Glucocorticoids increase neuropeptide Y and agouti-related peptide gene expression via adenosine monophosphate-activated protein kinase signaling in the arcuate nucleus of rats

Recent studies suggest that the AMP-activated protein kinase (AMPK) signaling in the hypothalamus is the master regulator of energy balance. We reported in previous studies that glucocorticoids play a permissive role in the regulation of orexigenic neuropeptide Y (Npy) gene expression in the arcuate nucleus. In this study, we examined whether any cross talk occurs between glucocorticoids and AMPK signaling in the hypothalamus to regulate Npy as well as agouti-related peptide (Agrp) gene expression in the arcuate nucleus. In the hypothalamic organotypic cultures, the addition to the medium of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribofuranoside, increased phosphorylated AMPK (p-AMPK) as well as phosphorylated acetyl-coenzyme A carboxylase (p-ACC) in the explants, accompanied by significant increases in Npy and Agrp gene expression in the arcuate nucleus. The incubation with dexamethasone (DEX) also activated AMPK signaling in the explants, accompanied by significant increases in Npy and Agrp gene expression in the arcuate nucleus. The addition of the AMPK inhibitor compound C to the medium, which blocked increases of p-AMPK and p-ACC by DEX, significantly attenuated Npy and Agrp gene expression stimulated by DEX. Furthermore, p-AMPK and p-ACC levels in the arcuate nucleus were significantly decreased in adrenalectomized rats compared with sham-operated rats, and a replacement of glucocorticoids reversed the AMPK signaling in adrenalectomized rats. Thus, our data demonstrated that glucocorticoids up-regulate the Npy and Agrp gene expression in the arcuate nucleus through AMPK signaling, suggesting that the activation of the hypothalamic APMK signaling by glucocorticoids might be essential to the energy homeostasis.     

Effects of intra- and extrahepatic portal systemic shunts on insulin metabolism

To study the effects of intra- and extrahepatic portal-systemic shunts on insulin degradation, 11 patients with liver cirrhosis and 7 noncirrhotic patients with liver disease were studied with percutaneous transhepatic catheterization. Insulin levels in portal and peripheral blood were measured simultaneously for 1-2 hr after intravenous administration of glucose. The degrees of intra- and extrahepatic portal-systemic shunting were measured with this technique using 131I-macroaggregated albumin and 99mTc-macroaggregated albumin. The amount of insulin secreted and insulin degraded were assessed from the areas under blood concentration curves for portal and peripheral blood. Insulin degradation was significantly reduced in cirrhotics compared to noncirrhotics with liver disease, although there was no difference in the amount of insulin secreted between these two groups. It was also correlated significantly with the degree of intrahepatic shunting but not with the degree of extrahepatic shunting. These results suggest that intrahepatic shunting plays an important role in the reduction of insulin degradation in cirrhosis.     

Flow cytometric examination of p53 protein in primary tumors and metastases to the liver and lymph nodes of colorectal cancer

PURPOSE AND METHODS: To confirm prognostic significance of overexpression of p53 in cases of colorectal cancer, expression of p53 protein was examined by flow cytometry in 113 cases of colorectal cancer and its metastasis to the liver and lymph nodes. RESULTS: Overexpression of p53 was found in 44 (39 percent) of the 113 primary tumors. There were no significant correlations among the level of p53 protein in the primary tumor, clinicopathologic features, and prognosis of colorectal cancer. Overexpression of p53 protein was detected in 72 percent (18/25) of liver metastases and in 40 percent (10/25) of lymph node métastases. Frequency of samples that were positive for p53 was significantly higher for liver metastases than for primary tumors and lymph node metastases (P<0.01). By comparing overexpression of p53 in primary tumors with that in corresponding secondary tumors, a decrease of more than 5 percent in the fluorescence index, compared with primary tumor, was not found in liver metastasis but was found in 20 percent of lymph node metastases. Incidence of cases with lower level expression of p53, compared with primary tumor, was significantly higher in lymph node metastases (32 percent) than in liver metastases (8 percent;P<0.05). CONCLUSIONS: From these results, it seems possible that overexpression of p53 may not be a good prognostic indicator of colorectal cancer and may be influenced by environments of the tumor.Presented at the meeting of the Japanese Gastroenterological Surgery, Fukui City, Japan, July 20 and 21, 1995.     

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones

In Japan the composition of gallstones is changing rapidly from the once-predominant brownpigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 ±10 vs. 146 ±8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 α-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 α-hydroxy-4-cholesten-3-one 12 α-hydroxylase (12 α-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 α-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 α-hydroxylase and 12 α-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 02454226) from the Ministry of Education, Science and Culture of Japan, and a grant from University of Tsukuba Project Research.     

