Publications by authors named "M Antonenko"

6 Publications

ADIPOCYTOKINES LEPTIN AND ADIPONEСTIN AS PREDICTORS OF GENERALIZED PERIODONTITIS ASSOCIATED WITH OBESITY.

Georgian Med News 2021 Mar(312):42-46

Bogomolets National Medical University, Institute of Postgraduate Education, Department of Dentistry, Kyiv, Ukraine.

In recent years, according to the WHO, more than 1,9 billion people over the age of 18 are overweight, of whom more than 650 million are obese, with an annual trend. Studies in recent decades have shown that obese young people with generalized periodontitis have abnormalities in protein, fat and carbohydrate metabolism, which contributes to the early destruction of the periodontal tissue complex and rapid tooth loss. The aim of our study was to examine changes in serum leptin and adiponectin in patients with generalized periodontitis on the background of obesity. The study involved 94 people aged 19 to 35 years. Patients were divided into 3 groups: 32 patients with generalized periodontitis on the background of overweight, 40 patients with generalized periodontitis and obesity, and the control group - 22 healthy individuals of the same age category. The content of leptin and adiponectin in the serum was determined by enzyme-linked immunosorbent assay (ELISA) ELISA. The study was performed by analyzing venous blood (2 ml) in a BD Vacutainer tube and then centrifuging on LDN and Mediagnost GmbH analyzers and test systems (Germany). Studies allow us to conclude that in the serum of patients with generalized periodontitis on the background of overweight and obesity there is an imbalance of adipokines leptin and adiponectin. The obtained data are consistent with the literature, according to which, an increase in BMI is accompanied by an increase in leptin production and a decrease in adiponectin levels. These disorders were more pronounced in patients with generalized periodontitis on the background of obesity. Such an imbalance in adipose tissue may stimulate the production of pro-inflammatory cytokines and contribute to the progression of periodontal disease in such patients.
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March 2021

DIVERSITY OF TREATMENT OF GENERALIZED PERIODONTAL DISEASES IN PATIENTS WITH ANOREXIA NERVOSA.

Georgian Med News 2020 Sep(306):46-51

Bogomolets National Medical University, Institute Postgraduate Education, Department of Dentistry, Kyiv, Ukraine.

Generalized parodontal diseases (GPD) consistently occupy one of the leading places in the structure of dental diseases. Early diagnosis of the initial degree of generalized parodontitis (GP) is an effective way of secondary prevention. This is due to the complexity of understanding the etio-pathogenetic mechanisms of the development generalized parodontal diseases (GPD) and the high association of them with a number of diseases of the internal organs and systems with common points of contact between interdependence and mutual influence, in particular with anorexia nervosa (AN). The aim of this research was to develop a protocol for the treatment of GP in patients with AN. The object - 60 patients (mean age 26±3.8 years), with a diagnosis of GP, I-II degree, chronic, and AN, restrictive, which by simple randomization were divided into three groups (randomized by sex, age of patients, underlying and comorbidy diagnosis) to study the clinical effectiveness of our proposed method. Clinical, radiological, hygienic, immunological, biochemical, psychological and statistical methods were used. Conclusions. Thus, as a result of the proposed treatment protocol, the largest number of satisfactory treatment results was observed in group III patients (85.0±8.0%) with the inclusion of drugs that affect the pathogenetic mechanisms of the disease, including normalization of local immunity, markers of decline oxidative-antioxidant stress, radiological data of normalization of bone tissue of the alveolar process, a tendency to reduce microbial and tissue sensitization.
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September 2020

EARLY POSTOPERATIVE COMPLICATIONS IN DENTAL IMPLANT PATIENTS.

Georgian Med News 2020 May(302):23-28

Bohomolets National Medical University, Institute Post-graduate Education, Department of Therapeutic Stomatology; Department of Dentistry, Kyiv, Ukraine.

