Serum autotaxin is a prognostic indicator of liver-related events in patients with non-alcoholic fatty liver disease.

BACKGROUND: Circulating autotaxin (ATX) levels have been reported to correlate with liver inflammation activity and liver fibrosis severity in patients with non-alcoholic fatty liver disease (NAFLD). The objective of this study is to investigate whether serum ATX could predict liver-related events (LRE) in NAFLD patients. METHODS: This retrospective investigation includes 309 biopsy-proven NAFLD patients registered at Shinshu University Hospital. All patients are followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, hepatic encephalopathy, ascites, and esophagogastric varices, is investigated in relation to ATX levels at the time of liver biopsy. RESULTS: During the median follow-up period of 7.0 years, LRE are observed in 20 patients (6.5%). The area under the receiver operating characteristic curve and cut-off value of serum ATX for predicting LRE are 0.81 and 1.227 mg/l, respectively. Multivariate Cox proportional hazards models for LRE determine ATX and advanced fibrosis as independently associated factors. Furthermore, in a competing risk analysis that considered non-liver-related death as a competing event, ATX (HR 2.29, 95% CI 1.22-4.30, p = 0.010) is identified as an independent factor associated with LRE, along with advanced fibrosis (HR 8.01, 95% CI 2.10-30.60, p = 0.002). The predictive utility of ATX for LRE is validated in an independent cohort. CONCLUSIONS: Serum ATX may serve as a predictive marker for LRE in patients with NAFLD.

In non-alcoholic fatty liver disease (NAFLD), fat accumulates and can cause damage within the liver. The disease is becoming increasingly common worldwide. It is therefore important to identify individuals with NAFLD who are at higher risk of developing severe liver complications. In this study, we found that NAFLD patients with elevated levels of a substance called autotaxin (ATX) in their blood were more prone to liver-related issues. Thus, it is crucial for doctors to give special attention to NAFLD patients exhibiting high ATX levels. Through close ATX monitoring and appropriate treatment, doctors can potentially enhance their health outcomes and prevent the onset of more severe liver complications.

Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis: A Decision Tree Approach.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers. MATERIALS AND METHODS: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 µg/g. The outcomes were then confirmed in a validation cohort of 26 patients. RESULTS: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort. CONCLUSIONS: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI.

Splenic artery pseudoaneurysm resulting from gastric ulcer presenting acute upper gastrointestinal bleeding.

Splenic artery pseudoaneurysm (SAP) is a rare entity, which occurs when the arterial wall is composed only of the intima and media mainly caused by pancreatitis, or abdominal trauma. Regardless of size, SAP is a high mortality disease that carries a high risk of rupture, causing abdominal pain and severe pancreatic and gastrointestinal bleeding. Here, we describe a rare case of SAP rupture caused by a large gastric ulcer due to Helicobacter pylori infection and NSAIDs use. Understanding the characteristic enhanced CT images of SAP, the complications of splenic infarction, and the therapeutic efficacy of arterial embolization is essential for the clinician to properly diagnose and treat SAP.

[A case of "colitis-like intestinal Behçet's disease" accompanied by ulcerative colitis after the development of myelodysplastic syndrome].

A 71-year-old man developed ulcerative colitis (UC) at 48 years of age. As a steroid-dependent case with poor UC control, the patient was treated with azathioprine, which resulted in clinical remission. However, a blood test revealed pancytopenia. Bone marrow examination confirmed the diagnosis of myelodysplastic syndrome (MDS). During the patient's clinical course, multiple round ulcers appeared in the terminal ileum. We suspected concomitant "colitis-like intestinal Behçet's disease" (BD). Treatment with adalimumab resolved the ulcers. To the best of our knowledge, this is a rare case of intestinal BD accompanying UC after MDS.

AC-Electroosmosis-Assisted Surface Plasmon Resonance Sensing for Enhancing Protein Signals with a Simple Kretschmann Configuration.

