Effect of cerebrospinal fluid drainage pressure in descending and thoracoabdominal aortic repair: a prospective multicenter observational study.

PURPOSE: Cerebrospinal fluid drainage (CSFD) is recommended during open or endovascular thoracic aortic repair. However, the incidence of CSFD complications is still high. Recently, CSF pressure has been kept high to avoid complications, but the efficacy of CSFD at higher pressures has not been confirmed. We hypothesize that CSFD at higher pressures is effective for preventing motor deficits. METHODS: This prospective observational study included 14 hospitals that are members of the Japanese Society of Cardiovascular Anesthesiologists. Patients who underwent thoracic and thoracoabdominal aortic repair were divided into four groups: Group 1, CSF pressure around 10 mmHg; Group 2, CSF pressure around 15 mmHg; Group 3, CSFD initiated when motor evoked potential amplitudes decreased; and Group 4, no CSFD. We assessed the association between the CSFD group and motor deficits using mixed-effects logistic regression with a random intercept for the institution. RESULTS: Of 1072 patients in the study, 84 patients (open surgery, 51; thoracic endovascular aortic repair, 33) had motor deficits at discharge. Groups 1 and 2 were not associated with motor deficits (Group 1, odds ratio (OR): 1.53, 95% confidence interval (95% CI): 0.71-3.29, p = 0.276; Group 2, OR: 1.73, 95% CI: 0.62-4.82) when compared with Group 4. Group 3 was significantly more prone to motor deficits than Group 4 (OR: 2.56, 95% CI: 1.27-5.17, p = 0.009). CONCLUSION: CSFD is not associated with motor deficits in thoracic and thoracoabdominal aortic repair with CSF pressure around 10 or 15 mmHg.

Cerebrospinal fluid drainage to prevent postoperative spinal cord injury in thoracic aortic repair.

BACKGROUND: Cerebrospinal fluid drainage (CSFD) is recommended as a spinal cord protective strategy in open and endovascular thoracic aortic repair. Although small studies support the use of CSFD, systematic reviews have not suggested definite conclusion and a large-scale study is needed. Therefore, we reviewed medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open and endovascular repair) at multiple institutions to assess the association between CSFD and postoperative motor deficits. METHODS: Patients included in this study underwent descending or thoracoabdominal aortic repair between 2000 and 2013 at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery. We conducted a retrospective study to investigate whether motor-evoked potential monitoring is effective in reducing motor deficits in thoracic aortic aneurysm repair. We use the same dataset to examine whether CSFD reduces motor deficits after propensity score matching. RESULTS: We reviewed data from 1214 patients [open surgery, 601 (49.5%); endovascular repair, 613 (50.5%)]. CSFD was performed in 417 patients and not performed in the remaining 797 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. After propensity score matching (n = 700), mixed-effects logistic regression performed revealed that CSFD is associated with postoperative motor deficits at discharge [adjusted odds ratio (OR), 3.87; 95% confidence interval (CI), 2.30-6.51]. CONCLUSION: CSFD may not be effective for postoperative motor deficits at discharge.

Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation.

During prometaphase, dense microtubule nucleation sites at centrosomes form robust spindles that align chromosomes promptly. Failure of centrosome maturation leaves chromosomes scattered, as seen routinely in cancer cells, including myelodysplastic syndrome (MDS). We previously reported that the Miki (LOC253012) gene is frequently deleted in MDS patients, and that low levels of Miki are associated with abnormal mitosis. Here we demonstrate that Miki localizes to the Golgi apparatus and is poly(ADP-ribosyl)ated by tankyrase-1 during late G2 and prophase. PARsylated Miki then translocates to mitotic centrosomes and anchors CG-NAP, a large scaffold protein of the γ-tubulin ring complex. Due to impairment of microtubule aster formation, cells in which tankyrase-1, Miki, or CG-NAP expression is downregulated all show prometaphase disturbances, including scattered and lagging chromosomes. Our data suggest that PARsylation of Miki by tankyrase-1 is a key initial event promoting prometaphase.

A practical guide for anesthetic management during intraoperative motor evoked potential monitoring.

