Effects of Chinese herbal medicine and cold exposure on plasma glucose, leucine and energy metabolism in sheep.

An experiment was carried out to assess the feeding effect of Chinese herbal medicine on N balance, ruminal fermentation characteristics, kinetics of plasma glucose, leucine and energy metabolism in sheep kept at thermoneutral environment (23°C) or exposed to cold (2-4°C). Four sheep were subjected to either mixed hay (MH-diet) or hay supplemented with 2% of a traditional nourishing Chinese herbal medicine mixture (Astragalus root, Angelica root and Atractylodes rhizome; CHM-diet) over two 23-day periods using a crossover design. Cold exposure was conducted for 5 days. The isotope dilution of [U-13 C]glucose with open circuit calorimetry was used to determine the turnover and oxidation rates of plasma glucose and metabolic heat production. The rate of plasma leucine turnover was measured with an isotope dilution method using [1-13 C]leucine. N intake was higher, N excretion through faeces was lower and N digestibility was higher for the CHM-diet than the MH-diet. Rumen pH was lower, concentration of rumen NH3 was higher, concentrations of rumen total VFA and acetate tended to be higher and propionate was higher for the CHM-diet compared with the MH-diet. Turnover rate of plasma glucose was higher for the CHM-diet than the MH-diet and increased during cold exposure. Oxidation rate of plasma glucose did not differ between diets and also between environments. Turnover rate of plasma leucine was higher for the CHM-diet compared with the MH-diet but remained similar between environments. Heat production was greater for the CHM-diet than the MH-diet and increased during cold exposure. No significant diet × environment interaction was detected. The present results demonstrated that plasma glucose and energy metabolism were enhanced by both Chinese herbal medicine and cold exposure; plasma leucine metabolism was enhanced by Chinese herbal medicine but with lack of change in response to cold exposure in sheep under the conditions of the current experiment.

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction.

PURPOSE OF INVESTIGATION: Dexamethasone (DEX) is often administered to prevent paclitaxel (PTX)-induced hypersensitivity reactions (HSR). The DEX dose is reduced when administered in combination with aprepitant (APR). However, the influence of that dose reduction on PTX-induced HSR has not been thoroughly studied. The present authors aimed to investigate the effects of the combined administration of APR and DEX on PTX-induced HSR. MATERIALS AND METHODS: Fifty-one patients who received a three-week PTX regimen in combination with APR and DEX were retrospectively analysed. The authors compared the dose of DEX with the incidence of HSR and other toxicities. RESULTS: Patients were stratified into two groups depending on the DEX dose, > 20 mg (group D, 33 patients), and < 12 mg (group reD, 26 patients). The incidence of HSR in Groups D and reD were 51.5% (17/33) and 53.8% (14/26), respectively. The frequencies of other toxicities between the groups were comparable. CONCLUSION: The findings suggest that although a reduction in DEX dose is possible when APR is co-administered, this does not affect the PTX-induced HSR. However, adverse effect should be closely monitored.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.

BACKGROUND: Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC. METHODS: The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription-polymerase chain reactions and examined for correlations with GEM sensitivity. RESULTS: The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively). CONCLUSION: hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.

Structural phase transition and magnetic-field effect on the modulated structure in GdBaCo2O5+δ (δ < 0.5).

We investigated the crystal structures of an ordered perovskite-type cobaltate, GdBaCo2O(5+δ) (δ < 0.5), at elevated temperatures by transmission electron microscopy. Above the magnetic ordering temperature, we observed a first-order structural phase transition between the low-temperature tetragonal 3a(p) × 3a(p) and high-temperature orthorhombic 1a(p) × 2a(p) superstructure phases (where a(p) is the perovskite-unit cell). Upon the application of a magnetic field, an incommensurate phase emerges around the structural phase-transition temperature, which indicates a magnetic-field-induced structural phase transition via no magnetic ordering in the ordered perovskite-type cobaltate.

Comprehensive diagnostic ability of endocytoscopy compared with biopsy for colorectal neoplasms: a prospective randomized noninferiority trial.

