I.M. Sechenov First Moscow State Medical University

About: I.M. Sechenov First Moscow State Medical University is a education organization based out in Moscow, Russia. It is known for research contribution in the topics: Medicine & Population. The organization has 7984 authors who have published 9355 publications receiving 68997 citations.

Classical Examples of the Concept of the ASIA Syndrome.

Abstract: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjogren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

Medicinal Plants as a Potential and Successful Treatment Option in the Context of Atherosclerosis

Abstract: Atherosclerosis is a chronic multifactorial disease characterized by mainly changes of blood lipids profile and inflammation in vessel wall. The cardiovascular disease based on atherosclerosis is currently the leading cause of mortality in developed countries. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects such as anti-inflammatory, antioxidant, anti-atherogenic, hypotensive, lipid-lowering, anti-thrombotic. Moreover, most of medicinal plants are characterized by their pleiotropic anti-atherosclerotic action. In addition, the medicinal plants-derived pharmacological substances and/or compounds are characterized by relative safety and fewer side effects that allows considering them as one of potential anti-atherosclerotic effective agents. The direct anti-atherosclerotic effect of some medicinal plants was confirmed in clinical trials of carotid Intima-media thickness (IMT) progression during long-term medication with medicinal plants. This review attempted to determine the current status of the databases PubMed and Scopus (until November, 2019) to investigate the medicinal plants possessing anti-atherosclerotic activity in experimental and clinical studies.

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.

Abstract: We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n = 15, normal cognition, treatable seizures), 2) intermediate epilepsy (n = 33, mild ID, partially pharmaco-responsive), 3) developmental and epileptic encephalopathy (DEE, n = 177, severe ID, majority pharmaco-resistant), 4) generalized epilepsy (n = 20, mild to moderate ID, frequently with absence seizures), 5) unclassifiable epilepsy (n = 127), and 6) neurodevelopmental disorder without epilepsy (n = 20, mild to moderate ID). Groups 1-3 presented with focal or multifocal seizures (median age of onset: four months) and focal epileptiform discharges, whereas the onset of seizures in group 4 was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human NaV1.6 channels and whole-cell patch-clamping. Two variants causing DEE showed a strong gain-of-function (GOF, hyperpolarising shift of steady-state activation, strongly increased neuronal firing rate), and one variant causing BFIE or intermediate epilepsy showed a mild GOF (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (LOF, reduced current amplitudes, depolarising shift of steady-state activation, reduced neuronal firing). Including previous studies, functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested GOF variant had either focal (97, groups 1-3), or unclassifiable epilepsy (39), whereas 34 with a LOF variant had either generalized (14), no (11) or unclassifiable (6) epilepsy; only three had DEE. Computational modeling in the GOF group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. GOF variant carriers responded significantly better to sodium channel blockers (SCBs) than to other anti-seizure medications, and the same applied for all individuals of groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of LOF variant carriers and the extent of the electrophysiological dysfunction of the GOF variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that SCBs present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.

Diagnosis and Treatment of Peptic Ulcer in Adults (Clinical Guidelines of the Russian Gastroenterological Association, Russian Society of Colorectal Surgeons and the Russian Endoscopic Society)

Abstract: Aim . These clinical recommendations present up-to-date methods for the diagnosis and treatment of peptic ulcer. The recommendations are intended for gastroenterologists and general practitioners. General provisions. Peptic ulcer (PU) represents a chronic relapsing disease occurring with alternating periods of exacerbation and remission. The main manifestation of the disease is the formation of a defect (ulcer) in the wall of the stomach and duodenum. Most cases of peptic ulcer are pathogenetically associated with the infection of H. pylori . PU can be an independent disease or represent symptomatic ulcers of the stomach and duodenum (medicinal, as a result of stress or endocrine pathologies, associated with chronic diseases of internal organs). In the absence of contraindications, esophagogastroduodenoscopy is recommended for all patients with suspected ulcer with the purpose of confirming the diagnosis. In order to determine indications for eradication therapy, all ulcer patients should be tested for the presence of H. pylori using a 13 C-breath test or a stool antigen test. In the case of simultaneous endoscopy, rapid urease test can be used. For the prevention of subsequent relapses of ulcer, all PU patients with confirmed H. pylori should undergo eradication therapy. In addition, in order to achieve ulcer healing, 4–6 week antisecretory therapy with proton pump inhibitors is recommended. Clinical recommendations contain criteria for assessing the quality of medical care, an algorithm of the doctor’s actions, as well as information for patients. Conclusions . These clinical recommendations present modern ideas about the etiology and pathogenesis of peptic ulcer disease, its clinical manifestations, methods of laboratory and instrumental diagnostics and basic approaches to conservative and surgical treatment.