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

Neuroleptanalgesia and colonoscopy in awake patients. Report on 432 cases

Dans une série de 432 coloscopies effectuées sous neuroleptanalgésie vigile (Dropéridol 10 mg + Fentanyl 100 mg), les durées moyennes des examens ont été respectivement de 18 minutes pour la coloscopie complète, de 20 minutes pour la coloscopie avec iléoscopie, et de 19 minutes en cas de polypectomie. Aucun incident (dépression respiratoire, trouble circulatoire) n'a été observé. Le taux de participation à une coloscopie de contrôle a été de 88% (104/118 patients reconvoqués). La méthode nécessite une courte hospitalisation (24 heures)

in rats :

The biliary secretion of rats is diverted from the choledoch duct to the bladder. These rats are resuscitated by sub-cutaneous injections of a salt solution and then infected with Trichinella spiralis larvae. It is shown that the number of adult worms is increased (+ 66 %); as is the female larvae production (+ 51 %); the females’ lenght is also increased (+ 25 %). 40 days after the infection the number of muscular larvae is considerably increased (+ 79 %) in comparison with control rats. Secretory IgA (SIgA) from rats bile were tested in vitro on the female production of larvae. This larvae production was more inhibited (59 %) by immune SIgA than by control SIgA (25 %)

Detection and follow‐up of fibroblast growth factor receptor 3 expression on bone marrow and circulating plasma cells by flow cytometry in patients with t(4;14) multiple myeloma

Summary The t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases, indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which has potential transforming activity and may represent a therapeutic target. To detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive newly diagnosed ( n = 116) or relapsing ( n = 74) MM patients was studied by flow cytometry (FC) using anti‐CD138 and anti‐FGFR3 antibodies. FC data was compared to real time quantitative‐polymerase chain reaction (RQ‐PCR) of the IGH‐MMSET and FGFR3 transcripts. An IGH‐MMSET transcript was found in 24/200 patients (12%). In 20 of these, FC detected CD138 + /FGFR3 + cells. No expression of FGFR3 was detected in the 4 FGFR3 − cases by RQ‐PCR. FGFR3 was never expressed on PC without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally, coexisting FGFR3 + and FGFR3 − CPC were observed. Fluorescent in situ hybridisation (FISH) analysis of the FGFR3 − subclones showed deletion of the der(14) in one patient. In conclusion, as a supplemental method to RQ‐PCR or FISH, FC analysis of FGFR3 expression is a reliable and routinely available method for the detection and management of new therapeutic approaches of t(4;14) MM