record the muscle activity of the vastus lateralis muscle and decomposed the signals with the convolution kernel compensation technique to extract the signals of individual MUs. We calculated the degree of degeneration of the central lesion-specific binding ratio by dopamine transporter single-photon emission computed tomography. The primary, novel results were as follows: (1) moderate-to-strong correlations were observed between the degree of degeneration of the central lesion and MU firing behavior; (2) a moderate correlation was observed between clinical measures of disease severity and MU firing behavior; and (3) the methods of predicting central nervous system degeneration from MU firing behavior abnormalities had a high detection accuracy with an area under the curve >0.83. These findings suggest that abnormalities in MU activity can be used to predict central nervous system degeneration following PD

Randomized phase II study of pemetrexed or pemetrexed plus bevacizumab for elderly patients with previously untreated non-squamous non-small cell lung cancer: Results of the Lung Oncology Group in Kyushu (LOGIK1201)

Objectives: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pem + bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). Patients and methods: The eligibility criteria were as follows: NSqNSCLC, no prior therapy,stage IIIB/IV disease or postoperative recurrence, age: ?75 years, performance status (PS): 0?1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio)to receive Pem or Pem + Bev. The primary endpoint was progression-free survival (PFS).The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. Results: Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/female = 23/17; median age (range) = 78 (75?83); stage IIIB/IV/postoperative recurrence = 1/30/9; PS 0/1 = 11/29. All cases involved adenocarcinoma.There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pem + Bev groups were 5.4 (3.0?7.4) and 5.5 (3.6?9.9) months, respectively (p = 0.66). The response rate was significantly higher in the Pem + Bev group(15% vs. 55%, p = 0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, p = 0.58). Grade 3 and 4 leukopenia, neutropenia,and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pem + Bev group (median: 1,522,008 vs. 3,368,428 JPY, p = 0.01). No treatment-related deaths occurred. Conclusions: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pem + Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ?75 years