Role of Folic Acid in Type 2 Diabetes

The metabolic condition known as diabetes mellitus is marked by hyperglycemia, a host of symptoms affecting the heart, kidneys, nerves, and other organs. Diabetes nephropathy is one of the leading causes of diabetic impermanence and morbid state. Low parameters of pteroylglutamic acid in the blood are associated with Diabetic Nephropathy, whereas endothelial dysfunction increases the risk for T2D. Endothelial dysfunction is associated with diabetes, which perhaps is caused by the disjunction of the endothelial nitric oxide (NO) synthase enzyme, which reduces NO availability. Because folic acid can repair the disjunction of NO synthase, we sought to see if pteroylglutamic acid supplementation may affect the function of the endothelial layer and inflammatory indicators in type 2 diabetes patients who did not have vascular disease. Recent studies have shown that pteroylglutamic acid also has direct benefits on the function of endo, in addition to its natural function of lowering homocysteine. Folic acid might serve as a "biomarker" for the function of endothelial cells. Many mechanisms have been linked to higher total homocysteine levels and type 2 diabetes risk in diabetic patients. Higher folic acid levels altered endothelial-dependent vasodilation in T2D patients. In patients with coronary heart disease (CAD), folic acid supplementation has been found to reduce homocysteine parameters and improve the function of the endothelial layer. On the other hand, RCTs looking at IR and T2D outcomes have shown mixed results. Several mechanisms link higher total homocysteine levels to increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2D). Treatment with folate has been shown to bring down homocysteine parameters and improve the endothelium functions in people with coronary heart disease (CAD). Randomized controlled trials (RCTs) on IR and T2D outcomes, on the other hand, have produced a wide range of results.

Endotelial dysfunction in condition of neoplastic intoxication

In patients with cancer, the risk of pulmonary embolism increases 4-7 times compared to other patients of the same age and similar concomitant diseases. The greatest risk exists after surgery and during chemotherapy. An increase in the risk of thrombosis in cancer patients is a multifactorial complex phenomenon, the causes of which are an increase in the number of platelets, changes in the rheological properties of blood, as well as reactive structural changes in the vascular wall, valves and endotheliocytes. The latter factor of pathogenesis is insufficiently studied and is not used to assess the risks of thrombosis and prevent thrombosis in cancer patients. However, this topic is promising in the search for opportunities to study the pathogenesis of pulmonary embolism, and, accordingly, to assess the risks in different groups of patients and methods of prevention and options for clinical tactics in cases of venous thrombosis.Objective. To find out the dynamics of the concentration of lipid peroxidation products, in particular the activity of phospholipase and catalase in experimental neoplastic intoxication. Material and methods. For the experiment, 12 sexually mature nonlinear male rats with a body weight of 170-180 g were selected. by injecting 7.2 mg/kg into the rat interscapular area at the rate of 0.1 ml of dimethylhydrazine hydrochloride (DMG) solution 1.2 – DMG (SIGMA-ALDRICH CHEMIE, Japan, D161802 series), previously diluted with isotonic sodium chloride solution per 10 grams of rat body weight, a tumor was modeled intoxication. On day 30 of the experiment, the animals were sacrificed, and the material of the venous wall of the lower extremities was studied for the morphological structure of the vascular wall.Results and Discussion. Morphological examination of the drug revealed platelet thinning, desquamation and microscopic reorganization of endotheliocytes, focal loss of endothelial layer integrity, and wavy thickening of the intima. This complex of phenomena can be the basis of the pathogenesis of thrombosis in combination with a violation of hemodynamics and rheological properties of blood. On day 30 of the experiment, a morphological study of the drug was performed on the venous wall of rats.Conclusions. Changes that were detected after modeling chronic tumor intoxication include endothelium changes in the form of desquamation and reorganization, violation of the integrity of the endothelial layer, wavy thickening of the intima, fibrotic changes in all the membranes of the vessel.

