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1.
ESMO Open ; 9(5): 102924, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38796287

RESUMEN

BACKGROUND: DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline. PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR. RESULTS: As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1. CONCLUSIONS: Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.


Asunto(s)
Ado-Trastuzumab Emtansina , Neoplasias Encefálicas , Neoplasias de la Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Trastuzumab/uso terapéutico , Trastuzumab/farmacología , Persona de Mediana Edad , Ado-Trastuzumab Emtansina/uso terapéutico , Ado-Trastuzumab Emtansina/farmacología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Supervivencia sin Progresión
2.
Acta Naturae ; 16(1): 59-66, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38698956

RESUMEN

The design of new effective cancer treatment methods is a promising and important research field in translational medicine. Oncolytic viruses can induce immunogenic cell death by activating the body's immune system to recognize tumor cells. This work presents the results for optimizing the production of recombinant vesicular stomatitis viruses (rVSVs). To ensure the assembly of viral particles, we developed the HEK293TN-T7 cell line, which stably expresses DNA-dependent RNA polymerase 7 for viral genome transcription, and obtained helper plasmids encoding viral genes under the control of the CAG promoter. The oncolytic activity of the purified virus preparation was assessed in a murine model of B16F10Red melanoma cells expressing a red fluorescent protein. The presented method makes it possible to obtain purified viral preparations with a high titer and oncolytic activity. The amplification of viral particles in a HEK293 suspension culture allows for rapid scalability. Therefore, the developed approach can be used to obtain other recombinant VSV-based oncolytic viruses for tumor immunotherapy.

3.
Khirurgiia (Mosk) ; (12): 34-42, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-38088839

RESUMEN

Usually, gastrointestinal tumors (GIT) invading great vessels are acknowledged to be irresectable. Along with that, we can expect positive oncological results only when there is combination treatment with radical surgery (R0 resection). In this article we share the first experience of small intestinal autotransplantation as a method of radical surgery in locally advanced GIT. We conducted the analysis of outcomes of three patients (with pancreas cancer (n=2) and neuroendocrine tumor of caecum (n=1), with neoplastic process involving to superior mesenteric artery and vein. We analyzed intraoperative aspects and algorithm of small intestinal autotransplantation. Long-term outcomes with 1.5-13 months of observing time are presented. On the basis of conducted analysis the authors suggest the possibility of small intestinal autotransplantation in referral centers with strict personalized approach and multidisciplinary surgical team.


Asunto(s)
Neoplasias Gastrointestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Trasplante Autólogo , Intestino Delgado/cirugía , Intestino Delgado/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología
4.
Khirurgiia (Mosk) ; (12): 67-82, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-38088843

RESUMEN

BACKGRAUND: Chronic mesenteric ischemia is more often accompanied by clinical signs characteristic of colitis. Acute mesenteric ischemia, unlike chronic, is accompanied by nonspecific symptoms and is a serious disease that requires urgent diagnosis. AIMS: The aim of the study was to evaluate the effectiveness of MSCT in the diagnosis of acute and chronic mesenteric ischemia based on our observations. MATERIALS AND METHODS: The retrospective study included 135 patients with abdominalgia and suspected mesenteric ischemia who underwent multiphase CT of the abdominal cavity with intravenous bolus contrast enhancement. Group 1 included 105 patients with mesenteric ischemia; group 2 included 30, without confirmed mesenteric ischemia, with the presence of a symptom of mesenteric ischemia in the form of abdominalgia. RESULTS: We studied 135 patients, including 105 patients with mesenteric ischemia, 59 women and 46 men of average age 60±14.9 years. The acute form of ischemia (58%) was determined 1.5 times more often than the chronic one. Occlusive and nonocclusive acute mesenteric ischemia occurred in equal proportions. Mesenteric arterial thrombosis was the cause of acute mesenteric ischemia in 23% of cases. Mesenteric venous thrombosis was the cause of chronic intestinal ischemia in 61%, in 5% - acute form. Mixed arterial-venous genesis of mesenteric ischemia was determined in 4% against the background of strangulation obstruction. Dunbar syndrome as a cause of chronic intestinal ischemia was diagnosed in 16%. Chronic ischemic enterocolitis accounted for 10% of all cases of mesenteric ischemia and 23% of chronic ischemia. Symptoms and symptom complexes characteristic of the studied series of diseases with acute or chronic mesenteric ischemia were delineated. Sensitivity, specificity and prognostic value of CT with intravenous bolus contrast enhancement in diagnostics of diseases accompanied by mesenteric ischemia reached 100%. CONCLUSIONS: Multiphase CT of the abdominal cavity with bolus contrast enhancement is highly informative in the diagnosis of acute and chronic forms of mesenteric ischemia. Direct CT signs of impaired blood flow in the arteries or veins of the mesentery were indisputable. Indirect signs of mesenteric ischemia were aimed at a thorough analysis of the condition of mesenteric vessels.


