Photoinduced α-Aminoalkylation of Sulfonylarenes with Alkylamines.

α-Aminoalkylation of sulfonylarenes with alkylamines was found to be induced by photoirradiation. Here various types of alkylamines, such as trialkylamines, dialkylamines, N,N-dialkylanilines and N-alkylanilines as well as sulfonylarenes containing an azole, azine, heterole or benzene ring are available. The reaction proceeds through a homolytic aromatic substitution (HAS) process consisting of addition of an α-aminoalkyl radical to a sulfonylarene and elimination of the sulfonyl radical to give the α-arylalkylamine, where photoirradiation is considered to induce homolysis of sulfonylarenes leading to the generation of α-aminoalkyl radicals that make a radical chain operative.

SEM Observation of the Filter after Administration of Blinatumomab: A Possibility of Leakage during Home Administration Using a Portable Infusion Pump.

Blinatumomab (Blincyto® injection solution) is classified as a bispecific T-cell engaging (BiTE) antibody and is intended for the treatment of relapsed/refractory acute lymphoblastic leukemia. It requires continuous infusion to maintain therapeutic levels. Therefore, it is often administered at home. Monoclonal antibodies, which are administered intravenously, have the potential to leak depending on the nature of the administration devices. Therefore, we investigated device-associated causes of blinatumomab leakage. We observed no apparent changes to the filter and its materials after exposure to the injection solution and surfactant. From scanning electron microscopic images, precipitate on the surface of the filters was observed after physical stimulation of the injection solution. Therefore, physical stimulations should be avoided during the prolonged administration of blinatumomab. In conclusion, the findings of this study assist in the safe administration of antibodies using portable infusion pumps, taking into consideration the composition of drug excipients and the choice of filter type and structure.

[Laparoscopic Proximal Gastrectomy with Supra-Pancreatic Dissection First Approach].

BACKGROUND: In laparoscopic proximal gastrectomy(LPG)with esophago-gastro anastomosis, the key of obtaining good surgical view is how to exclude the stomach from the supra-pancreatic area. METHODS: We could get good surgical view at the supra-pancreatic area with gastro-ptosis by firstly dissecting lesser curvature. Followed by the supra-pancreatic dissection we could efficiently dissect the gastro-splenic ligament from cranial side. We performed this procedure in 20 cases with upper gastric cancer. We evaluate the surgical outcomes of this procedure(S group)comparing to that of the previous procedure in 14 cases(G group). RESULTS: The median operative time in S group was significantly shorter than that in G group (226 min vs 249 min, p=0.02). Other data were similar in 2 groups. CONCLUSIONS: The short-term clinical outcomes of LPG with supra-pancreatic dissection first approach revealed that this technique is safe and feasible.

Development of imaging biomarker for esophageal cancer using intravoxel incoherent motion MRI.

BACKGROUND: Intravoxel incoherent motion MRI (IVIM-MRI) can quantify micro-perfusion at the capillary level in the tissue. The purpose of this study is to measure tumor perfusion using IVIM-MRI, and evaluate its value as a biomarker to predict prognosis in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 109 ESCC patients (93 men and 16 women; median age: 72) who underwent IVIM-MRI prior to treatment between February 2018 and August 2020 were retrospectively investigated. Both mean apparent diffusion coefficient (ADC) value and mean perfusion-related parameter (PP) value of the primary tumor were measured using three b values of 0, 400, and 1000 s/mm2 based on the IVIM model. We analyzed associations of these parameters with clinical stage and disease-specific survival (DSS). RESULTS: Lower ADC and PP values of the tumor were significantly associated with the higher clinical T stage (p < 0.0001, p < 0.0001, respectively). In Kaplan-Meier analyses, patients with lower PP value tumors (< 18.94, median) had significantly worse DSS (p < 0.0001), while tumor ADC value did not show a significant correlation with DSS. In a multivariate analysis, PP value of the tumor was an independent prognostic factor for DSS (p = 0.0027). CONCLUSIONS: Quantification of tumor perfusion using IVIM-MRI can be a non-invasive prognostic biomarker of ESCC, reflecting clinical stage and survival.

[A Case of Gastric Cancer with Necrotic Lymph Node Perforation in the Stomach during Chemotherapy].

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.

γ-oryzanol ameliorates the acute stress induced by behavioral anxiety testing in mice.

