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

Prevalence and morphometric analysis of three-rooted mandibular first molars in a Brazilian subpopulation

ABSTRACT The knowledge of the internal anatomy of three-rooted mandibular molars may help clinicians to diagnose and plan the root canal treatment in order to provide adequate therapy when this variation is present. Objectives: To determine the prevalence of three-rooted mandibular molars in a Brazilian population using cone beam computed tomography (CBCT) and to analyze the anatomy of mandibular first molars with three roots through micro-CT. Material and Methods: CBCT images of 116 patients were reviewed to determine the prevalence of three-rooted first mandibular molars in a Brazilian subpopulation. Furthermore, with the use of micro-CT, 55 extracted three-rooted mandibular first molars were scanned and reconstructed to assess root length, distance between canal orifices, apical diameter, Vertucci's classification, presence of apical delta, number of foramina and furcations, lateral and accessory canals. The distance between the orifice on the pulp chamber floor and the beginning of the curvature and the angle of canal curvature were analyzed in the distolingual root. Data were compared using the Kruskal-Wallis test (α=0.05). Results: The prevalence of three-rooted mandibular first molars was of 2.58%. Mesial roots showed complex distribution of the root canal system in comparison to the distal roots. The median of major diameters of mesiobuccal, mesiolingual and single mesial canals were: 0.34, 0.41 and 0.60 mm, respectively. The higher values of major diameters were found in the distobuccal canals (0.56 mm) and the lower diameters in the distolingual canals (0.29 mm). The lowest orifice distance was found between the mesial canals (MB-ML) and the highest distance between the distal root canals (DB-DL). Almost all distal roots had one root canal and one apical foramen with few accessory canals. Conclusions: Distolingual root generally has short length, severe curvature and a single root canal with low apical diameter

Absence of evidence for the conservation outcomes of systematic conservation planning around the globe : A systematic map

Background Systematic conservation planning is a discipline concerned with the prioritisation of resources for biodiversity conservation and is often used in the design or assessment of terrestrial and marine protected area networks. Despite being an evidence-based discipline, to date there has been no comprehensive review of the outcomes of systematic conservation plans and assessments of the relative effectiveness of applications in different contexts. To address this fundamental gap in knowledge, our primary research question was: what is the extent, distribution and robustness of evidence on conservation outcomes of systematic conservation planning around the globe? Methods A systematic mapping exercise was undertaken using standardised search terms across 29 sources, including publication databases, online repositories and a wide range of grey literature sources. The review team screened articles recursively, first by title only, then abstract and finally by full-text, using inclusion criteria related to systematic conservation plans conducted at sub-global scales and reported on since 1983. We sought studies that reported outcomes relating to natural, human, social, financial or institutional outcomes and which employed robust evaluation study designs. The following information was extracted from included studies: bibliographic details, background information including location of study and broad objectives of the plan, study design, reported outcomes and context. Results Of the approximately 10,000 unique articles returned through our searches, 1209 were included for full-text screening and 43 studies reported outcomes of conservation planning interventions. However, only three studies involved the use of evaluation study designs which are suitably rigorous for inclusion, according to best-practice guidelines. The three included studies were undertaken in the Gulf of California (Mexico), Réunion Island, and The Nature Conservancy’s landholdings across the USA. The studies varied widely in context, purpose and outcomes. Study designs were non-experimental or qualitative, and involved use of spatial landholdings over time, stakeholder surveys and modelling of alternative planning scenarios. Conclusion Rigorous evaluations of systematic conservation plans are currently not published in academic journals or made publicly available elsewhere. Despite frequent claims relating to positive implications and outcomes of these planning activities, we show that evaluations are probably rarely conducted. This finding does not imply systematic conservation planning is not effective but highlights a significant gap in our understanding of how, when and why it may or may not be effective. Our results also corroborate claims that the literature on systematic conservation planning is dominated by methodological studies, rather than those that focus on implementation and outcomes, and support the case that this is a problematic imbalance in the literature. We emphasise the need for academics and practitioners to publish the outcomes of systematic conservation planning exercises and to consider employing robust evaluation methodologies when reporting project outcomes. Adequate reporting of outcomes will in turn enable transparency and accountability between institutions and funding bodies as well as improving the science and practice of conservation planning