Ménétrier Disease; 2-Year-Old Boy Presenting With Prolonged Emesis, Generalized Edema and Chance Histopathological Finding of Cytomegalovirus Gastritis: A Case Report

Ménétrier disease (MD) is characterized by enlarged gastric folds with associated protein losing gastropathy. In children it is a rare and self-limited cause of protein losing gastropathy. We report a case of a 2-year-old male who presented with prolonged, refractory emesis and peripheral edema. Workup revealed severe hypoalbuminemia, hypoproteinemia, iron deficiency anemia, and high stool alpha-1 antitrypsin. Hepatic protein synthesis was normal with no urinary protein loss. Endoscopy showed antrum sparing, severe erosive gastritis in body and fundus, characteristic of MD. Histologic examination displayed inflammation with eosinophilia, foveolar hyperplasia, atrophic oxyntic epithelium, and rare CMV inclusions. Patient received antiviral therapy, intravenous albumin, diuretic and was discharged on high protein diet. Follow-up revealed clinical recovery, with endoscopy and histology showing normal gastric mucosa throughout the stomach. It is important to remain vigilant of this condition in pediatric population and to include it in the differential diagnosis in cases of protein losing gastroenteropathy.

Ménétrier Disease; 2-Year-Old Boy Presenting With Prolonged Emesis, Generalized Edema and Chance Histopathological Finding of Cytomegalovirus Gastritis: A Case Report

Ménétrier disease (MD) is characterized by enlarged gastric folds with associated protein losing gastropathy. In children it is a rare and self-limited cause of protein losing gastropathy. We report a case of a 2-year-old male who presented with prolonged, refractory emesis and peripheral edema. Workup revealed severe hypoalbuminemia, hypoproteinemia, iron deficiency anemia, and high stool alpha-1 antitrypsin. Hepatic protein synthesis was normal with no urinary protein loss. Endoscopy showed antrum sparing, severe erosive gastritis in body and fundus, characteristic of MD. Histologic examination displayed inflammation with eosinophilia, foveolar hyperplasia, atrophic oxyntic epithelium, and rare CMV inclusions. Patient received antiviral therapy, intravenous albumin, diuretic and was discharged on high protein diet. Follow-up revealed clinical recovery, with endoscopy and histology showing normal gastric mucosa throughout the stomach. It is important to remain vigilant of this condition in pediatric population and to include it in the differential diagnosis in cases of protein losing gastroenteropathy.

An Increase in Liver Polyamine Concentration Contributes to the Tryptophan-Induced Acute Stimulation of Rat Hepatic Protein Synthesis

Tryptophan has a unique role as a nutritional signaling molecule that regulates protein synthesis in mouse and rat liver. However, the mechanism underlying the stimulating actions of tryptophan on hepatic protein synthesis remains unclear. Proteomic and metabolomic analyses were performed to identify candidate proteins and metabolites likely to play a role in the stimulation of protein synthesis by tryptophan. Overnight-fasted rats were orally administered L-tryptophan and then sacrificed 1 or 3 h after administration. Four differentially expressed protein spots were detected in rat liver at 3 h after tryptophan administration, of which one was identified as an ornithine aminotransferase (OAT) precursor. OAT is the main catabolic enzyme for ornithine, and its expression was significantly decreased by tryptophan administration. The concentration of ornithine was increased in the liver at 3 h after tryptophan administration. Ornithine is a precursor for polyamine biosynthesis. Significantly increased concentrations of polyamines were found in the liver at 3 h after administration of tryptophan. Additionally, enhanced hepatic protein synthesis was demonstrated by oral administration of putrescine. We speculate that the increase in ornithine level through suppression of OAT expression by tryptophan administration may lead to accelerated polyamine synthesis, thereby promoting protein synthesis in the liver.

Correction of the the liver morpho-functional state with stem cells in acute hepatitis

Цель работы - изучение влияния сочетанной трансплантации мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток на регенерацию печени в физиологических условиях и в условиях токсического гепатита. Методика. Эксперименты выполнены на 84 белых лабораторных мышах-самцах, возраст 7-8 мес. Токсический гепатит вызывали внутрибрюшинным введением четыреххлористого углерода (CCl4 в дозе 50 мкг/кг. Животным опытной группы в хвостовую вену вводили мультипотентные мезенхимальные стромальные (ММСК, 4 млн клеток/кг) и гемопоэтические стволовые клетки (ГСК, 330 тыс. клеток/кг). Для инъекции полученные клетки суспендировали в 0,2 мл 0,9 % раствора NaCl. Животным контрольной группы внутривенно вводили 0,2 мл 0,9 % раствора NaCl. Внутривенные введения осуществляли через 1 ч после введения четыреххлористого углерода однократно. Для трансплантации использовали ММСК третьего пассажа, а ГСК не подвергались культивированию. Изучали влияние сочетанной трансплантации ММСК и ГСК на биохимические показатели периферической крови и морфометрические показатели печени в физиологических условиях и после введения CCl4 на 1-е, 3-и, 7-е сут. Результаты. Показано, что проведение сочетанной трансплантации мультипотентных мезенхимальных стромальных и гемопоэтических стволовых клеток при токсическом гепатите приводило к снижению активности ферментов цитолиза, активации белоксинтезирующей функции печени. Также отмечалось увеличение количества гепатоцитов, повышение митотической активности, что указывает на активацию внутриклеточной регенерации. Обнаруженное увеличение числа двуядерных гепатоцитов, размеров ядра, ядерно-цитоплазматического соотношения говорит об усилении процесса внутриклеточной регенерации в печени. The aim of the work was studying the effect of combined transplantation of multipotent mesenchymal stromal and hematopoietic stem cells on regeneration of the liver under the physiological conditions and in toxic hepatitis. Methods. Experiments were performed on 84 white laboratory male mice aged 7-8 months. Toxic hepatitis was induced by administration of carbon tetrachloride (CCl4) at a dose of 50 µg/kg, i.p. Mice were divided into experimental and control groups. The experimental group received caudal vein injections of multipotent mesenchymal stromal (MMSC) and hematopoietic stem cells (HSC) derived from the placenta chorion of female mice at respective doses of 4M cells/kg and 330K cells/kg suspended in 0.2 ml of 0.9% NaCl. Control animals were given 0.2 ml of 0.9 % NaCl, i.v. Intravenous injections were performed once 1 hour following the administration of carbon tetrachloride. MMSCs of the third passage were used for transplantation, while transplanted HSCs were not cultured. Effects of the combined MMSC and HSC transplantation on blood biochemistry and liver morphometry were studied under the physiological conditions and at 1, 3, and 7 days after administration of CCl4. Results. In toxic hepatitis, the combined transplantation of multipotent mesenchymal stromal and hematopoietic stem cells resulted in decreased activity of cytolytic enzymes, activation of hepatic protein synthesis, increased number of hepatocytes, and increased mitotic activity indicative of activation of intracellular regeneration. Increases in the number of binuclear hepatocytes, nucleus size, and the nuclear-cytoplasmic ratio suggested an enhancement of intracellular regeneration in the liver.

