Репозиторий Университета

© 2018, Polish Urological Association. All rights reserved. Introduction In order to investigate the efficacy and safety of Afalaza in men with benign prostatic hyperplasia (BPH) at risk of progression, this multicenter, double-blind, placebo-controlled, randomized clinical trial was performed. Derived by technological treatment of antibodies to prostate-specific antigen (PSA) and endothelial nitric oxide synthase (eNOs), Afalaza was previously proved to modulate its molecular targets. The mechanism of action of the drug is associated with the modulating effect of the antibiodies (RA-Abs) on the molecular targets (PSA and eNOS) by way of conformational changes. Material and methods A total of 249 patients aged 45–60 years with BPH and moderate lower urinary tract symptoms (LUTS), total prostate volume (TPV) ≥30 cm3, Qmax 10–15 ml/s, and serum PSA<4 ng/ml were randomly assigned to receive either Afalaza (n = 125) or placebo (n = 124) for 12 months. Changes in BPH/LUTS symptoms (according to the International Prostate Symptom Score), Qmax, TPV, PSA, BPH clinical progression, occurrence of acure urinary retention (AUR) events or BPH-related surgery were estimated as the study endpoints. Results IPSS mean change was-3.7 ±3.0 (95% CI-4.3 to-3.2) after 12 months of Afalaza (vs.-2.9 ±2.4; 95% CI-3.3 to-2.4 in placebo; р = 0.02). Qmax growth was 2.5 ±4.3 ml/s (vs. 1.4 ±3.3 in placebo; p = 0.049), TPV reduced by 11.8 ±16.0% (vs. 6.5 ±14.7%; p = 0.01, and PSA remained unchanged. Afalaza therapy resulted in a significant decrease in the total sum of BPH progression symptoms (p = 0.01). The maximum effect of Afalaza was registered after 12 months without a tendency to form a ‘plateau’. During the study, no patients experienced AUR or BPH-related surgery. Conclusions A 12-month course of Afalaza therapy is effective and safe for patients with BPH. The results of end points measurements revealed asignificant advantage of Afalaza compared to placebo in the overall symptoms benefit and a decline in the risk of BPH progression. ClinicalTrials.gov: NCT01716104.

© 2018 Istituto Superiore di Sanita. All Rights Reserved. Parkinson disease is one of the common age-related motor neurodegenerative diseases, in which dopamine neurons degeneration is considered to be pathognomic for the development of motor disfunction. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which is considered to be a key regulator of neuronal plasticity. BDNF, being a large molecule, does not pass through the blood-brain barrier (BBB). Synthetic polymer nanoparticles (NP), covered by surfactant, provide the phenomenon of “Trojan hoarse” and enable BDNF to penetrate into the brain tissue. For modelling of parkinsonism we used an intraperitoneal (i.p.) injection of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which was injected to the C57BL/6 mice with subsequest treatment with normal saline (group 1), BDNF (group 2), nanoparticulate BDNF (group 3) and surfactant-coated nanoparticulate BDNF (group 4). After 90 min, 24 hours, 72 hours and 7 days manifestations of parkinsonism were evaluated using behavioural tests of open field, rota-rod, assessment of the tremor, length of the body and pace. At the end of experiment the brain was sampled for histological evaluation of changes in the striatum and midbrain and concentration of BDNF in the brain tissues. The results of the experiments demonstrated that nanoparticulate BDNF covered with surfactant significanltly reduced rigidity of the skeletal muscles, oligokinesia and tremor, and also significantly increased BDNF concentration in the brain tissues.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review summarizes the state-of-the-art in the problem of assessment of the safety of domperidone - a prokinetic and anti-emetic drug belonging to those most widely used in clinical practice. Special attention is devoted to the potential cardiotoxicity of domperidone, mechanisms of adverse effects development, and risk factors. For reducing the risk of development of dose-dependent side effects, new drugs have been created and used so as to maintain the active agent concentration in the blood plasma within the therapeutic range. Another method of increasing the efficacy and safety of domperidone treatment is based on the potentiation effect. An example is the use of domperidone in a fixed combination with omeprazole (Omez-DSR), in which a the prokinetic is present in a modified release form, which ensures uniform delivery of the acting agent into blood flow (without drug concentration +AJM-peaks+AJQ-related to increased risk of dose-dependent adverse drug reactions.

