The liver constantly encounters food‐derived antigens and bacterial components such as lipopolysaccharide translocated from the gut into the portal vein. Bacterial components stimulate Toll‐like ...receptors (TLR), which are expressed on Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells, endothelial cells and dendritic cells and recognize specific pathogen‐associated molecular patterns. The signaling of TLR to its main ligand triggers inflammation. Usually, in order to protect against hyperactivation of the immune system and to prevent organ failure by persistent inflammation, TLR tolerance to repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural killer T cells are key components of innate immunity. Decreased numbers and impaired ability of these cells lead to failures in immune tolerance, resulting in persistent inflammation. Recently, the activation of inflammasome was revealed to control the secretion of pro‐inflammatory cytokines such as interleukin‐1β in response to bacterial pathogens. Innate immunity seems to be an important contributor to the pathogenesis of fatty liver disease and autoimmune liver disease. Recently, probiotics were reported to affect various liver diseases via shifts in gut microbiota and the stability of intestinal permeability. However, many unresolved questions remain. Further analysis will be needed to gain a more comprehensive understanding of the association of innate immunity with the pathogenesis of various liver diseases.
OGATA Koan (1810–63) was a physician and the director of Tekijuku, and he contributed to Western medicine in the late Edo period. Osaka University preserves two of his medicine chests. One of the ...chests, which was used in his last years (the second chest) contained 22 glass bottles and 6 wooden cylinders. These bottles and cylinders contained formulated medicines; however, about half cannot be opened because of the long-term storage. It is necessary to comprehend the physical property of both the containers and their contents for investigation of this adequate preservation method; however, destructive analysis is not allowed. To analyze the medicines sealed in the glass bottles, we focused on muonic X-ray analysis, which has high transmittance. First, we certified the analytical methods using a historical medicinal specimen preserved in Osaka University. Thereafter, we applied the method on the bottles stored in the second chest. X-ray fluorescence identified the glass of those bottles to be lead potash glass. Among these bottles, we chose the bottle with the label “甘,” which contains white powdered medication, for muonic X-ray analysis. We identified the contents of the medication in the glass to be Hg
2
Cl
2
. Through this study, we first applied muonic X-ray analysis on the medical inheritances and succeeded to detect the elements contained both in the container and in the contents of the sealed bottle. This would be a new method for nondestructive analysis of such cultural properties.
Graphic abstract
Elemental analysis based on muonic X-rays resulting from muon irradiation provides information about bulk material composition without causing damage, which is essential in the case of precious or ...otherwise unreachable samples, such as in archeology and planetary science. We developed a three-dimensional (3D) elemental analysis technique by combining the elemental analysis method based on negative muons with an imaging cadmium telluride double-sided strip detector (CdTe-DSD) designed for the hard X-ray and soft Formula: see text-ray observation. A muon irradiation experiment using spherical plastic samples was conducted at the Japan Proton Accelerator Research Complex (J-PARC); a set of projection images was taken by the CdTe-DSD, equipped with a pinhole collimator, for different sample rotation angles. The projection images measured by the CdTe-DSD were utilized to obtain a 3D volumetric phantom by using the maximum likelihood expectation maximization algorithm. The reconstructed phantom successfully revealed the 3D distribution of carbon in the bulk samples and the stopping depth of the muons. This result demonstrated the feasibility of the proposed non-destructive 3D elemental analysis method for bulk material analysis based on muonic X-rays.
Metallic Li deposited on the anode is known to induce short circuiting and degradation of the charge capacity of Li-ion batteries. However, no reliable technique is currently available to observe ...such Li metal without removing the case of the battery. An elemental analysis using muonic X-rays is proposed here because of its unique properties of nondestructive measurement, high sensitivity to light elements, and depth resolution. We demonstrated that this technique can be applied to detection of Li deposited on the surface of an anode containing Li ions, using a fully charged anode with Li deposited due to overcharge in an Al-laminated plastic pouch. The basis for the detection method is the difference in the atomic Coulomb capture ratio of the negative muons between the Li metal and ions. We have found, as a result, that the intensity of the muonic X-rays from metallic Li was approximately 50 times higher than that from Li ions. Consequently, the Li metal on the anode was clearly distinguishable from the intercalated Li ions in the anode. Furthermore, measurements of two overcharged anodes with 1.3 and 2.7 mg of metallic Li deposition, respectively, indicated that this technique is suitable for quantitative analysis. Distribution analysis is also possible, as shown by a preliminary observation on an overcharged anode from the back side. Therefore, this technique offers a new approach to the analysis of Li deposited on the anode of a Li-ion pouch battery.