Asunto(s)
Isquemia Mesentérica , Trombosis , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Isquemia Mesentérica/diagnóstico por imagen , Isquemia Mesentérica/etiología , Estudios Retrospectivos , Enfermedad Aguda , Isquemia/diagnóstico por imagen , Isquemia/etiología , Tomografía Computarizada por Rayos X/métodos , Enfermedad Crónica , Trombosis/complicaciones , Arterias Mesentéricas
5.
Khirurgiia (Mosk) ; (10): 129-132, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37916567

RESUMEN

The authors describe 2 patients with rare gastric diseases and indications for gastrectomy with delayed esophagojejunostomy for objective causes. In one case, they could not determine extent of resection, and other patient had hemorrhagic shock. Damage control principle was applied in both cases.


Asunto(s)
Laparoscopía , Neoplasias Gástricas , Humanos , Yeyunostomía/efectos adversos , Esofagostomía/efectos adversos , Neoplasias Gástricas/cirugía , Anastomosis Quirúrgica , Gastrectomía/efectos adversos
6.
Khirurgiia (Mosk) ; (7): 29-36, 2023.
Artículo en Ruso | MEDLINE | ID: mdl-37379403

RESUMEN

OBJECTIVE: To analyze the immediate and long-term results of simultaneous surgical treatment in patients with upper gastrointestinal cancer and cardiovascular diseases. MATERIAL AND METHODS: There were 9 patients with upper gastrointestinal cancer and cardiovascular diseases who underwent simultaneous surgical treatment. We assessed safety and efficacy of this approach. Mean age of patients was 65.7±5.7 years. Coronary artery disease was diagnosed in 3 patients, aortic valve disease - 1 patient, abdominal aortic aneurysm - 2; 4 patients suffered from isolated mitral valve disease, stenosis of the left vertebral artery, internal and external carotid arteries and Leriche syndrome. RESULTS: Considering immediate and long-term postoperative results, we can emphasize advisability of simultaneous surgeries in appropriate patients.


Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Neoplasias Gastrointestinales , Enfermedades de las Válvulas Cardíacas , Humanos , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Válvula Mitral/cirugía , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/cirugía , Resultado del Tratamiento , Estenosis de la Válvula Aórtica/cirugía
7.
Artículo en Ruso | MEDLINE | ID: mdl-36719118

RESUMEN

The review examines the impact of the COVID-19 pandemic on the prevalence, manifestation, as well as the possibility of preventing and treating behavioral (non-chemical) addictions. Particular attention is paid to various manifestations of Internet addiction (IA): gaming, gambling, cybersexual and food addiction (FA). During the pandemic, Internet use increased significantly, leading to an increase in IA, mainly due to gaming, which correlated with the level of psychosocial problems. The increase in gambling occurred mainly in individuals with addiction or risk groups, while in the population the frequency of gambling decreased or did not change. Immediately after the start of the COVID-19 pandemic, the number of requests to porn sites increased dramatically, suggesting an increase in cybersex addiction. However, longitudinal studies in adolescents show a slight decrease in the interest in pornography in boys, and an increase from an initially low level in girls. The proportion of eating disorders and FA significantly increased. An increase in FA was associated with depression, anxiety, and also in obese individuals. In the era of COVID-19 prevention practices and general remedial activity should take into account the needs of the general population, emphasizing the importance of self-regulating and balanced lifestyles with moderate and sensible Internet use during the pandemic.