We evaluated the anxiolytic effect of γ-oryzanol (GORZ) and elucidated the molecular mechanisms involved in its inhibition of behavioral test-induced anxiety. Behavioral tests were conducted on day 13, and mice were subjected to 30 min of acute restraint stress treatment (ARST) before sacrifice on day 16. In other group, behavioral tests were conducted on day 13 and 14 after ARST. 0.5% GORZ significantly weakened the effect of behavioral stress, but not the effect of strong ARST. GORZ downregulated ARST-induced cFos levels in the cerebral cortex. In conclusion, GORZ has potential ant-anxiety effect in the treatment of weak behavioral test-induced stress.

[A Case of Colon Metastasis from Invasive Lobular Carcinoma of the Breast].

The patient was a 48-year-old woman. She consulted our hospital with a chief complaint of vomiting. Colonoscopy showed stenosis and edematous mucosa, and biopsy was performed. Histological examination demonstrated the lesion to be colonic metastasis of breast cancer, invasive lobular carcinoma. Although colorectal metastasis of breast cancer has a poor prognosis and chemotherapy is considered as the main treatment modality, hormone therapy is also a treatment option depending on the condition.

Cytokine-dependent activation of JAK-STAT pathway in Saccharomyces cerevisiae.

Protein phosphorylation is an important post-translational modification for intracellular signaling molecules, mostly found in serine and threonine residues. Tyrosine phosphorylations are very few events (less than 0.1% to phosphorylated serine/threonine residues), but capable of governing cell fate decisions involved in proliferation, differentiation, apoptosis, and oncogenic transformation. Hence, it is important for drug discovery and system biology to measure the intracellular level of phosphotyrosine. Although mammalian cells have been conventionally utilized for this purpose, accurate determination of phosphotyrosine level often suffers from high background due to the unexpected crosstalk among endogenous signaling molecules. This situation led us firstly to establish the ligand-induced activation of homomeric receptor tyrosine kinase (i.e., epidermal growth factor receptor) in Saccharomyces cerevisiae, a lower eukaryote possessing organelles similar to higher eukaryote but not showing substantial level of tyrosine kinase activity. In this study, we expressed heteromeric receptor tyrosine kinase (i.e., a complex of interleukin-5 receptor (IL5R) α chain, common ß chain, and JAK2 tyrosine kinase) in yeast. When coexpressed with a cell wall-anchored form of IL5, the yeast exerted the autophosphorylation of JAK2, followed by the phosphorylation of transcription factor STAT5a and subsequent nuclear accumulation of phosphorylated STAT5a. Taken together, yeast could be an ideal host for sensitive detection of phosphotyrosine generated by a wide variety of tyrosine kinases. Biotechnol. Bioeng. 2016;113: 1796-1804. © 2016 Wiley Periodicals, Inc.

Efficient diagnosis of Sjögren's syndrome to reduce the burden on patients.

OBJECTIVE: The purpose of this study was to investigate the procedures for efficiently diagnosing Sjögren's syndrome to reduce patient burden. METHODS: This study analyzed data from 254 Japanese patients diagnosed with Sjögren's syndrome out of 4967 who visited our clinic complaining of xerostomia. RESULTS: Of the 254 Sjögren's syndrome patients, 140 fulfilled the criteria proposed by the Committee on Sjögren's Syndrome of the Ministry of Health and Welfare of Japan, 228 fulfilled the criteria proposed by the American-European Consensus Group, and 69 fulfilled the criteria proposed by the American College of Rheumatology. Numbers of definitive cases varied with each set of criteria. Logistic regression analysis was used to analyze useful examination items for definitive diagnosis of Sjögren's syndrome, demonstrating that anti-Ro/SSA (odds ratio (OR), 7.165), lip biopsy (OR, 4.273), sialography (OR, 2.402), and ANA (OR, 0.678) correlated significantly with definitive diagnosis of Sjögren's syndrome. CONCLUSIONS: These results suggest that the following diagnostic procedure for Sjögren's syndrome would reduce burden on patients. When clinicians choose examination items for diagnosing Sjögren's syndrome, they should first select which criteria to use. Then, to minimize the number of examination items, examinations should be performed in order of anti-SSA antibody, lip biopsy, and parotid gland sialography.

Design Rationale for CO2 Separation Membranes with Micropatterned Surface Structures.