The Effect of Bioregulators Isolated from Blood Serum and Cornea of the Bovin’s Eye on the Condition of Tissue and Cells of the Rabbit Corneas during Cultivation and Storage

Objective: to study the condition of the cornea, as well as its epithelial and endothelial cells, while maintaining in vitro at various temperature conditions, under the influence of a number of factors, including bioregulators isolated from blood serum and cornea of the bovine, and epidermal growth factor.Methods. The study was carried out on rabbit corneas stored at temperatures of +4, –86 °C, as well as the cultivation of endothelial and epithelial cells isolated from the cornea after storage at these temperatures, followed by histological and immunohistochemical studies.Results. Storage of the cornea at +4 °C for 10 days leads to corneal edema and significantly reduces their transparency, both bioregulators partially prevent a decrease in the transparency of the cornea, while the endothelial layer lyses in groups with the addition of epidermal growth factor and corneal bioregulator; but remains in the cornea with the addition of a serum bioregulator. All three factors contribute to the preservation of the Bowman membrane. In the corneas stored at –86 °C on the 30th day, a preserved endothelial layer was observed, and the epithelium retained its multilayering in all groups with the addition of factors other than the control group. In the control samples, the epithelial layer partially exfoliated, the endothelial layer was almost completely lysed. Both bioregulators stimulated the proliferation of cells isolated from the native cornea and enhanced the action of the epidermal growth factor. Similar results were obtained on cells isolated from stored corneas for 2 weeks at –86 °C. In the case of combined use of the epidermal growth factor and bioregulators on the 30th day, the endothelial layer was mainly preserved, the Descemet’s membrane was not broken. In the control samples, the epithelium was mainly single-layered, partially exfoliated, and the endothelial layer was completely lysed.Conclusion. Storage of cornea during hypothermia (+4 °С) does not provide corneal viability for longer than 10 days. Storage under conditions of cryopreservation (–86 °C) ensures the viability of the cornea for 60 days. Adding bioregulators and an epidermal growth factor to the basic preservation medium allows one to obtain a structurally safe and viable cornea, while all cellular layers of the cornea, including the endothelial layer, are preserved and viable.

Pilot identification of the Live-1/Prox-1 expressing lymphatic vessels and lymphatic elements in the unaffected and affected human brain

We report here a pilot identification of the presence of the lumenized Lyve-1/Prox-1-expressing vessels with distinct walls composed of a single endothelial layer in the unaffected brain and with intraventricular hemorrhages. These lymphatic vessels (LVs) have valves and an undulating shape in the distal region that is the classical characteristic of lymphatic precollectors. Furthermore, we identified Lyve-1/Prox-1-expressing lymphatic elements in the enlarged perivascular spaces. These pioneering results might be a revolutionary step in our understanding of anatomy and physiology of the cerebral lymphatics and stimulate a reassessment of basic assumptions in the aetiology of brain diseases associated with lymphatic dysfunction. The discovery of the cerebral LVs is a crucial step in the development of breakthrough technologies of modulations of lymphatic removing of toxins and blood from the brain.

Shunt coronarography in patients with recurrent stenocardia in long term after aorto-coronary bypass

Проблема профилактики и диагностики стеноза - окклюзирования шунтов после аорто - коронарного шунтирования в отдаленном периоде остается нерешенной. Наиболее часто закрываются шунты в течение первого года, возникновение окклюзии венозных шунтов в течение первого года после операции наблюдаются у 25-30% больных, в дальнейшем в течении 5-7 лет частота окклюзии составляет около 2% в год, после этого срока 5% в год. Артериальные шунты остаются проходимы до 98%, и в основном причиной их дисфункции является прогрессирование атеросклеротического процесса и технические погрешности. Основными причинами которые могут привести к нарушению функции шунта в отдаленном периоде считают [1, 2, 4, 6, 8] следующие: 1-техническое (повреждение эндотелиального слоя и стенки аутовенозного трансплантата при его взятии (ретроспективный анализ), чрезмерная длина и перегиб шунта (на шунтографии), натяжение шунта из-за недостаточной его длины, неправильный выбор места наложения дистального анастомоза) [11,12,13]. 2- анатомические факторы[3, 5, 7] . 3 - общие факторы (низкая объемная скорость кровотока по шунту, нестабильность общей гемодинамики, массивные сращения в полости перикарда, гиперкоагуляция, гнойный медиастинит, длительное лихорадочное состояние и неадекватный прием антикоагулянтов. 4 - прогрессирование атеросклероза [9]. 5- использование венозных трансплантантов как одна из важных причин стеноза - окклюзии шунта [10]. The Problem of stenosis prevention and diagnostics - occlusion of shunts after aorto-coronary bypass in long term remains unaddressed. Typically, shunts are closed within the first year, emergence of phleboid shunts occlusion within the first year after surgical intervention is observed in 25-30% of patients, and further frequency of occlusion within 5-7 years is about 2% per year, 5% per year after this term. Arterial shunts is passable up to 98%, and mainly the reason for their dysfunction is the atherosclerotic process progression and technical faults. The main reasons which can results in shunt dysfunction in long term are the following [1, 2, 4, 6, 8]: 1-technical (damage of endothelial layer and paries of autovenous transplant during its drawing (retrospective analysis), excess length and shunt bend (at the shuntography), shunt tension because of its insufficient length, improper location of distal anastomosis application) [11,12,13]. 2- anatomical factors [3, 5, 7] . 3 - general factors (low volumetric blood flow along the shunt, instability of general hemodynamics, dense adhesion in pericardial cavity, hypercoagulability, purulent mediastinitis, prolonged febrile state and inadequate intake of anticoagulants. 4 - atherosclerosis prgression [9]. 5- using venous transplants as one of the important reasons of stenosis - shunt occlusion [10].

