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1.
Georgian Med News ; (349): 72-74, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38963205

RESUMO

Acid-related diseases (ARD) are the most common among digestive diseases. The main goals of therapy of ARD are to reduce the influence of aggression factors (production of HCl, pepsin) and increase the protective properties of the mucous membrane of the upper digestive tract. Also currently in medicine, one of the therapeutic and preventive methods is the use of chloride-hydrocarbonate sodium boron mineral waters. In this study, we compared the efficacy of table mineral waters in the therapy of induced gastropathy in Wistar rats. The study of the effect of mineral waters on the gastric mucosa of Wistar rats has provided valuable information that can be applied in medical practice for the treatment and prevention of various diseases of the gastrointestinal tract in humans. Careful analysis of the data obtained has shown that certain types of mineral waters can significantly reduce inflammatory processes and promote regeneration of the gastric mucosa, which makes them a useful addition to traditional treatment methods such as pharmacotherapy.


Assuntos
Mucosa Gástrica , Águas Minerais , Ratos Wistar , Animais , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Ratos , Masculino , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
2.
Zh Nevrol Psikhiatr Im S S Korsakova ; 124(4. Vyp. 2): 56-63, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38696152

RESUMO

The most common cause of severe cognitive impairment in adults is Alzheimer's disease (AD). Depending on the age of onset, AD is divided into early (<65 years) and late (≥65 years) forms. Early-onset AD (EOAD) is significantly less common than later-onset AD (LOAD) and accounts for only about 5-10% of cases. However, its medical and social significance, as a disease leading to loss of ability to work and legal capacity, as well as premature death in patients aged 40-64 years, is extremely high. Patients with EOAD compared with LOAD have a greater number of atypical clinical variants - 25% and 6-12.5%, respectively, which complicates the differential diagnosis of EOAD with other neurodegenerative diseases. However, the typical classical amnestic variant predominates in both EOAD and LOAD. Also, patients with EOAD have peculiarities according to neuroimaging data: when performing MRI of the brain, patients with EOAD often have more pronounced parietal atrophy and less pronounced hippocampal atrophy compared to patients with LOAD. The article pays attention to the features of the clinical and neuroimaging data in patients with EOAD; a case of a patient with EOAD is presented.


Assuntos
Idade de Início , Doença de Alzheimer , Imageamento por Ressonância Magnética , Neuroimagem , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/diagnóstico , Neuroimagem/métodos , Pessoa de Meia-Idade , Atrofia/diagnóstico por imagem , Diagnóstico Diferencial , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia
3.
Georgian Med News ; (348): 151-153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38807409

RESUMO

Rebamipide contributes to the improvement of blood supply of the GI mucosa, activates its barrier function, activates alkaline secretion of the stomach, increases proliferation and metabolism of epithelial cells of the GI tract, cleanses the mucosa from hydroxyl radicals and suppresses superoxides, produced by polymorphonuclear leukocytes and neutrophils in the presence of Helicobacter pylori, protects the GI mucosa from bacterial invasion and the damaging effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the mucosa. Rebamipide, originally developed as a treatment for gastric ulcers, has attracted the attention of researchers as a potential drug for the treatment of UC due to its ability to stimulate mucus production, reduce oxidative stress, and decrease inflammation. Due to the presence of these properties, it is hypothesized that rebamipide may have a protective effect on the intestinal mucosa during prolonged inflammation, making it a promising candidate for inclusion in therapeutic strategies for ulcerative colitis. The results of this study suggest that rebamipide holds potential therapeutic benefits for the treatment of ulcerative colitis.


Assuntos
Alanina , Colite Ulcerativa , Quinolonas , Quinolonas/uso terapêutico , Quinolonas/farmacologia , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/farmacologia , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Ratos , Antiulcerosos/uso terapêutico , Antiulcerosos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Masculino , Progressão da Doença , Modelos Animais de Doenças , Ratos Wistar
4.
Zh Nevrol Psikhiatr Im S S Korsakova ; 124(3. Vyp. 2): 23-29, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38512091

