Serum albumin and mortality risk in a hyperendemic area of HCV infection in Japan

<p>Abstract</p> <p>Background</p> <p>Hypoalbuminemia has been shown to be associated with increased mortality. We reported a mass screening in 1990 of X town in Japan, which demonstrated a high prevalence of hepatitis C virus (HCV) infection. This follow-up study determined, through a period of 12 years, whether serum albumin levels impact on the life prognosis of the residents of X town.</p> <p>Results</p> <p>Of the 509 subjects, 69 had died and 55 had moved to other regions by 2002. Therefore, we analyzed 454 people for whom we could confirm life and death between 1990 and 2002. Albumin levels were assigned to two groups, low (<4.0 g/L, group A) and normal (≥4.0 g/L, group B). Of the 454 subjects analyzed, 25 were in group A and 429 in group B and the mortality was 68.0% (17/25 cases, P < 0.00001 vs. group B) and 12.1% (52/429), respectively. Mortality from hepatocellular carcinoma (HCC) was 66.7% in group A (6/9 cases, P = 0.01 vs. group B) and 15.8% (3/19) in group B. According to multivariate analysis, five factors - 50 years or older, low albumin level (<4.0 g/L), abnormal AST level, history of smoking, and absence of alcohol consumption - were associated with death. The adjusted odds ratios for these five factors were 20.65, 10.79, 2.58, 2.24 and 2.08, respectively, and each was statistically significant.</p> <p>Conclusions</p> <p>We show that the serum albumin level is an independent risk factor for mortality from all causes in the residents of X town and an important prognostic indicator. Improvement of hypoalbuminaemia should be considered for improvement of prognosis.</p

The Gut Microbiota and Their Metabolites in Human Arterial Stiffness

Aim: Gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) have vasodilator properties in animal and human ex vivo arteries. However, the role of the gut microbiota and SCFAs in arterial stiffness in humans is still unclear. Here we aimed to determine associations between the gut microbiome, SCFA and their G-protein coupled sensing receptors (GPCRs) in relation to human arterial stiffness. / Methods: Ambulatory arterial stiffness index (AASI) was determined from ambulatory blood pressure (BP) monitoring in 69 participants from regional and metropolitan regions in Australia (55.1% women; mean, 59.8± SD, 7.26 years of age). The gut microbiome was determined by 16S rRNA sequencing, SCFA levels by gas chromatography, and GPCR expression in circulating immune cells by real-time PCR. / Results: There was no association between metrics of bacterial α and β diversity and AASI or AASI quartiles in men and women. We identified two main bacteria taxa that were associated with AASI quartiles: Lactobacillus spp. was only present in the lowest quartile, while Clostridium spp. was present in all quartiles but the lowest. AASI was positively associated with higher levels of plasma, but not faecal, butyrate. Finally, we identified that the expression of GPR43 (FFAR2) and GPR41 (FFAR3) in circulating immune cells were negatively associated with AASI. / Conclusions: Our results suggest that arterial stiffness is associated with lower levels of the metabolite-sensing receptors GPR41/GPR43 in humans, blunting its response to BP-lowering metabolites such as butyrate. The role of Lactobacillus spp. and Clostridium spp., as well as butyrate-sensing receptors GPR41/GPR43, in human arterial stiffness needs to be determined

A retrospective case-control study of hepatitis C virus infection and oral lichen planus in Japan: association study with mutations in the core and NS5A region of hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to assess the prevalence of hepatitis C virus (HCV) infection in Japanese patients with oral lichen planus and identify the impact of amino acid (aa) substitutions in the HCV core region and IFN-sensitivity-determining region (ISDR) of nonstructural protein 5A (NS5A) associated with lichen planus.</p> <p>Methods</p> <p>In this retrospective study, 59 patients (group 1-A) with oral lichen planus among 226 consecutive patients who visited our hospital and 85 individuals (group 1-B, controls) with normal oral mucosa were investigated for the presence of liver disease and HCV infection. Risk factors for the presence of oral lichen planus were assessed by logistic regression analysis. We compared aa substitutions in the HCV core region (70 and/or 91) and ISDR of NS5A of 12 patients with oral lichen planus (group 2-A) and 7 patients who did not have oral lichen planus (group 2-B) among patients (high viral loads, genotype 1b) who received interferon (IFN) therapy in group1-A.</p> <p>Results</p> <p>The prevalence of anti-HCV and HCV RNA was 67.80% (40/59) and 59.32% (35/59), respectively, in group 1-A and 31.76% (27/85) and 16.47% (14/85), respectively, in group 1-B. The prevalence of anti-HCV (<it>P </it>< 0.0001) and HCV RNA (<it>P </it>< 0.0001) in group 1-A was significantly higher than those in group 1-B. According to multivariate analysis, three factors - positivity for HCV RNA, low albumin level (< 4.0 g/dL), and history of smoking - were associated with the development of oral lichen planus. The adjusted odds ratios for these three factors were 6.58, 3.53 and 2.58, respectively, and each was statistically significant. No significant differences in viral factors, such as aa substitutions in the core region and ISDR of NS5A, were detected between the two groups (groups 2-A and -B).</p> <p>Conclusion</p> <p>We observed a high prevalence of HCV infection in patients with oral lichen planus. Longstanding HCV infection, hypoalbuminemia, and smoking were significant risk factors for the presence of oral lichen planus in patients. It is advisable for Japanese patients with lichen planus to be tested for HCV infection during medical examination.</p

Intestinal adhesion due to previous uterine surgery as a risk factor for delayed diagnosis of uterine rupture: a case report

