Vasotoxic Effects of Anticancer Therapy: a Review of Current Data

Cardiovascular and oncological diseases are the leading causes of adult death in the world. Despite proven efficacy, anticancer drugs can cause severe cardiovascular complications. Recently, data have appeared on the possible vasotoxic effects of chemotherapy drugs, which can manifest themselves as the progression of arterial hypertension and atherosclerosis, the development of myocardial ischemia and acute coronary syndrome, the formation of venous and arterial thrombosis. The key mechanism for the development of vasotoxicity is endothelial dysfunction, and anticancer drugs can also affect the processes of thrombosis. The review presents the results of 12 selected observational retro- and prospective studies involving cancer patients receiving presumably vasotoxic therapy. Data on the frequency of occurrence and possibilities for the prevention of vasotoxicity are presented

Oxidation-resistant nano-reinforced PC-refractories of modified phenol formaldehyde resin. Part 3. Formation mechanism of organic-inorganic complexes during low-temperature synthesis of nanoparticles of additional antioxidants and their effectiveness

SiC nanoparticles that could be used as an antioxidant for periclase-carbon (PC) refractories were synthesized from the organic—inorganic complex (‒СН₃)‒(SiO₂)n that formed during heating of silicon alkoxide and thermal destruction of its gels. Use of phenolformaldehyde resins modified with silicon alkoxide and its sols was proposed and enabled the formation of an organic—inorganic complex (-СН₃)‒(SiO₂)n‒С with a high C content. This increased the yield of SiC synthesized in the carbon binder. The addition of Ni precursors (additional antioxidant) formed an even more complicated organic—inorganic complex. Use of the complex (‒СН₃)‒(SiO₂)n‒Ni(NiO)‒С together with Al improved the operating characteristics of the PC refractories. It was found that their resistance to oxidation was increased after the complex antioxidant Al + SiC + Ni(NiO) formed

Atrial Fibrillation in Cancer Patients: Who is at Risk?

Cancer is the second leading cause of mortality in the world, second only to cardiovascular diseases. Simultaneously cancer mortality has been steadily decreasing due to the development  of new chemotherapy and targeted  drugs  and the improvement  of existing  treatment protocols.  Improving the prognosis of treatment of cancer patients leads to an unexpected  result - more patients are faced with side effects of cancer treatment. Cardiotoxicity, including  arrhythmia, has  become  a significant  factor  to reduce  the effectiveness  of cancer  patient’s  treatment.  Atrial  fibrillation  is frequent  and persistent a rhythm disorder, affecting  all categories  of patients, especially the elderly. An association  between these two conditions  can be expected, considering the fact that in old age the prevalence of malignant neoplasms  and comorbid pathology predisposing to the onset of AF is high. Therefore, AF may be an additional  factor negatively  influencing the prognosis and treatment tactics in patients with malignant neoplasms. A comprehensive search was conducted  using the keywords  “cancer”, “atrial fibrillation” and “cardiotoxicity” using the PubMed,  Scopus and Cohrane  databases. We reviewed publications having the relationship between AF and cancer. The literature review considered 61 publications on the prevalence of AF in cancer patients, classification, mechanisms of development, the effect of anticancer drugs and other treatment methods on this group of patients. Analyzed articles include clinical guidelines, consensus  expert opinions,  systematic  reviews,  meta-analyzes, and previously  published  reviews of the literature. The problem of cardiotoxic  complications diagnostics is evaluated separately,  incl. arrhythmias, and their monitoring in cancer patients. Therefore, the direction of medicine named "Cardio-oncology" comes to the fore. Interdisciplinary interaction will allow identify cardiotoxic  manifestations at the subclinical stage and optimize anticancer treatment

Oxidation resistance of nano-reinforced PC-refractories modified with phenol formaldehyde resin. Part 4. Thermodynamic evaluation of phase formation within Mg–O–C–Al, Mg–O–C–Ni and МgO‒Al₂O₃‒NiO‒SiO₂ systems using SiC + Al + Ni (NiO) complex antioxidant