Here, we report the design rationale of CO2 separation membranes with micropatterned surface structures. Thin film composite (TFC) membranes with micropatterned surface structures were fabricated by spray coating amine-containing hydrogel particles on the top of micropatterned porous support membranes, which were synthesized by a polymerization-induced phase separation process in a micromold (PIPsµM). The pore size of the support membranes was optimized by tuning the proportion of good and poor solvents for the polymerization process so that the microgels would be assembled as a defect-free separation layer. The relationship between the size of the micropatterned structures on the surface of the support membrane and the thickness of the separation layer was optimized to maximize the surface area of the separation layer. The rationally designed micropatterned TFC membrane showed a CO2 permeability (835.8 GPU) proportional to the increase in surface area relative to the flat membrane with a high CO2/N2 selectivity of 58.7. The rational design for micropatterned TFC membranes will enable the development of inexpensive and high-performance functional membranes not only for CO2 separation but also for other applications such as water treatment and membrane reactors.

Effect of lipid emulsion on the central nervous system and cardiac toxicity of bupivacaine and levobupivacaine in awake rats.

PURPOSE: Despite numerous studies examining the effect of lipid emulsion on bupivacaine-induced cardiac toxicity, few studies have examined its effect on central nervous system (CNS) toxicity of local anesthetics. We investigated the effect of lipid emulsion on the CNS and cardiac toxicity of bupivacaine and levobupivacaine in awake, spontaneously breathing rats. METHODS: Male Sprague-Dawley rats were randomly allocated to control-bupivacaine (CB), control-levobupivacaine (CL), lipid-bupivacaine (LB), and lipid-levobupivacaine (LL) groups (n = 8 in each group). After infusion of saline (CB and CL groups) or 20 % lipid emulsion (LB and LL groups) for 5 min, bupivacaine (CB and LB groups) or levobupivacaine (CL and LL groups) was administered IV at 1 mg/kg/min. Cumulative dose of anesthetics and their plasma concentrations at the onset of convulsions and cardiac arrest were measured. RESULTS: The doses of bupivacaine for inducing convulsions and cardiac arrest in the LB group (8.8 ± 1.7 and 10.2 ± 1.5 mg/kg, respectively) were significantly larger than those in the CB group (5.9 ± 1.1 and 7.1 ± 1.3 mg/kg, respectively, p < 0.001 for both). The doses of levobupivacaine for inducing convulsions and cardiac arrest in the LL group (10.0 ± 2.0 and 13.7 ± 3.6 mg/kg, respectively) were significantly larger than those in the CL group (7.7 ± 1.6 and 9.4 ± 2.4 mg/kg, p = 0.03 and p = 0.02, respectively). Plasma concentrations of bupivacaine at the onset of convulsions and cardiac arrest in the LB group (12.9 ± 2.9 and 41.4 ± 5.2 µg/ml, respectively) were significantly higher than those in the CB group (7.9 ± 1.2 and 21.6 ± 3.3 µg/ml, respectively, p < 0.001 for both). Plasma concentrations of levobupivacaine at the onset of convulsions and cardiac arrest in the LL group (17.5 ± 1.5 and 47.6 ± 6.1 µg/ml, respectively) were significantly higher than in the CL group (10.9 ± 2.2 and 29.2 ± 3.5 µg/ml, respectively, p < 0.001 for both). CONCLUSIONS: Lipid emulsion decreased CNS and cardiac toxicity of both bupivacaine and levobupivacaine.

[Chrono-nutrition and chrono-exercise].

The circadian rhythm controls many physiological functions, such as feeding, motor activity, endocrine secretion and autonomic nerve. Regular feeding pattern can entrain the peripheral circadian clock, whereas peripheral clock systems can control the absorption distribution, metabolism and excretion of nutrients, suggesting mutual interactions between circadian clocks and nutrition/food. The interactions were so-called by "chrono-nutrition", and bigger meals for breakfast were good for entrainment of peripheral clock and protection of obesity. Similar to chrono-nutrition the timing of exercise ("chrono-exercise") is important for both entrainment signals and energy expenditure. Evening exercise and/or feeding then exercise was good timing exercise for protection of obesity. Taken all, it is suggested that timing of feeding and exercise is now one of key factors for metabolic syndrome.

Effects of organic components in cuttlebone on the morphological and mechanical properties of peroxide cross-linked cuttlebone/natural rubber composites.