Asunto(s)
Conducta Adictiva , COVID-19 , Juego de Azar , Juegos de Video , Masculino , Adolescente , Femenino , Humanos , Pandemias , COVID-19/epidemiología , Conducta Adictiva/psicología , Juego de Azar/epidemiología , Juego de Azar/psicología , Juego de Azar/terapia
8.
Appl Biochem Microbiol ; 58(7): 878-886, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532244

RESUMEN

Influenza viruses cause acute respiratory infections, especially in the autumn-winter period. They are characterized by a high mutation frequency and cause annual seasonal epidemics. The detection of antibodies that neutralize the virus is an important criterion in the assessment of population immunity and the influenza vaccine effectiveness. In this study, a method for determining the titer of virus-neutralizing antibodies in blood serum has been developed. A new test called the luciferase neutralization assay uses a bioluminescent signal for detection. The assay is based on engineered influenza reporter viruses with various surface antigens and a nanoluciferase reporter protein in the NS1 reading frame. Using the developed method, we studied paired sera of volunteers obtained before and after vaccination. The proposed assay was compared with the conventional antibody assessment methods (microneutralization and hemagglutination inhibition assay); a high degree of correlation was observed. At the same time, the use of the luciferase neutralization assay made it possible to reduce the time required for the analysis and to simplify the detection procedure. Supplementary Information: The online version contains supplementary material available at 10.1134/S0003683822070067.

9.
Dokl Biochem Biophys ; 507(1): 237-241, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36580213

RESUMEN

The aim of this work was to design and characterize peptides based on the α-helices h1 and h2 of the ACE2 receptor, forming the interaction interface between the receptor-binding domain (RBD) of the SARS-CoV-2 S protein and the cellular ACE2 receptor. Monomeric and heterodimeric peptides connected by disulfide bonds at different positions were synthesized. Solubility, RBD-binding affinity, and peptide helicity were experimentally measured, and molecular dynamics simulation was performed in various solvents. It was established that the preservation of the helical conformation is a necessary condition for the binding of peptides to RBD. The peptides have a low degree of helicity and low affinity for RBD in water. Dimeric peptides have a higher degree of helicity than monomeric ones, probably due to the mutual influence of helices. The degree of helicity of the peptides in trifluoroethanol is the highest; however, for in vitro studies, the most suitable solvent is a water-ethanol mixture.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Humanos , Simulación de Dinámica Molecular , Péptidos , Unión Proteica , SARS-CoV-2
10.
Soft Matter ; 18(38): 7441-7451, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36134729

RESUMEN

The paper presents the results of an experimental and numerical study of some properties of multimode liquid crystal waveguide structures. The nematic 4-cyano-4'-pentylbiphenyl (5CB) was used as a liquid crystal. A description of the experiments performed and some of the techniques used are given. Scattering diagrams are presented that characterize the features of propagation in a multimode liquid-crystal waveguide of one and many modes. It is shown that when an external repetitively pulsed electric field is switched on, the attenuation and size of inhomogeneities decrease. To explain this effect, the classical theory of liquid crystal director fluctuations is used. For the first time some properties of a liquid-crystal waveguide are described with explicit allowance for the two-dimensional Frederiks model. The two-dimensional nature of the liquid crystal director reorientation effects in our case (including under the action of an electric impulse-periodic field) required the involvement of the three-dimensional theory of light scattering in an LC waveguide and, as a consequence, the study of two-dimensional scattering diagrams in experiments, which make it possible to consider the two-dimensional nature of the behavior of the LC director. The relevance and importance of such studies are related both to the practical use and prospects of using liquid crystal materials in various high-speed and low-energy integrated-optical devices, for example, in communication elements, modulators, and sensors.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35960292

RESUMEN

The article considers specifics of health-preserving culture of family members of serviceman and parameters of its sociological assessment. It is proved that military personnel consider family as social element of military collective and at the same time as sociocultural subsystem of military unit. The latter determines subordination of sociocultural interests of serviceman family to interests of development of military organization, which manifests itself as a factor complicating development, strengthening contradictions in system of health-preserving culture of this family. It is proved that in modern conditions it is necessary to strengthen state regulation of processes of formation of health-preserving culture of family of serviceman by inclusion in system of existing programs of physical culture and sports of military units of entire serviceman family, activation of interaction of military health experts in order to develop knowledge, formation of specific norms, rules of health-preserving behavior of family of military personnel; by provision of organizational, sociocultural, economic conditions for self-development of culture of health-preserving behavior of family members of serviceman; by activation of external social control, expansion and improvement of effectiveness of army social services, prevention and suppression of destructive health behavioral practices not only of serviceman, but also of his family members.


Asunto(s)
Personal Militar , Humanos , Federación de Rusia
12.
Br J Cancer ; 126(11): 1548-1554, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35440667

RESUMEN

BACKGROUND: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. METHODS: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1-5 and 8-12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1-14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. RESULTS: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0-23.7) with TT-B and 17.7 months (95% CI: 12.6-19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55-1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. CONCLUSIONS: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. CLINICAL TRIAL INFORMATION: NCT02743221 (clinicaltrials.gov).


