Rapid Effect of Treatment of Psoriatic Erythrocytes with the Synthetic Retinoid Acitretin to Increase 8-Azido Cyclic AMP Bindings to the RI Regulatory Subunit

We have recently demonstrated a deficiency in the cyclic adenosine monophosphate (cAMP) – dependent protein kinases (PKA), the intracellular mediator of AMP, in psoriasis. This enzyme defect is expressed in fibroblasts and in red blood cells isolated from psoriatic patients. In these cells, the abnormality noted in cAMP binding to PKA correlates well with the severity of the disease and is corrected by long-term treatment with etretinate. In this study, we determined the effect of oral administration of acitretin in four psoriatic patients on the altered cAMP binding observed with the RI regulatory subunit of PKA in erythrocytes prepared from these patients. Acitretin (30 mg/day) induced a rapid (within 1 h) increase in the ability of the RI regulatory subunit of erythrocytes to bind the 8-azido[32P]cAMP photoaffinity analogue of cAMP. The maximal plateau for this effect of acitretin was observed within 24 h of treatment and preceded the clinical improvement of the disease. The effect of acitretin was dose-dependent, with the maximal response observed at 40 mg acitretin/d. In addition, the rapid exposure (15 mm) of erythrocytes isolated from untreated patients exhibiting severe psoriasis to acitretin also promoted an increase in binding of 8-azido[32P]cAMP to the RI cAMP binding protein. Retinoic acid and 13-cis-retinoic acid were as efficient as acitretin in inducing the increase in binding of 8- azido[32P]cAMP to the RI regulatory subunit, whereas arotinoid was without effect. These results suggest that acitretin may act to modify PKA (the RI regulatory subunit) at the post-transcriptional level, and this may reflect, in part, on the mechanism of action of this synthetic retinoid. Further, monitoring this biochemical event may be helpful in determining the choice of retinoid therapy and in the management of its pharmacology

Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature

<p>Abstract</p> <p>Background</p> <p>Somatotropinoma, a pituitary adenoma characterised by excessive production of growth hormone (GH), is extremely rare in childhood. A genetic defect is evident in some cases; known genetic changes include: multiple endocrine neoplasia type 1 (MEN1<it>)</it>; Carney complex; McCune-Albright syndrome; and, more recently identified, aryl hydrocarbon receptor-interacting protein (AIP). We describe seven children with somatotropinoma with a special focus on the differences between genetic and sporadic forms.</p> <p>Methods</p> <p>Seven children who presented in our regional network between 1992 and 2008 were included in this retrospective analysis. First-type therapy was somatostatin (SMS) analogues or transsphenoidal surgery. Control was defined as when insulin-like growth factor-1 (IGF-1) levels were within the normal range for the patient's age at 6 months after therapy, associated with decreasing tumour volume.</p> <p>Results</p> <p>Patients were aged 5-17 years and the majority (n = 6) were male. Four patients had an identified genetic mutation (McCune-Albright syndrome: n = 1; MEN1: n = 1; AIP: n = 2); the remaining three cases were sporadic. Accelerated growth rate was reported as the first clinical sign in four patients. Five patients presented with macroadenoma; invasion was noted in four of them (sporadic: n = 1; genetic: n = 3). Six patients were treated with SMS analogues; normalisation of IGF-1 occurred in one patient who had a sporadic intrasellar macroadenoma. Multiple types of therapy were necessary in all patients with an identified genetic mutation (4 types: n = 1; 3 types: n = 2; 2 types: n = 1), whereas two of the three patients with sporadic somatotropinoma required only one type of therapy.</p> <p>Conclusions</p> <p>This is the first series that analyzes the therapeutic response of somatotropinoma in paediatric patients with identified genetic defects. We found that, in children, genetic somatotropinomas are more invasive than sporadic somatotropinomas. Furthermore, SMS analogues appear to be less effective for treating genetic somatotropinoma than sporadic somatotropinoma.</p

Integrated process for extraction and formulation in emulsions of active molecules from fresh passion fruits (Passiflora edulis Sims)

Intensified green processes were investigated to extract several classes of active molecules from fresh purple passion fruits, and to prepare emulsions directly by extrusion for the fruit comprehensive utilization. A thermo-mechanical treatment was carried out through a discontinuous process from the edible part and through a continuous process by twin-screw extrusion using the whole fruit. Only mechanical energy was applied to the materials to generate a liquid fraction (filtrate) and a solid residue. Lipid contents of the obtained filtrates ranged from 0.5 to 2.6 g/100 g close to the extractible lipophilic part. Polyphenols extraction was improved when using the whole fruit and with the addition of water in extrusion. In-situ emulsions with droplets sizes between 2 and 8 μm were obtained. Emulsions obtained after extrusion showed an enhanced stability. This way represents a green alternative method to solvent extractions applied to the different parts of the fruit, and leads to bio-based emulsions enriched in vegetable oil, natural antioxidants and emulsifiers, such as phospholipids, proteins, polysaccharides, pectins and polyphenols