The clarification of the role of organic components in cuttlebone particles on the morphological and mechanical properties in terms of the strain-induced crystallization (SIC) of peroxide cross-linked cuttlebone/natural rubber (NR) composites was revealed for the first time in this study. The organic components in cuttlebone particles affected the increased bound rubber layers and the decreased rubber chain orientation due to the formation of interfacial interactions (filler-to-filler and/or filler-to-rubber interactions). During SIC, the presence of organic components in cuttlebone particles did not significantly affect the crystallinity index and crystallite size in cuttlebone/NR composites. The increased moduli in the stress-strain curve resulted from the presence of biofiller, SIC, and organic components in the cuttlebone. Therefore, the presence of organic components in biofiller is an important factor in improving the mechanical properties of green rubber composite materials.

[Anesthetic management for mitral valve replacement in a patient with mitral stenosis and dilated cardiomyopathy].

A 69-year-old man who has mitral stenosis concomitantly with dilated cardiomyopathy underwent mitral valve replacement. The preoperative left ventricular ejection fraction was 23%. Preoperative dobutamine stress echocardiography showed poor response. High dose fentanyl was administered for induction and maintenance of general anesthesia, and blood pressure was kept with vasoconstrictors. Circulatory assist with milrinone and intraaortic balloon pumping after the cardiopulmonary bypass enabled us to obtain stable hemodynamics.

The Relationship between the Lunar Phase, Menstrual Cycle Onset and Subjective Sleep Quality among Women of Reproductive Age.

The aim of the present study was to investigate the association among lunar cycle, menstrual cycle onset, and subjective sleep quality. Menstrual cycle onset data from the six most recent menstrual cycles were obtained for 529 women (aged 25-39 years) using the smartphone app Luna Luna. We also collected questionnaire survey data on sleep quality from each participant. Overall, there was no association between the onset of menstrual cycle and lunar phase. Interestingly, the proportion of good sleepers with menstrual cycle beginning during the light period was significantly higher than that during the dark period, while the proportion of poor sleepers with menstrual cycle beginning during the dark period was significantly higher than that during the light period. When participants were categorized by the combination of lunar phases (light, dark, neutral periods) in the two most recent menstrual cycle onsets, the "both dark period" group and the "other (light and dark) period" group showed the lowest proportion of good sleepers. Menstrual cycle onset in the dark period was associated with a deterioration in subsequent subjective sleep quality, which was more apparent with consecutive onsets in the dark period or at a rapidly changing lunar phase.

Pharmacokinetics of lidocaine, bupivacaine, and levobupivacaine in plasma and brain in awake rats.

BACKGROUND: We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats. METHODS: Lidocaine (0.5 mg x kg x min), bupivacaine (0.1 mg x kg x min), or levobupivacaine (0.1 mg x kg x min) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dialysate were collected during infusion and for 2 h after termination of infusion. Concentrations of anesthetics in the cerebral extracellular fluid were measured by microdialysis using the retrodialysis calibration method. Tissue-to-plasma partition coefficients calculated from the total (protein-bound and unbound) and unbound concentrations in plasma and brain as well as pharmacokinetic parameters in plasma and cerebral extracellular fluid were compared among the three anesthetics. RESULTS: There were no differences in plasma total or unbound concentrations between bupivacaine and levobupivacaine. Concentrations of bupivacaine in the cerebral extracellular fluid were significantly higher than levobupivacaine (P < 0.001). Despite no differences in the ratio of total brain concentration to total plasma concentration among the three anesthetics, the ratio of cerebral extracellular fluid concentration to plasma unbound fraction of bupivacaine was significantly higher than lidocaine and levobupivacaine (0.58 +/- 0.09, 0.47 +/- 0.18, and 0.40 +/- 0.09, respectively; P = 0.03 and 0.003, respectively). CONCLUSIONS: Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.

Effect of remifentanil on cardiovascular and bispectral index responses following the induction of anesthesia with midazolam and subsequent tracheal intubation.