Results are given for the synthesis and co-existence of phases formed from components of complex organic- inorganic antioxidant formed during modification of phenol-formaldehyde resin (PFR) and graphite with silica alkoxide and inorganic or organic nickel precursors. Thermodynamic analysis is given for the Mg–Al–C and Mg–O–Ni–C systems. It is shown that the periclase and carbon can coexist with aluminum and nickel, and also that oxidized antioxidants Al₂O₃ and NiO can interact respectively with the periclase and with the synthesized SiC formed during modification of PFR with silica. In considering the NiO‒MgO‒Al₂O₃‒SiO₂ system it is established that during service noble spinel will be synthesized from the complex antioxidant components, facilitating an increase in PC-refractory durability in service

Potential of primary drug prevention of cardiotoxicity in the context of anticancer therapy

Aim. To search early signs of cardiotoxicity in patients receiving anticancer therapy and evaluate the effectiveness of cardioprotection with an angiotensin-converting enzyme inhibitor, beta-blocker and myocardial cytoprotector.Material and methods. The study included 98 patients with high and very high risk of cardiotoxicity according to the Mayo Clinic scale (USA). Cancer patients with hypertension were offered cardioprotective treatment with a fixed-dose combination of perindopril and bisoprolol, and patients with very high risk and concomitant coronary artery disease additionally trimetazidine.The patients were divided into 2 following groups: the experimental group (n=50), where patients were prescribed cardioprotective therapy, and the control group (n=48), which consisted of patients who refused or had contraindications to cardioprotection. All patients underwent an examination, including the collection of complaints and anamnesis, physical examination, electrocardiography and echocardiography with an assessment of left ventricular (LV) global longitudinal strain before chemotherapy and 1, 3, 6, 9 and 12 months after initiation of anticancer therapy.Results. In patients of the control group, by the end of the follow-up, the left atrial volume index and LV end-diastolic volume index significantly increased. In the main group, these indicators did not change significantly. In the control group, by the final visit, the LV ejection fraction significantly decreased in comparison with the initial value and the value in the first group. After 6, 9 and 12 months, there was a significant decrease in the LV global longitudinal strain in the control group, while in the main group this indicator remained within the normal range. The mortality rate in the control group was significantly higher (15% vs 2% in the experimental group). In the experimental group, cardiotoxic complications occurred in 28%, while in the control group — in 78% of patients.Conclusion. The study demonstrated the significant importance of cardiac monitoring and primary drug prevention of cardiotoxicity of anticancer therapy. A sig nificant deterioration in LV systolic function was shown in patients with a high and very high risk of cardiotoxicity who did not receive cardioprotective therapy, while its high efficiency was demonstrated in patients of the experimental group

Використання 2,3-дихлор-1,4-нафтохінону для спектрофотометричного визначення ацетилцистеїну в лікарських препаратах