Oral vancomycin versus metronidazole for the treatment of Clostridioides difficile infection: Meta-analysis of randomized controlled trials

At present, vancomycin (VCM) and metronidazole (MNZ) are used for the first-line standard treatment of Clostridioides difficile infection (CDI). However, their differential use has not been sufficiently investigated. In this study, a meta-analysis on differences in the efficacy for CDI between VCM and MNZ was performed. Reports of randomized controlled studies using VCM or MNZ to treat CDI were surveyed. Meta-analysis was performed using the Mantel-Haenszel method and random-effects model, and the risk ratio and 95% confidence interval were calculated. Excluding overlapping reports, 1043 reports were extracted and 5 randomized controlled studies were extracted. There was no difference in therapeutic effects for CDI between VCM and MNZ (RR = 1.08, 95% CI (0.99–1.17), p = 0.09, I² = 37%). On subgroup analysis by the severity, there was no difference in the clinical effects for CDI between VCM and MNZ in non-severe cases (risk ratio: 1.09, 95% confidence interval: 1.00–1.19, p = 0.06), but the clinical effects of VCM were significantly higher than those of MNZ in severe cases (risk ratio: 1.19, 95% confidence interval: 1.02–1.39, p = 0.03). No significant difference was noted in the recurrence rate, incidence of adverse event, time to exhibit therapeutic effects, or judgment of the bacteriological effects. As the therapeutic effects of VCM were superior in severe CDI cases, VCM should be considered first in severe cases.     

Sonographic localization of a retained urethral foreign body in an elderly patient

A retained urethral foreign body is an uncommon presentation in the Emergency Department. The diagnosis and treatment of retained urethral foreign bodies are determined by their size, location, shape, and mobility and often require specialty consultation and operative intervention. In this case of a 74‐year‐old man with a self‐inserted, retained urethral foreign body, we present the utility of a bedside ultrasound to detect the depth, size, and distance from the meatus of the object to guide the approach to extraction of the object at the bedside in the Emergency Department. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46 :296–298, 2018     

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review

Clinical Rheumatology - Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin...     

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for...     

Impact of age on the prognostic value of number of lymph nodes retrieved in patients with stage II colorectal cancer

Purpose

A small number of lymph nodes retrieved (NLNR) is a known risk factor in stage II colorectal cancer. NLNR is influenced by age, but little is known about whether the impact of small NLNR on survival differs with age. This retrospective study sought to determine such impact in elderly patients with stage II colorectal cancer.

Methods

We reviewed data for 2100 patients with stage II colorectal cancer who underwent surgery without adjuvant chemotherapy between January 1997 and December 2003. The optimal cutoff value of NLNR for survival was determined, and the impact of small NLNR on survival was analyzed. The association between age and NLNR was evaluated. The relation between age and risk of small NLNR with respect to survival was then assessed to determine the impact of small NLNR on elderly patients’ survival.

Results

The optimal cutoff value of NLNR was determined as 6. The small NLNR group (SNG) showed significantly worse prognosis than the large NLNR group (LNG) (p?<?0.001). Age, surgical method, and scope of lymph node dissection were significantly associated with NLNR. A potential interaction was noted between age and risk of small NLNR in relation to relapse-free survival (RFS). Five-year RFS was significantly worse in SNG than in LNG for elderly patients (41.7 and 76.4 %, respectively; p?<?0.001) but not for non-elderly patients (75.9 and 84.6 %, respectively; p?=?0.083).

Conclusions

NLNR <6 was identified to be an important prognostic factor for elderly patients with stage II colorectal cancer.

     

Respiratory function after esophagectomy for patients with esophageal cancer

BACKGROUND/AIMS: Postoperative respiratory hypofunction sometime ruins quality of life of patients with esophageal cancer. From 1993, we introduced transhiatal esophagectomy without thoracotomy as a less invasive surgery to prevent postoperative respiratory complications for patients who have relatively early stage of esophageal cancer and have preoperative respiratory complication, or who are older in age. In this study, postoperative long-term evaluation of respiratory functions of patients with esophageal cancer who underwent esophagectomy was performed. METHODOLOGY: Among the patients with esophageal cancer who underwent esophagectomy in our hospital between 1993 and 1995, we selected 13 patients who underwent transhiatal esophagectomy (transhiatal group) and 9 patients who underwent transthoracic esophagectomy (transthoracic group). Conventional respiratory function tests (VC, vital capacity; FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; FEV1/FVC, ratio of FEV1 to FVC; PEF, peak expiratory flow) were compared between the two groups at 3, 6, and 12 months after operation. RESULTS: In the transhiatal group, postoperative average values of VC, FVC, and FEV1 recovered 92%, 98%, and 93% of preoperative average values at 6 months after operation, while in the transthoracic group, the average values of VC, FVC, and FEV1 were still 78%, 78%, and 72% of preoperative average values at 6 months after operation. Postoperative respiratory complications were detected in 4 patients (transhiatal: 2 and transthoracic: 2). The recovery rates of VC, FVC, FEV1, FEV1/FVC, and PEF at 6 months after operation of these 4 patients were not different from those of 18 patients without postoperative respiratory complications. CONCLUSIONS: In patients treated with transthoracic esophagectomy, postoperative respiratory hypofunctions continued over 6 months after surgery. However, postoperative respiratory complications may not be related with the long-term postoperative respiratory hypofunction in patients with esophageal cancer.