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab , Capecitabina/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/patología , Combinación de Medicamentos , Humanos , Pirrolidinas , Neoplasias del Recto/tratamiento farmacológico , Análisis de Supervivencia , Timina , Trifluridina/efectos adversos
13.
Philos Trans A Math Phys Eng Sci ; 380(2217): 20200321, 2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-34974721

RESUMEN

Structure formation during solidification of a Pd-Ni-Cu-P melt is studied. It is demonstrated that changes in the heat transfer conditions lead to a nonlinear change in the characteristics of the structure. The article presents the regimes of cooling the samples and the results of their structure and composition studies. It is found that a decrease in the cooling rate of the alloy leads to an increase in the size, proportion and composition of nanoinclusions in an amorphous matrix. X-ray diffraction method, electron probe microanalysis, transmission microscopy and scanning calorimetry are used for samples characterization. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

14.
Biochem Mosc Suppl B Biomed Chem ; 15(4): 274-280, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34745440

RESUMEN

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin-converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which terminal cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond. In the chimeric molecule X2, the disulfide bond was located in the middle of each precursor peptide molecule. The precursors h1 and h2 mimic amino acid sequences of α1- and α2-helices of the ACE2 extracellular peptidase domain, respectively, keeping intact most of the amino acid residues involved in the interaction with RBD. The aim of the work was to evaluate the binding efficiency of chimeric molecules and their constituent peptides with RBD (particularly in dependence of the middle and terminal methods of fixing the initial peptides h1 and h2). The proposed polypeptides and chimeric molecules were synthesized by chemical methods, purified to 95-97% purity, and characterized by HPLC and MALDI-TOF mass spectrometry. Binding of these peptides to the SARS-CoV-2 RBD was evaluated by microthermophoresis with recombinant domains corresponding in sequence to the original Chinese (GenBank ID NC_045512.2) and the British (B. 1.1.7, GISAID EPI_ISL_683466) variants. The original RBD of the Chinese variant bound to three synthesized peptides: linear h2 and both chimeric variants. Chimeric peptides were also bound to the RBD of the British variant. The antiviral activity of the proposed peptides was evaluated in Vero cell line.

15.
Sovrem Tekhnologii Med ; 12(4): 119-126, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34795999

RESUMEN

Apoptosis is the main feature of inflammatory-fibroproliferative disorders of the vessel wall. Studies in animal models have shown that smooth muscle cells (SMCs) cultured from endarterectomy specimens from the affected area proliferate more slowly and display higher apoptotic indices than SMCs derived from the normal vessel wall. Apoptotic cells were found in the destabilized atherosclerotic plaques, as well as in the samples with restenosis of the reconstruction area. Injury to the vessel wall causes two waves of apoptosis. The first wave is the rapid apoptosis in the media that occurs within a few hours after injury and leads to a marked reduction in the number of vascular wall cells. The second wave of apoptosis occurs much later (from several days to weeks) and is limited by the SMCs within the developing neointima. Up to 14% of the neointimal SMCs undergo apoptosis 20 days after balloon angioplasty. Ligation of the external carotid artery in a rabbit model led to a marked decrease in blood flow in the common carotid artery, which correlated with the increased apoptosis of endothelial cells and SMCs. Angioplasty-induced death of SMCs is regulated by a redox-sensitive signaling pathway, and topical administration of antioxidants can minimize vascular cell loss. On the whole, studies show that apoptosis is prevalent in vascular lesions, controlling the viability of both inflammatory and vascular cells, determining the cellular composition of the vessel wall. The main markers of apoptosis (Fas, Fas ligand, p53, Bcl-2, Bax) and cell proliferation (toll receptor) have been considered in the current review.


