RENAL HEMODYNAMICS EVALUATION IN PATIENTS SUFFERING FROM RHEUMATOID ARTHRITIS WITH AND WITHOUT COMORBID HYPERTENSION

Aim. To study the features of renal arterial blood flow in patients suffering from rheumatoid arthritis, its interaction with visual markers of atherosclerosis in the presence of comorbid hypertension.Materials and methods. 113 patients with rheumatoid arthritis (RA) were enrolled into this study. Depending on the comorbidity of hypertension the patients were divided into two groups: without (n=53) and with hypertension (n=60). The comparison group consisted of 41 patients with arterial hypertension without RA. Clinical characteristics and blood biochemistry of all the patients were measured. Renal arterial resistance index (RI), presence of atherosclerotic plaques (ASP) in the carotid arteries were assessed by ultrasound scan.Results. In this investigation we report the correlation of the of renal resistive index (RI) and ultrasound signs of carotid atherosclerosis with hypertension in patients with RA. It was found out that there is the increase of RI in RA associated with the age of patients, the onset of the disease at a later age, the presence of atherosclerotic plaques in the carotid arteries and hypertension. In addition, patients with RA had a high frequency of bilateral RI increase by more than 0.7 (64%). Patients with bilateral high RI had a two-fold increase in the registration rate of atherosclerotic plaques in both group of patients with RA.Conclusion. Increased renal arteries RI in patients with RA is a factor associated with the comorbid hypertension and accompanied by more significant atherosclerotic changes in the carotid arteries in the form of an increased incidence of atherosclerotic plaques

Анти-адгезивная стратегия в разработке комплексных противодифтерийных вакцин как перспективная мера снижения циркуляции Corynebacterium diphtheriae среди населения

A study is devoted to the development of new bacterial diphtheria vaccines aimed at prevention adhesion of microbial cells to host’s pharyngeal epithelial cells and thus limit colonization of mucous membranes, bacteria carrier state formation and promoted to C. diphtheriaе circulation decrease among the population. As a base of the candidate-vaccine we suggest the diphtheria bacterial antigenic preparation obtained by use of electro-magnetic radiation of ultrahigh frequency from a culture of C. diphtheriaе, var. gravis, tox +.Исследование посвящено разработке новых бактериальных дифтерийных вакцин, направленных на предупреждение колонизации слизистых оболочек, формирование бактерионосительства и способствующих снижению циркуляции C. diphtheriaе среди населения. В качестве основы кандидат-вакцины предлагается дифтерийный бактериальный антигенный препарат, полученный с помощью электро-магнитного излучения сверхвысокой частоты из культуры C. diphtheriaе, var. gravis, tox +

Anti-adhesive Strategy in Development of Combined Antidiphtheritic Vaccine as a Perspective Preventive Measure of Corynebacteria diphtheriae Circulation Among the Population

A study is devoted to the development of new bacterial diphtheria vaccines aimed at prevention adhesion of microbial cells to host’s pharyngeal epithelial cells and thus limit colonization of mucous membranes, bacteria carrier state formation and promoted to C. diphtheriaе circulation decrease among the population. As a base of the candidate-vaccine we suggest the diphtheria bacterial antigenic preparation obtained by use of electro-magnetic radiation of ultrahigh frequency from a culture of C. diphtheriaе, var. gravis, tox +

METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO), described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO), described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount of toxin it's examined the WHO's proposal to use an intradermal method on guinea pigs and tests on cell cultures. Attention is drawn to the fact that the determination of specific toxicity in cell culture can be carried out at presence of the approval of this method of a national control authority and sensitivity rates no less than in experiments on guinea pigs. The determining of specific toxicity of ready vaccine by subcutaneous method is described. The publication gave a test for elevated toxicity of the final product by intraperitoneal infection of mice and guinea pigs. It’s cited the WHO recommendations aimed at removing the possibility of recovery of the refined toxin toxicity. Checking vaccines toxicity, pyrogenicity, sterility, allergenicity, teratogenicity, mutagenicity and immunogenicity mainly performed on laboratory animals. The review examined the unreliability of animal experiments and the need to find alternative methods for determining the toxicity without their use particularly in light of the “3R”concept. Methods for determining diphtherial toxin using cell cultures is considered, namely, colony overlay test (COT), tests using a monolayer of HeLa cell culture, a culture of Vero cells (kidney cells of african green monkeys ), a culture of CHO cells (cells of Chinese hamster ovary), which are based on the toxin cytopathic effect on sensitive cell culture. Their advantages and disadvantages are listed. An alternative method for the quantitative detection of C. diphtheriae toxin using the polystyrene plate coated with monoclonal antibody to the part of the diphtheria toxin which defines its binding to the cell, is described. It’s regarded the cytotoxic effect of diphtheria toxin on cells of the immune system of mice and guinea pigs: splenocytes, adhesive phagocytes i B- lymphocytes

Анти-адгезивная стратегия в разработке комплексных противодифтерийных вакцин как перспективная мера снижения циркуляции Corynebacterium diphtheriae среди населения

A study is devoted to the development of new bacterial diphtheria vaccines aimed at prevention adhesion of microbial cells to host’s pharyngeal epithelial cells and thus limit colonization of mucous membranes, bacteria carrier state formation and promoted to C. diphtheriaе circulation decrease among the population. As a base of the candidate-vaccine we suggest the diphtheria bacterial antigenic preparation obtained by use of electro-magnetic radiation of ultrahigh frequency from a culture of C. diphtheriaе, var. gravis, tox +.Исследование посвящено разработке новых бактериальных дифтерийных вакцин, направленных на предупреждение колонизации слизистых оболочек, формирование бактерионосительства и способствующих снижению циркуляции C. diphtheriaе среди населения. В качестве основы кандидат-вакцины предлагается дифтерийный бактериальный антигенный препарат, полученный с помощью электро-магнитного излучения сверхвысокой частоты из культуры C. diphtheriaе, var. gravis, tox +.</p