<p>Abstract</p> <p>Introduction</p> <p>Uterine rupture is a life-threatening condition both to mothers and fetuses. Its early diagnosis and treatment may save their lives. Previous myomectomy is a high risk factor for uterine rupture. Intestinal adhesion due to previous myomectomy may also prevent early diagnosis of uterine rupture.</p> <p>Case presentation</p> <p>A 38-year-old primiparous non-laboring Japanese woman with a history of myomectomy was admitted in her 34^thweek due to lower abdominal pain. Although the pain was slight and her vital signs were stable, computed tomography revealed massive fluid collection in her abdominal cavity, which led us to perform a laparotomy. Uterine rupture had occurred at the site of the previous myomectomy; however, the small intestine was adhered tightly to the rupture, thus masking it. The baby was delivered through a low uterine segment transverse incision. The ruptured uterine wall was reconstructed.</p> <p>Conclusion</p> <p>Intestinal adhesion due to a prior myomectomy occluded a uterine rupture, possibly masking its symptoms and signs, which may have prevented early diagnosis.</p

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Influence of hypoxia on the domiciliation of Mesenchymal Stem Cells after infusion into rats: possibilities of targeting pulmonary artery remodeling via cells therapies?

BACKGROUND: Bone marrow (BM) cells are promising tools for vascular therapies. Here, we focused on the possibility of targeting the hypoxia-induced pulmonary artery hypertension remodeling with systemic delivery of BM-derived mesenchymal stem cells (MSCs) into non-irradiated rats. METHODS: Six-week-old Wistar rats were exposed to 3-week chronic hypoxia leading to pulmonary artery wall remodeling. Domiciliation of adhesive BM-derived CD45(- )CD73(+ )CD90(+ )MSCs was first studied after a single intravenous infusion of Indium-111-labeled MSCs followed by whole body scintigraphies and autoradiographies of different harvested organs. In a second set of experiments, enhanced-GFP labeling allowed to observe distribution at later times using sequential infusions during the 3-week hypoxia exposure. RESULTS: A 30% pulmonary retention was observed by scintigraphies and no differences were observed in the global repartition between hypoxic and control groups. Intrapulmonary radioactivity repartition was homogenous in both groups, as shown by autoradiographies. BM-derived GFP-labeled MSCs were observed with a global repartition in liver, in spleen, in lung parenchyma and rarely in the adventitial layer of remodeled vessels. Furthermore this global repartition was not modified by hypoxia. Interestingly, these cells displayed in vivo bone marrow homing, proving a preservation of their viability and function. Bone marrow homing of GFP-labeled MSCs was increased in the hypoxic group. CONCLUSION: Adhesive BM-derived CD45(- )CD73(+ )CD90(+ )MSCs are not integrated in the pulmonary arteries remodeled media after repeated intravenous infusions in contrast to previously described in systemic vascular remodeling or with endothelial progenitor cells infusions

Carcinoma Arising from Brunner's Gland in the Duodenum after 17 Years of Observation – A Case Report and Literature Review

A 60-year-old man presented with melena and hematemesis in 1984. Esophagogastroduodenoscopy (EGD) detected a small protruding lesion in the duodenal bulb, which was diagnosed as Brunner's adenoma. No significant change was detected in subsequent annual EGD and biopsies for 10 years, after which the patient was not observed for 7 years. The patient presented with melena again in 2001. The lesion had changed shape to become a 10 mm sessile tumor with a central depression, and following a biopsy was diagnosed as an adenocarcinoma. The patient underwent partial resection of the duodenum. Histopathological assessment showed acidophilic cells with swollen nuclei, and clear cells forming a tubular or papillary tubule in the mucosal lamina propria and submucosal layer. The tumor cells stained positive for lysozyme, indicating that they arose from Brunner's gland. The patient showed no sign of recurrence and was disease-free for more than 34 months after surgery. The patient died of pneumonia. This is an extremely rare case of primary duodenal carcinoma arising from Brunner's gland in a patient observed for 17 years

Pitavastatin suppresses diethylnitrosamine-induced liver preneoplasms in male C57BL/KsJ-db/db obese mice

<p>Abstract</p> <p>Background</p> <p>Obesity and related metabolic abnormalities, including inflammation and lipid accumulation in the liver, play a role in liver carcinogenesis. Adipocytokine imbalances, such as decreased serum adiponectin levels, are also involved in obesity-related liver tumorigenesis. In the present study, we examined the effects of pitavastatin - a drug used for the treatment of hyperlipidemia - on the development of diethylnitrosamine (DEN)-induced liver preneoplastic lesions in C57BL/KsJ-<it>db/db </it>(<it>db/db</it>) obese mice.</p> <p>Methods</p> <p>Male <it>db/db </it>mice were administered tap water containing 40 ppm DEN for 2 weeks and were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 14 weeks.</p> <p>Results</p> <p>At sacrifice, feeding with 10 ppm pitavastatin significantly inhibited the development of hepatic premalignant lesions, foci of cellular alteration, as compared to that in the untreated group by inducing apoptosis, but inhibiting cell proliferation. Pitavastatin improved liver steatosis and activated the AMPK-α protein in the liver. It also decreased free fatty acid and aminotransferases levels, while increasing adiponectin levels in the serum. The serum levels of tumor necrosis factor (TNF)-α and the expression of <it>TNF-α </it>and <it>interleukin-6 </it>mRNAs in the liver were decreased by pitavastatin treatment, suggesting attenuation of the chronic inflammation induced by excess fat deposition.</p> <p>Conclusions</p> <p>Pitavastatin is effective in inhibiting the early phase of obesity-related liver tumorigenesis and, therefore, may be useful in the chemoprevention of liver cancer in obese individuals.</p