Nitrogen Oxide (NO) in the Pathogenesis of Preeclampsia.

The concentrations of nitric oxide (NO) donors in the plasma of pregnant women with preeclampsia is several times higher than in healthy pregnant women. Antihypertensive drugs acting not through the NO-mediated mechanisms normalized BP in some women with preeclampsia, but did not significantly reduce the levels of NO donors in the plasma. It appears that preeclampsia is associated with insufficient NO availability for the targets, rather than low intensity of NO synthesis. The concentration of NO donor molecules in the plasma can therefore be a useful additional diagnostic marker of preeclampsia.

Diastolic Dysfunction of the Left and Right Ventricles in Patients with Calcium Pyrophosphate Crystal Storage Disease and Osteoarthritis.

The frequency and risk factors for the development of diastolic dysfunction (DD) in patients with CPPD and OA have not been studied. The objective of this study was to determine the frequency and identify risk factors (RF) for the development of DD of the left and right ventricles (LV and RV) in patients with calcium pyrophosphate crystal deposition disease (CPPD) and osteoarthritis (OA). The study included 26 patients with CPPD and with knee OA 18-65 years old, matched in age and gender, without cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and rheumatic diseases. Conventional risk factors (TRF) of CVD were assessed, and echocardiography was performed. The frequency of DD in patients with CPPD and OA was quite high and almost did not differ in both groups: it was detected in 19 patients, of which 11 (42%) had CPPD and 8 (31%) had OA (p = 0.39). Type 1 LV DD was detected in 10 (39%) patients with CPPD and in 8 (31%) with OA (p = 0.11); type 1RV DD was detected in 8 (31%) patients with CPPD and in 7 (27%) patients with OA (p = 0.17); and type 1 LV DD and RV DD was detected in 7 (27%) patients with both CPPD and with OA. DD types 2 and 3 were not detected in both groups. There were no differences in both groups in CV risk factors, except for the level of CRP (it was higher in CPPD) (p = 0.03). In the CPPD group, mean values of LV E/E' (p = 0.02), LVDT (p = 0.03), LVMI (p = 0.04) were significantly higher than in patients with OA. On the contrary, in patients with OA, indices EDV (p = 0.004) and TVC (p = 0.02) were higher. There were direct correlations between diastolic function indices and the following factors in CPPD: LVL, PWLV and PTH level (r = 0.7, p <0.005), LV E' and PTH level (r = 0.7, p < 0.005). Inverse correlations were found between the level of PTH and IS (r = -0.5, p < 0.005), LVMI (r = -0.5, p < 0.005), and the level of vitamin D and VDDT (r = -0.6, p < 0.005). Direct correlations in OA were found between the level of CRP and PVAdiast (r = 0.6, p < 0.005), and the level of sUA (r = 0.7, p < 0.005), and the level of vitamin D and E/E'LV (r = 0.6, p < 0.005). A high prevalence of LV and RV DD was found in patients with CPPD and OA. The presence of DD in CPPD was associated with lower vitamin D levels, and in OA with a higher level of sUA and a lower level of PTH.

Interleukin 6 Signalling in Heart Failure With Preserved and Reduced Ejection Fraction.

AIM: Identification of interleukin-6 (IL-6) signaling pathways in patients with chronic heart failure (CHF). MATERIAL AND METHODS: The diversity of IL-6 effects is due to the presence of classical signaling and trans-signaling pathways. The study included 164 patients with CHF hospitalized for acute decompensated heart failure (ADHF), of which 129 had reduced left ventricular ejection fraction (HFrEF), and 35 had preserved ejection fraction (HFpEF). Blood concentrations of IL-6, soluble IL-6 receptor (sIL-6R), soluble transducer protein gp130 (sgp130), and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: Patients with HFpEF had lower concentrations of IL-6 (6.15 [2.78, 10.65] pg/ml) and hsCRP (11.27 [5.84, 24.40] mg/ml) than patients with HFrEF (9.20 [4.70; 15.62] pg/ml and 17.23 [8.70; 34.51 mg/ml], respectively). In contrast, concentrations of rIL-6R were higher in HFpEF (59.06 [40.00; 75.85] ng/ml) than in HFrEF (49.15 [38.20; 64.89] ng/ml). Concentrations of sgp130 were not significantly different. In patients with HFrEF, positive correlations were found between the concentrations of IL-6 and hsCRP, IL-6 and rIL-6R, and IL-6 and sgp130, while in patients with HFpEF, there was a correlation only between IL-6 and hsCRP, which appeared stronger than in patients with HFrEF (r=0.698; p<0.001 and r=0.297; p<0.05, respectively). CONCLUSION: Classical IL-6 signaling and trans-signaling are expressed to different degrees in patients with HFrEF and HFpEF in ADHF. The results of the study supplement the existing knowledge about the pathogenesis of inflammation in CHF and may contribute to the development of new methods and approaches to the treatment of the disease.

