In Vivo Toxicity of Intravenously Administered Silica and Silicon Nanoparticles

Both silicon and silica nanoparticles (SiNPs and SiO2NPs, respectively) are currently considered to be promising carriers for targeted drug delivery. However, the available data on their in vivo toxicity are limited. The present study was aimed at investigation of SiNP and SiO2NP (mean diameter 10 and 13 nm, respectively) toxicity using both morphological and functional criteria. Hematological and biochemical parameters were assessed in Sprague-Dawley rats 5, 21 and 60 days after administration of NPs. Inner ear function was determined using otoacoustic emission testing at 21 and 60 days after infusion of NPs. Furthermore, the histological structure of liver, spleen and kidney samples was analyzed. Intravenous infusion of SiNPs or SiO2NPs (7 mg/kg) was not associated with significant changes in hemodynamic parameters. Hearing function remained unchanged over the entire observation period. Both inter- and intragroup changes in blood counts and biochemical markers were non-significant. Histological findings included the appearance of foreign body-type granulomas in the liver and spleen as well as microgranulation in the liver after administration of NPs. The number of granulomas was significantly lower after administration of SiNPs compared with SiO2NPs. In conclusion, both tested types of NPs are relatively biocompatible nanomaterials, at least when considering acute toxicity

Russian Association of Endocrinologists clinical practice guidelines for diagnosis and treatment of pheochromocytoma and paraganglioma

Russian clinical practice guidelines are dedicated to the management of patients with pheochromocytoma and paraganglioma

Novel Gene Mutations Regulating Immune Responses in Autoimmune Polyglandular Syndrome With an Atypical Course

Context: Autoimmune polyglandular syndrome (APS) is a cluster of endocrine disorders arising from immune dysregulation, often combined with damage to nonendocrine organs. There are 2 types of APS: type 1 and type 2 (APS-1 and APS-2, respectively). In clinical practice, an atypical course of APS is often observed. Objective: This work aims to find a novel genetic predictor of APS. Methods: We performed exome sequencing in 2 patients with an atypical clinical APS picture and members of their families. Patient A presented with a manifestation of APS-2 in early childhood and patient B with a late manifestation of the main components of APS-1. Results: In patient B, we identified inherited compound mutations as a novel combination of the c.769C \u3e T and c.821delG alleles of AIRE and genetic variation in the CIITA gene. No homozygous or compound mutations in AIRE were found in patient A, but we did reveal mutations in genes encoding regulatory proteins of innate and acquired immunity in this patient. Conclusion: Our data revealed novel combination of mutations in the AIRE gene in atypical APS and imply that mutations in immune-related genes may modify the clinical manifestation of APS in AIRE-mutation carriers and contribute to the development of autoimmune pathology in non-AIRE carriers with atypical APS

Association of Alleles of Human Leukocyte Antigen Class II Genes and Severity of COVID-19 in Patients of the ‘Red Zone’ of the Endocrinology Research Center, Moscow, Russia

The aim of this study was to assess the correlations of clinical features of patients with moderate and severe courses of COVID-19, comorbidity (endocrine, autoimmune, cardiovascular, oncological, and pulmonary diseases), and alleles of the HLA class II system genes. One hundred COVID-19 patients hospitalized in the Endocrinology Research Centre, Moscow, Russia, were analyzed for age, gender, smoking, comorbidity, and invasive mechanical ventilation. Computer tomography was used to assess the severity of the disease. HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles were identified in samples from 100 patients and samples from 327 randomly selected individuals collected in the prepandemic period (control group). There was no association of gender, age, weight, body mass index, smoking, and comorbidity with the severity of COVID-19. Allele DQB1*06:02-8 was more common in patients (p p p = 0.0011, respectively). DQB1*06:02-8 can probably be considered as predisposing to moderate and severe COVID-19, and DQB1*06:01 can be considered as protective. No association of these alleles with comorbidity was found. Our results suggest that carriers of predisposing alleles, with cardiovascular and non-autoimmune endocrine diseases, should take more stringent preventive measures, and if infected, a more aggressive COVID-19 treatment strategy should be used

Clinical Response to Personalized Exercise Therapy in Heart Failure Patients with Reduced Ejection Fraction Is Accompanied by Skeletal Muscle Histological Alterations

Heart failure (HF) is associated with skeletal muscle wasting and exercise intolerance. This study aimed to evaluate the exercise-induced clinical response and histological alterations. One hundred and forty-four HF patients were enrolled. The individual training program was determined as a workload at or close to the lactate threshold (LT1); clinical data were collected before and after 12 weeks/6 months of training. The muscle biopsies from eight patients were taken before and after 12 weeks of training: histology analysis was used to evaluate muscle morphology. Most of the patients demonstrated a positive response after 12 weeks of the physical rehabilitation program in one or several parameters tested, and 30% of those showed improvement in all four of the following parameters: oxygen uptake (VO2) peak, left ventricular ejection fraction (LVEF), exercise tolerance (ET), and quality of life (QOL); the walking speed at LT1 after six months of training showed a significant rise. Along with clinical response, the histological analysis detected a small but significant decrease in both fiber and endomysium thickness after the exercise training course indicating the stabilization of muscle mechanotransduction system. Together, our data show that the beneficial effect of personalized exercise therapy in HF patients depends, at least in part, on the improvement in skeletal muscle physiological and biochemical performance

Russian Association of Endocrinologists clinical practice guideline for adrenal incidentalomas differential diagnosis

This article discusses the management guidelines for serendipitously diagnosed adrenal masses cases, assessment of their hormonal activity and malignancy potential, pro- and contra indications for surgical treatment and follow-up algorithm for hormonally inactive tumors. Hypercathecholaminemya, endogenous hypercortisolism, primary hyperaldosteronism should be considered as variants of specific hormonal activity of tumor. The midnight suppression test with dexametasone 1 mg is recommended in all cases. Evaluation of basal ACTH in case of negative result of the test with dexametasone 1 mg (absence of morning cortisol level suppression) should be considered as confirmation test. For primary diagnosis of pheohromocytoma/paraganglioma (PPGL) a free plasma or fractionated urine methanephrines concentrations evaluation should be recommended. If test is positive, comprehensive examination to exclude or confirm PPGL is necessity. The aldosterone/rennin ratio exposure should be considered for patients with arterial hypertension to exclude primary hyperaldosteronism. To evaluate malignant pattern of a tumor in all unclear cases should be provide assessment of computed tomography quantitative indices. Adrenal incidentalomas treatment guidelines isnt considered in the field of this recommendations and reported in relevant guidelines