12(S)-hydroxyheptadeca-5Z, 8E, 10E–trienoic acid is a natural ligand for leukotriene B4 receptor 2

Activated blood platelets and macrophages metabolize prostaglandin H2 into thromboxane A2 and 12(S)-hydroxyheptadeca-5Z, 8E, 10E–trienoic acid (12-HHT) in an equimolar ratio through the action of thromboxane synthase. Although it has been shown that 12-HHT is abundant in tissues and bodily fluids, this compound has long been viewed as a by-product lacking any specific function. We show that 12-HHT is a natural ligand for leukotriene B4 (LTB4) receptor-2 (BLT2), a G protein–coupled receptor that was originally identified as a low-affinity receptor for LTB4. BLT2 agonistic activity in lipid fractions from rat small intestine was identified as 12-HHT using high-performance liquid chromatography and mass spectrometry. Exogenously expressed BLT2 in mammalian cells was activated by synthetic 12-HHT, as assessed by guanosine 5′-O-(3-thio) triphosphate binding, the activation of intracellular signaling pathways, and chemotaxis assay. Displacement analysis using [3H]LTB4 showed that 12-HHT binds to BLT2 with a higher affinity than LTB4. Lipid extracts from cyclooxygenase 1–deficient mice failed to activate BLT2. Bone marrow–derived mast cells (BMMCs) isolated from wild-type mice migrated toward a low concentration of 12-HHT, whereas BMMCs from BLT2-deficient mice did not. We conclude that 12-HHT is a natural lipid agonist of BLT2 in vivo and induces chemotaxis of mast cells

A Case of Ischemic Colonic Stenosis of the Splenic Flexure

Ischemic colitis is characterized by lesions arising from colonic ischemia. The treatment of choice is surgery, and resection of the affected segment is often life saving. This study presents a case of segmental ischemic colonic stenosis of the splenic flexure. A 70-year-old woman was admitted to our hospital with abdominal pain and distension. Physical examination revealed mild tenderness of the left-upper abdomen but no peritoneal signs. A computed tomography scan demonstrated a thickening of the splenic flexure of the colon with active inflammation. A gastrografin enema revealed a 5-cm-long tight stricture at the left transverse colon, which suggested a subileus. Surgery for segmental ischemic colonic stenosis was performed because the stricture did not respond to treatment. Pathological examination revealed features typical of ischemic colitis, including ulceration and segmental colonic stenosis of the splenic flexure, but revealed no evidence of tumors, lymph node swelling, or vascular disorder

Anastomotic Recurrence due to Tumor Implantation using the Double Stapling Technique after Curative Surgery for Sigmoid Colon Cancer

Recurrence at the site of a stapled anastomosis is generally believed to result from the luminal implantation of viable cancer cells during stapling. We report a 57-year-old woman who underwent radical surgery for sigmoid colon cancer and developed anastomotic recurrence ten months after the initial operation. Her serum carcinoembryonic antigen (CEA) levels were within normal limits during the postoperative follow-up. The patient subsequently underwent a partial colon resection for the anastomotic recurrence. The clinicopathological findings revealed that possible tumor cell implantation caused the recurrence. We encountered a case of anastomotic recurrence due to possible tumor implantation after curative surgery for sigmoid colon cancer. Follow-up colonoscopy was more helpful for the diagnosis of anastomotic recurrence than CEA monitoring

Case Report of a Crohn\u27s Disease (CD) Patient with Anastomotic Stenosis Unrelated to Postoperative Recurrence of CD

Crohn\u27s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. It frequently involves the ileum, colon, and anorectum. A 66-year-old man with CD had undergone a partial intestinal resection of the ileum for CD 27 years previously, and had been hospitalized several times, including two months prior to referral. The patient was admitted to our hospital with abdominal pain and distension. A computed tomography (CT) scan demonstrated an anastomotic stenosis with active inflammation and proximal intestinal extension. Colonoscopic examination revealed no abnormalities in the colon or rectum. A contrast Gastrografin enema revealed a stenosis in the ileum and a tight stricture at 3 cm with inflammation. We performed an ileocecal resection for an anastomotic stenosis due to possible recurrence of CD. Pathological examination showed no evidence of CD activity at the anastomotic region, indicating no recurrence of CD

Peroxisome proliferator-activated receptor α (PPARα) mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer.</p> <p>Methods</p> <p>The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system.</p> <p>Results</p> <p>The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections.</p> <p>Conclusion</p> <p>The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.</p

Influence of the combination of SGLT2 inhibitors and GLP-1 receptor agonists on eGFR decline in type 2 diabetes: post-hoc analysis of RECAP study

Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this post hoc analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group, n = 331; SGLT2i-preceding group, n = 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: −3.5 ± 9.4 mL/min/1.73 m2/year, post: −0.4 ± 6.3 mL/min/1.73 m2/year, p &lt; 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: −2.0 ± 10.9 mL/min/1.73 m2/year, post: −1.8 ± 5.4 mL/min/1.73 m2/year, p = 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits—especially annual eGFR decline—of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug

Method to Minimize Power Peaking in Refueling Schedule of Boiling Water Reactor

A method of optimizing fuel assembly allocation is proposed for a certain type of refueling schedule problem of Boiling Water Reactor (BWRJ in which cycle length and number of fresh fuel assemblies to be loaded are predetermined. The optimization is aimed at minimizing power peaking factor. The problem is decomposed into two subproblems: one to optimize the global region-wise shuffling scheme and the other to optimize assembly allocation. Linear programming is iteratively solved in the former subproblem such that the maximum excess reactivity is minimized and a direct search method is used in the latter subproblem. The method is successfully applied to the 2nd and the 3rd cycle refueling schedule problems of a 460 MWe BWR. The optimized reloading patterns are compared with other non-optimal patterns which have much simpler or more symmetrical shuffi ing schemes. The optimization shows merit in reducing power peaking without sacrificing the cycle length.

Impact of acute cholecystitis comorbidity on prognosis after surgery for gallbladder cancer: a propensity score analysis

Abstract Background Cholecystitis can represent a comorbidity during gallbladder cancer surgery; nonetheless, the prognostic impact of acute cholecystitis comorbidity remains unclear. This study aimed to evaluate the impact of acute cholecystitis comorbidity on prognosis after gallbladder cancer surgery, with adjustment for background factors using propensity score analysis. Methods A total of 218 patients who underwent gallbladder cancer surgery at our institute between 1986 and 2022 were retrospectively included in the analysis. Patients were divided into two groups according to the presence or absence of acute cholecystitis at the time of surgery. Background factors were adjusted by including intraoperative bile leakage as a covariate in propensity score calculation. Overall survival and recurrence-free survival were compared between the two groups using one-to-one propensity score matching and inverse probability weighting. Results Of the 218 patients, 37 had coexisting acute cholecystitis. In one-to-one propensity score matching, the overall survival time in the acute cholecystitis group tended to be shorter than that in the non-acute cholecystitis group, although not significantly (hazard ratio, 2.41; 95% confidence interval, 0.96–6.06). Other analyses using inverse probability weighting showed significantly poor overall survival in the acute cholecystitis group. Regarding recurrence-free survival in propensity score matching, the acute cholecystitis group showed a significantly shorter duration than the non-acute cholecystitis group (hazard ratio, 6.69; 95% confidence interval, 1.46–30.6). The inverse probability weighting-adjusted analysis also indicated a significantly higher risk of recurrence in the acute cholecystitis group. Conclusions Acute cholecystitis comorbidity at the time of gallbladder cancer surgery may have a negative impact on gallbladder cancer prognosis