[Organizing pneumonia as a pulmonary manifestation of post-COVID syndrome: features of diagnosis and treatment].

Treatment of patients with long-term persistent symptoms after COVID-19 is an urgent problem for clinicians around the world. One of the most significant manifestations of post-COVID-19 syndrome is organizing pneumonia that is usually treat with corticosteroids. The paper presents a clinical case of typical course of post-COVID-19 organizing pneumonia in a patient without previous lung disease. Risk factors, diagnostic methods and treatment options in this group of patients are also discuss.

[Risk factors of kidney injury in patients with COVID-19].

AIM: To determine the incidence and risk factors of acute kidney injury (AKI) in Russian cohort of patients with COVID-19. MATERIALS AND METHODS: We included 315 patients, who were hospitalized with COVID-19 from October 2020 till February 2021. The diagnosis was established on the basis of the positive SARS-CoV-2 swab test and/or typical radiologic findings on CT scans. RESULTS: AKI complicated the clinical course in 92 (29.21%) cases. The independent risk factors of AKI were female sex, underline chronic kidney disease and the highest level of C-reactive protein during hospitalization. In the general group of patients were 41 (13%) lethal cases, in the group with AKI 32 (34.8%). Compared with those without AKI, patients with AKI had 4.065 (95% confidence interval 2.154 to 7.671) times the odds of death. Respiratory support, the highest serum creatinine and glucose levels appeared to be the risk factors of death among patients with AKI in the multivariable Cox regression. CONCLUSION: The clinical course of COVID-19 was complicated by AKI in 29% cases. The independent risk factors of AKI in patients with COVID-19 are underline chronic kidney disease, circulatory disorder and the highest level of C-reactive protein during hospitalization.

[Risk factors for the early development of septic shock in patients with severe COVID-19].

AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

[Visceral leishmaniasis: a challenging diagnosis in internal medicine].

Leishmaniasis is a vector-born parasitic disease characterized by predominant cutaneous or visceral involvement with fever, hepatosplenomegaly and anemia. Leishmaniasis has relatively high prevalence in tropical and subtropical areas. Several sporadic and mostly imported cases are detected in Russian Federation. Nevertheless, some local incidents are noted in southern areas (Crimea, Dagestan). Lack of epidemiological alertness hampers confirmation of diagnosis and may lead to incorrect treatment. The article summarizes current state of knowledge in epidemiology, diagnostic approach and treatment of leishmaniasis. Particular clinical case is discussed.

Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel.

The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37-91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6ß-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)-CC, 4 (4.9%)-CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)-GG, 3 (3.7%)-AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46-26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6ß-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.

[Lower limb varicose veins as a manifestation of undifferentiated connective tissue dysplasia].

Analysed herein are the data of 737 patients (a total of 745 lower limbs) suffering from lower-limb varicose veins (LLVV) and subjected to treatment at the Surgical Department consisting of crossectomy, truncal and tributary phlebectomy, dissection of perforant veins exclusively in the basin of the great saphenous vein. Relapses during five-year follow up occurred in 13.8% (102/745) of cases. Based on clinical signs and laboratory findings we studied the effect of the factor of undifferentiated connective tissue dysplasia (UDCTD) on the development of lower-limb varicosity. We carried out comparative analysis in the groups with relapsing LLVV (n=43), without relapses (n=39) and control group comprising volunteers not suffering from LLVV (n=37). The median of blood serum total oxiprolin concentration in LLVV patients both with and without relapses was elevated and amounted to 18.4 (IR 14.9-19.65) and 14.3 (IR 13.1-16.5) versus 8.35 (5.75-9.75) µmol/l, respectively. The mode of the clinical parameter of UDCTD degree in accordance with the rating scale of Smolnova T.Yu. (2003) in the group of patients with LLVV relapses turned out to be higher (Mo=19) than in the group of patients without relapses (Mo=10, p=0.003). The lowest score was in the control group. In patients having immediate relatives with LLVV the level of blood serum total oxiprolin and clinical scores of LLVV turned out to be statistically significantly higher. Hence, based on the obtained during the study clinical and laboratory findings it may be supposed that undifferentiated connective tissue dysplasia plays an important part in the development of both lower limb varicosity and relapses thereof.