The aim of research was the development and validation ofspectrophotometric method foracetylcysteine assay in pharmaceutical formulations.Тhe proposed method is based on the reaction with 2,3-dichloro-1,4-naphthoquinone and the formation of colored products that exhibit absorption maxima at 425 nm.IntroductionMany analytical methods have been published for acetylcysteine assay in pharmaceutical formulations as high-performance liquid chromatography (HPLC), fluorimetry and chemiluminescence. Some of these methods are time consuming or require expensive equipment. Other published methods suffer from lack of selectivity and sensitivity. Spectrophotometry is the most widely used technique in pharmaceutical analysis because it is simple, economic, and easily available to most quality control laboratories.In the present work, we propose a simple and accurate spectrophotometric method for acetylcysteine assay in pharmaceutical formulations.Materials and MethodsReagents: Reference standard acetylcysteinesubstance; 2,3-dichloro-1,4-naphthoquinone. All chemicals and solvents were of analytical grade.DMFA was used as a solvent.Pharmaceutical preparations:powder for oral solution «ACC 200» 200 mgseries number50026151 (Salutas Pharma CmbH, Germany); effervescent tablets  «Fluimucil» 600 mg (Zambon S.P.A., Italy) and «ACC LONG» 600 mg (Salutas Pharma CmbH, Germany) series numbers 321284 and DH2740; solution for injections «Fluimucil» 100 mg/ml (Zambon S.P.A., Italy)series number28002492.Solutions:Acetylcysteine stock solution (0,16%);DMFAsolution of 2,3-dichloro-1,4-naphthoquinone (4%).EquipmentAnalytical balance (ABT-120-5DM); UV-VIS spectrophotometer (Specord 200); water bath (MemmertWNB 7-45);quartz cells.ResultsAcetylcysteine was determined using a spectrophotometric method based on the reaction with 2,3-dichloro-1,4-naphthoquinone to form yellow colored reaction products with absorption maxima at 425 nm. The effect of reaction time and temperature was studied. It was found that the reaction requires heating at 95°С for 10 min.The proposed method is valid according to the validation requirements of Ukrainian Pharmacopeia. The following parameters were considered: range of application, linearity, accuracy, robustness, precision of the results.ConclusionThe proposed spectrophotometric method for quantitative determination of acetylcysteine in pharmaceutical formulations was found to be simple, precise, accurate, linear, robust and rugged during validation. Further this method can be recommended for routine quantitative determination of the studied drugs in quality control laboratories.Актуальной проблемой современного фармацевтического анализа является создание эффективных и экономичных методик количественного определения лекарственных веществ. Цель работы – разработка и валидация новой спектрофотометрической методики количественного определения ацетилцистеина в лекарственных формах. Установлено, что ацетилцистеин реагирует с 2,3-дихлор-1,4-нафтохиноном с образованием окрашенного продукта реакции с максимумом абсорбции при 425 нм. Предложенная методика отвечает требованиям Государственной фармакопеи Украины, предъявляемым к методикам количественного анализа лекарственных веществ. Результаты исследования показывают, что методика является высокочувствительной, точной, простой в выполнении и пригодной для использования в лабораториях Государственной инспекции по контролю качества лекарственных веществ, а также отделах технического контроля химико-фармацевтических предприятий.Актуальною проблемою сучасного фармацевтичного аналізу є створення ефективних та економічних методик кількісного визначення лікарських речовин. Мета роботи полягала в розробці та валідації нової спектрофотометричної методики кількісного визначення ацетилцистеїну в лікарських формах. Встановили, що ацетилцистеїн реагує з 2,3-дихлор-1,4-нафтохіноном з утворенням забарвленого продукту реакції з максимумом абсорбції при 425 нм. Запропонована методика відповідає вимогам Державної фармакопеї України щодо методик кількісного аналізу лікарських речовин. Результати дослідження свідчать, що методика є високочутливою, точною, простою у виконанні та придатною для використання в лабораторіях Державної інспекції з контролю якості лікарських речовин, а також відділах технічного контролю хіміко-фармацевтичних підприємств

SPECTROPHOTOMETRIC DETERMINATION OF ACETYLCYSTEINE IN PHARMACEUTICAL FORMULATIONS USING 2,3-DICHLORO-1,4-NAPTHOQUINONE

The aim of research was the development and validation ofspectrophotometric method foracetylcysteine assay in pharmaceutical formulations.Тhe proposed method is based on the reaction with 2,3-dichloro-1,4-naphthoquinone and the formation of colored products that exhibit absorption maxima at 425 nm. Introduction Many analytical methods have been published for acetylcysteine assay in pharmaceutical formulations as high-performance liquid chromatography (HPLC), fluorimetry and chemiluminescence. Some of these methods are time consuming or require expensive equipment. Other published methods suffer from lack of selectivity and sensitivity. Spectrophotometry is the most widely used technique in pharmaceutical analysis because it is simple, economic, and easily available to most quality control laboratories. In the present work, we propose a simple and accurate spectrophotometric method for acetylcysteine assay in pharmaceutical formulations. Materials and Methods Reagents: Reference standard acetylcysteinesubstance; 2,3-dichloro-1,4-naphthoquinone. All chemicals and solvents were of analytical grade. DMFA was used as a solvent. Pharmaceutical preparations:powder for oral solution «ACC 200» 200 mgseries number50026151 (Salutas Pharma CmbH, Germany); effervescent tablets «Fluimucil» 600 mg (Zambon S.P.A., Italy) and «ACC LONG» 600 mg (Salutas Pharma CmbH, Germany) series numbers 321284 and DH2740; solution for injections «Fluimucil» 100 mg/ml (Zambon S.P.A., Italy)series number28002492. Solutions: Acetylcysteine stock solution (0,16%); DMFAsolution of 2,3-dichloro-1,4-naphthoquinone (4%). Equipment Analytical balance (ABT-120-5DM); UV-VIS spectrophotometer (Specord 200); water bath (MemmertWNB 7-45);quartz cells. Results Acetylcysteine was determined using a spectrophotometric method based on the reaction with 2,3-dichloro-1,4-naphthoquinone to form yellow colored reaction products with absorption maxima at 425 nm. The effect of reaction time and temperature was studied. It was found that the reaction requires heating at 95°С for 10 min. The proposed method is valid according to the validation requirements of Ukrainian Pharmacopeia. The following parameters were considered: range of application, linearity, accuracy, robustness, precision of the results. Conclusion The proposed spectrophotometric method for quantitative determination of acetylcysteine in pharmaceutical formulations was found to be simple, precise, accurate, linear, robust and rugged during validation. Further this method can be recommended for routine quantitative determination of the studied drugs in quality control laboratories

ПОРІВНЯЛЬНА ХАРАКТЕРИСТИКА НАКІСТКОВОГО ОСТЕОСИНТЕЗУ ПРИ ПЕРЕЛОМАХ ПЛЕЧОВОЇ КІСТКИ

The authors adduce the results of a clinical case follow-up over 61 patients with fractures of the humerus who have been treated, using external fixation. It has been demonstrated that patients operated by means of nail-plate fixation with angular stability were characterized by such higher parameters of the postoperative condition: the evidence of strength arm flexing, the ability to abduct the arm, external and internal rotation, evidencing of better indices of the quality of life in this particular cohort of patients and the advantages of the technology in question.Приведены результаты клинического наблюдения за 61 больным с переломами плечевой кости, которых пролечено с применением накостного остеосинтеза. У пациентов, прооперированных с использованием остеосинтеза пластинами с угловой стабильностью, выше оказались следующие показатели послеоперационного состояния: выраженность силы, сгибание руки, способность отведения руки, наружная и внутренняя ротация, что свидетельствует о лучших показателях качества жизни больных и преимущества указанной технологии.Наведені результати динамічного клінічного спостереження за 61 хворим з переломами плечової кістки, яких проліковано із застосуванням накісткового остеосинтезу. Показано, що в пацієнтів, прооперованих з використанням остеосинтезу пластинами з кутовою стабільністю, вищими виявилися такі показники післяопераційного стану: вираженість сили, згинання руки, здатність відводити руку, зовнішня та внутрішня ротація, що свідчить про кращі показники якості життя у даної категорії хворих та переваги вказаної технології

PREDICTIVE VALUE OF ECHOCARDIOGRAPHY IN POST MYOCARDIAL INFARCTION SETTING. PART 2

Echocardiography is a useful tool for risk stratification and prognosis assessment after myocardial infarction. It was shown, that for prediction related data acquisition, it is possible to apply multiple echocardiographic parameters, such as the volumes and ejection fraction of the left ventricle, wall motion index, left atrium volume, and existence of atrial regurgitation. Development of the method of tissue Doppler and “speckle-tracking” led to invention of novel prediction parameters, as deformation, deformation velocity, dissynchrony of the left ventricle. Method of contrast echocardiography makes it to evaluate myocardial perfusion and safety of microvascularity, gives valuable data on myocardial viability, which is closely related to prognosis. Stress echocardiography makes it to assess myocardial ischemia and find viable myocardium, and the Doppler of coronary arteries — to evaluate coronary flow reserve. Finally, 3D echo makes possible the gathering of optimal data on the volumes, functioning and sphericity of the left ventricle, which are significant parameters of long term prognosis