Assessment of the Biochemical Status of Workers Manufacturing Ethylbenzene and Styrene

Introduction: Production of ethylbenzene and styrene (EBS) is one of the most important stages in organic synthesis. The products have general toxic, hepatotoxic, irritating and narcotic effects on the human body. Severe exposures to EВS can induce pronounced disorders of the central nervous system such as styrene sickness and encephalopathy and of peripheral blood such as leukopenia and lymphocytosis. Materials and methods: We studied homeostasis indices in 376 workers of the main professional groups engaged in the production of EBS including equipment operators, repairmen, and instrumentation and automation fitters. Results: We established an increase in lipid peroxidation by the level of malondialdehyde amid an increase in catalase activity and a decrease in blood retinol and α-tocopherol levels. We also noted an increased activity of indicator enzymes including ALT, AST, GGT, and alkaline phosphatase. Significant changes in lipid metabolism in the form of cholesterolemia, triglyceridemia, a higher atherogenic index, and lower cholesterol of non-atherogenic blood serum lipids demonstrating atherogenic changes in the body were revealed. Conclusions: The earliest prenosological disorders in the body of the examined workers included an impaired hepatic protein synthesis, the development of cytolysis processes and a change in the integrity and functional activity of the liver cell in individuals, an imbalance in the oxidant-antioxidant system, one of the reasons of which was the adverse occupational exposure to hazardous chemicals. An increase in catalase activity is a protective compensatory reaction during the activation of free radical oxidation processes.

Short-term changes in diet composition do not affect in vivo hepatic protein synthesis in rats

Protein synthesis is critical to protein homeostasis (proteostasis), and modifications in protein synthesis influence lifespan and the development of comorbidities associated with obesity. In the present study, we examined the acute response of liver protein synthesis to either high-fat or high-sucrose diets in order to elucidate nutrient-mediated regulation of hepatic protein synthesis in the absence of body fat accumulation. Total and endoplasmic reticulum-associated protein syntheses were assessed by use of the stable isotope, deuterium oxide (2H2O), in rats provided a control diet or diets enriched in polyunsaturated fat, saturated fat, or sucrose for 2, 4, or 7 days. The three experimental diets increased hepatic triglycerides 46–91% on day 7 and fasting insulin levels 83–117% on day 7, but did not result in differences in body weight when compared with control ( n = 6/diet/time). The fraction of newly synthesized proteins in total liver lysates and microsomes was not significantly different among dietary groups ( n = 3/diet/time). To determine whether the experimental diets provoked a transcriptional response to enhance the capacity for protein synthesis, we also measured a panel of genes linked to amino acid transport, synthesis, and processing. There were no significant differences in any of the genes measured among groups. Therefore, dietary treatments that have been linked to impaired proteostasis and that promote hepatic steatosis and insulin resistance, did not result in significant changes in total or ER-associated protein synthesis in the liver over a 7-day period.

Hepatitis

Hepatitis A (HAV) and E (HEV) viruses are spread via the fecal-oral route. Hepatitis B virus (HBV) exposure is via occupational or recreational activities. Hepatitis D virus (HDV; also spread parentally) can only coinfect or superinfect those with chronic HBV. Hepatitis C (HCV) transmission is predominantly parenteral; the highest risk group is injection drug users. Prodromal-period patients with acute hepatitis present with vague constitutional symptoms when serum transaminases peak, with elevated serum bilirubin and varying levels of hepatic protein synthesis impairment; during the icteric phase, patients develop abdominal pain, hepatomegaly, and jaundice. Acute hepatitis has limited therapy; treatment is predominantly supportive. However, most adults with acute phase HAV, HBV, HDV, and HEV spontaneously clear the virus. Most individuals with HCV develop chronic hepatitis. Patients with known HAV, HBV, or HEV exposures may be eligible for post-exposure prophylaxis to reduce their risk of infection.