A surface plasmon resonance (SPR) sensor chip fabricated with a comb-shaped microelectrode array to supply alternating current (AC) voltage is reported. The chip induces circulating flow near the surface (i.e., AC electroosmosis). The circulating flow provides a mixing effect, which enhances the binding of the analyte molecules. We evaluated the SPR characteristics of the chip and demonstrated an improvement in protein binding to the chip surface. SPR sensor chips with comb-shaped microelectrodes were fabricated using standard UV lithography. Sensing experiments were conducted using a standard Kretschmann-type SPR measurement system. To demonstrate the mixing effect of AC electroosmosis, we evaluated the binding of immunoglobulin G molecules onto the sensor surface where anti-immunoglobulin G antibodies were covalently immobilized. The result indicates that the amount of binding increases by a factor of 1.7 above that achieved by using a conventional chip, suggesting enhancement of the protein signal.

[A Case of Histological Response of Grade 3 Achieved by Preoperative Chemotherapy with S-1/Oxaliplatin(SOX)].

Histological response of Grade 3 is relatively rare in gastric cancer patients but has recently been observed occasionally. We report the histological response of Grade 3 achieved by S-1/oxaliplatin(SOX)therapy. A 66-year-old man had suffered from epigastralgia when hungry. After 1 month, he visited the department of gastroenterology of our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor at the lesser curvature of middle gastric body, and poorly differentiated adenocarcinoma was detected by the biopsy examination. Abdominal/pelvic enhanced CT showed wall thickening of the lower gastric body, enlarged regional lymph nodes and para-aortic lymph nodes(No. 16b1). We diagnosed it with Stage Ⅳ. He received 4 courses of SOX therapy. After chemotherapy, upper gastrointestinal endoscopy revealed a residual tumor, although biopsy showed no cancer cells. Abdominal/pelvic enhanced CT showed significantly reduced lymph nodes despite the thickening of the gastric wall. PET-CT revealed indistinct para-aortic lymph nodes. Distal gastrectomy, D2 dissection without para-aortic lymph nodes dissection, and Billroth Ⅰ reconstruction were performed. Histological findings showed no cancer cells in the main lesion or lymph nodes, with only previous cancer cells suspected. The histological response was Grade 3. SOX therapy might be employed in the future as chemotherapy before conversion surgery for Stage Ⅳ gastric cancer.

[A Case of Percutaneous Transhepatic Duodenal Drainage for Duodenal Stump Suture Failure after Gastrectomy].

79-year-old man underwent laparoscopic distal gastrectomy with early gastric cancer 0-Ⅱc lesion on the greater curvature side of the lower body of the gastric body on gastric cancer screening. On the 10th day after the operation, abdominal pain and fever were observed, and CT revealed suture failure and intra-abdominal abscess. Partial gastrectomy and Roux- en-Y reconstruction were performed in emergency surgery, but duodenal stump suture failure was observed on the third day of reoperation. For duodenal stump suture failure, a catheter was placed in the duodenum by applying PTCD technology, and drainage of the bile duct and duodenal contents was performed, and conservative healing was successful. Duodenal stump suture failure after Roux-en-Y reconstruction is intractable and can sometimes result in death with severe infection and intra-abdominal hemorrhage. Here, we report a case in which duodenal stump suture failure was completely cured by percutaneous transhepatic duodenal drainage, with some literary consideration.

Neuromuscular activation of the knee and hip extensor muscles during high-intensity interval and moderate-intensity constant cycling.

We aimed to test the hypothesis that the magnitude of differences in muscle activation of the knee and hip extensor muscles between high-intensity interval exercise (HIE) and moderate-intensity constant exercise (CE) would be greater for the gluteus maximus than for the quadriceps femoris muscle. Participants were 11 male middle- or long-distance runners. The HIE (4 sets, 4-min induration, performed at 80-85%VO2peak and followed by a 3-min period of cycling at < 30%VO2peak) and CE (28-min, performed at or near 60%VO2peak) were completed on different days, with the total exercise duration and work being identical for both protocols. Surface electromyography (EMG) was recorded from the following muscles: vastus lateralis, vastus medialis, rectus femoris, gluteus maximus, and biceps femoris. The EMG amplitude, normalised over a period of 28 min for both protocols, was significantly greater during HIE than during CE for the gluteus maximus (HIE: 43 ±â€¯4% versus CE: 24 ±â€¯7%) and rectus femoris (HIE: 62 ±â€¯23% versus CE: 47 ±â€¯18%), but had no effect of the exercise protocol on the EMG amplitude of other muscles. These findings indicate that the relative contribution of the gluteus maximus and rectus femoris to the cycling movement can be enhanced using a HIE protocol, in middle- and long-distance runners.