RESUMO

OBJECTIVE: To evaluate the relationship between the severity of post-stroke cognitive impairment (PSCI) and coagulation parameters assessed using the dynamic thrombophotometry. MATERIAL AND METHODS: Thirty-five patients with hemispheric ischemic stroke (IS) with moderate neurological deficit at admission were included. All patients underwent a comprehensive clinical and instrumental assessment according to the current guidelines. On days 10-14, the cognitive status of patients was assessed using the Montreal Cognitive Assessment (MoCA). Coagulation parameters were assessed using the dynamic thrombophotometry at admission, on 6-8th days and 13-15th days from the onset of the disease. A database of laboratory studies of 30 apparently healthy volunteers was used as a comparison group. RESULTS: Data analysis revealed that a number of spatial and temporal parameters were within the reference values, and there were no significant changes over time. Nevertheless, though the optical density of the fibrin clot (D) was within the reference values, it showed a steady increase from the admission by the end of the 1st week of the disease (p=0.007) and by 13-15th days (p=0.009). Correlation and multivariate linear regression, including baseline stroke symptom severity, showed significant associations (p<0.01 in all tests) between the higher optical density of the fibrin clot (D) on days 6-8 and 13-15 and lower MoCA score, confirming the negative effect of altered hemostatic parameters on cognitive function in IS patients. CONCLUSION: The increase of optical density of the fibrin clot (D) by 6-8th and 13-15th days is a potential prognostic biomarker for the early development of PSCI.


Assuntos
Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Coagulação Sanguínea , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Fibrina
5.
Artigo em Russo | MEDLINE | ID: mdl-37796067

RESUMO

OBJECTIVE: To identify the relationship of neuropsychological changes in patients with Alzheimer's disease (AD) and primary open-angle glaucoma (POAG) and to evaluate the results of magnetic resonance (MR)-morphometry in patients with these diseases. MATERIAL AND METHODS: We examined 32 patients (median age 67 [61.25; 76.75] years, 78.1% women) diagnosed with AD and POAG. The patients were divided into the AD group (n=16) and the POAG group (n=16). Complaints and anamnesis were collected for all patients, neurological status and neuropsychological status were assessed. MRI of the brain, followed by morphometry, was performed. RESULTS: Cognitive impairments (CI) were revealed in patients of both groups. The severity of CI in patients with AD was more pronounced than in patients with POAG (p<0.001). Alzheimer's type of CI was detected in both groups. MR-morphometry revealed a decrease in the volume of the left hippocampus, the volume of the right and left amygdala as well as a decrease in the thickness of the right and left entorhinal cortex in the AD group compared with the POAG group (p<0.05). A significant decrease in the thickness of the right medial orbitofrontal cortex was found in the POAG group compared with the AD group (p<0.05). CONCLUSION: In AD and POAG, there is a similarity of the neuropsychological profile, which reflects the neurodegeneration characteristic of these diseases. MRI morphometry requires an assessment of both volumes and thickness of brain structures. A neuroimaging pattern identified in patients with POAG can be regarded as an indicator of the glaucomatous process.


Assuntos
Doença de Alzheimer , Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Feminino , Idoso , Masculino , Doença de Alzheimer/diagnóstico , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/patologia , Imageamento por Ressonância Magnética/métodos , Glaucoma/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Espectroscopia de Ressonância Magnética
6.
Artigo em Russo | MEDLINE | ID: mdl-37382988

RESUMO

The article presents data on biomarkers for the early diagnosis of Alzheimer's disease (AD). Particular attention is paid to potential neuroimaging and ophthalmological markers, such methods of early diagnosis of AD as MRI with post-processing data processing and assessment of the volume of brain structures and cortical thickness - MRI morphometry, as well as optical coherence tomography are described. The article shows the relationship between AD and primary open-angle glaucoma and considers a case of AD in a patient with primary open-angle glaucoma.


Assuntos
Doença de Alzheimer , Glaucoma de Ângulo Aberto , Humanos , Doença de Alzheimer/diagnóstico por imagem , Glaucoma de Ângulo Aberto/diagnóstico , Diagnóstico Precoce , Pacientes , Encéfalo
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 123(4. Vyp. 2): 65-73, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37141131

RESUMO

OBJECTIVE: To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. MATERIAL AND METHODS: This cross-sectional study included 4520 participants, of which 50.4% (n=2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% (n=2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. RESULTS: The GWAS on anhedonia did not reveal the variants with genome-wide significant association (p<10-8). The most significant (p=9.71×10-7) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant (p<0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer (p=0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype (p=0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A (p=0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases (p=0.01, OR=0.9988, 95% CI (0.9980-0.9997)). CONCLUSION: The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.


