Humidification of Base Flow Gas during Adult High-Frequency Oscillatory Ventilation:An Experimental Study Using a Lung Model

In adult high-frequency oscillatory ventilation (HFOV) with an R100 artificial ventilator, exhaled gas from patientʼs lung may warm the temperature probe and thereby disturb the humidification of base flow (BF) gas. We measured the humidity of BF gas during HFOV with frequencies of 6, 8 and 10Hz, maximum stroke volumes (SV) of 285, 205, and 160ml at the respective frequencies, and, BFs of 20, 30, 40l/min using an original lung model. The R100 device was equipped with a heated humidifier, HummaxⅡ, consisting of a porous hollow fiber in circuit. A 50-cm length of circuit was added between temperature probe (located at 50cm proximal from Y-piece) and the hollow fiber. The lung model was made of a plastic container and a circuit equipped with another HummaxⅡ. The lung model temperature was controlled at 37℃. The HummaxⅡ of the R100 was inactivated in study-1 and was set at 35℃ or 37℃ in study-2. The humidity was measured at the distal end of the added circuit in study-1 and at the proximal end in study-2. In study-1, humidity was detected at 6Hz (SV 285ml) and BF 20l/min, indicating the direct reach of the exhaled gas from the lung model to the temperature probe. In study-2 the absolute humidity of the BF gas decreased by increasing SV and by increasing BF and it was low with setting of 35℃. In this study setting, increasing the SV induced significant reduction of humidification of the BF gas during HFOV with R100

Respiratory complex I in mitochondrial membrane catalyzes oversized ubiquinones

NADH-ubiquinone (UQ) oxidoreductase (complex I) couples electron transfer from NADH to UQ with proton translocation in its membrane part. The UQ reduction step is key to triggering proton translocation. Structural studies have identified a long, narrow, tunnel-like cavity within complex I, through which UQ may access a deep reaction site. To elucidate the physiological relevance of this UQ-accessing tunnel, we previously investigated whether a series of oversized UQs (OS-UQs), whose tail moiety is too large to enter and transit the narrow tunnel, can be catalytically reduced by complex I using the native enzyme in bovine heart submitochondrial particles (SMPs) and the isolated enzyme reconstituted into liposomes. Nevertheless, the physiological relevance remained unclear because some amphiphilic OS-UQs were reduced in SMPs but not in proteoliposomes, and investigation of extremely hydrophobic OS-UQs was not possible in SMPs. To uniformly assess the electron transfer activities of all OS-UQs with the native complex I, here we present a new assay system using SMPs, which were fused with liposomes incorporating OS-UQ and supplemented with a parasitic quinol oxidase to recycle reduced OS-UQ. In this system, all OS-UQs tested were reduced by the native enzyme, and the reduction was coupled with proton translocation. This finding does not support the canonical tunnel model. We propose that the UQ reaction cavity is flexibly open in the native enzyme to allow OS-UQs to access the reaction site, but their access is obstructed in the isolated enzyme as the cavity is altered by detergent-solubilizing from the mitochondrial membrane

Mean Lung Pressure during Adult High-Frequency Oscillatory Ventilation: An Experimental Study Using a Lung Model

In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance: 19.3ml/cmH2O) with or without a resistor (20cmH2O/l/sec). The ventilator settings were as follows: mean airway pressure (MAP), 30cmH2O;frequency, 5-15Hz (every 1Hz);airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV

Importance of Fatty Acid Compositions in Patients with Peripheral Arterial Disease

Objective: Importance of fatty acid components and imbalances has emerged in coronary heart disease. In this study, we analyzed fatty acids and ankle-brachial index (ABI) in a Japanese cohort. Methods: Peripheral arterial disease (PAD) was diagnosed in 101 patients by ABI <= 0.90 and/or by angiography. Traditional cardiovascular risk factors and components of serum fatty acids were examined in all patients (mean age 73.2 +/- 0.9 years; 81 males), and compared with those in 373 age- and sex-matched control subjects with no evidence of PAD. Results: The presence of PAD (mean ABI: 0.71 +/- 0.02) was independently associated with low levels of gamma-linolenic acid (GLA) (OR: 0.90; 95% CI: 0.85-0.96; P = 0.002), eicosapentaenoic acid: arachidonic acid (EPA: AA) ratio (OR: 0.38; 95% CI: 0.17-0.86; P = 0.021), and estimated glomerular filtration rate (OR: 0.97; 95% CI: 0.96-0.98; P<0.0001), and with a high hemoglobin A1c level (OR: 1.34; 95% CI: 1.06-1.69; P = 0.013). Individuals with lower levels of GLA (<= 7.95 mu g/mL) and a lower EPA: AA ratio (<= 0.55) had the lowest ABI (0.96 +/- 0.02, N = 90), while the highest ABI (1.12 +/- 0.01, N = 78) was observed in individuals with higher values of both GLA and EPA: AA ratio (P<0.0001). Conclusion: A low level of GLA and a low EPA: AA ratio are independently associated with the presence of PAD. Specific fatty acid abnormalities and imbalances could lead to new strategies for risk stratification and prevention in PAD patients.ArticlePLOS ONE. 9(9):e107003 (2014)journal articl

Effect of suprascapular nerve injury on muscle and regenerated enthesis in a rat rotator cuff tear model

