Experimental study on stabilometric complex for terrainkur in overweight people.

Overweight and obesity is a multifactorial, multisystem disease declared a global epidemic by the World Health Organization (WHO) as early as in 1997. At least 30% of the working-age population in Russia is overweight. Only the use of physical activity as an integral (basic) part of obesity treatment and maintenance of the body weight achieved in the course of treatment can achieve durable and long-lasting treatment results as well as significant changes in the body structure (fat/non-fat body weight ratio). Terrainkur (therapeutic walking) is a method of spa treatment that combines climatotherapy and physical therapy. One of the problems in physical activity in obese people is the difficulty they experience in exercising due to the impaired walking pattern caused by imbalances in the muscle chains, including pelvic region, cervical region, which reduces endurance and commitment to physical activity. The study found that the exposure group (Terrainkur) showed lower values of "total fat", "metabolic age", "basic caloric value" compared to initial results and the control group; the exposure group (Terrainkur) showed a decrease in the deviation of the centre of body axis projection from the proper axis, the percentage of non-compliance with the proper fluctuations of the foot underextension. These changes contributed to the elimination of terrainkur restrictions and, as a result, improved the patient compliance during the terrainkur exercises.

Mineral water inhalations for bronchial asthma: a meta-analysis.

Bronchial asthma (BA) is a common disease that contributes significantly to the incidence rate and death rate worldwide. A widespread treatment method is the use of inhalations of mineral waters, with conflicting information about their effectiveness. Purpose of the study was to assess the generalized effect power of the course of inhalations of mineral waters on the disease progress in patients with BA. A search of randomized clinical studies in data bases Pubmed, EMBASE, ELibrary, MedPilot amd CyberLeninka, according to PRISMA strategy, published between 1986 and July 2021. Standardized difference of mean values and their 95% of CI were employed for calculation using the random effects model. The meta-analysis drawing on 1266 sources included 14 studies, with 2 of them being randomized controlled clinical studies, including the results of the treatment of 525 patients. All 14 articles contain a conclusion that the inhalation of mineral water has a positive effect on the course of the disease in patients with BA. The analysis demonstrated that the group of patients after mineral water inhalations, compared with the control group, showed improvement of forced expiratory volume (FEV1), expressed both in % of the norm and in liters. The standardized difference of mean values FEV1 (%) (Hedge's g) was 8.2 (95% CI: 5.87 - 10.59; 100%), FEV1 values (liter.) (Hedge's g) was 0.69 (95% CI: -0.33-1.05). A significant heterogeneity of the results of individual studies was found (Q=124.96; tau2 = 14.55, I2 = 69.13%, p<0.0001 and Q=2.35; tau2 = 0, I2 = 0%, p<0.0001). Patients with mild, moderate, and hormone-dependent BA with a controlled and partially controlled disease course, after mineral water inhalations, compared with the control group, demonstrated a statistically significant decrease in the frequency and intensity of the cardinal symptoms of BA and improvement of FEV1.

Local ozone therapy options for lumbosacral dorsopathy.

The characteristic resistance of dorsopathies to conventional therapy explains the attention to new technologies that combine several therapeutic links and, in particular, ozone therapy. The study involved 90 patients under the age of 55 in the exacerbation phase of lumbar and sacrum dorsopathy with the leading vascular component. The patients were divided into three groups, in which basic medical and physical treatment was given. At the same time, ozone therapy was used the first two groups: the 1st group received standard ozone therapy, with a predominant selection of algic zones, the 2nd - according to the rules of biopuncture, affecting the complex of segmental, distant and "vascular" points. In the 3rd control group, the correction was limited to a standard therapeutic complex. The verification of the observed changes was carried out through clinical, psychological and electrophysiological analysis. As a result, both ozone therapy schemes (effective in 69% and 73% of observations respectively) were found to have a reliable advantage over the base complex, where 49% of patients demonstrated improvement. Differences within the ozone therapy groups themselves related to the achievement of a stable effect (in the 2nd group 2.6 days earlier) and the degree of reduction of vaso-reflex reactions (observed in 50% and 75% of observations respectively). Thus, by bringing in additional control methods, it has been proven that the implementation of ozone therapy in compliance with the rules of biopuncture ensures faster and more sustainable effects.