BACKGROUND AND STUDY AIMS: Endocytoscopy enables observation at 450-fold magnification during gastrointestinal endoscopy, allowing on-site "optical biopsy." We compared the accuracies of endocytoscopy and standard biopsy for the diagnosis of colorectal neoplasms. PATIENTS AND METHODS: We performed a randomized, controlled, open-label trial of patients with colorectal lesions (≥ 5 mm) detected during colonoscopy in a tertiary referral center. We randomly assigned the 203 detected lesions of 170 eligible patients to either the endocytoscopy or standard biopsy group. An on-site endoscopist assessed the histopathology of the endocytoscopy group lesions according to the endocytoscopic findings, whereas a pathologist later assessed standard biopsy group lesions by microscopic examination of the biopsy specimens. We calculated the diagnostic accuracies in both groups with reference to the final histopathology of the resected specimens. The primary endpoint was to determine whether the diagnostic accuracy of endocytoscopy for neoplastic lesions was noninferior to that of standard biopsy (with a predefined noninferiority margin of 10%). Analyses were by intention-to-treat and per-protocol. The study is registered, number UMIN000003923. RESULTS: Overall, 102 lesions in the endocytoscopy group and 101 in the standard biopsy group were available for primary outcome analysis. There were no complications. The diagnostic accuracy of endocytoscopy for the discrimination of neoplastic lesions was 94.1% (95% confidence interval 87.6% to 97.8%), whereas that of standard biopsy was 96.0% (90.2% to 98.9%), which is within the noninferiority margin (absolute difference -1.9%, -8.6% to +5.0%). CONCLUSIONS: Endocytoscopy is noninferior to standard biopsy for the discrimination of neoplastic lesions. With its advantage of providing an on-site diagnosis, endocytoscopy could provide a novel alternative to standard biopsy in routine colonoscopy.

Successful endovascular repair of ruptured isolated bilateral internal iliac artery aneurysms.

INTRODUCTION: Due to their anatomic location, internal iliac artery aneurysms are difficult to treat surgically. An endovascular approach can be helpful, even in ruptured cases. REPORT: We report a 71-year-old male with ruptured isolated bilateral internal iliac artery aneurysms. The aneurysms were treated with embolisation of the branching arteries of the bilateral internal iliac arteries followed by placement of a stent graft covering the orifice of the bilateral internal iliac arteries. The patient tolerated this procedure well. DISCUSSION: Even in patients with ruptured aneurysms, endovascular treatment for internal iliac artery aneurysms can be a good treatment option.

Quantitative evaluation of the outcomes of revascularization procedures for peripheral arterial disease using indocyanine green angiography.

OBJECTIVES: We performed indocyanine green angiography (ICGA) in patients with peripheral arterial disease (PAD), and established a method for the quantitative measurement of appropriate parameters to assess peripheral perfusion and the applicability of ICGA tests. METHODS: Twenty-one patients with PAD underwent revascularization procedures with pre- and postinterventional ICGA tests. The ICGA parameters, which included the magnitude of intensity of indocyanine green, the time to maximum intensity, and the time from fluorescence onset to half the maximum intensity (T1/2) were compared with the ankle-brachial pressure index, toe -brachial pressure index, and toe pressure. We evaluated these parameters for regions of interest (ROIs). RESULTS: T1/2 was the strongest parameter among all parameters of the ICGA tests. ROI 3, which included the distal region of the first metatarsal bone, correlated more significantly with the traditional measurements than the other ROIs. A value of T1/2 >20 seconds for ROI 3 was significantly correlated with a toe pressure of <50 mmHg (sensitivity: 0.77, specificity: 0.80). CONCLUSIONS: ICGA can be used to assess peripheral tissue perfusion. By measuring the value of T1/2 in ROI 3, ICGA tests can be used to evaluate the outcomes of revascularization procedures.

Presenilin-1 mutations downregulate the signalling pathway of the unfolded-protein response.