Possible ways to improve the safety of diphtherial vaccines

Стаття присвячена розробці підходів до підвищення безпечності дифтерійних вакцин шляхом застосування пероральної бустер-імунізації та заміни ад’юванту гідроксиду алюмінію на бактерійний антиген. Перевага мукозальних препаратів обумовлена стимулюванням імунної відповіді у цілому і локально, у місцях вхідних воріт патогенів, зменшенням реактогенності завдяки природному шляху введення. Відмова від гідроксиду алюмінію у дифтерійних вакцинах і заміна його на ад’ювант бактерійного походження відкриває можливість уникнути нейротоксичної та аутоімунної дії хімічної речовини, підвищити імуногенність дифтерійного анатоксину, стимулювати реакції Тh1-клітинного захисту організму, сприяти активізації систем уродженого імунітету та антиколонізаційної резистентності. Піддослідних кролів вакцинували препаратами нативного очищеного дифтерійного анатоксину, дифтерійної вакцини АД-М, експериментальними комбінованими вакцинними препаратами, які містили бактерійні антигени, виготовлені з музейних культур C. рseudodiphtheriticum, C. diphtheriae var. mitis tox–, C. diphtheriae, var. gravis, tox+ за допомогою ультразвукової дезінтеграції мікробних клітин за авторським методом. По даним РПГА із сироватками крові щеплених кролів, показано, що пероральний шлях вакцинації дає можливість одержати набагато більш напружений гуморальний захист у порівнянні з підшкірним щепленням навіть при первинній імунізації. Продемонстровано ефективну ад’ювантну дію препаратів поверхневих антигенів клітинної стінки C. diphtheriae різної міри очищення при введенні їх до складу НОДА; Статья посвящена разработке подходов к повышению безопасности дифтерийных вакцин путем применения пероральной бустер-иммунизации и замены адъюванта гидроксида алюминия на бактериальный антиген. Преимущества мукозальных препаратов обусловлены стимулированием иммунного ответа в целом и локально, в местах входных ворот патогенов, уменьшением реактогенности благодаря природному пути введения. Отказ от гидроксида алюминия в дифтерийных вакцинах и замена его на адъювант бактериального происхождения открывает возможность избежать нейротоксического и аутоиммунного действия химического вещества, повысить иммуногенность дифтерийного анатоксина, стимулировать реакции Тh1-клеточной защиты организма, содействовать активизации систем врожденного иммунитета и антиколонизационной резистентности. Подопытных кролей вакцинировали препаратами нативного очищенного дифтерийного анатоксина, дифтерийной вакциной АД-М, экспериментальными комбинированными вакцинными препаратами, которые со- держали бактериальные антигены, полученные из музейных культур C. рseudodiphtheriticum, C. diphtheriae var. mitis tox–, C.diphtheriae, var. gravis, tox+ при помощи ультразвуковой дезинтеграции микробных клеток авторским способом. По данным РПГА с сыворотками крови привитых кролей показано, что пероральный путь вакцинации дает возможность получить гораздо более напряженный гуморальный иммунитет по сравнению с подкожной прививкой даже при первичной иммунизации. Продемонстрировано эффективное адъювантное действие препаратов поверхностных антигенов клеточной стенки C. diphtheriae разной степени очистки при введении их в состав НОДА; Existing diphtheria vaccines cause local reactions (erythema, infiltration) from 10% and over 50% of vaccinations, the risk of which in frequency and severity increases with each subsequent booster dose of the vaccine, from early adolescence. The article is devoted to the development of approaches to increasing the safety of diphtheria vaccines by using oral booster immunization and replacement of the chemical adjuvant of aluminum hydroxide by bacterial antigen. The advantages of mucosal preparations are due to the stimulation of the immune response in general and locally, at the entrance gate of pathogens. Replacing the parenteral method of immunization with oral, which is characterized by naturalness, non-invasiveness, painlessness, does not psychologically traumatize, is also one of the possible ways to reduce the reactogenicity of the diphtheria vaccine. The refusal of the adjuvant of aluminum hydroxide in diphtheria vaccines and its replacement by an adjuvant of bacterial origin opens the possibility of avoiding the neurotoxic and autoimmune action of the chemical, increasing the immunogenicity of diphtheria toxoid, stimulating the Th1-cell defense of the organism, promoting the activation of innate immunity systems and anti-colonization resistance. Experimental rabbits were vaccinated with mono-preparations of native purified diphtheria toxoid (NPDT) and diphtheria vaccine AD-M, experimental combined vaccine preparations that contained bacterial antigens obtained from museum cultures C. pseudodiphtheriticum, C. diphtheriae var. mitis tox-, C. diphtheriae, var. gravis, tox+ by means of ultrasonic disintegration of microbial cells according to the author’s method. According to the RPHA with blood sera of rabbits vaccinated with the drugs studied, it has been shown that the oral route of vaccination makes it possible to obtain much more intense humoral immunity in comparison with subcutaneous vaccination even with primary dose of vaccine: the titers of antitoxic antibodies in the first-second week, respectively, were 8 and 5.6 times higher. The maximum level of antibodies in the initial oral administration of NPDT was obtained on the second week after inoculation – 0.17 IU/ml, and with subcutaneous administration – in the fourth week – 0.06 IU/ml. With the reintroduction of the NPDT, the advantage of the oral route of immunization became even more apparent: from the second week the levels of antitoxic antibodies differed by more than 100 times. The maximum titre of humoral immunity against diphtheria were revealed in the second and third week – 21.3 and 16.0 IU/ml, respectively. At the same time, the subcutaneous administration of the NPDT made it possible to obtain the maximum level of antibodies – 6.4 IU/ml in the first week after repeated vaccination, and then the antibody titers decreased from 0.2 to 0.06 IU/ml. The effective adjuvant effect of preparations of surface antigens of the C. diphtheriae cell wall of different degree of purification upon their introduction into the NPDT was demonstrated. The average geometric titres of antibodies in seropositive rabbits, according to the RPHA, obtained at the first, second and third weeks after vaccination, significantly exceeded the conventional protective level (0.1 IU/ml) by more than 2 times. In the control, with subcutaneous administration of the drug NODA (2 Lf), seroconversion did not occur during the whole experimental observation period