[About new possibilities for optimizing the postoperative period in tonsillectomy]. / O novykh vozmozhnostyakh optimizatsii postoperatsionnogo perioda pri tonzillektomii.

Tonsillectomy is one of the most frequent surgical interventions in otorhinolaryngology. This surgical is always accompanied by the development of reactive inflammatory phenomena and pain syndrome. The effectiveness and safety of tonsillectomy can be improved through the use of topical treatment in the postoperative period, including antiseptics in the form of a spray. An observational study was conducted at the Department of Otorhinolaryngology of the Russian University of Medicine of the Ministry of Health of the Russian Federation, the purpose of which was to evaluate the clinical efficacy, tolerability and safety of Viroxynol for oral and throat mucosa in patients after tonsillectomy. As a result of the analysis of the data obtained, it was found that the use of Viroxynol for the mucous membrane of the oral cavity and throat in the treatment of patients in the early postoperative period causes a pronounced clinical effect, reduces the need for additional medications, allows faster reduction of pain syndrome against the background of relief of reactive inflammatory phenomena, improves the quality of life of patients, accelerates the healing process, reduces the risk of bacterial inflammation. The drug may be recommended for use in patients after tonsillectomy.

[Restorative capability of traditional Chinese medicine in autoimmune diseases of nervous system: a literature review]. / Vosstanovitel'nyi potentsial traditsionnoi kitaiskoi meditsiny pri autoimmunnykh zabolevaniyakh nervnoi sistemy: obzor literatury.

Autoimmune diseases of the nervous system are characterized by the formation of pronounced neurological deficiency and often lead to disability. Complementary medicine as an adjuvant or preventive therapy of various diseases, including autoimmune ones, is increasingly attracting the attention of doctors and researchers. Traditional Chinese medicine (TCM) has a complex of treatment methods, including acupuncture, phytotherapy, nutrition, physical exercises and other methods that are often used in common with the recognized approaches of the official medical science. The article describes the TCM methods application in autoimmune diseases of nervous system, presents the practical experience of using acupuncture, phytotherapy, diet, physical exercises. It was concluded that TCM is important and frequently underestimated health care resource, especially in prevention and treatment of autoimmune diseases of nervous system.

Effect of Lysine Acridone Acetate on the Level of Apoptosis and Expression of Apoptosis-Associated Proteins during Antioncogenic Therapy in Colorectal Cancer in Mice.

We studied the mechanism of action of cytostatics with the addition of lysine acridone acetate to evaluate the possibility of its use for improving the effectiveness of antioncogenic therapy in colorectal cancer. In Nude mouse model, the level of apoptosis (TUNEL) and expression of proteins CD95, p53, Bcl-2, histone H3, and Ki-67 (immunohistochemistry) were assessed in primary tumor biopsy specimens. It has been shown that cytostatic treatment led to stimulation of p53-mediated apoptosis and suppression of proliferation (Ki-67 expression) of tumor cells, and apoptosis level was increased in groups receiving lysine acridone acetate. H3 expression in the experimental groups was changed.

Binding of Iron (II) Ions by Aqueous Extractions from Yerba Mate (Ilex paraguariensis).