Semi‐Siccative Oils and Bioactive Fractions Isolated from Reunion Island Fruit Co‐Product: Two Case Studies

Semi-Siccative Oils and Bioactive Fractions Isolatedfrom Reunion Island Fruit Co-Product: Two Case StudiesAlice Delvar, Pascale de Caro,* Yanis Caro,* Alain Shum Cheong Sing, Rudy Thomas,and Christine RaynaudThis paper focused on the use of agro-industrial wastes of strawberry guava (Psidiumcattleianum) and passion fruit (Passiflora edulis) generated by the agriculturalindustry on Reunion Island, according to two routes: extraction of semi-siccative oilsfrom the seeds and extraction of bioactive compounds from residual pulp and peels.Oil content, fatty acid, carotenoids, tocopherol, and sterol concentrations aredetermined in the seed oils obtained by four different extraction processes usingSoxhlet extraction, extraction by hexane and ethanol, mechanical pressing andsupercritical-carbon dioxide (SC-CO2) extraction. The oil extraction yields ranged from15 to 30% w/w for strawberry guava and passion fruit, respectively. Both oils areclassified as semi-siccative and had a similar total unsaturated fatty acid content(88%) with a prevalence of linoleic acid (70–78%). High contents in phytosterols andinα-tocopherol are particularly detected in strawberry guava oil. The antioxidantactivities of the bioactive compounds extracted by water and ethanol from pulp andpeels are characterized byα,α-diphenyl-β-picrylhydrazyl (DPPH) test. After purificationon polymeric resin, significant antioxidant activities are recorded (half maximalinhibitory concentration (IC50) from 11 to 50 g L-1) and are related to polyphenolcontents (20.7 to 42.5 g gallic acid equivalents (GAE)/100 g dry extract).Practical Applications: There is a great interest on the use of tropical fruit wastesbecause of their large availabilities. Strawberry guava and passion fruit are often usedin the food industry, for juice and jam production. The seeds, pulp, and peel residuesare in fact a by-product of their industrial processing, which should be valuablyprocessed instead of just throwing away. We can state that the extracted seed (richin polyunsaturated fatty acids) of strawberry guava and passion fruit can be used inthe industrial production of emulsions, paints, and varnishes. Within the positiveaspects of the study, one can also distinguish the use of these tropical fruit by-products as beneficial sources of many valuable bioactive compounds, for example,carotenoids, tocopherols, phytosterols, and especially polyphenols, for functionalformulations. Moreover, it may be the experimental basis for further developmentand use in food industr

Erratum: Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders (The American Journal of Human Genetics (2020) 106(3) (356–370), (S0002929720300197), (10.1016/j.ajhg.2020.01.019))

(The American Journal of Human Genetics 106, 356–370; March 5, 2020) In the version of this paper originally published, the underlying cause for Hunter McAlpine syndrome was incorrectly described in Table 1. The relevant description has been changed to read “Chr5q35-qter duplication involving NSD1” in the updated Table 1 reflected here. The authors apologize for this error

Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders

Éléments filmographiques

Raynaud Pascale. Éléments filmographiques. In: 1895, revue d'histoire du cinéma, numéro hors-série, 1997. Le relief au cinéma. pp. 189-196

Témoignage 1. Programmer le cinéma au musée : pour une conscience critique du spectateur

« Le Cinéma contient [tous les arts], les ordonne et les accorde tous en multipliant par la sienne propre leur puissance. »Élie Faure, Fonction du cinéma La présence d’une programmation de cinéma dans un musée est ancienne. Dès 1935, en effet, Alfred H. Barr, premier directeur du MoMA, mettait sur pied une Film Library, création assortie, dès l’inauguration du musée en 1939, d’une programmation culturelle de grande ampleur présentée dans une salle de quatre cent cinquante places intégrée au b..

Éléments filmographiques

Raynaud Pascale. Éléments filmographiques. In: 1895, revue d'histoire du cinéma, numéro hors-série, 1997. Le relief au cinéma. pp. 189-196

Byllis (Albanie), bâtiments proto-byzantins du site. Présentation du site, fortifications, basiliques A, C et D

International audienc