[The effect of acute alcohol intoxication on some parameters of nitrogenous metabolism in rats with alloxan diabetes].

Acute alcohol intoxication in rats with alloxan diabetes is accompanied by the increase of urea and uric acid and by the decrease in free fatty acids in serum. In the liver of experimental animals the increase of activity of glutamate dehydrogenase, AMP deaminase, and tyrosine transaminase was found.

Nitrogen metabolism in rats with experimental diabetes during acute alcohol intoxication.

The concentrations of urea and uric acid increased, while the content of free amino acids decreased in blood serum from rats with alloxan-induced diabetes during acute alcohol intoxication. Activities of glutamate dehydrogenase, AMP deaminase, and tyrosine aminotransferase in the liver of experimental animals increased.

[Parameters of energy and nitrogen metabolism in rats under insulin-induced hypoglycemia].

Repeated severe insulin-induced hypoglycemia in rats has led to an increase in aminotransferase, glutaminase, and glutamate dehydrogenase activities in the liver; protease activities in tissues; and in blood serum levels of free fatty acids, urea, and uric acid. These changes are indicative of gluconeogenesis activation in animals exposed to hyperinsulinization. Decreased rates of glycolysis and glycogenolysis, reduced activities of NADP-dependent dehydrogenases, and substantial changes in the activities of enzymes responsible for metabolism of nucleotides and transmitter amino acids have been observed in the brain. All these changes are mainly associated with hypoglycemia and activation of the contrainsular system and can play a significant role in pathogenesis of posthypoglycemic encephalopathy.

[Rat metabolic parameters in multiple insulin hy- 44poglycemia].

Hypoglycemic coma was induced with 40 U of insulin per kg body weight. The animals experiencing 7 hypoglycemic comas at 2-day intervals and killed during the last coma were found to have elevated serum levels of free fatty acids, urea, and uric acid; hepatic glycogen levels remained normal. In the liver, the activities of aspartate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2), glutaminase (EC 3.5.1.2), glutamate dehydrogenase (EC 1.4.1.3), succinate dehydrogenase (EC 1.3.99.1), and lactate dehydrogenase (EC 1.1.1.27) were enhanced and the rate of lactate generation increased when glucose and glycogen were used as substrates. Such changes were absent in initially healthy animals during the first hypoglycemic coma. They are indicative of increases in the catabolism of amino acids and in the activation of gluconeogenesls in the rats experiencing insulin hypoglycemia many times and they are associated with the stimulation of the contramsular apparatus in hypoglycemia.

[Energy metabolic changes and nerve cell damage in rats exposed to multiple administration of large-dose insulin].

The brains of rats that had experienced 5-7 hypoglycemic comas on day 2 of the rehabilitative period after the last coma showed increases in the activity NAD-isocitrate dehydrogenase and in the catabolism of adenylonucleotides and decreases in the activities ofNADH dehydrogenase, mitochondrial NADP-isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, glutathione reductase, and superoxide dismutase, and no changes in the rate of glycolysis. Placing the brain slices in the hypoosmolar medium added by Fe2+ and ascorbate caused the higher yield oflactate dehydrogenase into the incubation medium. In this case, there was a significant elevation in the concentration ofmalonic dialdehyde in the brain slices from the experimental rats. The findings suggest that energy metabolic disturbances and activated lipid peroxidation are involved in the pathogenesis of postglycemic encephalopathy.

[Changes of some energy exchange parameters in the rat heart under insulin hypoglycemia].

Hypoglycemic coma induced by administration of a large dose of insulin, was accompanied by the increased rates of glycolysis, glycogenolysis, activity of lactate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, and increased concentration of glycogen. Under these conditions triacylglycerol content decreased administration of the large dose of insulin to rats with alloxan diabetes increased not only rates of glycolysis, glycogenolysis and lactate dehydrogenase activity and also activities of aspartate transaminase and glutamate dehydrogenase. Data obtained suggest the increased utilization of amino acids for energy supply of myocardium under conditions of hypoglycemia induced by insulin adminisration to diabetic animals.