We studied the ability of an aqueous extract from yerba mate and a dry extract obtained on the basis of this aqueous extract to remove Fe(II) ions from an aqueous medium. Aqueous extracts from mate dose-dependently reduced the concentration of free Fe(II) ions assayed by the reaction with 1,10-phenanthroline. This can be attributed to polyphenolic compounds with iron-chelating properties present in aqueous extracts from mate, namely quercetin, rutin, caffeic and chlorogenic acids. These substances effectively removed Fe(II) ions from the medium (the initial concentration of these ions was 15 µM) in the concentration range of 20-30 µM. Binding of Fe(II) ions by aqueous mate extracts (due to the formation of chelate complexes with the participation of polyphenolic compounds) modified their absorption spectra in the visible region. Binding of Fe(II) ions can be a mechanism of the antioxidant action of yerba mate.

Ischemia-Modified Albumin and Antioxidant Protection in Newborns with Asphyxia of Varying Severity.

The content of ischemia-modified albumin (IMA), serum albumin, and antioxidant capacity of blood serum was studied in healthy newborns and in newborns with moderate and severe asphyxia on days 1-2 and 3-4 of the postnatal period. Changes in these indicators were found in both groups of newborns with birth asphyxia in comparison with the group of healthy newborns and were more pronounced in children with severe asphyxia. An increase in the IMA level (by 1.6 times; p<0.001) and antioxidant capacity of blood serum (by 2.4 times; p<0.001) and a decrease in serum albumin content (by 1.5 times; p<0.001) were found in severe asphyxia on days 1-2. Analysis of changes in these indicators by days 3-4 allows to talk about a decrease in the intensity of free-radical reactions in newborns with birth asphyxia during complex therapy.

[Complications of percutaneous endoscopic gastrostomy in intensive care patients with dysphagia associated with neurological disorders]. / Oslozhneniya chreskozhnoi endoskopicheskoi gastrostomii u reanimatsionnykh bol'nykh s sindromom disfagii tsentral'nogo geneza.

OBJECTIVE: To develop an effective method for percutaneous endoscopic gastrostomy using gastropexy technology. MATERIAL AND METHODS: We retrospectively analyzed 260 ICU patients with dysphagia associated with neurological disorders between 2010 and 2020. All patients were divided into two groups: the main group (n=50) - percutaneous endoscopic gastrostomy with gastropexy, control group (n=210) - surgery without fixing the anterior wall of the stomach to the abdominal wall. RESULTS. G: Astropexy significantly reduced the incidence of postoperative complications (p=0.045) and severe complications (grade IIIa and higher) (χ2=3.701, p=0.055). Early postoperative complications occurred in 20 (7.7%) patients. Surgery and subsequent treatment were associated with normalization of leukocyte count (p=0.041), C-reactive protein (p=0.024) and serum albumin (p=0.0012). Mortality was similar in both groups. Overall 30-day mortality rate in both groups was 20.8% that was associated with clinical severity of patients. Percutaneous endoscopic gastrostomy was not the direct cause of death in any case. However, complications of endoscopic gastrostomy aggravated the underlying disease in 2.9% of cases. CONCLUSION: Percutaneous endoscopic gastrostomy with gastropexy reduces the incidence of postoperative complications.

[New effects of a topical antimicrobial (agent) in the treatment of acute tonsillopharyngitis]. / Novye effekty topicheskogo antimikrobnogo preparata v lechenii ostrogo tonzillofaringita.

Sore throat is the leading symptom of acute tonsillopharyngitis associated with previous acute respiratory viral infections, including COVID-19. The pathogenesis of these nosologies is based on the cumulative result of the primary direct damaging effect of viruses and secondary alternative inflammatory changes in the mucosal epithelium in the focus of infection, which, against the background of changes in the functions of the regional microbiota, leads to the development of viral-bacterial inflammation that goes beyond the protective-reparative level. In the treatment of acute tonsillopharyngitis after exclusion of GABHS etiology, topical etiotropic drugs are often used. It is desirable to achieve a uniform distribution of active ingredients, and to maximize the use of additional pharmacological capabilities (irrigation-eliminative action, reparative effect). To build up the evidence base for the effectiveness of just such medicines on the basis of the Department of Otorhinolaryngology of the Moscow State Medical University named after. A.I. Evdokimov, an observational prospective comparative study was conducted, using, in addition to the clinical assessment method, cytomorphological approaches (cytomorphometry). The results of the study demonstrated that gargling with a solution of hydroxymethylquinoxylindioxide (Dioxydin 0.25 mg/ml solution for topical application) in adult patients with acute tonsillopharyngitis provides rapid relief of pain, a decrease in the severity of inflammation symptoms, and also makes it possible to achieve limitation of the degree of destruction of the epithelium in the height of inflammation and a more complete and rapid recovery of the damaged mucous membrane by the time of recovery.