Effect of solvents and glutathione on the decomposition of the nitrosyl iron complex with N-ethylthiourea ligands: An experimental and theoretical study.

Dinitrosyl iron complexes (DNICs) are a depot and potential source of free NO in organisms. Their synthetic analog, N-ethylthiourea DNIC [Fe(SC(NH2)(NHC2H5))2(NO)2]+Cl-∙[Fe(SC(NH2)(NHC2H5))Cl(NO)2]0 (complex 1), as cardioprotective and cytostatic agent is a promising prodrug for the treatment of socially relevant diseases. In this work, transformation mechanism of complex 1 has been studied in anaerobic aqueous solution (pH = 7.0), DMSO, and ethanol. It was shown that the solvent has a significant effect on the decomposition of complex. According to EPR-spectroscopy, only cationic part of complex is found upon its dissolution in water; only neutral part is retained in DMSO, and both fragments are present in ethanol. Effective generation of NO occurs in an aqueous solution. The structures of the decomposition products were proposed for all solvents, their UV-spectra and rate constants were calculated. From the experimental and theoretical data obtained, it follows that complex 1 is most stable in DMSO. Solutions of complex in a DMSO-water mixture can be used to improve its bioavailability in further in vitro and in vivo studies. Also, we have analyzed its interaction with glutathione (GSH), which can participate in the metabolism of this compound. This study shows that complex 1 reacts with GSH to form a new binuclear DNIC with two GS--ligands. It was found that the resulting complex is a more prolonged NO-donor than the initial one: k = 6.1∙10-3·s-1 in buffer, k = 6.4∙10-5 s-1 with GSH. This reaction may prevent S-glutathionylation of the essential enzyme systems and is important for metabolism of complex, associated with its antitumor activity.

Analgesic effects of high-frequency and low-frequency TENS currents in patients with distal neuropathy.

Currently, diabetes mellitus (DM) is relevant problem, both for its prevalence and complications, including distal polyneuropathy (DPNP). At the same time, discussions continue on analgesic efficacy of transcutaneous electrical nerve stimulation (TENS) in DPNP. Aim of this study was to conduct a multi-faceted assessment of pain syndrome in these patients before and after TENS, taking into account levels of polyneuropathy, its severity and age of patients. The study was conducted in accordance with the research of the Federal State Budgetary Institution of the National Medical Research Center for Rehabilitation and Balneology of the Ministry of Health of the Russian Federation (CTR No. 121040100062-3) and with the permission of the Local Ethics Committee (IRB No. 2 dated 14.01.2021). The study included 75 patients with DM type II with DPNP, which are distributed into 3 groups of 25 people: Group 1a, patients received high-frequency TENS (HF); Group Ib, patients received low-frequency TENS (LF); as control, Group C received a standard method of pharmacological therapy without physiotherapy. Intensity of DPNP was evaluated before and after the course of treatment using a visual analog scale (VAS), the McGill Pain Questionnaire (MPQ), and a graphical linear analysis of pain on the neuropathic pain diagnostic questionnaire 4 (DN4) scale. TENS provides an analgesic effect that may exceed pharmacotherapy in terms of efficacy and safety. There was a 65.9% reduction in neuropathic pain according to VAS after a course of application, with the effects remaining up to 34% during the 6-month follow-up. HF TENS provided a higher significant analgesic effects than LF TENS, as it ensures the reduction of pain syndrome according to VAS by 25.8% (p <0.01), and total estimated characteristics - 35.5% (p <0.01), and touch - in at 58.1% (p = 0.001) and according to the scales of the MPQ (S) and DN4 - by 21% (p = 0.007). The observed differences in analgesic effects between HF TENS and LF TENS are based on analyses of pain in the immediate and long-term follow-up periods of type II DM patients with DPNP. These results, based on summation of the estimated parameters of the international pain scales support expectation of an expansion of the the use of analgesic TENS in aging patients suffering with DM of varying severity and extent of DPNP damage, a goal of great scientific and practical importance.