Postoperative motor dysfunction can develop after spinal surgery, neurosurgery and aortic surgery, in which there is a risk of injury of motor pathway. In order to prevent such devastating complication, intraoperative monitoring of motor evoked potentials (MEP) has been conducted. However, to prevent postoperative motor dysfunction, proper understanding of MEP monitoring and proper anesthetic managements are required. Especially, a variety of anesthetics and neuromuscular blocking agent are known to attenuate MEP responses. In addition to the selection of anesthetic regime to record the baseline and control MEP, the measures to keep the level of hypnosis and muscular relaxation at constant are crucial to detect the changes of MEP responses after the surgical manipulation. Once the changes of MEP are observed based on the institutional alarm criteria, multidisciplinary team members should share the results of MEP monitoring and respond to check the status of monitoring and recover the possible motor nerve injury. Prevention of MEP-related adverse effects is also important to be considered. The Working Group of Japanese Society of Anesthesiologists (JSA) developed this practical guide aimed to help ensure safe and successful surgery through appropriate anesthetic management during intraoperative MEP monitoring.

Interfacial Dynamics in the Spontaneous Motion of an Aqueous Droplet.

Self-propelled droplets can spontaneously move using chemical energy. In several reports of self-propelled droplets, interfacial chemical reactions occur at the oil/aqueous interface to induce the Marangoni flow. While the dynamics of interfacial tension is essential to the droplet motion, there are few reports that quantitatively discuss the moving mechanism based on interfacial tension measurements. In this study, we focused on the self-propelled motion of an aqueous droplet in the oil phase, where the surfactant monoolein reacts with bromine at the interface, and estimated the physicochemical parameters related to the droplet motion based on the time series of interfacial tension. These results may reveal the general mechanism for the self-propelled motion of aqueous/oil droplets driven by the interfacial chemical reaction.

Association Between Motor-Evoked Potentials and Spinal Cord Damage Diagnosed With Magnetic Resonance Imaging After Thoracoabdominal and Descending Aortic Aneurysm Repair.

OBJECTIVES: The authors investigated the association between intraoperative motor-evoked potential (MEP) changes and the severity of spinal cord infarction diagnosed with magnetic resonance imaging (MRI) to clarify the discrepancy between them, which was observed in patients with postoperative motor deficits after thoracic and thoracoabdominal aortic surgery. DESIGN: A multicenter retrospective study. SETTING: Motor-evoked potential <25% of control values was deemed positive for spinal cord ischemia. The severity of spinal cord infarction was categorized into grades A to D based on previous studies using the most severe axial MRI slices. The associations between MRI grade, MEP changes, and motor deficits were examined using logistic regression. PARTICIPANTS: Twenty-three of 1,245 patients (from 1999 to 2013, at 12 hospitals in Japan) were extracted from medical records of patients who underwent thoracic and thoracoabdominal aortic repair, with intraoperative MEP examinations and postoperative spinal MRI. INTERVENTIONS: No intervention (observational study). MEASUREMENTS AND MAIN RESULTS: Motor-evoked potential <25% of control value was associated significantly with motor deficits at discharge (adjusted odds ratio [OR], 130.0; p = 0.041), but not with severity of spinal cord infarction (adjusted OR, 0.917; p = 0.931). Motor deficit at discharge was associated with severe spinal cord infarction (adjusted OR, 4.83; p = 0.043), MEP <25% (adjusted OR, 13.95; p = 0.031), and combined deficits (motor and sensory, motor and bowel or bladder, or sensory and bowel or bladder deficits; adjusted OR, 31.03; p = 0.072) in stepwise logistic regression analysis. CONCLUSION: Motor-evoked potential <25% was associated significantly with motor deficits at discharge, but not with the severity of spinal cord infarction.

Phosphorylation of epidermal growth factor receptor at serine 1047 in cultured lung alveolar epithelial cells by bradykinin B2 receptor stimulation.