Asunto(s)
Células Endoteliales , Músculo Liso Vascular , Animales , Apoptosis , Proliferación Celular , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/patología , Conejos
16.
Angiol Sosud Khir ; 27(3): 8-15, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-34528583

RESUMEN

AIM: This study was aimed at determining Bcl-2 and Bax proteins expression before and after reconstructive-repairing operations in patients with atherosclerosis obliterans of lower extremities and at assessing the effect of an antioxidant (vitamin E at a dose of 100 mg once daily for 1 month after surgery) on the dynamics of changes of Bcl-2 and Bax proteins in the postoperative period. PATIENTS AND METHODS: The study included a total of 60 patients with stage III-IV lower limb atherosclerosis obliterans. All patients underwent reconstructive-repairing operations on the arteries of the aortofemoral segment. After surgery the patients were divided into two groups. Group A included 30 patients who during 1 month received additionally to basic therapy vitamin E at a daily dose of 100 mg. Group B was composed of 30 patients receiving basic therapy alone according to the National guidelines of managing patients with peripheral artery disease. All patients before, on POD 1, and 1 month after surgery were subjected to venous blood test aimed at determining Bcl-2 and Bax apoptosis proteins expression by means of enzyme-linked immunosorbent assay. RESULTS: In patients of groups A and B, the baseline level of Bcl-2 protein (4.75 and 4.2 ng/ml, respectively) was comparable with that in apparently healthy volunteers (5.3 ng/ml). The baseline levels of Bax protein in patients of the operated groups (26.9 and 26.0 ng/ml, respectively) were increased compared with the values in healthy volunteers (16.5 ng/ml). On POD 1 there was increased expression of Bax protein in Group A and B patients to 39.4 and 30.2 ng/ml, respectively. One month after surgery, Group B patients demonstrated a decrease in the Bcl-2 values below the baseline level - 1.1 ng/ml (p=0.003), with the Bax level continuing to increase - 36 ng/ml (p=0.004). In turn, Group A patients after 1 month were found to have increased levels of the Bcl-2 protein - 5.75 ng/ml, with the Bax level returning to the baseline values - 27.4 ng/ml. CONCLUSION: In stage III and IV lower limb obliterating atherosclerosis, the level of the Bax proapoptoric protein was higher than that in healthy volunteers. On POD 1, there occurred increased expression of the pro-apoptotic protein Bax and activation of apoptosis markers. On the background of using vitamin E at a dose of 100 mg once daily for 1 month, there was a decrease in level of the Bax propapoptotic protein (p=0.003) and an increase in level of the anti-apoptotic Bcl-2 protein level (p=0.0007).


Asunto(s)
Antioxidantes , Aterosclerosis , Antioxidantes/farmacología , Apoptosis , Arterias , Humanos , Proteína X Asociada a bcl-2
17.
Artículo en Ruso | MEDLINE | ID: mdl-34460161

RESUMEN

OBJECTIVE: To study was to test an associations of the preliminary genetic risk markers for Internet addiction (IA) with clinical, psychological and personality characteristics, taking into account the childhood traumatic experience, in 44 IA persons compared with 120 healthy individuals. MATERIAL AND METHODS: The study included 164 participants: 44 individuals with IZ (group IZ), male and female, aged 16 to 30 years in the absence of diagnoses of mental health problems. diseases from rubrics F00-09 and F20-29 (ICD-10) and 120 healthy (control group). RESULTS AND CONCLUSION: We have found an associations of the preliminary IA genetic risk markers with some personality traits and behavioral characteristics (TCI-125, TIPI) and with the childhood trauma experience (ACE IQ, CTQ), both for healthy individuals and to a greater extent for IA individuals, that may suggests the possible effects of the gene-environment interaction on a risk of developing IA. The data obtained on the structure of associations between IA genetic risk markers and individual psychological characteristics under the significant influence of the childhood trauma experience allow us to proceed with the construction of models for IA risk prediction taking into account the "gene - environment" interactions.


Asunto(s)
Conducta Adictiva , Trastornos Mentales , Conducta Adictiva/epidemiología , Conducta Adictiva/genética , Femenino , Humanos , Trastorno de Adicción a Internet , Masculino , Personalidad/genética , Adulto Joven
18.
Artículo en Ruso | MEDLINE | ID: mdl-34460170

RESUMEN

A combination of depression and alcohol use disorder (AUD) is a typical and most common example of a dual diagnosis at the intersection of general psychiatry and addiction psychiatry. A comorbidity of depression and AUD is more common than it can be brought about by mere coincidence, which might be explained to some extent by the synergetic effect of both diseases, with each of them complicating the course and worsening the prognosis of the other. Treatment protocols for patients with depression and comorbid AUD include antidepressants, specific medications for alcohol dependence, and psychotherapy. The first-line antidepressants in the treatment of patients with a comorbid combination of depression and alcohol use disorder, as in other clinical situations implying use of antidepressants, are selective serotonin reuptake inhibitors (SSRIs). Fluvoxamine has certain advantages over the other SSRIs in the treatment of patients with a depression and comorbid AUD.