Neuropsychological evaluation of cognitive disorders in children after COVID-19.

The article presents the results of neuropsychological remote and face-to-face testing of 25 children aged 12 to 17 years in the nearest (during and 1-2 weeks after the treatment) and later period (2-12 months) after COVID-19 infection with predominant respiratory tract infection, organized in Ekaterinburg in the State Autonomous Institution "Children's Hospital № 8". Indication of family contact with patients with a new coronavirus infection was found in all patients, a positive nasopharyngeal swab for SARS-CoV-2 RNA by PCR was found in 58%, non-focal neurological complaints were found in 54% of children. The control group consisted of 25 pupils of Moscow comprehensive schools (14 girls and 11 boys) aged between 12 and 16 years who were examined before the pandemic. The methods included: investigation of the kinesthetic, spatial, dynamic, graphic praxis; auditory-motor coordination; visual, object-constructive gnosis; auditory-speech, visual memory; voluntary attention; thinking. Significant differences with the results of neuropsychological tests performed in children in the control group were found, allowing us to assert impairment of memory, attention, visual gnosis, visual-spatial function, kinesthetic and dynamic praxis, verbal and non-verbal component of thinking. According to A.R. Luria's theory, the topic of the disorders involves the temporo-parieto-occipital, mediobasal, frontotemporal parts of the brain, the reticular formation and limbic structures. This necessitates the development of corrective educational programs and an in-depth diagnostic algorithm that determines the morphological substrate of cognitive disorders in children, who have undergone COVID-19.

Albumin as a prospective carrier of the nitrosyl iron complex with thiourea and thiosulfate ligands under aerobic conditions.

High-molecular-weight dinitrosyl iron complexes (DNICs) are formed in living systems and are a stable depot of nitrogen monoxide (NO). In this work, using experimental and theoretical methods, we investigated the interaction of their synthetic analog, a promising cardiotropic complex of the composition [Fe(SC(NH2)2)2(NO)2]2[Fe2(S2O3)2(NO)4], with bovine serum albumin (BSA) in aqueous aerobic solutions. We suggested that, under these conditions, the decomposition product of the initial complex with oxygen, the [Fe(NO)(NO2)]+ fragment, can bind in the hydrophobic pocket of the protein. As a result of this interaction, high-molecular-weight Fe(Cys34)(His39)(NO)(NO2) is formed. The binding constant of the complex with protein measured by the quenching of intrinsic fluorescence of BSA is 7.2 × 105 M-1. According to EPR and UV-spectroscopy data, the interaction of the complex with the protein leads to its significant stabilization. In addition to coordination binding, the studied complex can be adsorbed onto the protein surface due to weak intermolecular interactions, resulting in the prolonged generation of NO.

Simultaneous application of transcranial magnetic stimulation and low-frequency electrostatic field as treatment of carbohydrate and lipid disorders in patients with metabolic syndrome.