Glycolysis and oxidtion enzyme activity in rat brain during insulin-induced hypoglycemia against the background of alloxan-induced diabetes mellitus.

Insulin-induced hypoglycemic coma in animals with alloxan diabetes was observed at a higher basal glucose level in the blood compared to healthy animals. It was associated with inhibition of glycolysis and glycogenolysis and decreased activities of succinate dehydrogenase and glutamate dehydrogenase in the cerebral hemispheres and brainstem.

[The application wound sorption in complex treatment of destructive forms of erysipelas inflammation]. / Applikatsionnaia ranevaia sorbtsiia v kompleksnom lechenii destruktivnykh form rozhistogo vospaleniia.

The method of application wound sorption with sorbent Vaulen was used in treatment of erysipelatous inflammation in 49 patients. The first signs of healing appeared 1.5-2 times quicker, the rate of lessening the area of the wound surface was 21-35% greater. The period of staying in the hospital was 20-23% shorter.

Development of a purification procedure for the placental protein 14 involving metal-chelate affinity chromatography and hydrophobic interaction chromatography.

Placental protein 14 was isolated from the biological material of patients undergoing legal abortions. The major part of ballast protein was removed by ion-exchange chromatography on DEAE-Sepharose and CM-Sepharose. Albumin was separated by chromatography on Blue-Sepharose. Complete purification was obtained by metal-chelate affinity chromatography on Nickel-Chelate Sepharose and hydrophobic interaction chromatography on Phenyl-Sepharose and Octyl-Sepharose. The protein was not exposed to denaturing agents or extreme pH.

[Changes in indices of carbohydrate metabolism in suspended rats]. / Izmeneniia pokazatelei uglevodnogo obmena u krys pri vyveshivanii.

In the experiments with 35 white rats, it is found that on Days 7 and 14 of rat suspension in the head-down position the content of glycogen in both ventricles of the heart is significantly reduced. On Day 7 of the experiment, the glycogen content in m.gastrocnemius and concentration of glucose in the blood are lessened. The level of lactate in the blood and glycogen in the liver and m.soleus is not changed. The mass of body and skeletal muscles is diminished and the mass of ventricles of the heart is not changed.

[Changes in the enzyme-active region of the neuromuscular synapse of the gastrocnemius muscle in rats during hypokinesis]. / Izmeneniia fermentoaktivnoi zony neiromyshechnogo sinapsa ikronozhnoi myshtsy u krys pri gipokinezii.

Restraint of white rats in fight cages leads to diminution of the area of neuromuscular synapse with an intricate structure of the enzyme-active region and reduction of the number of neuromuscular synapses per one fiber in the gastrocnemius muscle. Signs of dystrophy of neuromuscular synapses with the intricate enzyme-active region are observed. These changes arise by day 14 of hypokinesia and become more pronounced by day 28.

[Activity of NADP-dependent dehydrogenases and level of recovery of pyridine nucleotides in the rat brain in insulin hypoglycemia and in the recuperative period]. / Aktivnost' NADF-zavisimykh degidrogenaz i uroven' vosstanovlennosti piridinovykh nukleotidov v mozge krys pri insulinovoi gipoglikemii i v vosstanovitel'nom periode.

Activity of NADP-dependent isocitrate- and malate dehydrogenases and the rate of NADP reduction into NAD+ were studied in various rat brain compartments during the hypoglycemic coma and within various periods after the coma cupping using glucose administration. Severe hypoglycemia was accompanied by distinct decrease in content of NADH x H+ in nervous tissue, while the enzymatic activity studied was not altered and content of NADPH x H+ was not decreased. Within the early restoration period activity of cytoplasmic NADP-malate dehydrogenase and content of NADPH x H+ were increased in brain tissue. Production of NADPH x H+ during hypoglycemic coma and after its cupping was maintained in nervous tissue at the adequately high level and did not affect the restoration-related synthesis.