Accumulating evidence indicates that epidermal growth factor receptor (EGFR) is desensitized by phosphorylation of serine 1047 (Ser1047). We and other groups have reported that stimulation of a receptor of tumor-necrosis factor α (TNFα) and Toll-like receptor 5 (TLR5) induced the phosphorylation of Ser1047 through activation of p38 mitogen-activated protein kinase (p38 MAPK) in cultured lung alveolar epithelial A549 cells. However, phosphorylation of EGFR at Ser1047 by stimulation of any G-protein coupled receptors (GPCRs) has not been reported in any cultured cells. In the present study, we first confirmed that A549 cells expressed bradykinin (BK) B2 receptor, and then, we examined whether BK treatment of A549 cells activated MAPKs and induced the phosphorylation of EGFR at Ser1047. Immunoblotting analysis and reporter gene assays indicated that BK activated the pathways of extracellular signal-regulated kinase (ERK) and p38 MAPK. Inhibitor studies suggested that Gq/11 was mainly involved in the activation of ERK and p38 MAPK. We found that stimulation of the BK B2 receptor, but not the BK B1 receptor, induced phosphorylation of EGFR at Ser1047. Pharmacological experiments indicated that both ERK and p38 MAPK were involved in the phosphorylation of EGFR. These results strongly suggested that BK regulates EGFR functions in lung alveolar epithelial cells. In addition, we found that BK treatment increased the mRNA level of dual specificity MAPK phosphatase 5 (DUSP5) in an ERK-dependent manner, which suggested that a negative feedback mechanism of ERK existed in the cells.

Clinical Utility of Intraoperative Motor-Evoked Potential Monitoring to Prevent Postoperative Spinal Cord Injury in Thoracic and Thoracoabdominal Aneurysm Repair: An Audit of the Japanese Association of Spinal Cord Protection in Aortic Surgery Database.

BACKGROUND: Spinal cord ischemic injury is the most devastating sequela of descending and thoracoabdominal aortic surgery. Motor-evoked potentials (MEPs) have been used to intraoperatively assess motor tract function, but it remains unclear whether MEP monitoring can decrease the incidence of postoperative motor deficits. Therefore, we reviewed multicenter medical records of patients who had undergone descending and thoracoabdominal aortic repair (both open surgery and endovascular repair) to assess the association of MEP monitoring with postoperative motor deficits. METHODS: Patients included in the study underwent descending or thoracoabdominal aortic repair at 12 hospitals belonging to the Japanese Association of Spinal Cord Protection in Aortic Surgery between 2000 and 2013. Using multivariable mixed-effects logistic regression analysis, we investigated whether intraoperative MEP monitoring was associated with postoperative motor deficits at discharge after open and endovascular aortic repair. RESULTS: We reviewed data from 1214 patients (open surgery, 601 [49.5%]; endovascular repair, 613 [50.5%]). MEP monitoring was performed in 631 patients and not performed in the remaining 583 patients. Postoperative motor deficits were observed in 75 (6.2%) patients at discharge. Multivariable logistic regression analysis revealed that postoperative motor deficits at discharge did not have a significant association with MEP monitoring (adjusted odds ratio [OR], 1.13; 95% confidence interval [CI], 0.69-1.88; P = .624), but with other factors: history of neural deficits (adjusted OR, 6.08; 95% CI, 3.10-11.91; P < .001), spinal drainage (adjusted OR, 2.14; 95% CI, 1.32-3.47; P = .002), and endovascular procedure (adjusted OR, 0.45; 95% CI, 0.27-0.76; P = .003). The sensitivity and specificity of MEP <25% of control value for motor deficits at discharge were 37.8% (95% CI, 26.5%-49.5%) and 95.5% (95% CI, 94.7%-96.4%), respectively. CONCLUSIONS: MEP monitoring was not significantly associated with motor deficits at discharge.

Periodic Oscillatory Motion of a Self-Propelled Motor Driven by Decomposition of H2 O2 by Catalase.

A self-propelled motor driven by the enzymatic reaction of catalase adsorbed onto a filter paper floating on an aqueous solution of H2 O2 was used to study nonlinear behavior in the motor's motion. An increase in the concentration of H2 O2 resulted in a change from no motion to irregular oscillatory motion, periodic oscillatory motion, and continuous motion. The mechanisms underlying oscillation and mode bifurcation are discussed based on experimental results on O2 bubble formation and growth on the underside of the motor.

3-Hydroxy-4-nitrobenzoic Acid as a MALDI Matrix for In-Source Decay.