The metabolic syndrome, which covers a wide variety of pathological concerns, is rapidly becoming a global pandemic. This syndrome is difficult to treat pharmacologically. Physiotherapy techniques, which have both local and systemic effects, can be employed as a suitable substitute. The purpose of this study was to investigate the therapeutic effects of a program of simultaneous physiotherapy that included migrant transcranial magnetic stimulation (TMS) and the exposure to an alternating low-frequency electrostatic field (LFEF) in the treatment of metabolic syndrome patients. Ninety patients were randomly assigned to three study groups. While continuing the usual drug therapy the first group (30 patients) received LFEF intervention, the second group (30 patients) received TMS, and the third group (30 patients) underwent the simultaneous use of these non-invasive techniques (LFEF + TMS). All treatments involved 10 sessions with daily frequency. In all the patients before and after treatment body weight, blood pressure parameters, levels of insulin, cortisol, glucose, total cholesterol, high density lipoproteins, malondialdehyde, and Schiff bases, the activity of the antioxidant enzymes catalase and of the superoxide dismutase were studied. The changes in the outcomes assessed revealed a different reaction to therapy with LFEF or TMS, as well as a greater benefit when both treatments were used at the same time. A simultaneous LFEF and TMS intervention seems a promising resource for the treatment of the metabolic syndrome, particularly of the lipid and carbohydrate metabolism disorders. However, further studies are needed to confirm these findings and investigate the underlying mechanisms.

Is relaxation exercise therapy effective in the management of patients with severe arterial hypertension?

Arterial hypertension (AH) is a burning problem in the world. Antihypertensive pharmacological therapy combined by physical exercises is well-studied in patients with mild and moderate AH. However, studies that have investigated relaxation in patients with severe AH in addition to drug therapy are lacking. Optimization of a comprehensive treatment for patients with severe AH, by using a multicomponent rational antihypertensive pharmacotherapy (PT) with subsequent application of relaxation exercise therapy (RET). The study involved 32 male patients with severe AH. Initially, clinical-instrumental and laboratory examination, blood pressure registration and daily arterial blood pressure monitoring were carried out. Suitable PT was selected for all the patients. 3 months after starting PT the patients were divided in 2 groups. The patients of the 1st group were prescribed RET in addition to PT. The 2nd group of patients continued receiving PT alone. 3 months later, average daily blood pressure (ADBP)-syst and ADBP-diast were compared in both groups. Three months after PT both groups demonstrated a significant decrease in ADBP-syst and ADBP diast, but these indicators remained higher than normal and did not reach the target level. Three months after the inclusion of RET in the comprehensive treatment, the 1st group demonstrated a significant decrease in ADBP (systolic and diastolic), not only in comparison with the initial data, but also with the data observed three months after PT. After 6 months, ADBP-syst and ADBP-diast in the 1st group were significantly lower compared with those of patients in the 2nd group. The inclusion of RET in addition to a multicomponent antihypertensive PT is a promising treatment option for severe AH.

Effect of albumin on the transformation of dinitrosyl iron complexes with thiourea ligands.

Interaction and transformation of the mononuclear cationic dinitrosyl iron complex [Fe(SC(NH2)2)2(NO)2]+ (complex 1) upon binding with bovine serum albumin (BSA) have been explored using kinetic measurements, UV-Vis and fluorescence spectroscopy, and computational molecular modeling. BSA was found to bind up to five molecules of complex 1 per one protein molecule; as a result, the rate of NO release by complex 1 into solution decreases by a factor of 10. The binding constant of complex 1 with BSA measured by the quenching of intrinsic fluorescence of BSA is 5 × 105 М-1. Molecular docking calculations at pH = 7 have determined five-six low-energy binding sites for complex 1 at subunits I and II of BSA. The most stable protein-ligand complexes are located at the protein pockets near Cys34. The spectroscopic measurements and docking calculations have shown that the decomposition product of complex 1, the Fe(NO)2+ fragment, can form an adduct Fe(Cys34)(His39)(NO)2 (complex 2) with the coordination bonds of Fe with atoms S of Cys34 and ND of His39. The structure of complex 2 was supported by the density functional calculations of the absorption spectrum. Decomposition of complex 2 leads to nitrosylation of BSA at atom S of Cys34. Complexes 1 (bound with BSA), 2 and the nitrosylated BSA can serve as NO depot in plasma.

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes.

Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed that the DNICs compounds modulate the mitochondria function by decreasing the mitochondrial membrane potential (ΔΨm). Results of flow cytometry showed that DNICs were not affected the proliferation, growth of fibroblasts. In addition, this study showed that DNICs did not affect glutathione levels and the formation of reactive oxygen species in cells. Moreover, results indicated that DNICs maintained the ATP equilibrium in cells. Taken together, these findings show that DNICs have protective properties in vitro. It was further suggested that DNICs may be uncouplers of oxidative phosphorylation in mitochondria and protective mechanism is mainly provided by the leakage of excess charge through the mitochondrial membrane. It is assumed that the DNICs have the therapeutic potential for treating cardiovascular diseases and for decreasing of chemotherapy-induced cardiotoxicity in cancer survivors.

NO-Donor Nitrosyl Iron Complex with 2-Aminophenolyl Ligand Induces Apoptosis and Inhibits NF-κB Function in HeLa Cells.

NO donating iron nitrosyl complex with 2-aminothiophenyl ligand (2-AmPh complex) was studied for its ability to cause cell death and affect nuclear factor kappa B (NF-κB) signaling. The complex inhibited viability of HeLa cells and induced cell death that was accompanied by loss of mitochondrial membrane potential and characteristic for apoptosis phosphatidylserine externalization. At IC50, 2-AmPh caused decrease in nuclear content of NF-κB p65 polypeptide and mRNA expression of NF-κB target genes encoding interleukin-8 and anti-apoptotic protein BIRC3. mRNA levels of interleukin-6 and anti-apoptotic protein BIRC2 encoding genes were not affected. Our data demonstrate that NO donating iron nitrosyl complex 2-AmPh can inhibit tumor cell viability and induce apoptosis that is preceded by impairment of NF-κB function and suppression of a subset of NF-κB target genes.

Reversible dissociation and ligand-glutathione exchange reaction in binuclear cationic tetranitrosyl iron complex with penicillamine.

This paper describes a comparative study of the decomposition of two nitrosyl iron complexes (NICs) with penicillamine thiolic ligands [Fe2(SC5H11NO2)2(NO)4]SO4 ·5H2O (I) and glutathione- (GSH-) ligands [Fe2(SC10H17N3O6)2(NO)4]SO4 ·2H2O (II), which spontaneously evolve to NO in aqueous medium. NO formation was measured by a sensor electrode and by spectrophotometric methods by measuring the formation of a hemoglobin- (Hb-) NO complex. The NO evolution reaction rate from (I) k 1 = (4.6 ± 0.1)·10(-3) s(-1) and the elimination rate constant of the penicillamine ligand k 2 = (1.8 ± 0.2)·10(-3) s(-1) at 25°C in 0.05 M phosphate buffer, pH 7.0, was calculated using kinetic modeling based on the experimental data. Both reactions are reversible. Spectrophotometry and mass-spectrometry methods have firmly shown that the penicillamine ligand is exchanged for GS(-) during decomposition of 1.5·10(-4) M (I) in the presence of 10(-3) M GSH, with 76% yield in 24 h. As has been established, such behaviour is caused by the resistance of (II) to decomposition due to the higher affinity of iron to GSH in the complex. The discovered reaction may impede S-glutathionylation of the essential enzyme systems in the presence of (I) and is important for metabolism of NIC, connected with its antitumor activity.

Decomposition of water-soluble mononitrosyl iron complexes with dithiocarbamates and of dinitrosyl iron complexes with thiol ligands in animal organisms.