Missense mutations in the human presenilin-1 (PS1) gene, which is found on chromosome 14, cause early-onset familial Alzheimer's disease (FAD). FAD-linked PS1 variants alter proteolytic processing of the amyloid precursor protein and cause an increase in vulnerability to apoptosis induced by various cell stresses. However, the mechanisms responsible for these phenomena are not clear. Here we report that mutations in PS1 affect the unfolded-protein response (UPR), which responds to the increased amount of unfolded proteins that accumulate in the endoplasmic reticulum (ER) under conditions that cause ER stress. PS1 mutations also lead to decreased expression of GRP78/Bip, a molecular chaperone, present in the ER, that can enable protein folding. Interestingly, GRP78 levels are reduced in the brains of Alzheimer's disease patients. The downregulation of UPR signalling by PS1 mutations is caused by disturbed function of IRE1, which is the proximal sensor of conditions in the ER lumen. Overexpression of GRP78 in neuroblastoma cells bearing PS1 mutants almost completely restores resistance to ER stress to the level of cells expressing wild-type PS1. These results show that mutations in PS1 may increase vulnerability to ER stress by altering the UPR signalling pathway.

Drainage surgery followed by postoperative irrigation with gentian violet for prosthetic graft infection caused by methicillin-resistant Staphylococcus aureus.

INTRODUCTION: Infection of a prosthetic graft is still associated with considerable morbidity and mortality. Conventionally, this vascular complication is treated by excising the infected graft, although prosthetic graft preservation is possible in selected cases. REPORT: We report the successful treatment of prosthetic graft infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in three patients, by performing drainage surgery with postoperative irrigation using gentian violet. DISCUSSION: The combination of drainage surgery and irrigation with gentian violet solution provides an alternative option to graft excision for prosthetic graft infection.

Role of coerulean noradrenergic neurones in general anaesthesia in rats.

BACKGROUND: Central noradrenergic neurones have a role in alertness, analgesia, and thermoregulation; these neurones are also involved in the mechanism of anaesthesia. Locus coeruleus neurones innervate various central nervous regions including the cerebral cortex and hippocampus, and are responsible for wakefulness and analgesia. We hypothesized that these neurones are also involved in both activation of the γ-aminobutyric acid type A (GABA(A)) receptor and inhibition of N-methyl-d-aspartate (NMDA) receptor-mediated anaesthesia. METHODS: Forty-seven male rats were used to compare duration of anaesthesia before and 10 days after noradrenergic neurone depletion after intraperitoneal (i.p.) administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 0, 5, and 50 mg kg(-1)). The animals received i.p. thiopental (GABA anaesthetic, 45 mg kg(-1)) or ketamine (NMDA anaesthetic, 100 mg kg(-1)). We also tested the effects of coerulean noradrenergic neurone depletion on i.p. ketamine analgesia (15 mg kg(-1)) using the hot-plate test in a further 21 male rats. At the end of each experiment, norepinephrine contents in the cerebral cortex and hippocampus were measured. RESULTS: I.P. DSP-4 5 and 50 mg kg(-1) significantly decreased ketamine anaesthesia duration by 12.7% and 22.4%, increased thiopental anaesthesia duration by 10.8% and 24.5%, and reduced ketamine-increased hot-plate latency by 55.2% and 68.1%, respectively. In addition, i.p. DSP-4 5 and 50 mg kg(-1) significantly reduced norepinephrine contents in coerulean brain regions by ∼20% and ∼75%, respectively. There were significant correlations between norepinephrine contents in coerulean brain regions and anaesthesia durations and ketamine analgesia. CONCLUSIONS: The present data indicate that coerulean noradrenergic neurones may be responsible for both GABA- and NMDA-mediated anaesthetic actions.

Postoperative transient tetraplegia in two patients caused by cervical spondylotic myelopathy.