POS0613 TOCILIZUMAB DECREASES ANGIOGENESIS IN RHEUMATOID ARTHRITIS THROUGH ITS REGULATORY EFFECT ON EMMPRIN/CD147

Background:Angiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is an immunosuppressant used in the treatment of RA patients, but its effects on angiogenesis and the molecular mechanisms regulating new blood vessel formation are not fully elucidated.Objectives:To evaluate the concentrations of pro- and anti-angiogenic factors in serum samples of RA patients, before and after the initiation of TCZ treatment and to explore in an in vitro co-culture system the mechanisms of TCZ action.Methods:We evaluated the concentrations of EMMPRIN, VEGF, MMP-9, IL-6, NGAL, endostatin and thrombospondin-1 (Tsp-1) using commercial ELISA kits from 40 RA patients, before and 4 months after the initiation of TCZ treatment. The levels of secreted EMMPRIN, VEGF MMP-9 and Tsp-1 were measured in an in vitro co-culture system of HT1080 fibroblasts and U937 monocytes with and without addition of anti-EMMPRIN blocking antibody. In the tube formation assay serum samples and supernatnats from the co-cultures were added to endothelial layer. Images were obtained after 6 hours of incubation and the number of closed lumens were counted in two separate fields. In the wound assay, supernatants from the co-cultures, with or without the addition of the anti-EMMPRIN antibody were added to the endothelial layer after scratching. The scratch site area was measured immediately and compared to the area after 24 hours of incubation to assess the distance of cell migration.Results:Study population included 40 RA patients, 33 (82.5%) females, mean age of 57.5±11.1 years, disease duration of 7.7±5.6 years, and 53.9% positive for rheumatoid factor initiating treatment with TCZ. In this patient cohort, 25/40 (62.5%) patients were classified as “responders” according to EULAR criteria.Following 4 mounts of treatment, statistically significant reductions in the levels of EMMPRIN/CD147 (p=0.035), without significant changes in serum levels of MMP-9, VEGF, MMP-3 and MMP-7 and of the anti-angiogenetic factors Tsp-1 and endostatin were found. A statistically significant decrease in the ratio between the pro-angiogenic factor EMMPRIN and the anti-angiogenic factor Tsp-1 that was calculated for each patient 4 months after initiating TCZ was found(p=0.031). The decrease in angiogenesis was manifested by the reduced number of closed lumen tube-like structures formed by EaHy926 endothelial cell line after incubation with serum samples 4 months after initiation of TCZ, relative to the number of closed lumens formed prior to TCZ initiation (p=0.007). The ratio between EMMPRIN and Tsp-1 was significantly reduced in the responding patients versus non-responders (p=0.033), while the levels of VEGF, MMP-9, Tsp-1, and EMMPRIN were unchanged.In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased in the co-culture, while the accumulation of the anti-angiogenic factor Tsp-1 was decreased. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation, and tube-like structure formation in functional assays.Conclusion:Our findings suggest an important role for EMMPRIN in mediating pro-angiogenic signals in RA patients, with EMMPRIN/Tsp-1 ratio serving as a marker of angiogenesis in RA. When administered to RA patients, TCZ in turn, exerts an anti-angiogenic effect through its regulation of EMMRPIN/CD147 levels.Disclosure of Interests:None declared