In-source decay (ISD) in matrix-assisted laser desorption/ionization (MALDI) is a rapid sequencing method for peptides. 1,5-Diaminonaphthalene (1,5-DAN) is a most frequently used matrix for ISD. However, using 1,5-DAN generates mainly c- and z-series ions by N-Cα bond cleavage, which makes it difficult to distinguish leucine (Leu) and isoleucine (Ile), and frequently lacks c(n-1)-series ions owing to proline (Pro) at residues n. Several oxidizing matrices generating a- and x-series ions accompanied by d-series ions by Cα-C bond cleavage have been reported, but an issue remained concerning their sensitivity. 3-Hydroxy-4-nitrobenzoic acid (3H4NBA) has been reported as a matrix for 2-nitrobenzenesulfenyl-labeled peptides by Matsuo et al. (Proteomics 2006, 6, 2042-2049). Here, we used 3H4NBA as an oxidizing matrix for ISD. As a result, numerous a- and d-series ions for amyloid ß 1-40 were generated with high sensitivity using 3H4NBA. Each of the two Leu and two Ile was identified by the d-series ions. The sensitivity of the a-series ions using 3H4NBA was a little lower than that of c-series ions using 1,5-DAN. The same tendency was observed for N-acetyl renin substrate and ACTH 18-39. The a-series ions were detected, even at the left side of Pro. The sensitivity of the a-series ions using 3H4NBA was higher than with other existing oxidizing matrices, such as 5-nitrosalicylic acid and 5-formyl salycilic acid. The ions were detected over the entire area of the matrix-analyte spot using 3H4NBA. 3H4NBA was confirmed to be a useful oxidizing matrix for ISD, leading to higher sequence coverage of peptides.

Membrane Protein Analyses Using Alkylated Trihydroxyacetophenone (ATHAP) as a MALDI Matrix.

Membrane proteins containing hydrophobic regions have been difficult to analyze using MALDI-MS, probably due to the use of conventional matrices with a low affinity for hydrophobic peptides. Recently, we reported 1-(2,4,6-trihydroxyphenyl)octan-1-one (alkylated trihydroxyacetophenone (ATHAP)) as a matrix for hydrophobic peptides. In this study, ATHAP was applied to analyze membrane proteins containing transmembrane domains. As a result, we detected intact molecular ions for bacteriorhodopsin (BR) containing seven transmembrane domains that are difficult to detect using 2,4,6-trihydroxyacetophenone or sinapinic acid, by using ATHAP. In addition, we detected digest ions containing all seven transmembrane domains that are difficult to detect using α-cyano-4-hydroxycinnamic acid (CHCA), by using ATHAP. Moreover, ions for hydrophobic digests containing a single transmembrane domain for cadherin 1 (CDH1), fibroblast growth factor receptor 4 (FGFR4), epithelial cell adhesion molecule (EPCAM) recombinant proteins, and human epidermal growth factor receptor type 2 (HER2) were detected with higher sensitivity using ATHAP than with CHCA, confirming that ATHAP improved the membrane protein analyses, especially for hydrophobic regions such as transmembrane domains.

In vitro and in vivo evidence for oxalate oxidase activity of a germin-like protein from azalea.

Germins and germin-like proteins (GLPs) comprise large families of extracellular plant glycoproteins that are structurally similar, yet they have been reported to have distinct biochemical activities: oxalate oxidase and superoxide dismutase activities, respectively. We expressed an azalea GLP (RmGLP2) in cultured cells of tobacco, and determined that the extracellular protein fraction and the recombinant RmGLP2 protein purified from these cells catalyzed the oxidation of oxalate. Notably, this activity is purportedly restricted to germin and has not been demonstrated for a GLP. Although the specific activity of the purified RmGLP2 protein was low compared with that of a previously characterized barley germin/oxalate oxidase, tobacco cells expressing RmGLP2 exhibited significantly reduced oxalate levels. Thus, RmGLP2 represents the first reported GLP with oxalate oxidase activity.

Dual selective nitration in Arabidopsis: Almost exclusive nitration of PsbO and PsbP, and highly susceptible nitration of four non-PSII proteins, including peroxiredoxin II E.