Assuntos
Anedonia , Análise da Randomização Mendeliana , Feminino , Masculino , Humanos , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , Estudos Transversais , Fenótipo , Polimorfismo de Nucleotídeo Único
8.
Mol Biol (Mosk) ; 57(2): 330-339, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37000660

RESUMO

2'-Deoxyuridine 5'-triphosphate nucleotide hydrolase (Dut) hydrolyzes dUTP to dUMP and pyrophosphate to prevent erroneous incorporation of dUMP from the dUTP metabolic pool into DNA. Dut is considered as a promising pharmacological target for antimetabolite therapy. Enzymatically active Dut is a trimer that binds the substrate at the interface between the subunits. High-speed nanoscale differential scanning fluorimetry (nanoDSF) was used to study how various physicochemical factors affect the stability of the Escherichia coli Dut trimer. Unlike with monomeric proteins, thermal unfolding of Dut occurred in two steps, the first one corresponding to dissociation of the trimer into monomeric subunits. Hydrophobic interactions and hydrogen bonds at the interfaces between the subunits were found to contribute most to trimer stabilization. The binding of nucleotide ligands partly stabilized the Dut trimer. In general, nanoDSF is a convenient assay for screening low-molecular-weight compounds for their ability to destabilize the active Dut trimer.


Assuntos
Escherichia coli , Nucleotídeos , Escherichia coli/genética , Hidrolases , Nucleotídeos de Desoxiuracil
9.
Inflamm Res ; 72(3): 425-427, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36567363

RESUMO

The following provides a summary of the 15th World Congress on Inflammation (WCI2022), which took place in Rome (Italy) from June 5 to 8, 2022. Presented are the main trends and most promising research developments in the field of inflammation, including identification of cellular and molecular mechanisms and investigation of new pathogenetic pathways, target molecules, genetic mechanisms, and new therapeutic strategies. In addition, described are the primary areas of research engaged in by leading scientific groups and national societies from various countries in the field of inflammatory pathology mechanisms.


Assuntos
Sociedades Médicas , Pesquisa Translacional Biomédica , Humanos , Inflamação
10.
Artigo em Russo | MEDLINE | ID: mdl-36279227

RESUMO

Alzheimer's disease (AD) is a common, progressive neurodegenerative disease characterized by abnormal deposition of ß-amyloid (Aß) and hyperphosphorylated tau protein. Despite the fact that biomarkers and methods of treating AD are currently being actively studied, there is still no therapy that can significantly reduce the progression of this disease. Therefore, the search for therapeutic disease-modifying strategies is becoming increasingly popular. One such strategy is the use of focused ultrasound (FUS) under MRI guidance using a contrast agent (microbubbles). Under the influence of low-intensity FUS, the blood-brain barrier (BBB) is temporarily opened, which is the main obstacle to the effective delivery of therapeutic compounds to the brain, imposing dimensional and biochemical restrictions on the passage of molecules. One of the processes associated with AD is BBB dysfunction, and therefore the study of the effects of FUS in patients with AD is of interest. The literature data show the effectiveness of FUS in animal models of AD. The researchers attribute the effectiveness of the method to the fact that exposure to FUS induces the opening of BBB and reduces the number of amyloid plaques. It has also been demonstrated that FUS can facilitate the delivery of therapeutic drugs to the brain. This allows considering FUS as a new non-invasive method of treatment. Further research is needed to assess the effectiveness of this method in patients with AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Animais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Proteínas tau , Meios de Contraste/metabolismo , Meios de Contraste/uso terapêutico , Doenças Neurodegenerativas/metabolismo , Barreira Hematoencefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Biomarcadores/metabolismo
11.
Artigo em Russo | MEDLINE | ID: mdl-36168682

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain, in which there are cognitive and behavioral disorders, but also visual impairment can occur. Deposits of beta-amyloid (Aß) were also found in the retina of AD patients. At the same time, primary open-angle glaucoma (POAG) occupies the first place among geronto-ophthalmic pathologies in patients with AD. POAG, like AD, is a neurodegenerative disease. AD and POAG have common symptoms, and therefore several common principles for their early diagnosis can be developed. Therefore, a promising direction is the search for biomarkers for the early detection of AD and POAG. Currently, the diagnosis of early AD biomarkers in cerebrospinal fluid and biomarkers in the brain (imaging of amyloid plaques and tau positron emission tomography) are well studied, while data in literature on using these biomarkers in patients with POAG is scarce. However, the above diagnostic methods are not considered in routine clinical practice due to their invasiveness and high cost. There is a growing need for conventional, affordable biomarkers for AD and POAG, as it is necessary to start treatment of prodromal conditions from symptoms to onset of symptoms. In this connection, biomarkers such as Aß and tau protein in blood serum and plasma are actively evaluated in patients with AD. In patients with POAG, there is no published data on studies of these biomarkers, which requires scientific research. Many authors discover the role of sirtuins (SIRT) in aging and age-related diseases, such as AD, glaucoma, age-related macular degeneration, and others. Possibly, SIRT could become potential biomarkers of neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Glaucoma de Ângulo Aberto , Doenças Neurodegenerativas , Sirtuínas , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Biomarcadores , Diagnóstico Precoce , Humanos , Fragmentos de Peptídeos , Proteínas tau
12.
Dokl Biochem Biophys ; 507(1): 380-382, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36787007

