STAPHYLOCOCCAL INFECTION IN DOGS (DIAGNOSIS, TREATMENT AND PREVENTION)

The paper provides characteristics of diagnostic methods, treatment and preventive measures for staphylococcal infection in dogs. Staphylococcal infection in dogs is an infectious disease caused primarily by staphylococcus virulent strains, characterized by various clinical forms, and it affects the dogs having defects in their immune system. Staphylococci produce a great number of pathogenicity factors (including toxins able to act independently). Therefore, it is rather difficult to apply tools of specific protection and prophylaxis. Skin and mucosa inflammation is the most common pathological condition observed in dogs. Clinical signs include: chronic septic condition with internal abscesses, different skin lesions accompanied by conjunctivitis, otitis, vulvitis, posthitis, rhinitis, sinusitis, cystitis, phlegmon, abscesses, pyometra, wound abscess, polyarthritis, gingivitis. In addition to the pathological agent, the following extra factors are needed for the disease clinical manifestation: immune deficiency, metabolic disorder, parasitic disease, manipulations resulting in damage to the skin and mucosa integrity. The fact that domestic animals can be a source of infection for people can be another reason behind an increasing interest in staphylococcal infection. A comprehensive approach is required to diagnose this disease. In addition to clinical examination, the following tests are needed biochemical blood test, bacteriological tests of biomaterials from animals, isolation of pure agent cultures and determination of sensitivity to antibacterial preparations in every particular case. Bacteriological tests are mandatory to make the final diagnosis. Treatment of dogs also requires a comprehensive approach including specific immunotherapy (active, with the use of anatoxins and antigens and passive with antistaphylococcal hyperimmune sera). Timely prevention and new approaches to treatment are crucial elements

Single local interleukin-2 treatment against transplanted and spontaneous mammary cancer

Immunotherapy is currently emerging mode of breast cancer therapy as efficacy of traditional therapies seems to reach plateau nowadays. First transplanted generation from non-SPF spontaneous BLRB mammary adenocarcinoma (MAC) were used as appropriate mouse model to examine whether single local interleukin-2 (IL-2) is efficient against mammary cancer. We showed that survival dynamics of syngeneic BLRB males with early emerging transplanted mammary cancer (short subclinical period) taken from naturally arisen female mammary carcinoma could be significantly improved by a single IL-2 treatment (2,5 × 106 IU per mouse) applied locally two weeks after MAC cell inoculation. However, the same IL-2 therapy mode applied to later emerging tumors (long subclinical period) of the same average size of 5 mm as late as eighth week after tumor cell inoculation notably shortened the survival of tumor-bearing mice. So, both the fundamental significance and applied implications of biphasic IL-2 effect on mammary cancer growth was shown

Создание ортотопических опухолей в молочной железе мышей BALB/C NUDE клетками рака молочной железы человека MCF-7 и ее VDAC-дефицитными производными