Protein tyrosine nitration is a selective process, as revealed in studies of animals. However, evidence for selective protein nitration in plants is scarce. In this study, Arabidopsis plants were exposed to air with or without nitrogen dioxide at 40 ppm for 8 h in light. Proteins extracted from whole leaves or isolated chloroplasts were subjected to 2D PAGE followed by SYPRO Ruby staining and immunoblotting using an anti-3-nitrotyrosine antibody. We determined the relative intensity of a spot on an immunoblot (designated RISI), and relative intensity of the corresponding spot on SYPRO Ruby gel (designated RISS). Proteins that exhibited a high RISI value and/or a high RISI/RISS ratio were considered selectively nitrated. In whole leaf proteins from exposed plants, all immunopositive spots were identified as PsbO1, PsbO2 or PsbP1 by PMF. Thus, nitration was exclusive to PsbO and PsbP, extrinsic proteins of photosystem II (PSII). Their RISI/RISS ratio was ≤1.5. Non-exposed plants showed very faint nitration. In purified chloroplast proteins, PsbO and PsbP accounted for >80% of the total RISI values, while four non-PSII proteins, including peroxiredoxin II E, exhibited high RISI/RISS ratios (2.5∼6.6). Tyr(9) of PsbO1 was identified as a nitration site. Thus, nitration is selective for two PSII and four non-PSII proteins in Arabidopsis.

[Motor Evoked Potentials and Aortic Surgery].

Motor dysfunction following descending and thoracoabdominal aortic surgery including thoracic endovascular aortic repair remains as one of their devastating complications, although several interventions have tried to preserve spinal cord blood flow during and after aortic aneurysm surgery for the purpose of reducing the incidence of postoperative paraplegia. One of the main limitations of protective strategies is the inability to assess the adequacy of spinal cord perfusion and spinal cord function intraoperatively. Advances in stimulation technique using short train pulses could make intraoperative monitoring of functional integrity of motor pathways possible by recording myogenic motor evoked potentials (MEP), which is a highly sensitive technique to assess spinal cord integrity, identifying insufficient blood flow. To reduce the risk of neurologic injury, anesthesiologists are required to properly understand monitoring of MEP and to manage anesthesia and hemodynamics appropriately. Here, we summarize the strategies for spinal cord protection, including the functional monitoring of spinal cord and anesthetic techniques.

[Anesthetic management of intra-aortic balloon occlusion (IABO) for seven cases of placenta accreta--a six year experience at our institute].

We studied retrospectively amount of bleeding, clamping time, and the presence or absence of ischemia-reperfusion injury in all seven cases of IABO performed for placenta accreta from 2007 to 2012 at our hospital. We also examined rSO2 change before and after clamping in four cases in which lower-limb rSO2 monitoring was performed with NIRS (near-infrared spectroscopy). There was no case suspected of ischemia-reperfusion injury during and after clamping with the amount of bleeding around 1,580-10,973 ml (mean 4,536 ml) and clamping time of 10-83 min (mean 44 min). No significant decrease was observed in lower-limb rSO2 with 73.5 ± 5.9% before clamping and 70.8 ± 5.6% (mean ± SD) after clamping.

[Case of sever septic shock following transurethral lithotripsy].

A 62-year-old man was scheduled for transurethral lithotripsy. Systemic shivering, vomiting and decreased blood pressure occurred after extubation. Blood gas analysis showed metabolic acidosis. After 45 minute observation, he became unconsciousness. He was reintubated. Elevated procalcitonin (PCT) and endotoxin activity assay (EAA) brought us to the diagnosis of severe septic shock. He was treated by a standard therapy conforming to early goal direct therapy and PMX-DHP with CHDF. He showed full recovery, and was discharged 9 days after the procedure. TUL is commonly performed, but it seldom leads to sepsis. We need to pay a careful attention peri- and postoperatively.

A Case of Trigeminal Neuralgia in an Adult Patient With Lambdoid Synostosis.