RESUMO

Obtaining genetically engineered NK cells is a developing area of immunotherapy. In this work, we analyzed the subset heterogeneity of NK cells subjected to retroviral transduction, taking into account the content of adaptive NK cell progenitors. It was shown that subsets KIR2DL2/DL3+, as well as CD57-KIR2DL2/DL3+NKG2C+, can be modified with greater efficiency than the corresponding subsets that do not carry the KIR2DL2/DL3 and NKG2C markers. After genetic modification, the CD57-KIR2DL2/DL3+NKG2C+ cells began to express CD57 de novo, acquiring the adaptive NK cell phenotype.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Humanos , Células Matadoras Naturais , Fenótipo
13.
Artigo em Russo | MEDLINE | ID: mdl-34693686

RESUMO

OBJECTIVE: To evaluate the clinical effects of ethylmethylhydroxypyridine malate (Ethoxidol) in patients with chronic cerebral ischemia in an outpatient practice. MATERIAL AND METHODS: 60 patients were examined, 58 patients with a diagnosis of cerebrovascular disease (chronic cerebral ischemia) completed the participation in the program. The average age of the patients is 61.2±8.2 years. Neurological complaints typical of patients with chronic cerebral ischemia were recorded. To assess the dynamics of neurological disorders during therapy were used: The Montreal Cognitive Assessment (MoCA), Multidimensional fatigue inventory (MFI-20), Berg Balance Scale (BBS), Tinnitus Handicap Inventory (THI), Clinical Global Impression of Improvement Scale (CGI). The doctors and the patients satisfaction with therapy was assessed using the Visual Analogue Scale (VAS); quality of life - by the VAS of the European Quality of Life Group (EQ-VAS). The course of therapy lasted 60 days. All patients received daily Ethoxidol chewable tablets 400 mg/day (2 tablets (200 mg) in the morning and 2 tablets (200 mg) in the evening). RESULTS: The results of the observational program showed high efficacy and good tolerability of Ethoxidol in patients with chronic cerebral ischemia. A statistically significant decrease in the severity of the clinical manifestations of chronic cerebral ischemia was noted as early as the 30th day of therapy, followed by maintaining a positive trend until the end of the course of treatment with the drug (60th day). On the therapy, the severity of asthenia, cognitive impairment, dizziness, balance disorders, and tinnitus decreased. There was a decrease in the severity of the condition and the presence of clinical improvement on the CGI scale; there was an increase in the quality of life of patients on the EQ-VAS scale. The majority of the patients and the doctors rated the therapy as effective and safe and were satisfied with it. No serious adverse events were reported. CONCLUSION: The data obtained allow us to consider Ethoxidol as an effective drug in the treatment of patients with chronic cerebral ischemia in an outpatient practice.


Assuntos
Isquemia Encefálica , Disfunção Cognitiva , Idoso , Astenia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Humanos , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Qualidade de Vida
14.
Vestn Otorinolaringol ; 85(6): 84-89, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33474924

RESUMO

INTRODUCTION: Acute tonsillopharyngitis (ATP) is a very common disease in children. In non-streptococcal ATP, systemic antibiotics are usually not indicated, but topical antimicrobial therapy is advisable. OBJECTIVE: To evaluate the effectiveness of the combination of cetylpyridinium chloride with gramicidin C in the form of a spray in children with ATP in a prospective multicenter non-interventional study.Patients and methods. The study included 94 patients aged 6-15 years with non-streptococcal ATP. A standard examination, assessment of the pain intensity in the throat using a visual analogue scale, assessment of the pain frequency during swallowing and a score assessment of objective manifestations were carried out. Sixty-eight patients of the main group received a combination of cetylpyridinium chloride with gramicidin C (Grammidin for children) in the form of a spray, 26 patients of the control group received throat irrigation with saline solution (based on sea water) for 7 days. Therapy was assessed after 1 day (by phone), 4 and 8 days (by examination). RESULTS: The groups of patients did not differ significantly in terms of demographic indicators and initial clinical manifestations. Body temperature initially did not differ, but was significantly lower in the main group after 1 (p=0.003) and 4 (p=0.04) days. The sore throat pain intensity decrease in the main group significantly exceeded this indicator in the control group after 1 (p<0.001) and 4 (p <0.001) days. Initially, swallowing pain was observed in all patients, after 4 days the complaint was significantly less frequent in the main group (p<0.001). The total assessment of objective data was significantly lower in the main group after 4 (p<0.001) and 8 (p<0.001) days. No adverse effects of pharmacotherapy were observed. CONCLUSIONS: The study showed high efficacy and safety of the cetylpyridinium chloride and gramicidin C (in the form of a spray) combination for non-streptococcal ATP in children aged 6-15 years.


