High efficacy of photodynamic therapy on rat endometrium after systemic administration of benzoporphyrin derivative monoacid ring A

BACKGROUND: The aim of this study was to evaluate the effect of the benzoporphyrin derivative monoacid ring A (verteporfin)‐mediated photodynamic therapy (PDT) on rat endometrium and to determine the optimal drug concentration for endometrial ablation. METHODS: Five minutes after i.v. injection of different concentrations of verteporfin into 24 female Sprague-Dawley rats, 630nm light treatment was delivered for 500 s (120J/cm2) to the left horn of the uterus. The 24 rats were divided into six groups according to the drug dose injected, four rats per group: group I (2 mg/kg), group II (1 mg/kg), and groups III, IV, V and VI with 0.5, 0.25, 0.125 and 0.0625mg/kg respectively. Four days later, the rat uteri were analysed by light microscopy. RESULTS: Endometrial destruction was seen in all six groups, with the most significant result in group I (P < 0.008). Conservation of the myometrium was most significant in groups III, IV, V and VI. Acute inflammatory cells in the stromal endometrium were recorded mainly in groups I and II. However, the drug dosage that was most significant in destroying the glands with conservation of the myometrium and not causing severe inflammation was between 0.5 and 0.125mg/kg. CONCLUSIONS: Verteporfin was effective in endometrial ablation in all our animal groups, and the dose range of 0.5-0.125mg/kg appeared to be adequate. This observation will have to be scaled for clinical applicatio

Identification des usages de Sclerocarya birrea (A. Rich) hoscht dans la zone du Ferlo (Senegal) et evaluation du potentiel biochimique et nutritionnel de son fruit

Le prunier d’Afrique ou Sclerocarya birrea est un arbre fruitier de la famille des Anacardiaceae, qui fournit aux populations des fruits consommables pendant la période de soudure. Bien que présente dans les régions à climat soudano-sahélien du Sénégal, sa zone de prédilection demeure le Ferlo. Elle y fait l’objet de réhabilitation dans la mise en place du programme de l’Union Africaine dite de la muraille verte. Malheureusement, peu d’études scientifiques n’ont encore fait mention de la composition nutritive des fruits issus de cette zone. Dans le cadre de la reconstitution du couvert végétal des zones arides, la connaissance des relations entre l’homme et son milieu s’avère importante. Ainsi, la présente étude est entreprise dans le but de connaître les usages de Sclerocarya birrea et les potentialités qu’offre son fruit. Des enquêtes ethnobotaniques ont permis de recueillir les connaissances sur les usages de l’espèce dans la zone du Ferlo (Sénégal). Des échantillons de fruits mûrs récoltés ont été analysés grâce à des techniques de dosages normalisés et conventionnelles. Les résultats révèlent que les populations du Ferlo connaissent bien S. birrea, dont l’usage médicinal est de loin le plus important (79%). En usage médicinal, les organes végétaux les plus utilisés sont les écorces et les feuilles. Les résultats obtenus sur la pulpe du fruit montrent qu'elle constitue une bonne source en vitamine C, en sucres, en Calcium, Magnésium, Potassium, Sodium et en Polyphénols totaux. L'huile de l'amande présente des caractéristiques qui dans l'ensemble restent dans la norme admise pour les huiles alimentaires. Ces résultats sont marqués par une forte variabilité de la composition physico-chimique qui semble être liées aux variations des conditions édaphiques et climatiques. Il ressort de cette analyse que le fruit de S. birrea constitue une excellente source de nutriments et peut valablement combler certaines carences nutritionnelles des populations autochtones. Par ailleurs, le fruit présente aussi des potentialités de transformation et de conservation qui doivent être explorées.Mots clés:  Sclerocarya birrea, fruits, usages, valeurs nutritionnelles, polyphénols, vitamine C, variabilité, FerloEnglish AbstractThe present study was undertaken to know the uses and some nutritional potentials of Sclerocarya birrea. The African plum tree called Sclerocarya birrea is a fruit tree of the Anacardiaceae family, which provides populations some consumable fruits during the lean season. Although it is present in Sudano-Sahelian regions of Senegal, its favorite repartition zone is the Ferlo. Sclerocarya birrea is being rehabilitated in the framework of the implementation of the African Union program called the “Green Wall”. Unfortunately, no scientific studies have mentioned the nutritional content of fruits coming from this area. In the context of the reconstitution of the vegetation cover, knowledge of the relations between man and his environment is important. Thus, the present study is undertaken with the aim of knowing the uses of Sclerocarya birrea and its fruits attibutes. According to that, ethnobotanical surveys have gathered knowledge on the species' uses in the Ferlo area (Senegal). Samples of ripe fruits harvested were analyzed using standard and conventional assay techniques. The results revealed that the populations of the Ferlo are well acquainted with Sclerocarya birrea and that its medicinal use is by far the most important (79%). In medicinal use, the most commonly used plant organs are barks and leaves. The results obtained on the pulp of the fruit showed that it is a good source of vitamin C, sugars, Calcium, Magnesium, Potassium, Sodium and total polyphenols. The almond oil has characteristics that remain within the accepted food standards. These results are marked by a high variability in the physicochemical composition, which appears to be linked to variations in edaphic and climatic conditions. The analysis shows that the fruit of Sclerocarya birrea is an excellent source of nutrients and can validly fill certain nutritional deficiencies of indigenous peoples. The fruit also has potential for transformation that needs to be explored.Keywords: Sclerocarya birrea, fruits, uses, nutritional values, polyphenols, vitamin C, variability, Ferl

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged &lt;70 y and in &gt;4% of those &gt;70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals &lt;70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals &lt;40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-α and/or IFN-ω are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or IFN-ω (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients &gt;80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or IFN-ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% &gt;80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals &lt;70 years, 2.3% between 70 and 80 years, and 6.3% &gt;80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases. © 2021 The Authors, some rights reserved