Endocrine ophthalmopathy: pharmacogenetic markers of efficiency of glucocorticoid therapy

2020 ◽  
Vol 75 (3) ◽  
pp. 250-255
Author(s):  
Olga S. Toropova ◽  
Alevtina F. Brovkina ◽  
Dmitry A. Sychev
Keyword(s):  
Soft Tissues ◽  
Plasma Cells ◽  
Clinical Symptoms ◽  
Morphological Changes ◽  
Cellular Tissue ◽  
Pathological Process ◽  
Glucocorticoid Therapy ◽  
Orbital Tissue ◽  
Endocrine Ophthalmopathy ◽  
The Many

The pathological process of endocrine ophthalmopathy is based on damage to the soft tissues of the orbit against the background of impaired thyroid function and even its euthyroid state. The pathogenetic mechanisms of the development of clinical symptoms of endocrine ophthalmopathy (EOP) are based on morphological changes in extraocular muscles (EOM) and orbital tissue: cellular tissue infiltration by representatives of the immune system (T- and B-lymphocytes, macrophages, mast and plasma cells), with the production of pro-inflammatory cytokines, fibroblasts and glycosaminoglycans, contributing to an increase in the contents of the orbit in volume with the development of exophthalmos and tissue fibrosis at the end of the inflammatory process. Glucocorticoids are the gold standard for the pathogenetic treatment of patients with clinical forms of endocrine ophthalmopathy: edematous exophthalmos and endocrine myopathy. The properties of drugs of this group are such that they can be used to suppress all stages of inflammation in the orbital tissues, preventing the progression of the disease. Despite the many years of experience in applying various glucocorticoid therapy techniques, to date there are no uniform criteria for the effectiveness of this treatment in patients with endocrine ophthalmopathy. The article presents the features of glucocorticoid therapy of endocrine ophthalmopathy, as well as literature data, on the basis of which attempts have been made to explain the causes of glucocorticoid resistance taking into account the pharmacogenetic profile.

Phenotypes of endocrine ophthalmopathy: clinical manifestation and tomographic characteristics

2019 ◽  
Vol 64 (6) ◽  
pp. 383-389
Author(s):  
Irina M. Belovalova ◽  
Natalya Yu. Sviridenko ◽  
Elena G. Bessmertnaya ◽  
Anna A. Chepurina ◽  
Marina S. Sheremeta ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Ophthalmological Examination ◽  
Autoimmune Process ◽  
Endocrine Orbitopathy ◽  
Anatomical Structures ◽  
Clinical Criteria ◽  
Orbital Tissue ◽  
Endocrine Ophthalmopathy ◽  
Clinical Variants ◽  
Visual Disturbances

The clinical manifetstations of endocrine orbitopathy (EOP) significantly because autoimmune process may involve various anatomical structures of the eye. Choosing an effective method for EOP treatment requires to determine the selectivity of orbital tissue damage, which is difficult when only clinical criteria are applied. 102 patients with EOP and Graves’ disease were examined. All patients underwent the standard ophthalmological examination and multispiral computed tomography of orbits. The analysis of clinical and tomographic parameters allowed us to distinguish 3 variants of EOP flow: classical, lipogenic, and myogenic. The prevailing symptoms of patients with the lipogenic variant were distinct exophthalmos without a disturbance of the function of extraocular muscles (EOM) and visual disturbances. Oculomotor disorders, diplopia, strabismus, and decreased vision were prevalent in patients with the myogenic variant. Patients with the classical variant suffered from exophthalmos, periorbital edema, and oculomotor disorders. The identification of independent clinical variants of EOP with specific clinical symptoms and different tomographic characteristics testifies different pathogenetic mechanisms of EOP development is to determine personalized approaches to treatment.

scholarly journals A Case of Rhizomelic Chondrodysplasia Punctata in Newborn

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Nalan Karabayır ◽  
Gonca Keskindemirci ◽  
Erdal Adal ◽  
Orhan Korkmaz
Keyword(s):  
Soft Tissues ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Chondrodysplasia Punctata ◽  
Long Bones ◽  
Rhizomelic Chondrodysplasia Punctata ◽  
Cervical Spinal Stenosis ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Severe Growth