[Features of molecular genetic diagnosis of verrucous leukoplakia]. / Osobennosti molekulyarno-geneticheskoi diagnostiki verrukoznoi leikoplakii.

OBJECTIVE: To evaluate the initial molecular genetic signs of malignancy of verrucous leukoplakia (VL). MATERIALS AND METHODS: The study of VL was carried out on biopsies of 21 patients with the diagnoses of verrucous hyperplasia (VH) (15 cases - 71.4%) and verrucous carcinoma (VC) (6 cases - 28.5%). Tissue antigens were determined using mouse monoclonal antibodies to the Ki-67 protein (MM1, Diagnostic Biosystems). Telomerase activity was determined using rabbit immunoglobulin (TRT, Abbiotec). The amplification of the TERC (Telomerase RNA Component) portion of the RNA of the third chromosome was studied by the FISH method. RESULTS: In the studied groups, high cell proliferation and significant differences between HC and VC were revealed. The amplification of TERC by the FISH method made it possible to carry out differential diagnostics between VG and VC. According to the results of the study, the amplification of the TERC gene was detected in 100% in VC and in 20% in VG. CONCLUSION: The FISH method makes it possible to detect VL malignancy at an early stage. Amplification of the TERC gene is characteristic of malignant transformation of epithelial cells in VC. In IG, as a rule, there was no amplification, which can serve as evidence of the benign nature of the pathology of COP.

[Modern H1 antihistamines in the treatment of patients with allergic rhinitis and comorbid acute respiratory infections]. / Sovremennye H1-antigistaminnye sredstva v terapii patsientov s allergicheskim rinitom i komorbidnymi ostrymi respiratornymi infektsiyami.

Patients with allergic rhinitis (AR) have a predisposition to frequent acute respiratory viral infections (ARVI). Inflammation of the mucous membrane of the nasal cavity and paranasal sinuses in such patients is more pronounced against the background of a combination of allergic and infectious inflammation. OBJECTIVE: To evaluate the effect of therapy using modern antihistamines on the condition and severity of symptoms in adult patients with exacerbation of AR caused by plant pollen (seasonal) (SAR) and the development of ARVI. MATERIAL AND METHODS: An observational study was conducted at the Department of Otorhinolaryngology of the Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Health of the Russian Federation from April to August 2021. Included are patients of both sexes aged 18 to 65 years with a previously (at least 1 year ago) verified diagnosis of mild and moderate acute SAR in the acute stage, who sought medical help for ARVI. All patients were prescribed therapy with the inclusion of a drug belonging to the pharmacological group of antihistamines of the 2nd generation (a course of 14 days). In addition, patients received symptomatic ARVI therapy according to indications, including nasal decongestants (as needed), antipyretic and antitussive drugs. RESULTS: Based on the data obtained, it was possible to prove that the use of modern antihistamines in patients comorbid with AR and ARVI has a pronounced therapeutic effect. Theoritin provides a therapeutic effect at an early stage in relation to nasal and non-nasal symptoms of SAR/ARVI, and also quickly improves the quality of life of patients, which makes its use promising for the treatment of ARVI against the background of AR. The drug has an antihistamine activity comparable to cetirizine and surpasses it in its ability to suppress an allergic inflammatory reaction, for example on the skin, as well as in the duration of preservation of the antihistamine effect. CONCLUSION: The presented results indicate the effectiveness of theoritin and cetirizine in the treatment of patients with seasonal exacerbation of allergic rhinitis, comorbid for acute respiratory viral infections.

Thermal Gating of Magnon Exchange in Magnetic Multilayers with Antiferromagnetic Spacers.

