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1.
IEEE Trans Biomed Circuits Syst ; 15(3): 629-641, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34232890

RESUMO

Recently, an electrical stimulation of the paralyzed muscle, as a potential therapy for restoring function of a denervated muscle system, has been debated as an innovative treatment in the management of patients with laryngeal paralysis. Numerous studies in acute and chronic animal models have demonstrated that electrical stimulation of the paralyzed posterior cricoarytenoideus muscle (PCA) offers an approach to induce vocal fold abduction and restore ventilation through the glottis. The study aims to test applicability of the controlled opening of the rima glottides via direct electrical stimulation of the posterior cricoarytenoideus muscle. We developed for this purpose a novel instrument system for the controlled larynx nerve stimulation. An acute experiment on the 4 years old pig showed effectiveness of the engineered stimulator. The controlled opening of rima glottidis of both posterior cricoarytenoid muscles and afterwards of both PCA muscle contraction were observed as a result of the electrical stimulation with the applied current in the range of 0.1-3 mA and pulse width of 1 ms and 10 ms. Performed research indicates a large potential of the novel nerve stimulator for the human larynx stimulation.


Assuntos
Terapia por Estimulação Elétrica , Paralisia das Pregas Vocais , Animais , Estimulação Elétrica , Eletromiografia , Humanos , Músculos Laríngeos , Contração Muscular , Suínos , Paralisia das Pregas Vocais/terapia
2.
Genet Test Mol Biomarkers ; 22(1): 51-54, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29345985

RESUMO

BACKGROUND: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome involved in the metabolism of nearly 50% of all medications. Thus, its effective concentration depends on multiple pharmacologic parameters. METHODS: The primary goal of our research was to study the correlation between the CYP3A family activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83 years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days after diagnosis and 20 mg/day for the follow-up period of 6 months. During the study period, Doppler ultrasound was performed weekly to assess the clot dynamics and recanalization time. RESULTS: We found a direct statistically reliable correlation between CYP3A4 activity and both peak and trough rivaroxaban levels. A correlation was also found between the initial clot length and the time to full recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found between either the glomerular filtration rate and peak rivaroxaban concentrations or between CYP3A4 activity and the treatment effectiveness parameters. No connection between renal function and rivaroxaban concentration was established in our study, which agrees with the clinical trials data that allow unlimited rivaroxaban use in patients with glomerular filtration rate >30 mL/min. CONCLUSIONS: The direct link between the initial clot length and time to full recanalization that has been found means that patients with more advanced stages of thrombosis need more time to reach recanalization than their counterparts with a less severe condition.


Assuntos
Citocromo P-450 CYP3A/metabolismo , Rivaroxabana/sangue , Trombose Venosa/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Citocromo P-450 CYP3A/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacocinética , Federação Russa , Trombose Venosa/sangue , Trombose Venosa/enzimologia
3.
Drug Metab Pers Ther ; 32(2): 109-114, 2017 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-28525318

RESUMO

BACKGROUND: Acenocoumarol dose is normally determined via step-by-step adjustment process based on International Normalized Ratio (INR) measurements. During this time, the risk of adverse reactions is especially high. Several genotype-based acenocoumarol dosing algorithms have been created to predict ideal doses at the start of anticoagulant therapy. METHODS: Nine dosing algorithms were selected through a literature search. These were evaluated using a cohort of 63 patients with atrial fibrillation receiving acenocoumarol therapy. RESULTS: None of the existing algorithms could predict the ideal acenocoumarol dose in 50% of Russian patients. The Wolkanin-Bartnik algorithtm based on European population was the best-performing one with the highest correlation values (r=0.397), mean absolute error (MAE) 0.82 (±0.61). EU-PACT also managed to give an estimate within the ideal range in 43% of the cases. The two least accurate results were yielded by the Indian population-based algorithms. Among patients receiving amiodarone, algorithms by Schie and Tong proved to be the most effective with the MAE of 0.48±0.42 mg/day and 0.56±0.31 mg/day, respectively. CONCLUSIONS: Patient ethnicity and amiodarone intake are factors that must be considered when building future algorithms. Further research is required to find the perfect dosing formula of acenocoumarol maintenance doses in Russian patients.


Assuntos
Acenocumarol/administração & dosagem , Algoritmos , Anticoagulantes/administração & dosagem , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos , Genótipo , Acenocumarol/efeitos adversos , Acenocumarol/uso terapêutico , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Carbono-Carbono Ligases/genética , Carbono-Carbono Ligases/metabolismo , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Federação Russa , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo
4.
Drug Metab Pers Ther ; 31(3): 173-8, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27662649

RESUMO

BACKGROUND: Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation. METHODS: Fifty patients aged 40-70 years were included. All patients received AC in the dose of 1-6 mg daily with a target international normalized ratio of 2.0-3.0. Genotyping for polymorphism markers C3435T for the ABCB1 gene, rs2108622 for the CYP4F2 gene, and rs11676382 for the GGCX gene were designed using polymerase chain reaction and restriction fragment length polymorphism. Statistical analysis was performed using the Fisher exact test and the Mann-Whitney U test. RESULTS: We found that CYP4F2 rs2108622 CT carriers required a higher AC dose than CC (p=0.0366), and CT and TT carriers required a higher AC dose than CC (p=0.0314). CONCLUSIONS: We found that ABCB1 CT and TT genotypes are associated with a higher risk of bleeding. No influence of ABCB1 and GGCX polymorphisms on the doses of AC was established. CYP4F2 could still be a genetic factor responsible for the personal variability of AC metabolism.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Acenocumarol/efeitos adversos , Fibrilação Atrial/complicações , Carbono-Carbono Ligases/genética , Família 4 do Citocromo P450/genética , Hemorragia/induzido quimicamente , Hemorragia/genética , Adulto , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , Relação Dose-Resposta a Droga , Feminino , Hemorragia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Federação Russa
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