We report two patients with cervical spondylotic myelopathy following non-cervical spine surgery. These cases revealed postoperative transient tetraplegia with respiratory insufficiency despite optimal anaesthetic management. Both patients showed no limitation of their neck movement at pre-operative airway examination. In addition, their necks had never been overextended during anaesthesia including tracheal intubation. However, postoperative magnetic resonance imaging showed cervical spondylotic myelopathy. Cervical disc herniation and protrusion of a hypertrophic ligamentum flavum caused spinal canal cord compression, and, these may lead to tetraplegia and phrenic nerve impairment. Their muscle weakness gradually improved and completely recovered the following morning. We should consider the existence of cervical spondylosis in the elderly patients over the age of 60 years.

Pedunculated colorectal polyps with heads ≤ 1 cm in diameter can be resected using cold snare polypectomy.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) is not recommended for the resection of pedunculated colorectal polyp. The aim of this study was to examine the adequacy of CSP compared to hot snare polypectomy (HSP) for the complete resection of pedunculated polyps with heads ≤ 1 cm in diameter. PATIENTS AND METHODS: This was a retrospective study of a cohort of consecutive outpatients who had resection of pedunculated polyps with heads 6-10 mm in diameter using either dedicated CSP or HSP from 2014 through 2019. The primary outcome measure was occurrence of delayed bleeding. Secondary outcome measures included total procedure time, en bloc resection rate, immediate bleeding, and number of clips used. RESULTS: 415 patients with 444 eligible polyps were enrolled; the CSP group (363 patients; 386 polyps) and HSP group (52 patients; 58 polyps). Patient characteristics, polyp characteristics and en bloc resection rate were similar between groups. The mean total procedure time and mean number (range) of hemostatic clips/ patient used were significantly lower with CSP than with HSP (18± 8 min vs. 25± 9 min, P<0.001; 1.1 ± 0.6 (1-3) vs.3.1 ± 1.6 (1-5), respectively, P<0.001). Delayed bleeding occurred significantly less frequently in the CSP, 0% (0/363 vs.3.8% (2/52) in the HSP group (P<0.001), although immediate bleeding was significantly higher in CSP than HSP (84% (325/386) vs. 12% (7/58), P<0.001). CONCLUSION: Pedunculated colorectal polyps with heads ≤ 1 cm can be removed using CSP, which has several advantages over HSP.

Usefulness of an artificial neural network for a beginner to achieve similar interpretations to an expert when examining myocardial perfusion images.

This study examined whether using an artificial neural network (ANN) helps beginners in diagnostic cardiac imaging to achieve similar results to experts when interpreting stress myocardial perfusion imaging (MPI). One hundred and thirty-eight patients underwent stress MPI with Tc-labeled agents. An expert and a beginner interpreted stress/rest MPI with or without the ANN and the results were compared. The myocardium was divided into 5 regions (the apex; septum; anterior; lateral, and inferior regions), and the defect score of myocardial blood flow was evaluated from 0 to 4, and SSS, SRS, and SDS were calculated. The ANN effect, defined as the difference in each of these scores between with and without the ANN, was calculated to investigate the influence of ANN on the interpreters' performance. We classified 2 groups (insignificant perfusion group and significant perfusion group) and compared them. In the same way, classified 2 groups (insignificant ischemia group and significant ischemia group) and compared them. Besides, we classified 2 groups (normal vessels group and multi-vessels group) and compared them. The ANN effect was smaller for the expert than for the beginner. Besides, the ANN effect for insignificant perfusion group, insignificant ischemia group and multi-vessels group were smaller for the expert than for the beginner. On the other hand, the ANN effect for significant perfusion group, significant ischemia group and normal vessels group were no significant. When interpreting MPI, beginners may achieve similar results to experts by using an ANN. Thus, interpreting MPI with ANN may be useful for beginners. Furthermore, when beginners interpret insignificant perfusion group, insignificant ischemia group and multi-vessel group, beginners may achieve similar results to experts by using an ANN.

A full-length cDNA resource for the pea aphid, Acyrthosiphon pisum.