We observe a strong thermally controlled magnon-mediated interlayer coupling of two ferromagnetic layers via an antiferromagnetic spacer in spin-valve type trilayers. The effect manifests itself as a coherent switching as well as collective resonant precession of the two ferromagnets, which can be controlled by varying temperature and the spacer thickness. We explain the observed behavior as due to a strong hybridization of the ferro- and antiferromagnetic magnon modes in the trilayer at temperatures just below the Néel temperature of the antiferromagnetic spacer.

[The methodology of prognostication of severe exacerbation of bronchial asthma and asthmatic status].

The modes of predicting chronic non-infectious diseases in clinical practice remain actual issues for general practitioner. The methodology of predicting severe exacerbation of bronchial asthma and asthmatic status during therapeutic care rendering in out-patient conditions is proposed. The methodology comprises sequential assessment in patient availability of predictors of severe exacerbation of bronchial asthma and asthmatic status with further calculation of indices of information values of each of them separately and as well as accumulated information value to evaluate their cumulative effect.

[Sensory test for fine motor skills of the hand - a pilot study]. / Test sensornoi diagnostiki tonkoi motoriki kisti ­ pilotnoe issledovanie.

The consequences of acute disorders of cerebral circulation significantly reduce the patient's life quality. According to official data, movement disorders are observed in 81.2% of surviving patients. Before and after rehabilitation, it is necessary to determine the degree of motor deficit in the affected hand. Currently used methods, such as video analysis, goniometry, dynamometry, spectrum of clinical scales, etc. have both advantages and disadvantages. OBJECTIVE: Conduct approbation of the «Method of rehabilitation assessment of fine motor function of the hand using a touch panel¼ and evaluate its diagnostic significance in the assessment of motor disorders. MATERIAL AND METHODS: The patients with the syndrome of mild and moderate hemiparesis in the recovery period of stroke, who are at the outpatient stage of rehabilitation, have been examined. The examination was carried out according to the standards of management of the recovery period of stroke, as well as using the author's method. RESULTS AND CONCLUSION: The tested «Method of rehabilitation assessment of fine motor function of the hand using a touch panel¼ showed reliability and statistical significance in comparison with clinical scales and can be integrated into the protocols of outpatient and remote rehabilitation.

Comparison of polymerase chain reaction and flow cytometry for measuring telomere length of human leukocytes.

Telomere length can be measured by polymerase chain reaction (PCR), allowing to obtain the absolute length of telomeres (ALT) in base pair, and by flow cytometry, which can only estimate the relative telomere length. The aim of the study was to compare the results of the two methods and to develop an accurate and reliable way of converting the relative telomere length to absolute. The peripheral blood from 21 donors was analyzed. Measurement of leukocyte telomere length by flow cytometry was carried out using a commercial Telomere PNA Kit / FITC (Dako, Denmark) with two CytoFLEX flow cytometers (Beckman Coulter, China) and BD FACSCanto II (Becton Dickinson, USA), obtaining the molecular equivalent of fluorescence (MEF). To measure telomere length by real-time PCR, calibrators with a known number of telomeric repeats were prepared. Two quantitative PCRs were carried out: one for telomeric repeats, the other for determining the number of genome-equivalents of DNA, three times for each sample, which made it possible to calculate ALT. A strong direct relationship was found between the MEF obtained with BD FACSCanto II and CytoFLEX (r = 0.97). Analysis of PCR and flow cytometry results showed a significant correlation between ALT and MEF. We calculated the regression equations of ALT and MEF for CytoFLEX - y = 0.0043x (r = 0.84) and for BD FACSCanto II - y = 0.0051x (r = 0.82). Correlation analysis showed a high comparability of telomere lengths measured by two methods. The obtained regression equations allow converting the results of flow cytometry into absolute values, allowing the comparison of the results of different research groups and the use of this method in clinical trials.

Comparison of cyclosporin variants B-E based on their structural properties and activity in mitochondrial membranes.

Cyclosporins B, C, D, and E were characterized by NMR spectroscopy, and backbone flexibility was studied by molecular dynamics simulation. Structures of the molecules were characterized by nuclear Overhauser effect spectroscopy, which revealed that the studied peptides have many common features. Molecular dynamics simulation showed that the backbone of cyclosporin E is relatively more rigid than in other peptides. Calcium-dependent swelling of liver mitochondria under the influence of four considered compounds was also investigated. Three of them were found to have the activity similar to cyclosporin A, inhibiting opening of the mitochondrial pore at concentrations within 100-300 nM. However, cyclosporin E did not show any biological effect at concentrations up to 1 µM. Results of this study agree with the idea on the correlation between the peptide chain flexibility and its bioavailability.