Rhizomelic chondrodysplasia punctate (RCDP) is a rare autosomal recessive peroxisomal disease. The main features of the disease are shortening of the proximal long bones, punctate calcifications located in the epiphyses of long bones and in soft tissues around joints and vertebral column, vertebral clefting, dysmorphic face, and severe growth retardation, whereas cervical spinal stenosis may also rarely be present. Imaging of the brain and spinal cord in patients with this disorder may aid prognosis and guide management decisions. We report the newborn diagnosed as CDP with cervical stenosis. Our aim is to discuss current knowledge on etiopathogenesis as well as radiological and clinical symptoms of diseases associated with CDP.

scholarly journals Regulation of mineralisation in bone and vascular tissue: a comparative review

2020 ◽  
Author(s):  
Lucie E Bourne ◽  
Caroline P Wheeler-Jones ◽  
Isabel R Orriss
Keyword(s):  
Soft Tissues ◽  
Vascular Tissue ◽  
Pathological Process ◽  
Signalling Molecules ◽  
Normal Bone ◽  
Comparative Review ◽  
Systemic Factors ◽  
Bone Mineralisation ◽  
Opposing Effects ◽  
Arterial Medial Calcification

Biomineralisation, the deposition of mineral onto a matrix, can be both a physiological and pathological process. Bone formation involves the secretion of an extracellular matrix (ECM) by osteoblasts and subsequent mineralisation of that matrix. It is regulated by a number of local and systemic factors and is necessary for maintenance of normal bone health. Conversely, mineralisation (or calcification) of soft tissues, including the vasculature, is detrimental to that tissue, leading to diseases such as arterial medial calcification (AMC). The mechanisms underlying AMC development are not fully defined, though it is thought that vascular smooth muscle cells (VSMCs) drive this complex, cell-mediated process. Similarly, AMC is regulated by a variety of enzymes and molecules, many of which have already been implicated in the regulation of bone mineralisation. This review will provide an overview of the similar, and sometimes opposing effects of these signalling molecules on the regulation of bone mineralisation and AMC.

scholarly journals Geno-phenotypic characteristics of Ehlers–Danlos syndrome: difficulties of disease type identification and approaches to pathogenetic treatment

2021 ◽  
Vol 66 (1) ◽  
pp. 22-30
Author(s):  
E. A. Nikolaeva ◽  
A. N. Semyachkina
Keyword(s):  
Connective Tissue ◽  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Symptomatic Treatment ◽  
Pathological Process ◽  
Social Adaptation ◽  
Molecular Defect ◽  
Ehlers Danlos Syndrome ◽  
Pathogenetic Therapy ◽  
Danlos Syndrome

Veltischev Researchand Clinical Institutefor Pediatricsofthe Pirogov Russian National Research Medical University, Moscow, Russia The article presents modern data on the most common monogenic connective tissue disease – Ehlers–Danlos syndrome. The authors describe two previous classifications of the syndrome: Berlin (1988) classification, which distinguishes 11 types of the disease, and Beyton (1998) classification, which includes 6 types of the syndrome and takes into account the results of molecular genetic studies. Particular attention is paid to a new classification, proposed by the International Consortium in 2017. This classification is based on the clinical and molecular genetic data and unites 13 types of Ehlers–Danlos syndrome, divided in 7 groups (A–G), depending on the main molecular defect. This defect determines the violation of various collagen structures (primary, spatial, cross-linking) and others constituents of the connective tissue (myomatrix, glycosaminoglycans, complement component, etc.). The classification provides general clinical symptoms for all types of the disease and comprehensive information on the specific signs of each of the 13 types of the syndrome.The authors discuss approaches to the pathogenetic therapy of the syndrome, the possibilities of symptomatic treatment, including both medications of different spectrum of action, and physiotherapeutic measures, exercise therapy. The complex of the listed therapeutic measures is aimed at stabilizing the main pathological process, preventing complications, improving the patient’s quality of life and social adaptation. The authors emphasize that correct patient management, targeted medical supervision and medical genetic counseling requires molecular genetic verification of the diagnosis.

scholarly journals Closed Fractures of the Distal Part of the Shin Bones. Different Types and Methods of the Treatment in Adolescence. Short Period Results

2021 ◽  
Vol 3 (1) ◽  
pp. 11-23
Author(s):  
Alexander I. Dorokhin ◽  
Alexander I. Krupatkin ◽  
Anastasia A. Adrianova ◽  
Vladimir I. Khudik ◽  
Dmitriy S. Sorokin ◽  
...  
Keyword(s):  
Distal Part ◽  
Clinical Investigation ◽  
Morphological Changes ◽  
Treatment Algorithm ◽  
Age Groups ◽  
Growth Zone ◽  
Difficult Problem ◽  
Pathological Process ◽  
X Rays ◽  
Short Period

Background.Fractures of the distal leg bones in children, due to the peculiarities of localization, the presence of a growth zone, the proximity of the joint and the involvement of the ligamentous apparatus in the pathological process, present a difficult problem in the choice of treatment and rehabilitation.Aims:In order to our aims we create the diagnostic and treatment algorithm in the system of early rehabilitation after fractures in the distal part of the shin bone in adolescence.Methods.Our clinical investigation based on the treatment of 56 patients in the age 817 years. Cohort of patients consist from three age groups: 811 years (n=13), 1214 years (n=28) and 1517 years (n=15). Examination was done with X-rays, CT and Ultrasound, specialy in the cases where the damage of ligamentous apparatus was suspicious. The main method of treatment was surgical osteosynthesis by pins, plates and screws. In the rehabilitation period the legs were immobilized by Plaster of Paris for 46 weeks.Results.In majority of cases the outcomes in the period of 68 weeks after trauma were good and satisfactory. The method of laser Doppler fluometry was performed in 16 cases in follow up period after trauma for examination of the regional blood circulation as a argumentation of regeneration process.Conclusion.The different choice in treatment of compound fractures of the distal part of the shin bones according to morphological changes in adolescence permits to aid good results in majority of caces.

scholarly journals The association gene’s TNFα G(308) with quantity of TNFα and degree of liver’s fibrosis in patients with chronic hepatitis C

2018 ◽  
Vol 22 (4) ◽  
pp. 682-685
Author(s):  
E.N. Usychenko ◽  
Yu.I. Bazhora ◽  
E.M. Usychenko ◽  
V.A. Gudz
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Chronic Hepatitis C ◽  
Degrees Of Freedom ◽  
Morphological Changes ◽  
Polymorphic Marker ◽  
Pathological Process ◽  
Hepatic Tissue ◽  
The Individual

The data on the polymorphism of cytokine genes associated with individual reactivity on the effects of hepatitis C virus, predict the rate of progression of liver fibrosis. The purpose of this work is study the association of the polymorphic marker G308A of the TNFα gene with its quantitative content and degree of liver fibrosis in patients with chronic hepatitis C. A total of 100 patients with CSF were examined. The polymorphism of G308A gene’s TNFα was studied by amplification of the corresponding genome zones by PCR. The assessment of the degree of fibrosis was performed using the non-invasive Fibrotest method. The study of the quantity of TNFα cytokine in serum of patients was performed by ELISA. The distribution of genotypes on the investigated polymorphic loci was verified using Pearson's χ2 criterion. The frequencies of alleles and genotypes in the groups were compared using Pearson's χ2 criterion with Yates correction for continuity with the number of degrees of freedom 1. In order to detect the correlation dependencies between the individual parameters, the Spearman correlation coefficient was applied. It was found that a smaller degree of fibrosis was observed in carriers of the GG TNFα genotype, and a greater degree of fibrosis in the carriers of the genotype AA TNFα (moderate feedback between the degree of fibrosis and the genotypes of TNFα). The higher content of TNFα is noted in the carriers of the AA genotype TNFα, the lower content of TNFα - in the carriers of the GG TNFα genotype (moderate feedback between the TNFα genotypes and the TNFα content). It has been established that a higher TNFα content is observed in patients with F1-F0 fibrosis, a lower TNFα content in patients with F2-F3 fibrosis (a strong correlation between the degree of fibrosis and the amount of TNFα cytokine). It is assumed that the production of the cytokine is determined at the genetic level, and the severity of changes in the cytokine profile in chronic hepatitis C affects the course of the pathological process. An increase in the TNFα content in chronic hepatitis C may be a marker for significant morphological changes in the hepatic tissue and high activity of the inflammatory process.

scholarly journals Fucoxanthin induced apoptotic cell death in oral squamous carcinoma (KB) cells

2021 ◽  
Vol 17 (1) ◽  
pp. 181-191
Author(s):  
Petchi Iyappan ◽  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Apoptotic Cell ◽  
Morphological Changes ◽  
Biological Activities ◽  
Squamous Carcinoma ◽  
Cancer Therapeutics ◽  
Kb Cells ◽  
Oral Squamous Carcinoma ◽  
The Many

Fucoxanthin (Fx) is an active compound commonly found in the many types of seaweed with numerous biological activities. The main goal of this investigation is to explore the effect of Fx against the cell proliferation, apoptotic induction and oxidative stress in the oral squamous (KB) cell line. Cytotoxicity of Fx was determined by MTT assay. The intracellular ROS production, mitochondrial membrane potential (MMP) and apoptosis induction in KB cells were examined through DCFH-DA, Rhodamine-123 and DAPI, and dual staining techniques. Effect of Fx on the antioxidant enzymes and lipid peroxidation in the KB cells was studied through the standard procedures. Fx treated KB cells showed morphological changes and reduced cell survival, which is exhibited by the cytotoxic activity of 50 μM/ml (IC50) Fx against the KB cells. The Fx treatment considerably induced the apoptotosis cells (EB/AO) and decreased the MMP (Rh-123) in KB cells. Further, it was pointed out that there was an increased lipid peroxidation (LPO) with decreased antioxidants (CAT, SOD and GSH). These results concluded that Fx has the cytotoxic effect against KB cells and has the potential to induce the apoptosis via increased oxidative stress. Hence, the Fx can be a promising agent for the treatment of oral cancer and it may lead to the development of cancer therapeutics.

scholarly journals Morphological changes of gastric and colonic mucosa in rats of different ages under the action of nanocrystalline cerium dioxide

2014 ◽  
Vol 68 (3) ◽  
pp. 46-50
Author(s):  
O. Iefimenko ◽  
O. Savchenko ◽  
T. Falalyeyeva ◽  
O. Kyric ◽  
M. Spivak
Keyword(s):  
Cerium Dioxide ◽  
Plasma Cells ◽  
Morphological Changes ◽  
Degenerative Changes ◽  
Control Group ◽  
Gastric Glands ◽  
Different Ages ◽  
Nanocrystalline Cerium Dioxide ◽  
Old Rats ◽  
Differentiation And Proliferation

We have studied the effect of nanocrystalline cerium dioxide (NCD) on the morphological state of the gastric mucosa and colon in rats of different ages. It was found the degenerative changes and dysregeneration (violation the ratio of value of major and parietal cells), atrophic or hyperplastic changes. NCD restored the processes of differentiation and proliferation of epithelial cells of gastric glands. In the control group of old rats mucosa of the colon was focal thinner, the cells had degenerative changes, it was observed the change in nuclear-cytoplasmic ratio of cells, were found foci of infiltration of lymphocytes, macrophages, plasma cells. NCD in old rats caused a decrease in the number of cells in a state of degeneration and apoptosis, increased proliferative activity of cells increased the number of goblet cells. Thus, NCD restored morpho-functional structure of the mucous of the stomach and colon.

Possibility of using recombinant monoclonal antibodies in the treatment of the coronavirus infection

2021 ◽  
pp. 8-13
Author(s):  
Vladimir Anatolievich Klimov
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Cells ◽  
Polyclonal Antibodies ◽  
Fatal Outcome ◽  
Humoral Response ◽  
Specific Protein ◽  
Pathological Process ◽  
Human Immune System ◽  
Risk Of Progression ◽  
Severe Degree

Monoclonal antibodies are successfully used to treat a number of viral diseases; they are produced by the plasma cells of the human immune system and are the result of a natural humoral response to the ingress of a certain antigen. Antibodies designed to target only one specific protein — in this case, the protein of the virus that causes COVID-19 — are called «monoclonal». Their purpose is to block the COVID-19 virus and prevent its penetration and replication in human cells, and their ultimate focus is on combating infectious manifestations. They are believed to cause fewer undesirable effects than convalescent plasma, which is essentially a complex of polyclonal antibodies and circulating immune complexes. Monoclonal antibodies can be synthesized in the laboratory using the blood serum of patients who have undergone this disease as a starting material. The use of monoclonal antibodies is indicated for patients with a mild and moderate form of the disease at a high risk of progression of the pathological process to a severe degree, which implies the need for hospitalization and a high probability of a fatal outcome.

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