[Two Cases of Goblet Cell Carcinoid of Appendix Treated with Oxaliplatin-Based Adjuvant Chemotherapy].

Although there are reports of goblet cell carcinoid(GCC)treated by chemotherapy using the treatment protocol for colon cancer, the benefit of chemotherapy for GCC remains controversial and unclear. Herein we report 2 cases of patients with GCC who were successfully treated by surgical resection and oxaliplatin-based adjuvant chemotherapy, without evidence of recurrence. The first case was a 57-year-old man who underwent laparoscopic ileocecal resection after being diagnosed with adenocarcinoma of the appendix by biopsy via colonoscopy. Pathological and immunohistochemical analyses demonstrated the presence of signet-ring-like cells, chromogranin A-positive and synaptophysin-positive cells, leading to a diagnosis of GCC of the appendix. Folinic acid, fluorouracil, oxaliplatin(FOLFOX)was administered for 6 months as an adjuvant chemotherapy. The patient has shown no signs of systematic metastasis and has been alive for more than 3 years after the operation. The second case was a 41-year-old woman who presented to our hospital complaining of lower abdominal pain starting 2 months previously. A computed tomography(CT)scan indicated a pelvic tumor, and she underwent ileocecal resection and hystero-oophorectomy due to an appendix tumor and an ovarian metastatic tumor. Pathological and immunohistochemical analyses demonstrated the presence of signet-ring-like cells, chromogranin A-positive, and synaptophysin-positive cells, confirming the diagnosis of GCC of the appendix. The patient received capecitabine and oxaliplatin(CapeOX)as an adjuvant chemotherapy for 6 months. The patient has been free from recurrence for 22 months following surgery.

Effects of 10-week walking and walking with home-based resistance training on muscle quality, muscle size, and physical functional tests in healthy older individuals.

BACKGROUND: Older individuals have been shown to present muscle atrophy in conjunction with increased fat fraction in some muscles. The proportion of fat and connective tissue within the skeletal muscle can be estimated from axial B-mode ultrasound images using echo intensity (EI). EI was used to calculate the index of muscle quality. Walking, home-based weight-bearing resistance training, and its combinations are considered simple, easy, and practical exercise interventions for older adults. The purpose of this study was to quantify the effects of walking and walking with home-based resistance training on muscle quality of older individuals. METHODS: Thirty-one participants performed walking training only (W-group; 72 ± 5 years) and 33 participants performed walking and home-based resistance training (WR-group; 73 ± 6 years). This study was a non-randomized controlled trial with no control group. All participants were instructed to walk 2 or 3 sets per week for 10 weeks (one set: 30-min continuous walking). In addition, the WR-group performed home-based weight-bearing resistance training. EI was measured as a muscle quality index using axial B-mode ultrasound images of the rectus femoris and vastus lateralis of the mid-thigh. We further averaged these parameters to obtain the EI of the quadriceps femoris (QF). Participants further performed five functional tests: sit-ups, supine up, sit-to-stand, 5-m maximal walk, and 6-min walk. RESULTS: QF EI was significantly decreased in both groups after training (W-group 69.9 ± 7.4 a.u. to 61.7 ± 7.0 a.u., WR-group 64.0 ± 9.5 a.u. to 51.1 ± 10.0 a.u.; P < 0.05), suggesting improved muscle quality. QF EI was further decreased in the WR-group compared with the W-group. The sit-up test in both groups and the sit-to-stand and 5-m maximal walk tests in the W-group were significantly improved after training. CONCLUSION: These results suggest that training-induced stimulation is associated with a decrease in EI in some thigh regions. Furthermore, the addition of home-based resistance training to walking would be effective for a greater reduction of EI.

Relationship between quadriceps echo intensity and functional and morphological characteristics in older men and women.