© Ima-Press Publishing House. All rights reserved. Objective: to investigate the effect of indapamide/perindopril fixed-dose combination (FC) on 24-hour blood pressure (BP) and cognitive functions in antihypertensive treatment-naive middle-aged patients with uncomplicated grade 1-2 essential arterial hypertension (EAH). Patients and methods. The open prospective study enrolled 25 patients (9 men and 16 women) aged 40-59 years with a diastolic BP of 90-109 mm Hg and/or a systolic BP of 140-179 mm Hg, as evidenced by routine measurements. As starting antihypertensive therapy, the patients received indapamide 1.25/perindopril 5 mg FC once daily in the morning; if necessary, after 2 weeks (if the routine blood pressure was ≥140/90 mm Hg) they took indapamide 2.5/perindopril 10 mg once daily in the morning. The follow-up period was 14-16 weeks. Before and at the end of the follow-up, the patients underwent 24-hour ambulatory BP monitoring (ABPM) and evaluation of cognitive functions using the Montreal Cognitive Assessment (MoCA), ten-words test (immediate and delayed word recall), verbal association test (literal and categorical associations), number connecting test (Trail making test (TMT), part A and numbers and letters connecting test (TMT) part B), and Stroop test. Results. At the end of the follow-up period, treatment with indapamide/perindopril fixed-dose combination showed a statistically significant reduction in BPs, as evidenced by routine measurements and ABPM (during 24-hour, and awake and sleep periods); a statistically significant cognitive improvement: an increase in the number of the so-called words in the ten-words test during both immediate (from 5.5±1.6 6.5±1.5 words; p=0.02 vs baseline) and delayed (from 6.2±1.7 to 7.4±1.4 words; p=vs baseline) recalls, a decrease in the performance time of TMT-B (from 112.6±42.5 to 90.4±28.4 sec; p=0.02) and Stroop test Part 3 (from 135.5±50.1 to 112.6±19.6 sec; p=0.02), and a larger number of called words in the categorical associations test (from 6.5±2.4 to 8.1±2.9 words; p=0.02). Conclusion. The results obtained indicate that in treatment-naive middle-aged patients with EAH, indapamide/perindopril fixed-dose combination assures an effective reduction in BPs, as evidenced by routine measurements and ABPM, also improves cognitive functions, particularly attention, information processing speed, semantic memory, cognitive flexibility, and short-term and long-term memory.

© 2018, Slovak Academy of Sciences. All rights reserved. The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands – ethylenediamine; 1,2-diaminocyclohexane; 2,2’:6’,2’’-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.

© 2018 Stolichnaya Izdatelskaya Kompaniya. In the article, with regard to current clinical recommendations, the place of combined antihypertensive therapy, especially triple drugs regimens, is considered in the treatment of patients with arterial hypertension. Special focus is given to the body of evidence for the efficacy of valsartan and amlodipine, as the reference drug of angiotensin II receptor blockers and calcium channel blockers, respectively. Not only their high antihypertensive properties are demonstrated, but also a favorable effect on target-organ protection and prognosis is described. In particular, the possibilities of valsartan in reducing the severity of left ventricular hypertrophy and microalbuminuria are described, and its unique properties in the class of sartans that allow the use of this drug in patients with ischemic heart disease and chronic heart failure are emphasized. Data on the antiatherosclerotic effects of amlodipine and its proven ability to reduce cardiovascular risk are presented. Current data are presented about their use in a fixed-dose combination with hydrochlorothiazide, including real clinical practice settings. The evidence base of high clinical efficacy, safety and metabolic neutrality of the triple combination of antihypertensive drugs valsartan, amlodipine and hydrochorothiazide is presented. The issues of increasing adherence of patients to treatment when prescribing fixed-dose combinations are considered. An algorithm for the selection of antihypertensive drugs in the form of monotherapy and combination therapy of two or three drugs depending on the clinical situation (the presence of certain target-organs damages and associated clinical conditions, primarily ischemic heart disease, atherosclerosis of carotid arteries and chronic heart failure) and the severity of the additional risk of cardiovascular complications..

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text

Chronic hepatitis B virus (HBV) infection has long remained a critical global health issue. Covalently closed circular DNA (cccDNA) is a persistent form of the HBV genome that maintains HBV chronicity. Decades of extensive research resulted in the two therapeutic options currently available: nucleot(s)ide analogs and interferon (IFN) therapy. A plethora of reliable markers to monitor HBV patients has been established, including the recently discovered encapsidated pregenomic RNA in serum, which can be used to determine treatment end-points and to predict the susceptibility of patients to IFN. Additionally, HBV RNA splice variants and cccDNA and its epigenetic modifications are associated with the clinical course and risks of hepatocellular carcinoma (HCC) and liver fibrosis. However, new antivirals, including CRISPR/Cas9, APOBEC-mediated degradation of cccDNA, and T-cell therapies aim at completely eliminating HBV, and it is clear that the diagnostic arsenal for defining the long-awaited sterilizing cure is missing. In this review, we discuss the currently available tools for detecting and measuring HBV RNAs and cccDNA, as well as the state-of-the-art in clinical implications of these markers, and debate needs and goals within the context of the sterilizing cure that is soon to come. View Full-Text

According to current guidelines, non-sedative H1-antihistamines (nsAH) are the first-line therapy of chronic spontaneous urticaria (CSU). But even up-dosed antihistamines (to four times the standard dose) produce symptom resolution in less than 50% of patients. Biomarkers that can predict the response to nsAH are still unknown. We carried out a prospective study and used discriminant analysis to evaluate the combination of D-dimer, fibrinogen, C-reac- tive protein and ESR values for predicting the outcome of treatment with levocetirizine in 84 CSU patients. We found that elevation of these parameters is associated with more active disease, low quality of life and lack of response to standard doses of levocetirizine. Thus, eval-uation of these markers may be considered useful before starting treatment with nsAH. The mechanisms behind the increase in these parameters in CSU patients need to be elucidated in further studies.