Background Massive rotator cuff tears (RCTs) are complicated by muscle atrophy, fibrosis, and intramuscular fatty degeneration, which are associated with postoperative tendon-to-bone healing failure and poor clinical outcomes. We evaluated muscle and enthesis changes in large tears with or without suprascapular nerve (SN) injury in a rat model. Methods Sixty-two adult Sprague-Dawley rats were divided into SN injury (+) and SN injury (–) groups (n=31 each), comprising tendon (supraspinatus [SSP]/infraspinatus [ISP]) and nerve resection and tendon resection only cases, respectively. Muscle weight measurement, histological evaluation, and biomechanical testing were performed 4, 8, and 12 weeks postoperatively. Ultrastructural analysis with block face imaging was performed 8 weeks postoperatively. Results SSP/ISP muscles in the SN injury (+) group appeared atrophic, with increased fatty tissue and decreased muscle weight, compared to those in the control and SN injury (–) groups. Immunoreactivity was only positive in the SN injury (+) group. Myofibril arrangement irregularity and mitochondrial swelling severity, along with number of fatty cells, were higher in the SN injury (+) group than in the SN injury (–) group. The bone-tendon junction enthesis was firm in the SN injury (–) group; this was atrophic and thinner in the SN injury (+) group, with decreased cell density and immature fibrocartilage. Mechanically, the tendon-bone insertion was significantly weaker in the SN injury (+) group than in the control and SN injury (+) groups. Conclusions In clinical settings, SN injury may cause severe fatty changes and inhibition of postoperative tendon healing in large RCTs. Level of evidence Basic research, controlled laboratory study

Effect of bihemispheric transcranial direct current stimulation on distal upper limb function and corticospinal tract excitability in a patient with subacute stroke: a case study

IntroductionActivation of the unaffected hemisphere contributes to motor function recovery post stroke in patients with severe upper limb motor paralysis. Transcranial direct current stimulation (tDCS) has been used in stroke rehabilitation to increase the excitability of motor-related areas. tDCS has been reported to improve upper limb motor function; nonetheless, its effects on corticospinal tract excitability and muscle activity patterns during upper limb exercise remain unclear. Additionally, it is unclear whether simultaneously applied bihemispheric tDCS is more effective than anodal tDCS, which stimulates only one hemisphere. This study examined the effects of bihemispheric tDCS training on corticospinal tract excitability and muscle activity patterns during upper limb movements in a patient with subacute stroke.MethodsIn this single-case retrospective study, the Fugl–Meyer Assessment, Box and Block Test, electromyography, and intermuscular coherence measurement were performed. Intermuscular coherence was calculated at 15–30 Hz, which reflects corticospinal tract excitability.ResultsThe results indicated that bihemispheric tDCS improved the Fugl–Meyer Assessment, Box and Block Test, co-contraction, and intermuscular coherence results, as compared with anodal tDCS. Discussion: These results reveal that upper limb training with bihemispheric tDCS improves corticospinal tract excitability and muscle activity patterns in patients with subacute stroke

Evaluating the Need for and Effect of Percutaneous Transluminal Angioplasty on Arteriovenous Fistulas by Using Total Recirculation Rate per Dialysis Session (“Clearance Gap”)

The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n＝45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to －0.2%). A significant correlation between these differences was apparent (r＝－0.436 and p＝0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis

Parkinson’s disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling

Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson’s disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA–deficient Drosophila exhibits defects in neurotransmission during early developmental stages and progressive cell loss throughout the brain, including degeneration of the DA neurons. Lipid analysis of brain tissues reveals that the acyl-chain length of phospholipids is shortened by iPLA2-VIA loss, which causes endoplasmic reticulum (ER) stress through membrane lipid disequilibrium. The introduction of wild-type human iPLA2-VIA or the mitochondria–ER contact site-resident protein C19orf12 in iPLA2-VIA–deficient flies rescues the phenotypes associated with altered lipid composition, ER stress, and DA neurodegeneration, whereas the introduction of a disease-associated missense mutant, iPLA2-VIA A80T, fails to suppress these phenotypes. The acceleration of α-Syn aggregation by iPLA2-VIA loss is suppressed by the administration of linoleic acid, correcting the brain lipid composition. Our findings suggest that membrane remodeling by iPLA2-VIA is required for the survival of DA neurons and α-Syn stability

Endogenous secretory receptor for advanced glycation end-products inhibits amyloid-β 1-42 uptake into mouse brain

The cell-surface receptor for advanced glycation end-products (RAGE) has been implicated in the development of diabetic vascular complications and Alzheimer\u27s disease. RAGE has been considered to be involved in amyloid-β 1-42 (Aβ 1-42) uptake into brain. In the present study, we demonstrate that endogenous secretory RAGE (esRAGE), a decoy form of RAGE generated by alternative RNA processing, is able to inhibit Aβ 1-42 influx into mouse brain. Surface plasmon resonance and competitive binding assays revealed that human Aβ 1-42 interacted with human esRAGE within the immunoglobulin V type region. We next examined the uptake and distribution of 125I-labeled human Aβ 1-42 in various organs and body fluids of newly created mice overexpressing human esRAGE as well as RAGE-null and wild-type (WT) mice. The transition of the 125I-labeled Aβ 1-42 from circulation to brain parenchyma peaked at 30 min after the injection into WT mice, but this was significantly blunted in esRAGE-overexpressing and RAGE-null mice. Significant reduction in 125I-labeled Aβ 1-42-derived photo-stimulated luminescence were marked in ventricles, cerebral cortex, hippocampus, especially CA1 and CA3 regions, putamen, and thalamus. The results thus suggest the potential of esRAGE in protection against the development of Alzheimer\u27s disease. © 2012 - IOS Press and the authors. All rights reserved.Thesis of Sugihara Takahiro / 学位論文 医学甲第2227 杉原 崇