Past and Future Prospects of Orthoptic Liver Transplantation

The hopes for liver transplantation have been increased by experience with the new immunosuppresive drug cyclosporin A. Optimal therapy with cyclosporin A has required steroid therapy, but the amounts of prednisone used have been a small fraction of those used in the past. © 1981, American Medical Association. All rights reserved

Synthesis of a Se0/Calcite Composite Using Hydrothermal Carbonation of Ca(OH)2 Coupled to a Complex Selenocystine Fragmentation

International audienceElemental selenium (Se0)/calcite composites were synthesized in a batch system by hydrothermal carbonation of calcium hydroxide under high CO2−Ar pressure (90 bar) and high temperature (90 °C) coupled to a complex selenocystine fragmentation. Under O2-poor conditions, the composite consisted predominantly of spherical, amorphous nanoparticles of elemental red selenium (<500 nm) deposited on the calcite matrix. Conversely, under O2-rich conditions, the composite consisted rod-shaped, well-crystallized microparticles of elemental gray selenium (<25 µm) dispersed in the calcite matrix. The carbonate matrix was constituted by nano- to microrhombohedral crystals (<2 µm) and micrometric agglomerates and/or aggregates (<5 µm). Our results present a new synthesis path to Se0/calcite composites, with spherical or rod-shaped Se0 morphology with high potential for medical (e.g., dietary supplement) or industrial (e.g., pigments) applications. Furthermore, this study may have implications in the field of biomineralization

Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients

From nine to 18 months ago, 66 patients were given 67 randomly matched cadaveric kidneys with cyclosporin A and steroid therapy. Nine of the recipients were undergoing retransplantation. The over-all kidney survival rate to date has been 77.6 per cent, and 78.8 per cent of the recipients are dialysis-free. The patient mortality in this learning phase was 13.3 per cent. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic use of this agent. One B-cell immunoblastic sarcoma was encountered which was monoclonal. It was not responsible for death. Another patient had a perforation of the intestine from a lymphoproliferative reaction in which the B cells were polyclonal. After jejunal resection a year ago, there were no further complications. This lesion was not classified as a lymphoma. Both lymphoproliferative lesions were associated with a rise in antibody to viral capsid antigen of Epstein-Barr virus. Results of this study have verified the effectiveness and relative safety of cyclosporin A with steroids for immunosuppression in human recipients of cadaveric kidneys

Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited. OBJECTIVES: The purpose of this study was to characterize vascular inflammation by hybrid 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Carotid, aortic, and ilio-femoral 18F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18F-FDG uptake) and plaques with or without inflammation (coincident 18F-FDG uptake). RESULTS: Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001). CONCLUSIONS: Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).The PESA study is cofunded equally by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Banco Santander. The study also receives funding from the Instituto de Salud Carlos III (PI15/02019) and the European Regional Development Fund (ERDF) “A way to make Europe.” The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Sanchez-González is an employee of Philips Healthcare. Dr. Bueno has received research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and MEDSCAPE-the heart.org.S

An anti-large T-antigen strategy to develop anti-JCV drugs

There are currently no JCV-specific therapies available for clinical use. This study evaluates viral large T antigen (LTA) as a potential target for drug development. LTA is a hexameric protein with a helicase activity that is powered by ATP binding and hydrolysis. The helicase and ATPase function is critical for viral replication and inhibition by small molecules would disrupt the viral life cycle. LTA is a valid target for discovery of anti-JCV drugs. The hits identified are reasonable starting points for medicinal chemistry to improve potency and selectivity. Screening of additional chemical libraries could also be considered to identify chemical structures that may be more potent with acceptable cytotoxicity

Cartographies of the Body in Pandemic Times

As Fox and Alldred (2020) note, culture/nature dualism has supplied post-Enlightenment philosophers, scientists and social scientists with a neat way to set limits on the respective Cartographies of the Body in Pandemic Times Saúde em Redes. 2022; 8 (3) 494 concerns of the social and natural sciences (see also Barad, 2007; Braidotti, 2013; Fullagar et al., 2019). This dualism has also enabled the creation of distinctions between “modern” (read “civilised”) and “traditional” (read “primitive”) bodies and ways of being-in-the-world. Yet, when critically exploring issues of embodiment, the influence of the built environment on well-being, climate transitions and/or the ongoing Covid-19 pandemic such distinctions start to become problematic, as eloquently argued in the last three decades by feminist, post-human, newmaterialist and political ecological –among others– debates and propositions. Giving continuity to an ongoing dialogue started in 2018 between scholars and activists from Latin America and Europe, we organized the online seminar “Re-assembling the nature-culture-body nexus: practices and epistemologies”. In this two-parts online event was explored how the interrelated domains of health, physical activity, and education can look like from perspectives that de-stabilise established ontological boundaries between nature, culture, the body, and their relationship. This paper is the transcription of the second session, called “Cartographies of the body in pandemic times”, and present the dialogues between Alice del Gobbo, Carla Panico, Gianluca De Fazio, Alexandre Fernandez Vaz and Eduardo Galak, researchers from Brazil, Italy Portugal and Argentina

Human organotypic retinal cultures (HORCs) as a chronic experimental model for investigation of retinal ganglion cell degeneration

There is a growing need for models of human diseases that utilise native, donated human tissue in order to model disease processes and develop novel therapeutic strategies. In this paper we assessed the suitability of adult human retinal explants as a potential model of chronic retinal ganglion cell (RGC) degeneration. Our results confirmed that RGC markers commonly used in rodent studies (NeuN, bIII Tubulin and Thy-1) were appropriate for labelling human RGCs and followed the expected differential expression patterns across, as well as throughout, the macular and para-macular regions of the retina. Furthermore, we showed that neither donor age nor post-mortem time (within 24 h) significantly affected the initial expression levels of RGC markers. In addition, the feasibility of using human post mortem donor tissue as a long-term model of RGC degeneration was determined with RGC protein being detectable up to 4 weeks in culture with an associated decline in RGC mRNA and significant, progressive, apoptotic labelling of NeuNþ cells. Differences in RGC apoptosis might have been influenced by medium compositions indicating that media constituents could play a role in supporting axotomised RGCs. We propose that using ex vivo human explants may prove to be a useful model for testing the effectiveness of neuroprotective strategies