Prospects of successful treatment of Parkinson's disease using apomorphine

Optimising the treatment of idiopathic Parkinson's disease is a complex, multifaceted and continuous process that directly affects quality of life. The main position of this examination is the need for individualised therapy that provides optimal motor function with the least negative consequences. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations with a potentially positive effect on non-motor symptoms, is the only antiparkinsonian drug whose ability to control motor symptoms is equivalent to that of levodopa. Subcutaneous injection is the most effective and affordable way to correct dopaminergic insufficiency in Parkinson's disease. The data of multi-centre studies presented in the review confirm the high efficiency, adequate tolerability, and prospects of using apomorphine in the complex pathogenetic therapy of the disease. This review provides historical background and summarises the structure, mechanism of action, pharmacodynamics, indications, contraindications, and side effects of subcutaneous apomorphine injections in the advanced stages of Parkinson's disease. Keywords: Parkinson's disease; apomorphine; pharmacokinetics; mechanism of action; clinical trials; indications: and contraindications

Hypercapnia-inducible factor: a hypothesis

Cells and tissues sense and respond to hypercapnia by global activation or down-regulation of hundreds of genes and switching on/off a number of signaling and metabolic pathways. We hypothesize for the first time that such complex rearrangements are hardly possible without subtle guidance by a specific master regulator which we suggest to name hypercapnia-inducible factor (HcIF). Whether there are structural and functional similarities between HcIF and HIF remain to be elucidated. However, there are reasons to believe that, as master genes, HcIF and HIF can cooperate or compete depending on the situation. Only further research will warrant existence of HcIF as a molecular master regulator of the response to hypercapnia. Key words: hypercapnia, hypoxia, gene expression, aging

COVID-19 associated changes in the right departments of the heart in the elderly people

Purpose of the work: to study the indicators characterizing heart lesions in elderly patients who had carried COVID-19. Materials and methods: 86 patients older than 60 years old, were examined, of whom 56 (32 women and 24 men) who have carried COVID-19 between 3 and 6 months before the study, and 30 patients (12 men and 18 women) who did not have COVID - 19 in the anamnesis. The patients have been examined clinically, electro and echocardiography have been performed. The results. Elderly patients during the post-covid period have complaints of shortness of breath, pain in the heart, swelling, coughing, weakness, which are more stable and intense than before the infection. Patients who have carried COVID-19 demonstrate the signs of a chronic pulmonary heart disease: increase in the size of a right ventricle and decrease of its contractile ability, increase in pressure in a pulmonary artery. Signs of a statistically significant moderate decrease of the contractility in the left ventricular were also identified. Conclusions. The statistically significant changes in the right departments of the heart among the patients with carried COVID-19 with persistent symptoms after infection were defined. Patients who have carried COVID-19 but have no symptoms did not differ statistically from the control group. Key words: COVID-19, old age, post- COVID period, right departments of the heart.

Estimating biological age by hematological blood parameters

For the estimation of the biological age (BA) of people based on hematological parameters of the clinical blood test there were used MLR and Deep Neural Networks. In the archive of the Institute of Gerontology NAMS of Ukraine there were selected people aged from 20 up to 90 years (440 men and 504 women), who had all hematological parameters within normal limits. When using the MLR method, the multiple correlation coefficients (R) have low values for both men (0.37) and women (0.38). The use of Deep Neural Networks has given good results. The values of the correlation coefficients between BA and chronological age were 0.92 for men and 0.79 for women. The average absolute error in determining BA was 3.68 years for the men and 6.55 years for the women. The developed method for assessing hematological age can be used in clinical practice to identify people with the risk of developing hematological pathology, as well as in population researches. Keywords: biological age, hematological blood parameters, deep neural network

Pharmacology-based toxicity assessment of molsidomine and ATP-LONG combination with singular and repetitive injections under experimental conditions

The aim of the work was to study toxic properties of the new combined drug which comprise nitrovasodilator molsidomine and adenosine- 5’-triphosphate in a form of coordination compound with histidine, magnesium, and potassium (ATP-LONG). The drug was examined for its acute and subacute toxicity on Balb/c mice and Wistar rats of reproductive age with peroral (p/o) and sublingual (s/l) administrations. It has been established that LD50 of the substance contains over 10000 mg/kg (p/o) and 5010 mg/kg (s/l), which corresponds to the category of Practically non-toxic substances. The repetitive administrations within a 28 day period of the conditionally therapeutic dose of 260 mg/hg (s/l) did not cause any negative impact on physiological, biochemical, histological values in male and female rats. In doses 1300 and 2080 mg/kg, which exceed conditionally therapeutic doses by 5 and 8 times, the combination was not changing clinical laboratory urine and blood values but induced histological changes such as dilation and plethora of capillaries along with edema of smooth muscle cells of the brain, myocardium, liver, spleen, kidneys, and adrenal glands in rats. Additionally, the particular dosages of the combined substance provoked irritation of the mucous membrane of the tongue. Detected effects of the drug do not carry any pathological character and can be viewed as a specific reaction of the organism to high doses of nitrovasodilator. However, the duration and reversibility of unwanted consequences of molsidomine overdose, particularly in its combined form, need further investigation. Keywords: combination of molsidomine and ATP-LONG, acute and subacute toxicity