Asunto(s)
Alcoholismo , Alcoholismo/complicaciones , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Antidepresivos/uso terapéutico , Depresión/diagnóstico , Depresión/tratamiento farmacológico , Depresión/epidemiología , Fluvoxamina , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
19.
Biomed Khim ; 67(3): 244-250, 2021 May.
Artículo en Ruso | MEDLINE | ID: mdl-34142531

RESUMEN

Computer simulation has been used to identify peptides that mimic the natural target of the SARS-CoV-2 coronavirus spike (S) protein, the angiotensin converting enzyme type 2 (ACE2) cell receptor. Based on the structure of the complex of the protein S receptor-binding domain (RBD) and ACE2, the design of chimeric molecules consisting of two 22-23-mer peptides linked to each other by disulfide bonds was carried out. The chimeric molecule X1 was a disulfide dimer, in which edge cysteine residues in the precursor molecules h1 and h2 were connected by the S-S bond. In the chimeric molecule X2, the disulfide bond was located in the middle of the molecule of each of the precursor peptides. The precursors h1 and h2 modelled amino acid sequences of α1- and α2-helices of the extracellular peptidase domain of ACE2, respectively, keeping intact most of the amino acid residues involved in the interaction with RBD. The aim of the work was to evaluate the binding efficiency of chimeric molecules and their RBD-peptides (particularly in dependence of the middle and edge methods of fixing the initial peptides h1 and h2). The proposed polypeptides and chimeric molecules were synthesized by chemical methods, purified (to 95-97% purity), and characterized by HPLC and MALDI-TOF mass spectrometry. The binding of the peptides to the SARS-CoV-2 RBD was evaluated by microthermophoresis with recombinant domains corresponding in sequence to the original Chinese (GenBank ID NC_045512.2) and the British (B. 1.1.7, GISAID EPI_ISL_683466) variants. Binding to the original RBD of the Chinese variant was detected in three synthesized peptides: linear h2 and both chimeric variants. Chimeric peptides were also bound to the RBD of the British variant with micromolar constants. The antiviral activity of the proposed peptides in Vero cell culture was also evaluated.


Asunto(s)
COVID-19 , Peptidil-Dipeptidasa A , Enzima Convertidora de Angiotensina 2 , Simulación por Computador , Humanos , Péptidos , Peptidil-Dipeptidasa A/genética , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo
20.
Artículo en Ruso | MEDLINE | ID: mdl-34037353

RESUMEN

OBJECTIVE: To compare the clinical efficacy of laser and radiofrequency denervation in patients with primary trigeminal neuralgia. MATERIAL AND METHODS: The study included 50 patients with primary trigeminal neuralgia who were operated on by laser (group I, n=25) or radiofrequency denervation (group II, n=25) in the period from 2018 to 2019. To assess the clinical efficacy, we analyzed the dynamics of the pain syndrome level according to the scale of facial pain and the quality of life according to the Short Form Medical Outcomes Study (SF-36), as well as patient satisfaction with the operation according to the Macnab scale, the presence of postoperative surgical complications and adverse effects of anesthesia. RESULTS: In the postoperative period, according to the scale of facial pain, a decrease in its intensity was noted in both study groups (p<0.001). Comparative analysis showed a comparable level of pain in the early postoperative period: at discharge (p=0.43) and 6 months after surgery (p=0.07). At the same time, after 12 months, lower scores on the scale of facial pain were noted in patients of group I (p=0.02). According to SF-36, a significant improvement in the physical and psychological components of health was determined in group I (p<0.001) and group II (p<0.05). Comparison of SF-36 scores in the long-term postoperative period revealed the best indicators in group I (p=0.02 and p=0.01, respectively). Comparative analysis verified a greater subjective satisfaction with the operation in group I, compared with group II (p<0.001). A comparable number of adverse effects of anesthesia was determined in both groups. Comparative analysis revealed a significantly greater number of postoperative surgical complications in group II (p=0.0017). CONCLUSION: Laser denervation and radiofrequency denervation are highly effective methods of minimally invasive treatment of primary trigeminal neuralgia.


Asunto(s)
Neuralgia del Trigémino , Desnervación , Humanos , Rayos Láser , Calidad de Vida , Resultado del Tratamiento , Neuralgia del Trigémino/cirugía
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