The age-related decrease in human skeletal muscle mass; i.e. sarcopenia, has received much attention, but an age-related increase in the ratio of adipose tissue to muscle tissue has received noticeably less. A few studies have shown that ultrasonographic echo intensity, an index of the adipose-to-muscle ratio, is negatively associated with functional capacity, but the best parameters by which to predict this ratio have not yet been established for older individuals. The purpose of this study was to assess the relationships between quadriceps femoris (QF) echo intensity and demographic, functional and morphological characteristics of older men and women. Sixty-four healthy men (n=27) and women (n=37) aged 62-88 years (72.0±5.0years) participated in this study. The echo intensity and muscle thickness of the QF were calculated using ultrasonography. Sit-up, supine-up, sit-to-stand, 5-m maximal walk and 6-min walk tests were performed. There were no significant differences in QF echo intensity between sexes, but QF echo intensity was significantly correlated with QF muscle thickness. Stepwise multiple regression analysis with QF echo intensity as a dependent variable revealed QF muscle thickness, sit-to-stand test in men and age, and QF muscle thickness and sit-to-stand test in women, to be significant variables. These results suggest that QF echo intensity can be explained by QF muscle thickness, sit-to-stand and/or age in older men and women; however, an "age" effect was present only in men.

[A case of long remission for about 5 years as an outpatient with second-line chemotherapy of weekly PTX after palliative distal gastrectomy for pStage IV advanced gastric cancer].

A 59-year-old man underwent palliative distal gastrectomy for Stage IV advanced gastric cancer with cytological and histopathological peritoneal dissemination. After surgery, he began to receive chemotherapy by S-1 oral administration as an outpatient. About one year and 9 months after surgery, cartinomatous peritonitis grew, and severe obstruction of gastrojejunostomy and dilatation of residual stomach were detected by CT tomography. Then, second-line chemotherapy by weekly paclitaxel(PTX)was started. After one course of weekly PTX was completed, he was feeling better gradually with obvious improvement of carcinomatous peritonitis, which was revealed by sequential CT tomography examinations. Weekly PTX chemotherapy has been continued successfully for 43 courses, and he remains alive today with a good QOL, about 5 years after surgery. He is an outpatient with only a grade 2 or less complication of peripheral neuropathy.

A synthetic strategy for a new series of oxo-centered tricobalt complexes with mixed bridging ligands of acetate and pyrazolate anions.

A new series of oxo-centered tricobalt(III, III, III) complexes, containing mixed bridges of acetate and pyrazolate anions, has been synthesized based on a strategy consisting of two stages. In the first stage, the reaction of cobalt(II) acetate tetrahydrate with pyrazole in the presence of oxidants, followed by purification with silica-gel column chromatography, afforded six tricobalt complexes: [Co(3)O(µ-OAc)(5)(µ-pz)(Hpz)(3)](PF(6)) (mono), two isomers of [Co(3)O(µ-OAc)(4)(µ-pz)(2)(Hpz)(3)](PF(6)) (bis-1 and bis-2), two isomers of [Co(3)O(µ-OAc)(3)(µ-pz)(3)(Hpz)(3)](PF(6)) (tris-2 and tris-3), and one isomer of [Co(3)O(µ-OAc)(2)(µ-pz)(4)(Hpz)(3)](PF(6)) (tetra-1). In the second stage, substitution reactions have been examined for the complexes obtained in the first stage. As a result, one acetate bridge in bis-1, bis-2, and tris-3 could be substituted with one pyrazolate site-selectively. Bis-1, bis-2, and tris-3 were converted to another isomer of [Co(3)O(µ-OAc)(3)(µ-pz)(3)(Hpz)(3)](PF(6)) (tris-1), tris-2, and tetra-1, respectively. Single-crystal X-ray diffraction studies found that in every complex acetato and pyrazolato work as bridging ligands, while pyrazole (Hpz) acts as a terminal ligand. Moreover, the electrochemical properties of the seven new tricobalt complexes (mono, bis-1, bis-2, tris-1, tris-2, tris-3, and tetra-1) were investigated by cyclic voltammetry and it was found that (1) each complex shows reversible redox behaviour corresponding to the Co(III)Co(III)Co(III)/Co(III)Co(III)Co(IV) couple and (2) the redox potential decreases from 1.21 V vs. Fc/Fc(+) in mono to 1.09 V vs. Fc/Fc(+) in tetra-1, as the number of pyrazolate bridges increases.

Protective effect of colored rice over white rice on Fenton reaction-based renal lipid peroxidation in rats.