The “Mix-Factor” is involved in the regulation of the organism's redox systems in the late stages of ontogenesis and affects the lifespan of animals

the content of lipid hydroperoxides in the serum and liver mitochondria in animals in the late stages of ontogenesis (12 and 33 months old, Wistar male rats) was investigated. The possible effect of the food additive (“mix factor”) on these parameters in 33 months old animals, if they received this supplement from 22 months age daily throughout life in a dose of 0.05 - 0.06 ml / 100 g of body weight was determined. Moreover, the lifespan of animals was determined if they started taking a mix – factor from 22 months and from 30.5 months age. The influence of the mix – factor on the ability of old animals to perform work was determined in a separate series of experiments. It was shown that from 22 to 33 months the content of lipid hydroperoxides in mitochondria and serum increased by 23% and 41%, respectively. The activity of glutathione peroxidase in the serum, mitochondria and erythrocytes decreased, and the activity of glutathione reductase decreased only in the post-mitochondrial fraction of the liver. At the same time, malate– isocitrate dehydrogenase and 6-phosphate dehydrogenase remained unchanged in 33 months old animals compared with 12 months old animals. If animals from 22 months age received a mix factor with drinking water in a dose of 0.05-0.06 mg / 100 g of body weight every day until the end of life, the content of lipid hydroperoxides and the activity of glutathione peroxidase and glutathione reductase of 33 months old animals did not differ from 12 months old animals. The survival curve in animals receiving the mix factor was shifted to the right from 25 to 28 months of age compared with the survival curve of control animals. If animals began to receive the mix – factor at a very old age (from 30.5 months age) until the end of life, their lifespan was longer than that of the control animals. The last ones lived to 41 months, while the animals of the control group lived to 36 months. At the same time, the mix – factor increased the ability of old animals to do work in the test “running in treadmill”. Key words: aging, redox-system, geroprotectors, lifespan

Impact of COVID-19 on the signs of human ageing

The symptoms of post-COVID-19 syndrome (PPCS) are nonspecific and similar to those signs of aging. Therefore, it was suggested that those who have recovered from COVID-19 have accelerating the aging of the body. The aim of this work was to assess the influence of COVID-19 on the frequency of signs of aging. To collect the data, there was used a developed questionnaire, which included 17 signs of aging. There were received the answers from 306 people at the age from 30 to 70 years old. Among them, 98 people have had COVID-19. The average age of the people in the post-COVID-19 and COVID-19-free groups was 51,3 ± 1,65 and 50,4 ± 1,17, respectively (p> 0,05). The frequency of 14 signs of aging was significantly (p <0,01) higher among post-COVID-19 people. Particularly significant differences between post-COVID-19 and COVID-19-free were in the group of people under the age of 50 years old. The data, received by us, allowed to develop a computational procedure for diagnosing of PPCS. The task of attributing of the surveyed people to the post-COVID-19 and COVID-19-free group in accordance with the presence of certain symptoms was solved with the help of the Bayesian method in Gubler's modification, multiple logistic regression and neural network analysis. The developed diagnostic procedures can be used for the identification of the people with a high probability of the developing of PPCS. Keywords: rate of aging, post-COVID-19 syndrome, questionnaire

Effect of ATP and molsidomine combination on contractile function of isolated adult and old rat hearts during adequate coronary perfusion, at ischemia and reperfusion

Pathology of the cardiovascular system occupies a major place in the structure of diseases of the elderly and old patients. Metabolic disturbances are very important in ischemic damages of myocardium in the elderly and old people. So, drugі with metabolic mechanism of action is very ppromising in the treatment of elderly patients with cardiovascular diseases. The relevance of this study is determined by the feasibility of using drugs of metabolic action, which have a beneficial effect on the metabolism of cardiomyocytes, improve blood supply to the myocardium, increase its contractile function. The effect of ATP-molsidomine combination on myocardial contractility in different age animals was stuiesy in vitro experiments. The experiments on the isolated hearts from adult and old rats have shown that combined use of ATP and molsidomine did not significantly affect the contractility of the isolated hearts of adult rats under different perfusion regimes. In old rats, the use of ATP-molsidomine combination had a positive effect on the contractile function of the myocardium under the influence of damaging factors (ischemia, reperfusion): prevented a decrease of left ventricular developing pressure and its first derivative (velocity of pressure rise and velocity of pressure decline) and accelerated its growth during reperfusion. Co-administration of ATP and molsidomine during ischemia had a positive effect on the heart rhythm and restored heart rate at the reperfusion period in adult and old rats. The results of the study indicate a positive effect of the ATP-molsidomine combination on the myocardial contractility in old rats. Combined use of ATP and molsidomine exerted a favourable influence on the heart rhythm under damaging factors both in the adult and old animals. Key words: ATP; molsidomine; isolated rat heart; myocardial contractility; ageing