19 Radioterapia ziarnicy złośliwej u dzieci w materiale I Zakładu Teleradioterapii Centrum

W latach 1986–1998 w I Zakładzie Radioterapii Centrum Onkologii w Warszawie leczono 97 dzieci z rozpoznaniem ziarnicy złośliwej, w wieku od 2 do 18 lat. Ponad połowa pacjentów (58%) była powyżej 10 roku życia. Obserwowano znaczną przewagę chłopców M.:F = 1,77. Przeważali pacjenci w I i w II stopniu zaawansowania klinicznego (63%) i bez objawów ogólnych (62%). W rozpoznaniu histopatologicznym najczęstsza była postać NS (50%) i MC (31%).Wszystkie dzieci otrzymały leczenie chemiczne przed napromienianiem. U 71 zastosowano program B-POPA, u 18 COPP/OPPA, u pozostałych 9 inne schematy leczenia. Pacjenci byli napromieniani na teren pierwotnie zajętych okolic węzłowych, promieniami telekobaltu-60. Stosowano dawki od 20 do 36 Gy, przeważnie 25 Gy (u 65%).Obecnie żyje 91 pacjentów, zmarło jedno dziecko, 5 stracono z obserwacji. Osiemdziesięciu pacjentówzyje żyje bez nawrotu choroby. U żadnego z pozostających w obserwacji dzieci nie stwierdzono póżnych powikłań po napromienianiu

Fruits of Hippophaë rhamnoides in human leukocytes and Caco-2 cell monolayer models—A question about their preventive role in lipopolysaccharide leakage and cytokine secretion in endotoxemia

Preparations from Hippophaë rhamnoides L. (sea buckthorn) have been traditionally used in the treatment of skin and digestive disorders, such as gastritis, gastric and duodenal ulcers, uterine erosions, as well as oral, rectal, and vaginal mucositis, in particular in the Himalayan and Eurasian regions. An influence of an aqueous extract from the fruits of H. rhamnoides (HR) on leakage of lipopolysaccharide (LPS) from Escherichia coli through gut epithelium developed from the human colorectal adenocarcinoma (Caco-2) monolayer in vitro and glucose transporter 2 (GLUT2) translocation were the principal objectives of the study. Additionally, the effect of HR on the production of pro- and anti-inflammatory cytokines (interleukins: IL-8, IL-1β, IL-10, IL-6; tumor necrosis factor: TNF-α) by the Caco-2 cell line, human neutrophils (PMN), and peripheral blood mononuclear cells (PBMC) was evaluated. The concentration of LPS on the apical and basolateral sides of the Caco-2 monolayer was evaluated with a Limulus Amebocyte Lysate (LAL) assay. GLUT2 translocation was evaluated using an immunostaining assay, whereas secretion of cytokines by cell cultures was established with an enzyme-linked immunosorbent (ELISA) assay. HR (500 μg/ml) significantly inhibited LPS leakage through epithelial monolayer in vitro in comparison with non-treated control. The treatment of Caco-2 cells with HR (50–100 μg/ml) showed GLUT2 expression similar to the non-treated control. HR decreased the secretion of most pro-inflammatory cytokines in all tested models. HR might prevent low-grade chronic inflammation caused by metabolic endotoxemia through the prevention of the absorption of LPS and decrease of chemotactic factors released by immune and epithelial cells, which support its use in metabolic disorders in traditional medicine

Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute—(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing “false neurotransmitters” (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB “leakage”), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF

Low dose cranial irradiation-induced cerebrovascular damage is reversible in mice

BACKGROUND: High-dose radiation-induced blood-brain barrier breakdown contributes to acute radiation toxicity syndrome and delayed brain injury, but there are few data on the effects of low dose cranial irradiation. Our goal was to measure blood-brain barrier changes after low (0.1 Gy), moderate (2 Gy) and high (10 Gy) dose irradiation under in vivo and in vitro conditions. METHODOLOGY: Cranial irradiation was performed on 10-day-old and 10-week-old mice. Blood-brain barrier permeability for Evans blue, body weight and number of peripheral mononuclear and circulating endothelial progenitor cells were evaluated 1, 4 and 26 weeks postirradiation. Barrier properties of primary mouse brain endothelial cells co-cultured with glial cells were determined by measurement of resistance and permeability for marker molecules and staining for interendothelial junctions. Endothelial senescence was determined by senescence associated β-galactosidase staining. PRINCIPLE FINDINGS: Extravasation of Evans blue increased in cerebrum and cerebellum in adult mice 1 week and in infant mice 4 weeks postirradiation at all treatment doses. Head irradiation with 10 Gy decreased body weight. The number of circulating endothelial progenitor cells in blood was decreased 1 day after irradiation with 0.1 and 2 Gy. Increase in the permeability of cultured brain endothelial monolayers for fluorescein and albumin was time- and radiation dose dependent and accompanied by changes in junctional immunostaining for claudin-5, ZO-1 and β-catenin. The number of cultured brain endothelial and glial cells decreased from third day of postirradiation and senescence in endothelial cells increased at 2 and 10 Gy. CONCLUSION: Not only high but low and moderate doses of cranial irradiation increase permeability of cerebral vessels in mice, but this effect is reversible by 6 months. In-vitro experiments suggest that irradiation changes junctional morphology, decreases cell number and causes senescence in brain endothelial cells