Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.     

18F-FDG PET/CT for monitoring anti-PD-1 therapy in patients with non-small cell lung cancer using SUV harmonization of results obtained with various types of PET/CT scanners used at different centers

Annals of Nuclear Medicine - The prognostic value of treatment response in patients with non-small cell lung cancer (NSCLC) treated with immune-checkpoint inhibitors (ICIs) shown by...     

Serum asymmetric dimethylarginine levels are independently associated with procollagen III N-terminal peptide in nonalcoholic fatty liver disease patients

Although impaired synthesis and/or bioavailability of nitric oxide are considered to contribute to insulin resistance and the progression of liver disease in nonalcoholic fatty liver disease, role of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, has not been examined. We examined retrospectively which anthropometric and metabolic parameters were independently associated with serum levels of asymmetric dimethylarginine in nonalcoholic fatty liver disease. A total of 194 consecutive biopsy-proven nonalcoholic fatty liver disease patients with or without type 2 diabetes were enrolled. Serum asymmetric dimethylarginine levels in nonalcoholic fatty liver disease patients were significantly higher, irrespective of the presence or absence of diabetes, than those in healthy control. Multiple stepwise regression analysis showed that decreased total protein and procollagen N-terminal peptide levels, markers of advanced liver disease and hepatic fibrosis, respectively, were independently associated with asymmetric dimethylarginine levels in nonalcoholic fatty liver disease subjects without diabetes, whereas soluble form of receptor for advanced glycation end products and density ratio of liver to spleen in computed tomography were independent correlates of asymmetric dimethylarginine in diabetic patients. The present study suggests that asymmetric dimethylarginine may be associated with nonalcoholic fatty liver disease, especially subjects without diabetes.     

Adoptive transfer of antithyrotropin receptor (TSHR) autoimmunity from TSHR knockout mice to athymic nude mice

We have recently shown that wild type mice are highly tolerant, whereas thyrotropin receptor (TSHR) knockout (KO) mice are susceptible to immunization with the mouse TSHR, the autoantigen in Graves' disease. However, because TSHR KO mice lack the endogenous TSHR, Graves-like hyperthyroidism cannot be expected to occur in these mice. We therefore performed adoptive transfer of splenocytes from TSHR KO mice into nude mice expressing the endogenous TSHR. Anti-TSHR autoantibodies were detected in approximately 50 % recipient mice 4 wk after adoptive transfer of splenocytes (5 × 10?/mouse) from TSHR KO mice immunized with adenovirus expressing mTSHR A subunit and persisted for 24 wk. Depletion of regulatory T cells by anti-CD25 antibody in the donor mice increased successful transfer rates without increasing antibody levels. Some recipient mice showed transient increases in thyroid-stimulating antibodies and T? levels 4-8 wk after transfer, but many became thyroid-blocking antibody positive and hypothyroid 24 wk later. Adoptive transfer of splenocytes from na?ve TSHR KO mice transiently induced very low antibody titers when the recipient mice were treated with anticytotoxic lymphocyte antigen 4 and antiprogrammed cell death 1 ligand 1 antibodies for 8 wk after transfer. Histologically, macrophages infiltrated the retrobulbar adipose tissues and extraocular muscles in a small fraction of the recipients. Our findings demonstrate successful adoptive transfer of anti-TSHR immune response from TSHR KO mice to nude mice. Although the recipient mice developed only transient and infrequent hyperthyroidism, followed by eventual hypothyroidism, induction of orbital inflammation suggests the possible role of anti-TSHR immune response for Graves' orbitopathy.     

A case of advanced hepatocellular carcinoma with lung, brain and lymph node metastases recurred 8 years after hepatectomy successfully treated by operation, radiation and systemic chemotherapy using S-1/CDDP

A 30-year-old man underwent a left lobectomy and S5/6 partial hepatectomy in August 2001 for hepatocellular carcinoma (HCC). A lung tumor was detected by positron emission tomography (PET-CT) 8 years after the surgery. In May 2010, he received pulmonary tumor resection and the histopathological findings revealed metastasis of HCC. However a metastatic brain tumor was detected by computed tomography (CT) in September 2010, therefore surgery and radiation therapy were subsequently performed. Thereafter, metastatic hilar lymph node appeared in December 2010, therefore we performed systemic chemotherapy using S-1/cisplatin combined with radiation therapy for the metastatic tumor. The tumor was markedly decreased and no shadow was detected by PET-CT. He has been followed up in the outpatient clinic with no recurrence.     

Predicting the Amount of Intraperitoneal Fluid Accumulation by Computed Tomography and Its Clinical Use in Patients With Perforated Peptic Ulcer

The correlation between the amount of peritoneal fluid and clinical parameters in patients with perforated peptic ulcer (PPU) has not been investigated. The authors'' objective was to derive a reliable formula for determining the amount of peritoneal fluid in patients with PPU before surgery, and to evaluate the correlation between the estimated amount of peritoneal fluid and clinical parameters. We investigated 62 consecutive patients who underwent emergency surgery for PPU, and in whom prediction of the amount of accumulated intraperitoneal fluid was possible by computed tomography (CT) using the methods described by Oriuchi et al. We examined the relationship between the predicted amount of accumulated intraperitoneal fluid and that measured during surgery, and the relationship between the amount of fluid predicted preoperatively or measured during surgery and several clinical parameters. There was a significant positive correlation between the amount of fluid predicted by CT scan and that measured during surgery. When patients with gastric ulcer and duodenal ulcer were analyzed collectively, the predicted amount of intraperitoneal fluid and the amount measured during surgery were each associated with the period from onset until CT scan, perforation size, the Mannheim peritoneal index, and the severity of postoperative complications according to the Clavien–Dindo classification. Our present results suggest that the method of Oriuchi et al is useful for predicting the amount of accumulated intraperitoneal fluid in patients with PPU, and that this would be potentially helpful for treatment decision-making and estimating the severity of postoperative complications.Key words: Peptic ulcer, Perforation, Peritoneal fluid, Gastric ulcer, Duodenal ulcer, Computed tomographyPerforated peptic ulcer (PPU) remains a life-threatening condition, especially in elderly patients for whom treatment is often delayed, with reported mortality rates of 10–40%.^1–3 Surgical treatment for PPU that includes simple closure or placement of an omental patch using a conventional open approach or laparoscopy has become widely accepted.⁴ A patient age of >60 years, delayed treatment, or shock at presentation are reported to be factors that predict an unfavorable outcome after surgery.^5,6 Computed tomography (CT) is reported to be a more sensitive diagnostic modality than conventional X-ray examination for detection of extra-luminal free air, recognition of the presence of peritoneal fluid, or even the perforation site.^7–13 Although the amount of accumulated peritoneal fluid may correlate with the severity of peritonitis caused by PPU, no adequate formula for predicting the amount of ascites before surgery has yet been reported. Oriuchi et al14 have proposed a simple method for calculating the amount of peritoneal fluid in gastric cancer patients with peritoneal carcinomatosis from CT scan images. In the present study, we calculated the amount of peritoneal fluid using Oriuchi''s method, and compared it with the actual amount of peritoneal fluid collected during surgery. In addition, we investigated the correlation between the amount of peritoneal fluid predicted preoperatively or that measured during surgery and several clinical parameters or operative outcome.