EPR studies have shown that water-soluble mononitrosyl iron complexes with N-methyl-d-glucamine dithiocarbamate (MNIC-MGD) (3 micromol) injected to intact mice were decomposed virtually completely within 1h. The total content of MNIC-MGD in animal urine did not exceed 30 nmol/ml. In the liver, a small amount of MNIC-MGD were converted into dinitrosyl iron complexes (30 nmol/g of liver tissue). The same was observed in intact rabbits in which MNIC-MGD formation was induced by endogenous or exogenous NO binding to NO traps, viz., iron complexes with MGD. In mice, the content of MNIC-MGD in urine samples did not change after bacterial lipopolysaccharide-induced expression of iNOS. It was supposed that MNIC-MGD decomposition in intact animals was largely due to the release of NO from the complexes and its further transfer to other specific acceptors. In mice with iNOS expression, the main contribution to MNIC-MGD decomposition was made by superoxide ions whose destructive effect is mediated by an oxidative mechanism. This effect could fully compensate the augmented synthesis of MNIC-MGD involving endogenous NO whose production was supported by iNOS. Water-soluble dinitrosyl iron complexes (DNIC) with various thiol-containing ligands and thiosulfate injected to intact mice were also decomposed; however, in this case the effect was less pronounced than in the case of MNIC-MGD. It was concluded that DNIC decomposition was largely due to the oxidative effect of superoxide ions on these complexes.

Dinitrosyl-iron complexes with thiol-containing ligands: spatial and electronic structures.

Parameters of the EPR signals of monomeric dinitrosyl-iron complexes with 1H-1,2,4-triazole-3-thiol (DNIC-MT), obtained by treating MT+ferrous iron in DMSO solution with gaseous NO, have been compared with those of the crystalline monomeric DNIC-MT with tetrahedral structure. Dissolved DNIC-MT were characterized by the isotropic EPR signal centered at g=2.03 with half-width of 0.7 mT and quintet hyperfine structure when recorded at ambient temperature or the anisotropic EPR signal with g( perpendicular)=2.045, g( parallel)=2.014 from frozen solution at 77 kappa, Cyrillic. DNIC-MT in crystalline state showed the structure-less symmetrical singlet EPR signal centered at g=2.03 and half-width of 1.7 mT at both room and liquid nitrogen temperature. The Lorentz shape of this signal indicates the strong exchange interaction between these complexes in the DNIC-MT crystal. Being dissolved in DMSO the crystalline sample of DNIC-MT demonstrated the EPR signal typical for DNIC-MT, obtained by treating MT+ferrous iron in DMSO solution with gaseous NO. Low spin (S=1/2) d(9) electron configuration of DNIC-MT with tetrahedral structure (formula [(MT-S(.))(2)Fe(-1)(NO(+))(2)](+)) was suggested to be responsible for the signal of DNIC-MT in crystalline state. Dissolving of the crystals of DNIC-MT may result in the change of their spatial and electronic structure, namely, tetrahedral structure of the complexes characterized by low spin d(9) electronic configuration transforms into a plane-square structure with d(7) electronic configuration and low spin S=1/2 state (formula [(MT- S(-))(2)Fe(+)(NO(+))(2)](+)). The latter was suggested to be characteristic of other DNICs with various thiol-containing ligands in the solutions. The proposed mechanism of these DNICs formation from ferrous iron, thiol and NO shows that the process could be accompanied by the ionization of NO molecules to NO(+) and NO(-) ions in the complexes. Detailed analysis of the shape of the EPR signals of these complexes provided additional information about the exchange interaction typical for DNIC-MT in crystals.

Protein-bound dinitrosyl-iron complexes appearing in blood of rabbit added with a low-molecular dinitrosyl-iron complex: EPR studies.

The formation of protein-bound dinitrosyl-iron complexes (DNIC) in blood plasma and packed red cell fraction has been demonstrated by the EPR method in the experiments on rabbits which were i/v injected with the low-molecular DNIC with thiosulphate. This formation was ensured by transfer of Fe(+)(NO(+))(2) moieties from low-molecular DNIC onto serum albumin or hemoglobin molecules. Protein-bound DNICs appeared immediately after low-molecular DNIC injection followed with gradually decreasing their amounts. The complexes could be detected by EPR technique during more than two days. The addition of water-soluble NO scavenger, the iron complex with N-methyl-d-glucamine dithiocarbamate (MGD) resulted in decomposition of a part of protein-bound DNICs and in effective excretion of secondary products (mainly mononitrosyl-iron complexes with MGD) from the blood flow.