Assuntos
Preparações Farmacêuticas , Faringite , Infecções Estreptocócicas , Adolescente , Antibacterianos , Criança , Humanos , Faringite/diagnóstico , Faringite/tratamento farmacológico , Estudos Prospectivos , Streptococcus pyogenes , Resultado do Tratamento
15.
Curr Pharm Des ; 25(6): 710-714, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931849

RESUMO

Acute focal ischemia is a main factor of pathogenesis of a number of widespread cardiovascular and cerebrovascular diseases, in particular, myocardial infarction and ischemic stroke. It is known that under the conditions of ischemia expression of intracellular heat shock proteins (HSPs), especially HSP70, grows greatly irrespective of the cell type. This stress-induced cell response is connected with cytoprotective properties of HSP70. The protective functions of HSP70 contribute to the cell survival under adverse conditions and inhibit development of programmed cell death. It was shown, that the level of HSP70 increases in cardiomyocytes and brain cells in response to ischemia, that was connected with cardioprotective and neuroprotective effects. Besides, in recent years, clinical studies of HSP70 have demonstrated elevated level of HSP70 in peripheral blood lymphocytes in groups of patients with ischemic stroke and myocardial infarction. This review indicates that HSP70 can serve as a target for developing new approaches to diagnostics and therapy of cardiovascular and cerebrovascular diseases.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , Proteínas de Choque Térmico HSP70/fisiologia , Encéfalo , Isquemia Encefálica , Humanos , Miócitos Cardíacos , Acidente Vascular Cerebral
16.
Acta Naturae ; 10(3): 85-91, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30397532

RESUMO

One important distinction between many tumor cell types and normal cells consists in the translocation of a number of intracellular proteins, in particular the 70 kDa heat shock protein (HSP70), to the surface of the plasma membrane. It has been demonstrated that such surface localization of HSP70 on tumor cells is recognized by cytotoxic effectors of the immune system, which increases their cytolytic activity. The mechanisms behind this interaction are not fully clear; however, the phenomenon of surface localization of HSP70 on cancer cells can be used to develop new approaches to antitumor immunotherapy. At the same time, it is known that the presence of HSP70 on a cell's surface is not a universal feature of cancer cells. Many types of tumor tissues do not express membrane-associated HSP70, which limits the clinical potential of these approaches. In this context, targeted delivery of exogenous HSP70 to the surface of cancer cells with the aim of attracting and activating the cytotoxic effectors of the immune system can be considered a promising means of antitumor immunotherapy. Molecular constructs containing recombinant mini-antibodies specific to tumor-associated antigens (in particular, antibodies specific to HER2/neu-antigen and other markers highly expressed on the surface of a wide range of cancer cells) can be used to target the delivery of HSP70 to tumor tissues. In order to assess the feasibility and effectiveness of this approach, recombinant constructs containing a mini-antibody specific to the HER2/ neu-antigen in the first module and HSP70 molecule or a fragment of this protein in the second module were developed in this study. Strong selective interaction between the modules was ensured by a cohesive unit formed by the barnase:barstar pair, a heterodimer characterized by an unusually high constant of association. During testing of the developed constructs in in vitro models the constructs exhibited targeted binding to tumor cells expressing the HER2/neu antigen and the agents had a significant stimulating effect on the cytotoxic activity of NK cells against the respective cancer cells.