Purpose to study the tumor-forming activity of wild-type MC F-7 cells carrying a full set of porins (VDAC 1, VDAC 2, VDAC 3), as well as their genetically modified cells, from which one of the isoforms was removed (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO, MC F -7 VDAC 3 KO).Material and Methods. The study was aimed at establishing of an animal model of orthotopic tumors in the mammary gland of immunodeficient BAL B/c nude mice by implanting a suspension of human breast cancer cells (MC F-7) and derivatives of these cells generated by targeted knockout of one of the selected mitochondrial porin isoforms (VDAC 1, VDAC 2 or VDAC 3). Suspensions of either wild-type MC F-7 cell lines containing all three porin isoforms (VDAC 1, VDAC 2 and VDAC 3) or their VDAC -deficient derivatives (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO) were injected into mammary fat pads of BAL B/c nude mice at a dose of 4x106 cells per injection. A pathomorphological analysis of the place of implantation of tumor cells, the tumor itself, as well as the organs of the abdominal and thoracic cavity was carried out.Results. The study shows the feasibility of successful creation of orthotopic tumors in the adipose tissue of immunodeficient BAL B/c nude mice with MC F-7 human breast cancer epithelial cells containing a complete set of mitochondrial porin isoforms and their VDAC -deficient derivatives. The tumor-forming activity of the implanted cells was shown to correlate with their cytotoxic effect on the internal organs of animals. Pathological analysis showed that all implanted cell cultures, such as MC F-7 WT, MC F-7 VDAC 2 KO and MC F-7 VDAC 3 KO, except for MC F-7 VDAC 1 KO cells, which did not form tumors, caused pathological changes in the lungs, liver and spleen, as well as the presence of other tumor-like lesions.Conclusion. The data obtained will be used to optimize the injection volume and cell number, as well as to refine the dynamics of tumor growth, suitable for studying the effect of anticancer drugs on tumors formed by human breast cancer cells (MC F-7) and its genetically modified VDAC -deficient derivatives.Цель исследования – изучить опухолеобразующую активность «диких» клеток MC F-7, несущих полный набор поринов (VDAC 1, VDAC 2, VDAC 3), а также их генетически модифицированных клеток, из которых удалена одна из изоформ (MC F-7 VDAC 1 KO, MC F-7 VDAC 2 KO, MC F-7 VDAC 3 KO).Материал и методы. Исследование направлено на создание животной модели ортотопических опухолей в молочной железе иммунодефицитных мышей BAL B/c Nude путем имплантации суспензии клеток рака молочной железы человека (MC F-7) и производных этих клеток, полученных нокаутом одной из выбранных изоформ митохондриальных поринов (VDAC 1, VDAC 2 или VDAC 3). Опухоли создавались путем инъекции в жировую ткань молочной железы мышей BAL B/c Nude суспензии клеточных линий либо диких MC F-7 (содержащих все три изоформы поринов, VDAC 1, VDAC 2 и VDAC 3) либо ее VDAC -дефицитных производных «MC F-7 VDAC 1 KO», «MC F-7 VDAC 2 KO» и «MC F-7 VDAC 3 KO» в дозе 4х106 клеток на одну инъекцию. Проведён патоморфологический анализ места имплантации опухолевых клеток, самой опухоли, а также органов брюшной и грудной полости.Результаты. Показана возможность успешного создания ортотопических опухолей в жировой ткани иммунодефицитных голых мышей BAL B/c Nude эпителиальными клетками рака молочной железы человека «MC F-7 WT», содержащими полный набор изоформ митохондриальных поринов и ее VDAC -дефицитными производными. Опухолеобразующая активность имплантированных клеток коррелирует с их цитотоксическим действием на внутренние органы животного. По результатам патоморфологического анализа можно сделать вывод о том, что за исключением клеток типа «MC F-7 VDAC 1 KO», которые не образовали опухолей, все остальные имплантированные клеточные культуры «MC F-7 WT», «MC F-7 VDAC 2 KO» и «MC F-7 VDAC 3 KO» вызывали патологические изменения состояния легких, печени и селезенки, а также наличие других опухолевидных новообразований.Заключение. Полученные данные будут использованы для оптимизации объема инъекции и количества клеток, а также для уточнения динамики роста опухолей, пригодного для изучения действия противоопухолевых препаратов на опухолях, образованных клетками рака молочной железы человека (MC F-7) и ее генетически модифицированными VDAC -дефицитными производными

On the need to improve the legislation on laboratory animals

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed

О необходимости совершенствования законодательства в сфере использования лабораторных животных

The authors have analyzed international experience in creating legal documents regulating the use of animals for scientific purposes. Topical issues related to the use of laboratory animals for scientific purposes in the Russian Federation, including for the purpose of preclinical studies on the efficacy and safety of new medicines, are discussed. The negative effects of the lack a clear and consistent legal framework for the organization and limits of the use of laboratory animals for research purposes in the Russian Federation are identified. Particular attention is paid to the issue of bioethics, the principles of ethical expertise of research activities involving laboratory animals and the issues of bioethical committees activities. The basic directions of perfection of normative-legal acts and methodological documents in the field of organization and limits of the use of laboratory animals for research purposes are proposed.Проведен анализ международного опыта создания нормативно-правовых документов, регламентирующих использование животных в научных целях. Рассмотрены актуальные вопросы, связанные с использованием лабораторных животных в научных целях в Российской Федерации, в том числе для целей проведения доклинических исследований эффективности и безопасности новых лекарственных средств. Выявлены негативные последствия отсутствия в Российской Федерации четкой и непротиворечивой законодательной базы в области организации и ограничений использования лабораторных животных в научных целях. Особое внимание уделено проблеме биоэтики, принципам проведения этической экспертизы научной деятельности с использованием лабораторных животных и вопросам организации деятельности биоэтических комиссий. Предложены основные направления совершенствования нормативно-правовых актов и методической документации в области организации и ограничений использования лабораторных животных в научных целях

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen