Amiodarone-induced thyrotoxicosis: state of the art

The review presents recent data on the pathogenesis, diagnosis and treatment of amiodarone-induced thyrotoxicosis (AIT), which is a frequent complication of amiodarone (Am) therapy. Changes in secretion and metabolism of thyroid hormones are described under the influence of short-term and long-term therapy. The development of AIT leads to worsening of arrhythmias, aggravation of circulatory insufficiency, deterioration of the patients condition. Two types of AIT are distinguished, as well as mixed form. Diagnostic criteria of AIT type 1 and AIT type 2 are described. The most informative test for differential diagnosis between first and second types of AIT and mixed forms is ultrasound examination of the thyroid gland with Doppler blood flow evaluation and radionuclide scanning with 99 mTc-sestaMIBI. Medical management is determined by the type of AIT, the state of cardiovascular system and the risk of recurrent arrhythmias. Pharmacological management of AIT depends on its type and comprises the use of anti-thyroid medications or glucocorticoids. The possibility of continuing antiarrhythmic amiodarone therapy in patients who underwent AIT is discussed. In patients with AIT type 1 and mixed form drug cancellation is required, if this is not possible radical treatment of thyrotoxicosis (radioiodine therapy, thyroidectomy) is applied. AIT type 2 is a self-limiting process with life-threatening arrhythmias, and amiodarone therapy can be continued. The effectiveness of radioiodine therapy for radical treatment of AIT type 1 and type 2 is shown in spite of low radioiodine capture. However, this issue requires further investigation and discussion. Plasmapheresis and thyroidectomy are used for rapid restoration of euthyroidfunction in severe patients

Body Height of Children with Bronchial Asthma of Various Severities

Influence of bronchial asthma (BA) severity on physical development in children patients was evaluated in comparison with healthy population. Materials and Methods. 1042 children and adolescents (768 boys) with atopic BA were evaluated. All children underwent standard examination in a clinical setting, including anthropometry. The control group included 875 healthy children of a comparable age (423 boys). Results. The fraction of patients with the normal, lower, and increased height among the whole group of patients with BA is close to the corresponding values in the healthy population (χ2=3.32, p=0.65). The fraction of BA patients with the reduced physical development is increased monotonically and significantly when the BA severity increases: healthy group, 8.2% (72/875), BA intermittent, 4.2% (6/144), BA mild persistent 9% (47/520), BA moderate persistent, 11.7% (36/308), and BA severe persistent, 24.3% (17/70) (χ2=45.6, p=0,0009). Conclusion. The fraction of the children with the reduced height is increased monotonically and significantly in the groups of increasing BA severities. At the same time, the fraction of such children in groups of intermittent and mild persistent BA practically does not differ from the conditionally healthy peers

4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing

4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors

4-methylumbelliferone Prevents Liver Fibrosis by Affecting Hyaluronan Deposition, FSTL1 Expression and Cell Localization

4-methylumbelliferone (4MU) is an inhibitor of hyaluronan deposition and an active substance of hymecromone, a choleretic and antispasmodic drug. 4MU reported to be anti-fibrotic in mouse models; however, precise mechanism of action still requires further investigation. Here we describe the cellular and molecular mechanisms of 4MU action on CCl4-induced liver fibrosis in mice using NGS transcriptome, Q-PCR and immunohistochemical analysis. Collagen and hyaluronan deposition were prevented by 4MU. The CCl4 stimulated expression of Col1a and αSMA were reduced, while the expression of the ECM catabolic gene Hyal1 was increased in the presence of 4MU. Bioinformatic analysis identified an activation of TGF-beta and Wnt/beta-catenin signaling pathways, and inhibition of the genes associated with lipid metabolism by CCL4 treatment, while 4MU restored key markers of these pathways to the control level. Immunohistochemical analysis reveals the suppression of hepatic stellate cells (HSCs) transdifferentiation to myofibroblasts by 4MU treatment. The drug affected the localization of HSCs and macrophages in the sites of fibrogenesis. CCl4 treatment induced the expression of FSTL1, which was downregulated by 4MU. Our results support the hypothesis that 4MU alleviates CCl4-induced liver fibrosis by reducing hyaluronan deposition and downregulating FSTL1 expression, accompanied by the suppression of HSC trans-differentiation and altered macrophage localization

4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing

4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors

Hematologic Features of Children and Adolescent Patients with Acute Hypersensitivity Reactions on Drugs and Food

Hematological parameters and blood biochemical markers were measured in 131 children and adolescent patients (70 boys) aged 2 to 17 years with acute hypersensitivity reactions induced by food (59 patients) and medicines (72 patients) in order to establish differences in clinical manifestations and hematological parameters in children with food and drug hypersensitivity and to elaborate the hematological criteria for differentiating the possible pathophysiological mechanisms of various types of hypersensitivity. Both groups of patients had comparable clinical symptoms with a predominance of skin lesions. The significant differences between the groups with drug- and food-induced hypersensitivity reactions were found in their red blood characteristics. In patients with hypersensitive reactions to drugs, significantly lower levels of erythrocytes and hemoglobin were found, while the median values of these parameters did not exceed the limits of reference values. These differences persisted also in the analysis of hemoglobin values, analyzed with accounting for the age and sex of patients. The reduction of hemoglobin was not accompanied by an increase in bilirubin in these patients. Thus, this fact does not support the assumption about the drug-induced hemolysis as a main effect influencing the hematological parameters. Hemogram evaluation performed during 7–10 days after admission demonstrated a higher level of hemoglobin in both groups. The biochemical markers were not significantly distinguished except bilirubin and alkaline phosphatase which were higher in patients with food-induced hypersensitivity

The Role of “Preventive Vaccination in Healthy Children and Children with Chronic Diseases” Discipline in the Specialist Training Curriculum in the Field of “Pediatrics”

This article presents the experience of teaching the discipline «Preventive Vaccination in Healthy Children and Children with Chronic Diseases». Its significance in preparation of students of pediatric departments of higher educational institutions of Russia is validated. It is shown that the majority of students have positive attitude to vaccination, however, they are not sufficiently informed about the organization of the process itself and they need to obtain such knowledge

Amino acid formulas in patients with food allergy

The article presents modern approaches to the use of balanced formulas for nutrition and diet correction in children with various forms of food allergies. The guidelines are based on all available up to date evidence on the efficacy, safety and utility of using such innovative medical technology as specialized amino acid formulas. This formula is the targeted medical intervention for food allergies and confirmed cow's milk protein allergy, and particularly for patients with reduced physical growth and development (growth rates included). The material is based on methodological guidelines on the amino acid formulas usage previously developed by specialist experts of the Union of pediatricians of Russia in 2020

Amino Acid Formulas in Patients with Gastrointestinal Diseases

Modern approaches for the management of children with gastrointestinal pathologies include optimal nutritional support that makes it possible to replete energy failure and restore essential nutrients balance. The article presents key information on gastrointestinal diseases in which modern amino acid formulas can be used to regulate nutritional status. The authors have conducted the extensive analysis of all available for now evidence on the efficacy, safety and utility of using such innovative medical technology as special elemental formula in gastrointestinal tract pathological conditions. This material is the basis for guidlines on the use of amino acid formulas developed by expert specialists of the Union of Pediatricians of Russia in 2020