Rice has been one of the most important grains. While polished white rice is favored, colored strains of rice, red, or black, have been maintained for religious purposes in Japan. We studied whether feeding of unpolished colored rice instead of white rice ameliorates oxidative renal tubular damage in rats induced by ferric nitrilotriacetate. Whereas renal lipid peroxidation was exacerbated in white rice-fed group in comparison with standard chow group, this exacerbation was not observed in red or black rice-fed groups. These changes were dependent on the proportion of colored rice to standard chow in the diet. Cyanidin 3-O-beta-D-glucoside was detectable neither in the serum nor kidney after one week of colored rice diet, but serum protocatechuic acid was significantly increased after black rice diet. There was a generalized decrease in the renal glutathione peroxidase activity in rice diet groups. Renal enzymatic activities of superoxide dismutase, glutathione S-transferase and NAD(P)H quinone reductase were not associated with the levels of lipid peroxidation. However, renal catalase activity was significantly increased in black rice-fed groups. These may partly explain the antioxidative effect. Furthermore, colored strains of rice are rich in proteins. Thus, our data warrants further investigation of the antioxidative effect of colored rice.

Intramuscular metastasis from gastric cancer.

Skeletal muscle is an uncommon site of hematogenous metastasis of gastric carcinoma. We report here a rare case of gastric carcinoma with multiple intramuscular metastases. Our patient had advanced gastric carcinoma and complained of left gluteal induration with tenderness. Because magnetic resonance imaging (MRI) revealed that the gluteal tumor showed iso-signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with reticulated texture around the tumor, and the patient had advanced gastric carcinoma, we speculated that the tumor was an intramuscular metastatic tumor from primary gastric carcinoma. There were also multiple intramuscular metastatic lesions in both gluteal muscles on the MRI findings that were not detected by physical examination. Therefore, the patient underwent total gastrectomy with combined resection of spleen, with subsequent chemotherapy. Three months after the operation, we excised the gluteal tumor to alleviate the gluteal pain. Histological examinations confirmed that the gluteal tumor was a metastasis from primary gastric carcinoma.

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver.

3-Nitrotyrosine (3-NT), a product of peroxynitrite reaction, is abundantly observed in hepatocytes adjacent to human metastatic colorectal carcinoma. To elucidate its biological significance, we undertook to identify nitric oxide (NO)-producing cells and apoptosis under oxidative stress. We observed strong inducible NO-synthase (iNOS) immunoreactivity in the hepatocytes adjacent to metastatic tumor, revealing an identical pattern to 3-NT immunostaining. Furthermore, intense 3-NT immunostaining of hepatocytes was associated with apoptosis whereas carcinoma cells near those hepatocytes presented high proliferating-cell nuclear antigen. Our results suggest that contact of metastatic tumor induces apoptosis in adjacent hepatocytes through peroxynitrite, thus permitting the proliferation of cancer cells.

Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis.

There is no doubt that oxidative stress occurs in patients with rheumatoid arthritis (RA) and play an important role in both inflammation and destruction of RA joints. Thioredoxin (TRX) is a ubiquitous redox-active protein and is known to be induced in several cells against oxidative stress and to be secreted extracellularly. To clarify whether plasma thioredoxin levels could be a marker for oxidative stress in patients with RA, we measured plasma TRX levels in patients with RA using a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) and investigated its relationship to TRX concentrations in the inflammatory joints. We have found that the plasma TRX levels of RA patients were significantly higher than those of normal subjects (86.8 +/-54.1 ng/ml versus 38.6 +/-18.5 ng/ml, P<0.0001). The plasma levels were correlated with the disease activity of RA and also with serum C-reactive protein (CRP) values (P<0.01). The concentration of TRX in synovial fluid (SF) from RA was 353.3 +/- 220.1 ng/ml (mean +/- S.D.) which was significantly higher than that in SF from osteoarthritis patients (70.6 +/- 31.0 ng/ml, P<0.0001). The SF TRX concentration was significantly correlated with the number of leukocytes infiltrating in SF and with the serum CRP levels. The serum TRX levels were significantly positively correlated with the SF TRX concentrations in RA patients (P<0.05). By the histological examination for synovial tissue of RA patients, TRX was shown to be present on the surface of synovial lining layer as well as in the leukocytes.Moreover, urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage by endogenously generated oxygen radicals, was significantly higher in RA patients than in healthy subjects (11.55 +/- 4.71 versus 7.76 +/- 2.26 ng/mg creatinine, P<0.0001). Plasma TRX levels were significantly correlated with urinary excretion of 8-OHdG (P<0.005). We concluded that plasma TRX level is a new biomarker for the disease activity of RA and may reflect higher levels of oxidative stress in RA patients.