Background
Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III ...trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without
Goshajinkigan
(GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG’s potential for reducing peripheral neuropathy in patients with colorectal cancer.
Methods
Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
Findings
An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908;
p
= 0.007).
Conclusion
Goshajinkigan
did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.
Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic ...reactive oxygen species. In this study, we investigated the effects of hydrogen‐rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine‐choline–deficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen‐rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor‐α, interleukin‐6, fatty acid synthesis–related genes, oxidative stress biomarker 8‐hydroxydeoxyguanosine (8‐OHdG), and apoptosis marker terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling (TUNEL)–positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator‐activated receptor‐α expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH‐related hepatocarcinogenesis model. Eight‐week‐old male STAM mice were divided into three experimental groups as follows: (1) control water (CW‐STAM); (2) hydrogen‐rich water (HW‐STAM); and (3) pioglitazone (PGZ‐STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW‐STAM and PGZ‐STAM groups than in the CW‐STAM group. The maximum tumor size was smaller in the HW‐STAM group than in the other groups. Conclusion: Consumption of hydrogen‐rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912–921)
Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for ...progression to cirrhosis and hepatocellular carcinoma (HCC). Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid), an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1) high-fat diet (HFD) (control group); 2) HFD mixed with 0.28% L-carnitine (L-carnitine group); and 3) HFD mixed with 0.01% α-tocopherol (α-tocopherol group). After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by upregulating the mitochondrial β-oxidation and redox system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The amount of C in steel, which is critical in determining its properties, is strongly influenced by steel production technology. We propose a novel method of quantifying the bulk C content in steel ...non-destructively using muons. This revolutionary method may be used not only in the quality control of steel in production, but also in analyzing precious steel archaeological artifacts. A negatively charged muon forms an atomic system owing to its negative charge, and is finally absorbed into the nucleus or decays to an electron. The lifetimes of muons differ significantly, depending on whether they are trapped by Fe or C atoms, and identifying the elemental content at the muon stoppage position is possible via muon lifetime measurements. The relationship between the muon capture probabilities of C/Fe and the elemental content of C exhibits a good linearity, and the C content in the steel may be quantitatively determined via muon lifetime measurements. Furthermore, by controlling the incident energies of the muons, they may be stopped in each layer of a stacked sample consisting of three types of steel plates with thicknesses of 0.5 mm, and we successfully determined the C contents in the range 0.20-1.03 wt% depth-selectively, without sample destruction.
Purpose
The aim of this multi-institutional study was to prospectively evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) protocol for colonic surgery.
Methods
The subjects ...of this study were 320 patients with an American Society of Anesthesiologists (ASA) grade I or II physical status. Patients underwent elective open or laparoscopic colonic resection or high anterior resection between April 2011 and January 2014 at one of six institutions. Three hospitals implemented an ERAS protocol (
n
= 159), and three administered conventional care (
n
= 161). The primary outcome measure was the surgical complication rate.
Results
Most operations, irrespective of group, were performed laparoscopically. The incidence of a surgical complication was 17.0 % in the ERAS group vs. 16.1 % in the conventional group (
P
= 0.842), in which several non-surgical complications also arose. Oral food intake was implemented earlier for the ERAS group vs. the conventional group, after a median (range) of 1 (1–31) vs. 3 (1–9) days for the ERAS vs. conventional care groups, respectively (
P
< 0.001). The median length of postoperative hospital stay was reduced by 5.5 days for the ERAS group, being 8.5 (5–41) vs. 14 (7–56) days for the ERAS vs. conventional care groups, respectively (
P
< 0.001).
Conclusion
This multi-institutional controlled study clearly demonstrated that an ERAS protocol was efficient, without increasing the complication risk.
A novel nondestructive light element analysis method for bulk materials using muon beams was demonstrated. This method is based on the lifetime measurement of muons in a material and performed by ...measuring muon-decay electrons and identifying elements using the atomic number based on muon lifetimes. Muon irradiation on pure iron and two steel samples with known carbon contents was conducted to prepare a calibration curve for the quantitative analysis. We also performed a muon lifetime measurement for a Japanese sword and successfully determined its carbon content as 0.51 wt% using the calibration curve, without sample destruction.
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