Marked Hypertriglyceridemia in a Patient with type 2 Diabetes Receiving SGLT2 Inhibitors.

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis.

A New Hepatitis Virus Test with Microliter-scale Fingertip Blood Collection in Japan.

We investigated whether a small amount of blood collected by fingertip blood sampling would be adequate in a mass examination for hepatitis virus infection in Japan. A cross-sectional survey was conducted at health fairs in Kasaoka City and Shodoshima Island, where participants took the hepatitis screening test. A total of 114 consecutive individuals who took the hepatitis screening test were enrolled. Twenty microliters of plasma was successfully obtained from all participants. Among the participants, two had positive results for HBs antigen and two were positive for anti-HCV; all four were > 60 years old and rarely visited the hospital. Thirty-three and 38 patients chronically infected with HBV and HCV, respectively, were examined for confirmatory assays at participating hospitals. All subjects with undetectable serum levels of HBs antigen and anti-HCV had undetectable levels of both markers in fingertip blood, and the levels in serum and fingertip blood were significantly correlated (p<0.01). The lower detection limit of HBs antigen was defined as 0.005 IU/ml, and the cut-off value of anti-HCV was 1.0 by using 10-µl fingertip blood samples. The fingertip blood sampling described herein may be adequate in mass examinations for hepatitis virus testing in Japan.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Correction: Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55.

[This corrects the article DOI: 10.1007/s13340-023-00623-3.].

Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55.

Introduction: To investigate changes in insulin requirements over time in patients who underwent hepatectomy and pancreatectomy with perioperative glycemic control by an artificial pancreas (STG-55). Materials and methods: We included 56 patients (22 hepatectomies and 34 pancreatectomies) who were treated with an artificial pancreas in the perioperative period and investigated the differences in insulin requirements by organ and surgical procedure. Results: The mean intraoperative blood glucose level and total insulin doses were higher in the hepatectomy group than in the pancreatectomy group. The dose of insulin infusion increased in hepatectomy, especially early in surgery, compared to pancreatectomy. In the hepatectomy group, there was a significant correlation between the total intraoperative insulin dose and Pringle time, and in all cases, there was a correlation with surgical time, bleeding volume, preoperative CPR, preoperative TDD, and weight. Conclusions: Perioperative insulin requirements may be mainly dependent on the surgical procedure, invasiveness, and organ. Preoperative prediction of insulin requirements for each surgical procedure contributes to good perioperative glycemic control and improvement of postoperative outcomes.

Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation.

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma.

Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC). Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44). Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated. Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging. Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

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 ß-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 ß-oxidation and redox system.