Trigeminal neuralgia (TN) is characterized by sudden, brief intense pain in the distribution of the unilateral trigeminal nerve (TGN). Neurovascular compression (NVC) of the TGN is the most common cause of TN. Recent studies have suggested that a structural anomaly of the posterior cranial fossa might be involved in the development of TN, and several studies have documented the association between NVC-related TN and congenital posterior cranial deformities in adults. We present the case of a 56-year-old woman with NVC-related TN and unilateral lambdoid synostosis (ULS), along with a literature review, to investigate the relationship between TN and structural anomalies of the posterior fossa. This is the first report of TN in an adult with ULS. Mild and asymptomatic cases of lambdoid synostosis might have a higher incidence of NVC-related TN in association with posterior cranial fossa deformities.

Alkylated trihydroxyacetophenone as a MALDI matrix for hydrophobic peptides.

Hydrophobic peptides are difficult to detect in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), because of the hydrophilic properties of conventional matrices and the low affinity for hydrophobic peptides. Recently, we reported on alkylated dihydroxybenzoic acid (ADHB) as a matrix additive for hydrophobic peptides; however, the peptides were detected in the rim of the matrix-analyte dried spot. Here, we report on a novel matrix, alkylated trihydroxyacetophenone (ATHAP), which is a 2,4,6-trihydroxyacetophenone derivative incorporating a hydrophobic alkyl chain on the acetyl group and thus is expected to have an affinity for hydrophobic peptides. ATHAP increased the sensitivity of hydrophobic peptides 10-fold compared with α-cyano-4-hydroxycinnamic acid (CHCA), in which the detection of hydrophilic peptides was suppressed. The peptides were detected throughout the entire matrix-analyte dried spot using ATHAP, overcoming the difficulty of finding a "sweet spot" when using ADHB. In addition, ATHAP functioned alone as a matrix, unlike ADHB as an additive. In phosphorylase b digests analysis, hydrophobic peptides, which were not detected with CHCA for 1 pmol, were detected with this matrix, confirming that ATHAP led to increased sequence coverage and may extend the range of target analytes in MALDI-MS.

Alkylated dihydroxybenzoic acid as a MALDI matrix additive for hydrophobic peptide analysis.

Hydrophobic peptides are generally difficult to detect using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) because the majority of MALDI matrixes are hydrophilic and therefore have a low affinity for hydrophobic peptides. Here, we report on a novel matrix additive, o-alkylated dihydroxybenzoic acid (ADHB), which is a 2,5-dihydroxybenzoic acid (DHB) derivative incorporating a hydrophobic alkyl chain on a hydroxyl group to improve its affinity for hydrophobic peptides, thereby improving MALDI-MS sensitivity. The addition of ADHB to the conventional matrix α-cyano-4-hydroxycinnamic acid (CHCA) improved the sensitivity of hydrophobic peptides 10- to 100-fold. The sequence coverage of phosphorylase b digest was increased using ADHB. MS imaging indicated that hydrophobic peptides were enriched in the rim of a matrix/analyte dried spot when ADHB was used. In conclusion, the addition of ADHB to the standard matrix led to improved sensitivity of hydrophobic peptides by MALDI-MS.

A sensitive method based on fluorescence-detected circular dichroism for protein local structure analysis.

We report an improved fluorescence-detected circular dichroism (FDCD)-based analytical method that is useful for probing protein three-dimensional structures. The method uses a novel FDCD device with an ellipsoidal mirror that functions on a standard circular dichroism (CD) spectrometer and eliminates all artifacts. Our experiments demonstrated three important findings. First, the method is applicable to any proteins either by using intrinsic fluorescence derived from tryptophan residues or by introducing a fluorescent label onto nonfluorescent proteins. Second, by using intrinsic fluorescence, FDCD spectroscopy can detect a structural change in the tertiary structure of metmyoglobin due to stepwise denaturation on a change in pH. Such changes could not be detected by conventional CD spectroscopy. Third, based on the typical advantages of fluorescence-based analyses, FDCD measurements enable observation of only the target proteins in a solution even in the presence of other peptides. Using our ellipsoidal mirror FDCD device, we could observe structural changes of fluorescently labeled calmodulin on binding with Ca(2+) and/or interacting with binding peptides. Because FDCD appears to reflect the protein's local structure around the fluorophore, it may provide a useful means for "pinpoint analysis" of protein structures.