Incretin-based drugs and risk of lung cancer among individuals with type 2 diabetes.

AIM: To assess whether dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists are associated with an increased lung cancer risk among individuals with type 2 diabetes. METHODS: We conducted a population-based cohort study using the UK Clinical Practice Research Datalink. We identified 130 340 individuals newly treated with antidiabetes drugs between January 2007 and March 2017, with follow-up until March 2018. We used a time-varying approach to model use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists compared with use of other second- or third-line antidiabetes drugs. We used Cox proportional hazards models to estimate the adjusted hazard ratios, with 95% CIs, of incident lung cancer associated with use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists, separately, by cumulative duration of use, and by time since initiation. RESULTS: A total of 790 individuals were newly diagnosed with lung cancer (median follow-up 4.6 years, incidence rate 1.5/1000 person-years, 95% CI 1.4-1.6). Compared with use of second-/third-line drugs, use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists was not associated with an increased lung cancer risk (hazard ratio 1.07, 95% CI 0.87-1.32, and hazard ratio 1.02, 95% CI 0.68-1.54, respectively). There was no evidence of duration-response relationships. CONCLUSIONS: In individuals with type 2 diabetes, use of incretin-based drugs was not associated with increased lung cancer risk.

The Role of the Brain in the Regulation of Peripheral Organs-Noradrenaline Sources in Neonatal Rats: Noradrenaline Synthesis Enzyme Activity.

This work is aimed at studying the mechanisms of reciprocal humoral regulation of noradrenaline-producing organs in rats in the perinatal period of development. The activity of noradrenaline synthesis enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase was measured in the brain and adrenal glands 48 and 72 h after the injection of immunotoxin (anti-dopamine-beta-hydroxylase-saporin) into the rat brain ventricles. It was shown that, 48 h after the immunotoxin injection into the brain, the activity of tyrosine hydroxylase in the brain decreased; however, 72 h after the injection it reached the control levels. This fact indicates that noradrenaline synthesis in the survived neurons increases. In the adrenal glands, 72 h after the immunotoxin injection into the brain, the activity of dopamine-beta-hydroxylase increased. This points to a compensatory increase in the rate of noradrenaline synthesis in the adrenal glands when the synthesis of noradrenaline in the brain is inhibited.

Characteristic of Dopamine-Producing System and Dopamine Receptors in the Suprachiasmatic Nucleus in Rats in Ontogenesis.

One of the features of the developing suprachiasmatic nucleus (SCN), the "biological clock" of the body, is the early expression of dopamine (DA) receptors in the absence of dopaminergic neurons as a source of DA. Only recently we showed that DA in SCN is synthesized together by nerve fibers containing only tyrosine hydroxylase (TH) and neurons containing only aromatic L-amino acid decarboxylase (AADC). This study was aimed to assess specific characteristics of the phenotype of TH-fibers in ontogenesis. For this purpose, PCR and immunohistochemical analysis of the expression of genes and proteins such as TH, AADC, vesicular monoamine transporter (VMAT), and receptors for DA (D1, D2) was performed. We have detected numerous TH-immunoreactive fibers in SCN of young and adult rats. VMAT was observed in some of them, which suggests vesicular storage of L-DOPA. Considering the key role of TH-fibers in cooperative synthesis of DA, we assumed the presence of their dopamine regulation. Using double immunolabeling, we showed that D1 and D2 are present in TH-fibers in adult rats, and only D1 in young rats. According to PCR, D1 and D2 are also expressed in neurons of SCN in adult rats and only D1 in young rats. Thus, it was shown for the first time that VMAT and D1 are coexpressed in TH-fibers synthesizing L-DOPA in SCN in young and adult rats, and also D2 receptors in adult rats, which suggests vesicular storage and dopamine regulation of L-DOPA secretion, respectively.