Large collections of full-length cDNAs are important resources for genome annotation and functional genomics. We report the creation of a collection of 50 599 full-length cDNA clones from the pea aphid, Acyrthosiphon pisum. Sequencing from 5' and 3' ends of the clones generated 97 828 high-quality expressed sequence tags, representing approximately 9000 genes. These sequences were imported to AphidBase and are shown to play crucial roles in both automatic gene prediction and manual annotation. Our detailed analyses demonstrated that the full-length cDNAs can further improve gene models and can even identify novel genes that are not included in the current version of the official gene set. This full-length cDNA collection can be utilized for a wide variety of functional studies, serving as a community resource for the study of the functional genomics of the pea aphid.

Changes in plasma orexin A during propofol-fentanyl anaesthesia in patients undergoing eye surgery.

BACKGROUND: Central orexinergic and noradrenergic neurones are involved in the control of sleep and wakefulness. In addition, previous reports suggest that both neurones may have an important role to play in general anaesthesia. In the present study, we have determined whether general anaesthesia would affect plasma orexin A (OXA) and norepinephrine concentrations. METHODS: Twenty-two patients undergoing elective ophthalmic surgery under general anaesthesia with propofol, fentanyl, and vecuronium were studied. Arterial blood was collected before and 1 and 2 h after induction of anaesthesia and at emergence to measure plasma OXA, propofol, norepinephrine, and epinephrine concentrations. During anaesthesia, the propofol infusion rate was changed to maintain the bispectral index between 40 and 50. RESULTS: Plasma OXA and norepinephrine did not change during anaesthesia but significantly increased after emergence compared with pre-anaesthesia [from 19.9 (sd 3.2) to 28.3 (4.3) pM, P<0.01, and from 1351 (146) to 1798 (251) pM, P<0.05, respectively]. Plasma epinephrine did not change. There was a significant correlation between plasma OXA and norepinephrine (P<0.05) and also between plasma propofol and OXA (P<0.05) and norepinephrine (P<0.01). CONCLUSIONS: We found that plasma OXA and norepinephrine significantly increased during emergence from propofol-fentanyl anaesthesia.

Differences in the pharmacokinetics of Cyp3a substrates in TSOD and streptozotocin-induced diabetic mice.

The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM). As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice. These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.

Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease.

BACKGROUND AND AIMS: Interleukin 17 (IL17) is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are still unclear. METHODS: Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed colonic mucosa of 72 patients with IBD (38 with Crohn's disease and 34 with ulcerative colitis), and normal colon of 38 control subjects. IL17 and interferon gamma (IFNgamma) were detected by ELISA in the supernatants of biopsies cultured ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs) incubated with IL12, IL23, IL1beta plus IL6, transforming growth factor beta1 (TGFbeta1), or anti-IL21 neutralising antibody. Intracellular flow cytometry was performed to analyse mucosal Th17 and Th1/Th17 cells. RESULTS: IL17 production by organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed mucosa and controls, and was equivalent in amount to IFNgamma. Anti-CD3/CD28-stimulated IBD LPMCs produced higher IL17 amounts compared to controls. The percentages of Th17 and Th1/Th17 cells were increased in patients with IBD. IL23 and IL1beta plus IL6 had no effect on IBD LPMC production of IL17; however, IL12 markedly increased IFNgamma production and decreased IL17 production. TGFbeta1 dose-dependently decreased IFNgamma, but had no significant inhibitory effect on IL17 production. Blocking IL21 significantly downregulated IL17 production. CONCLUSIONS: Our findings support a role for IL12, TGFbeta and IL21 in modulating IL17/IFNgamma production in IBD. The abundant IL17 in inflamed IBD mucosa may help explain the relative lack of efficacy of anti-IFNgamma antibodies in clinical trials of Crohn's disease.

A molecular chaperone inducer protects neurons from ER stress.

The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases and cerebral ischemia. In a screen for compounds that induce the ER-mediated chaperone BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa glucose-regulated protein), we identified BiP inducer X (BIX). BIX preferentially induced BiP with slight inductions of GRP94 (94 kDa glucose-regulated protein), calreticulin, and C/EBP homologous protein. The induction of BiP mRNA by BIX was mediated by activation of ER stress response elements upstream of the BiP gene, through the ATF6 (activating transcription factor 6) pathway. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Considering these results together, it appears that BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress.