Влияние локальной кортикостероидной терапии и такролимуса на морфофункциональные показатели кожи различных фототипов

Objective. To assess the effect of local corticosteroid therapy and Tacrolimus on the morphological and functional skin indices of different phototypes. Materials and methods. The authors conducted a complex assessment of the morphological and functional skin condition of different phototypes among healthy volunteers under the impact of corticosteroids and Tacrolimus. The study involved 20 healthy volunteers (10 people of the 1st and 2nd skin phototypes and 10 people of the 5th and 6th skin phototypes; 14 males and 6 females; mean age: 2з years). The morphological condition of the skin was assessed with the use of optical coherent tomography (Applied Physics Institute, Russian Academy of Sciences, Nizhny Novgorod) while the functional condition was assessed with the use of Multi Skin Test Center MC 750 (Courage+Khazaka Cologne, Germany). Results. The authors revealed that the application of local corticosteroids is accompanied with a reliable reduction in the epidermis thickness developing earlier in the subjects belonging to the 5th and 6th phototypes and, at the same time, increased transepidermal water loss and reduced corneous layer humidity. An increase in the corneous layer thickness accompanied by an increase in the humidity factor was registered in all phototypes in the areas where Tacrolimus was applied. It is possible to select the correct tactics of the anti-inflammatory therapy on the basis of monitoring the morphological and functional skin condition in the process of applying local corticosteroids: to determine the optimum duration of the corticosteroid therapy and switch to calcineurin inhibitors on a timely basis when there is a need to perform an antiinflammatory therapy to achieve the maximum efficacy with the minimum risk of complication development.Цель. Оценить влияние локальной кортикостероидной терапии и такролимуса на морфофункциональные показатели кожи различных фототипов. Материал и методы. Проведена комплексная оценка морфофункционального состояния кожи здоровых добровольцев различных фототипов под влиянием кортикостероидных средств и такролимуса. В исследовании приняли участие 20 здоровых добровольцев (10 человек I, II фототипов кожи и 10 человек V, VI фототипов; 14 мужчин и 6 женщин, средний возраст 23 года). Морфологическое состояние кожи изучали с помощью оптического когерентного томографа (ИПФ РАН, Нижний Новгород), функциональные — с помощью многофункционального комбайна Multi Skin Test Center MC 750 (“Courage + Khazaka Cologne”, Германия). Результаты. Установлено, что нанесение локальных кортикостероидов сопровождается достоверным уменьшением толщины эпидермиса, развивающимся в более ранние сроки у представителей V, VI фототипов, и параллельно наблюдающимся увеличением показателя трансэпидермальной потери воды и уменьшением показателя влажности рогового слоя. В зоне нанесения такролимуса зарегистрировано увеличение толщины рогового слоя у представителей всех фототипов, сопровождающееся увеличением показателя влажности. Мониторинг морфофункционального состояния кожи в процессе использования локальных кортикостероидов позволяет правильно выбрать тактику противовоспалительной терапии: определить оптимальную продолжительность кортикостероидной терапии и при необходимости продолжения противовоспалительной терапии осуществить своевременный переход на ингибиторы кальциневрина и таким образом добиться максимальной эффективности с минимальным риском развития осложнений

Oviduct fluid extracellular vesicles regulate polyspermy during porcine in vitro fertilisation

International audienceHigh polyspermy is one of the major limitations of porcine in vitro fertilisation (IVF). The addition of oviductal fluid (OF) during IVF reduces polyspermy without decreasing the fertilisation rate. Because extracellular vesicles (EVs) have been described as important OF components, the aim of this study was to evaluate the effect of porcine oviductal EVs (poEVs) on IVF efficiency compared with porcine OF (fresh and lyophilised). OF was collected from abattoir oviducts by phosphate-buffered saline flush, and poEVs were isolated by serial ultracentrifugation. Four IVF treatments were conducted: poEVs (0.2 mg mL(-1)), OF (10%), lyophilized and reconstituted pure OF (LOF; 1%) and IVF without supplementation (control). Penetration, monospermy and IVF efficiency were evaluated. Transmission electron microscopy showed an EVs population primarily composed of exosomes (83%; 30-150 nm). Supplementation with poEVs during IVF increased monospermy compared with control (44% vs 17%) while maintaining an acceptable penetration rate (61% vs 78% respectively) in a similar way to OF and LOF. Western blotting revealed poEVs proteins involved in early reproductive events, including zona pellucida hardening. In conclusion, our finding show that poEVs are key components of porcine OF and may play roles in porcine fertilisation and polyspermy regulation, suggesting that supplementation with poEVs is a reliable strategy to decrease porcine polyspermy and improve in vitro embryo production outcomes

Synthesis and Biological Evaluation of PSMA Ligands with Aromatic Residues and Fluorescent Conjugates Based on Them

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a suitable target for specific delivery of antitumor drugs and diagnostic agents due to its overexpression in prostate cancer cells. In the current work, we describe the design, synthesis, and biological evaluation of novel low-molecular PSMA ligands and conjugates with fluorescent dyes FAM-5, SulfoCy5, and SulfoCy7. In vitro evaluation of synthesized PSMA ligands on the activity of PSMA shows that the addition of aromatic amino acids into a linker structure leads to a significant increase in inhibition. The conjugates of the most potent ligand with FAM-5 as well as SulfoCy5 demonstrated high affinities to PSMA-expressing tumor cells in vitro. In vivo biodistribution in 22Rv1 xenografts in Balb/c nude mice of PSMA-SulfoCy5 and PSMA-SulfoCy7 conjugates with a novel PSMA ligand demonstrated good visualization of PSMA-expressing tumors. Also, the conjugate PSMA-SulfoCy7 demonstrated the absence of any explicit toxicity up to 87.9 mg/kg. © 2021 American Chemical Society. All rights reserved