PURPOSE: We examined the hypothesis that remifentanil decreases the bispectral index (BIS) as well as blunts cardiovascular responses to tracheal intubation during anesthesia with midazolam. METHODS: Sixty patients were randomly allocated to three groups according to the dose of remifentanil-0.1 (S), 0.2 (M), or 0.5 (L) microg kg(-1) min(-1), respectively. Infusion of remifentanil was started 5 min before the induction of general anesthesia with midazolam 0.2 mg/kg in all groups. Following the administration of vecuronium 0.1 mg/kg, the trachea was intubated 5 min after induction, and the infusion rate of remifentanil was then reduced to 0.05 microg kg(-1) min(-1) in all groups. Mean arterial blood pressure (MAP), heart rate (HR), BIS, and 95% spectral edge frequency (SEF95) were measured until 10 min after tracheal intubation. RESULTS: Infusion of remifentanil alone before the induction of anesthesia did not affect the hemodynamic or electroencephalographic parameters. MAP was significantly decreased after induction in all groups of patients (P < 0.01), with no differences among the three groups, while it was significantly increased after tracheal intubation in the patients of groups S and M, but not in those of group L. The HR did not change after induction in any of the groups, but it was also significantly increased after tracheal intubation of group S and M patients, although not in those of group L. The BIS decreased after induction, and both the BIS and SEF95 were significantly lower in group L patients than in those of group S (P < 0.01). All patients were unconscious after induction, and none complained of intraoperative awareness. CONCLUSION: In our patient cohort, remifentanil 0.5 microg kg(-1) min(-1) effectively decreased the BIS after the induction of general anesthesia with midazolam 0.2 mg/kg and suppressed the increase of MAP and HR in response to subsequent laryngoscopy and tracheal intubation.

Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations.

PURPOSE: To examine the relationships between effect-site concentrations and electroencephalographic parameters after the induction of general anesthesia with midazolam. METHODS: Twenty-four patients with American Society of Anesthesiologists status I or II were randomly allocated to receive either an intravenous (i.v.) bolus of midazolam 0.2 mg kg(-1) (small-dose group, n = 12) or 0.3 mg kg(-1) (large-dose group, n = 12) for induction of general anesthesia in a double-blind experimental design. The bispectral index (BIS), 95% spectral edge frequency (SEF95), spectral power density, and plasma concentrations of midazolam were measured for 60 min following the induction of general anesthesia. RESULTS: Plasma and simulated effect-site concentrations of midazolam were significantly higher in the large-dose group than in the small-dose group (P = 0.005 and <0.001, respectively). There was a correlation between the relative beta ratio and BIS (r (2) = 0.30, P < 0.001; n = 168); however, effect-site concentrations of midazolam showed no association with BIS, relative beta ratio, or SEF95 (r (2) = 0.07, 0.11 and 0.01, respectively; n = 168). The electroencephalographic spectral power density in the beta-band (>/=13 and <30 Hz) was significantly increased after induction and was significantly larger in the large-dose group than in the small-dose group (P = 0.009). CONCLUSION: Following the induction of general anesthesia with i.v. midazolam 0.2 or 0.3 mg kg(-1), the BIS was positively correlated with the relative beta ratio. Despite a rapid decrease in the plasma and effect-site concentrations of midazolam, the average BIS remained >60 for 60 min after induction, reflecting an increased power of the electroencephalographic high-frequency band.

[Prolonged apnea from rocuronium in a patient with hypermagnesemia after cesarean section: a case report].

A patient developed prolonged apnea after emergency cesarean section. The patient was a 38-year-old primiparous woman with myoma uteri and her body weight was 44.8 kg. She received intravenous magnesium sulfate 1 g x hr(-1) as tocolytic agent for threatened premature delivery. We performed rapid sequence induction of anesthesia with thiopental 250 mg and rocuronium 50 mg because she was suspected of full stomach. After the intubation, we did not administer any muscle relaxants during the operation. After the operation which was finished in 65 minutes, the effect of rocuronium remained for more than 100 minutes after its administration probably due to hypermagnesemia. Rocuronium shows rapid onset, and several studies indicate that it can be used for rapid sequence induction instead of suxamethonium. But rocuronium should be used carefully and its effect should be monitored in a patient with hypermagnesemia.

Effect of fatty acids on the accelerated sulfur vulcanization of rubber by active zinc/carboxylate complexes.

The effect of fatty acids with different aliphatic chain lengths on the accelerated vulcanization reaction of isoprene rubber was investigated through the generation of new intermediates composed of dinuclear bridging bidentate zinc/carboxylate complexes. Using the combination of in situ time-resolved Fourier-transform infrared spectroscopy and in situ time-resolved zinc K-edge X-ray absorption fine structure spectroscopy, the essential complex structure of the intermediates formed during the vulcanization reaction of isoprene rubber was determined to be independent of the aliphatic chain length of fatty acids. However, the reactivity of arachidic acid with ZnO was found to be low, which prolonged the induction period and curing time, and slowed down the curing rate in the vulcanization of isoprene rubber. These results help to understand the complicated vulcanization reaction of rubber, especially natural rubber, which inherently contains various fatty acids. The results obtained in this study are important for developing well-designed high-performance natural rubber products in the future.