Generalized parodontitis and caries complications lead to tooth loss in individuals of different age groups. As a result of this often there is a violation of the integrity of the dentition, which leads to functional disorders of the muscular apparatus, temporomandibular joint and cosmetic defects. The effective method of restoration of the integrity of the dentition is dental implantation. With this in mind, the issue of dental implantation is of particular importance and requires further development including different age groups. Aim of the study is to improve the results of dental implantation and to avoid its complications based on identification of the causes of dental implantation complications and development of preventative measures in people of different age groups. 65 patients aged 35-60 years with secondary adentia were under observation. The main study group included 45 patients aged 35-60 years with secondary adentia caused by periodontal disease. The control group included 20 patients of the same age with secondary adentia due to caries complications. All patients of the main and control groups were subjected to a comprehensive examination of the condition of the periodontal and peri-implant area prior to the implantation in the shortest time after surgery. Microbiological study was conducted in 65 patients to study the dynamics of colonization of oral microflora. Complications after implantation were identified in 24 (53.33%) patients in the main group. The most frequent complications were: disruption of wound healing in 7 (15,56%) patients, pus in postoperative wound in 8 (17.78%), expressed pain and altered sensitivity after implantation in 4 patients (8.89%) patients, perforation of the mandible in 1 (2.22%) patient, divergence of the wound edges without exposure of the implant in 4 (8.89%) patients. A large number (53.33%) of postoperative complications in patients of the main group with secondary adentia was due to generalized periodontitis. In patients of the main group at the early stage of dental implantation were revealed qualitative and quantitative changes in the microflora of the implanted furrow with increasing aggressiveness were revealed.
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May 2020

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials.

Neurobiol Dis 2020 06 28;139:104823. Epub 2020 Feb 28.

Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. Electronic address:

The DNA vaccine, AV-1959D, targeting N-terminal epitope of Aβ peptide, has been proven immunogenic in mice, rabbits, and non-human primates, while its therapeutic efficacy has been shown in mouse models of Alzheimer's disease (AD). Here we report for the first time on IND-enabling biodistribution and safety/toxicology studies of cGMP-grade AV-1959D vaccine in the Tg2576 mouse model of AD. We also tested acute neuropathology safety profiles of AV-1959D in another AD disease model, Tg-SwDI mice with established vascular and parenchymal Aβ pathology in a pre-clinical translational study. Biodistribution studies two days after the injection demonstrated high copy numbers of AV-1959D plasmid after single immunization of Tg2576 mice at the injection sites but not in the tissues of distant organs. Plasmids persisted at the injection sites of some mice 60 days after vaccination. In Tg2576 mice with established amyloid pathology, we did not observe short- or long-term toxicities after multiple immunizations with three doses of AV-1959D. Assessment of the repeated dose acute safety of AV-1959D in cerebral amyloid angiopathy (CAA) prone Tg-SwDI mice did not reveal any immunotherapy-induced vasogenic edema detected by magnetic resonance imaging (MRI) or increased microhemorrhages. Multiple immunizations of Tg-SwDI mice with AV-1959D did not induce T and B cell infiltration, glial activation, vascular deposition of Aβ, or neuronal degeneration (necrosis and apoptosis) greater than that in the control group determined by immunohistochemistry of brain tissues. Taken together, the safety data from two different mouse models of AD substantiate a favorable safety profile of the cGMP grade AV-1959D vaccine supporting its progression to first-in-human clinical trials.
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http://dx.doi.org/10.1016/j.nbd.2020.104823DOI Listing
June 2020

Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency.

Mol Neurodegener 2017 05 5;12(1):33. Epub 2017 May 5.

Department of Molecular Immunology, Institute for Molecular Medicine, 16371 Gothard St, Huntington Beach, CA, 92647, USA.

Background: The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD, whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time, pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore, targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation, becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau. Hence, we hypothesized that anti-Tau monoclonal antibodies (mAb) may recognize pathological, but not normal tau at very early stages of tauopathy and prevent or decrease the aggregation of this molecule.

Methods: Mouse mAbs were generated using standard hybridoma methodology. CDR grafting was used for humanization of mouse mAb. Humanized mAb (Armanezumab) was characterized and tested in vitro/ex vivo/in vivo using biochemical and immunological methods (HPLC, Biacore, ELISA, IHC, FRET, etc.). Stable DG44 cell line expressing Armanezumab was generated by clone selection with increased concentrations of methotrexate (MTX).

Results: A panel of mouse mAbs was generated, clone 1C9 was selected based on binding to pathological human tau with high affinity and humanized. Fine epitope mapping revealed conservation of the epitope of human tau recognized by the parent murine mAb and Armanezumab. Importantly, Armanezumab (i) bound to tau with high affinity as determined by Biacore; (ii) bound pathological tau in brains from AD, FTD and Pick's disease cases; (iii) inhibited seeding effect of aggregated tau from brain lysate of P301S Tg mice; (iv) inhibited cytotoxic effect of tau oligomers; (v) reduced total tau (HT7) and AT100, PHF1, AT8, AT180, p212, p214-positive tau species in brains of tau transgenic mice after intracranial injection. A stable CHO cell line producing >1.5 g/l humanized mAb, Armanezumab was generated.

Conclusion: These findings suggest that Armanezumab could be therapeutic in clinical studies for treatment of AD.
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http://dx.doi.org/10.1186/s13024-017-0172-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418694PMC
May 2017