17.
Bull Exp Biol Med ; 166(2): 241-244, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30488197

RESUMO

In patients with primary resectable breast cancer, a positive correlation between the age and the count of CD16+ lymphocytes and a negative correlation of this parameter with the number of regulatory CD4+CD25+CD127- cells and proliferative activity of Ki-67 tumor cells were revealed. Higher level of Ki-67 was associated with reduced number of effector lymphocytes (CD8+ and CD16+) and elevated content of regulatory CD8+CD11b-CD28- T cells. The absence of expression of estrogen receptors was associated with reduced cytotoxic potential of CD8+ T cell in comparison with ER+ breast cancer. The percentage of CD8+ lymphocytes (CD3+CD8+ and CD8+CD11b+CD28+) among lymphocytes infiltrating the tumor was higher in PR+ breast cancer than in PR- tumors. With increasing the tumor load, the number of lymphocytes expressing CD16 marker and their cytotoxic potential decreased.


Assuntos
Antígenos CD/imunologia , Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/patologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos T Reguladores/patologia , Antígenos CD/genética , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imunofenotipagem , Antígeno Ki-67/genética , Antígeno Ki-67/imunologia , Laringite , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Receptores de Estrogênio/genética , Receptores de Estrogênio/imunologia , Receptores de Progesterona/genética , Receptores de Progesterona/imunologia , Linfócitos T Reguladores/imunologia , Carga Tumoral
18.
Curr Pharm Des ; 24(24): 2810-2824, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30156154

RESUMO

Natural Killer (NK) cells belong to a unique subtype of lymphocytes with a great potential for cancer immunotherapy due to their ability to rapidly recognize and efficiently kill tumor cells. Their anti-cancer potential can be further increased by genetic and non-genetic modifications. However, the attempts of genetic improvements of NK cells over the past 20 years have been hampered by the difficulties of gene delivery into this cell type, thus preventing researchers from producing clinically relevant numbers of viable and biologically active NK cells. Currently, several successful approaches to genetic modification of NK cells have been described, and clinically applicable cell therapy products have been characterized. Now that we understand much better the ways of NK cell optimization to enhance their tumor regression-inducing capabilities, novel approaches to engineering NK surface receptors are being developed. In this review, we focus on the advantages and perspectives of various approaches to modification of NK cells. Positive results of several preclinical studies are described, demonstrating that genetically modified NK cells can be comparable to therapeutic T cells in their efficiency of recognizing and destroying tumor targets. Moreover, using allogenic NK cells to treat a number of cancer types might have even wider and eager clinical adoption than cytotoxic T cells due to a much decreased risk of graft versus host reaction inherent in NK cell-based immunotherapeutic products.


Assuntos
Engenharia Genética , Imunoterapia , Células Matadoras Naturais/citologia , Neoplasias/terapia , Humanos , Células Matadoras Naturais/imunologia , Neoplasias/imunologia
19.
Colloids Surf B Biointerfaces ; 167: 328-336, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29684902

RESUMO

Development of efficient biodegradable, environmentally responsive, biocompatible and non-toxic delivery system is needed for efficient gene delivery. As well known, properties of the vehicle are determined by the structure of carrier components. The aim of the current study was to estimate in vitro transfection efficacy of aliphatic di-, tri- and tetrapeptide-based cationic lipoplexes loaded with siRNA in function of a number of cationic groups using 2D (monolayer culture) and 3D (multicellular tumor spheroids) in vitro models. Physicochemical properties and cytotoxicity of the liposomes were found to be dependent upon a number of amino acid derivatives in an amphiphilic polar head. Uptake of liposomes loaded with nucleic acid (lipoplexes) and their localization in HEK293T cells was studied by confocal microscopy. The liposomes based on lipotripeptides had the highest transfection efficiency which was 20-fold higher than those fabricated from lipotetrapeptides.


Assuntos
Técnicas de Transferência de Genes , Lipopeptídeos/química , Modelos Biológicos , RNA Interferente Pequeno/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células HEK293 , Células HeLa , Humanos , Lipopeptídeos/farmacologia , Lipossomos/química , Microscopia Confocal , Tamanho da Partícula , RNA Interferente Pequeno/farmacologia , Propriedades de Superfície , Transfecção
20.
Dokl Biol Sci ; 483(1): 222-224, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30603942

RESUMO

New information on the microstructures, general morphology, and features of preservation of plates of a whalebone from the Miocene Kovran locality in the Kamchatka Peninsula are provided. The plates have a chevron-like bend which is absent in extant Balaenopteridae, Balaenidae, and Eschrichtiidae. This shape is possibly related to the filtration mechanism characteristic of these whales.


Assuntos
Osso e Ossos/ultraestrutura , Fósseis , Baleias , Animais , Sibéria , Baleias/anatomia & histologia , Baleias/classificação
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