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

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

First cases of Omicron in France are exhibiting mild symptoms, November 2021–January 2022

International audienceObjectivesWe aimed to investigate the first Omicron cases detected in France in order to assess case characteristics and provide supporting information on the possible impact of this variant on the healthcare system.MethodsA standardized questionnaire was used to collect information from confirmed and probable Omicron cases.ResultsMedian age of 468 investigated cases was 35 years, 376 were symptomatic (89%); 64% were vaccinated with two doses and 7% had received three doses. Loss of smell and taste were reported by 8.3% and 9% of cases, respectively. Seven cases were hospitalized, three of those were unvaccinated (including two with reported precondition). No admissions to intensive care and no deaths were reported.ConclusionsOur results confirm a mild clinical presentation among the first Omicron cases detected in France and highlight the importance for the national COVID-19 surveillance system to quickly detect and adapt to the emergence of a new variant