Manifestations Of Systemic Inflammation Research Articles

Schnitzler Syndrome: Clinical Case and Review of The Literature

Schnitzler syndrome is a rare auto-inflammatory disease with a chronic relapsing course, characterized by recurrent urticarial lesions and monoclonal gammopathy. The manifestations of systemic inflammation are complemented by fever, bone and muscle pain, arthralgia/arthritis, lymphadenopathy, hepato- or splenomegaly, increased levels of acute inflammatory markers. A biological marker of the disease is the monoclonal gammopathy. Patients show high risk to develop AA-amyloidosis and lymphoproliferative diseases. A patient with a 5-year delay in diagnosis, who has responded well to systemic corticosteroids is presented. A comprehensive review of the new insights of disease pathogenesis and therapy is also highlighted.

Hepatobiliary system and intestinal injury in new coronavirus infection (COVID-19): A retrospective study

An important area of effective control of the coronavirus disease 19 (COVID-19) pandemic is the study of the pathogenic features of severe acute respiratory syndrome coronavirus 2 infection, including those based on assessing the state of the intestinal microbiota and permeability. To study the clinical features of the new COVID-19 in patients with mild and moderate severity at the stage of hospitalization, to determine the role of hepatobiliary injury, intestinal permeability disorders, and changes in the qualitative and quantitative composition of the microbiota in the development of systemic inflammation in patients with COVID-19. The study was performed in 80 patients with COVID-19, with an average age of 45 years, 19 of whom had mild disease, and 61 had moderate disease severity. The scope of the examination included traditional clinical, laboratory, biochemical, instrumental, and radiation studies, as well as original methods for studying microbiota and intestinal permeability. The clinical course of COVID-19 was studied, and the clinical and biochemical features, manifestations of systemic inflammation, and intestinal microbiome changes in patients with mild and moderate severity were identified. Intestinal permeability characteristics against the background of COVID-19 were evaluated by measuring levels of proinflammatory cytokines, insulin, faecal calprotectin, and zonulin. This study highlights the role of intestinal permeability and microbiota as the main drivers of gastroenterological manifestations and increased COVID-19 severity.

Generalized Pustular Psoriasis: A Review of the Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment.

Generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis that is characterized by the abrupt widespread onset of small pustules accompanied by systemic manifestations of inflammation. It can arise in patients with a history of psoriasis as well as in those without, sometimes due to medication initiation or withdrawal, pregnancy, or infection. Generalized pustular psoriasis is thought to be driven primarily by innate immunity and unrestrained IL-36 cytokine activity. Recent genetic analyses have identified 3 genetic mutations that are associated with GPP-IL36RN, CARD14, and AP1S3-though these mutations only account for a minority of cases. There are many cutaneous pustular diseases that must be ruled out in the evaluation of a patient with suspected GPP, especially acute generalized exanthematous pustulosis (AGEP), and histologic analysis is the cornerstone of diagnosis. Although the quality of evidence to generate treatment recommendations for GPP is limited, management often includes utilization of systemic agents and/or biologics, usually with adjunctive topical treatment. Accumulating evidence suggests that biologic agents, especially infliximab, may be considered as first-line treatment of GPP, especially in severe acute cases, due to their abrupt onset of action and favorable side-effect profiles compared with oral systemic agents.

Bacterial Lysate Complex Administered Intranasally Suppresses Inflammation in an In Vivo Model of Aseptic Lymphadenitis.

The effect of a bacterial lysate complex IRS 19 on local and systemic manifestations of inflammation was studied in a rat model of aseptic lymphadenitis. Injection of λ-carrageenan into the cervical lymph node via surgical approach caused an increase in the thickness of the capsule, disturbances in histoarchitecture, the appearance of necrosis foci, histiocytosis of subcapsular and cerebral sinuses in the lymph node, as well as an increase in the level of TNFα in the blood serum and the number of circulating leukocytes and neutrophils. Course intranasal administration of bacterial lysate complex in this model dose-dependently reduced the level of these markers of the systemic inflammatory response and the severity of microstructural disorders in the affected lymph nodes. Thus, bacterial lysate complex after intranasal administration produces a systemic anti-inflammatory effect that goes beyond the respiratory tract.

Anti-inflammatory properties of the extract of maruna virgin (Tanacetum parthenium L.) on the model of chronic inflammation modeled by the Freund’ adjuvant in rats

Еhe aim of the study was to investigate the effectiveness of a thick extract of feverfew (Tanacetum parthenium L.) herb in chronic inflammation (adjuvant arthritis) in rats.
 The anti-inflammatory properties of the water-alcohol thick extract of feverfew (Tanacetum parthenium L.) herb (ETP) were studied in the model of adjuvant arthritis (ADA) (0.1 ml of Freund's adjuvant (PAF), once subcutaneously at the base of the tail of white nonlinear male rats (body weight 200–220 g). After 7 days, the introduction of PAF was repeated (subcutaneously in the right hind paw of rats). The animals were divided into 4 groups of 9 rats each, in the intact group – 6 animals. Distilled water (1 ml/100 g) was administered to positive control animals (PCs) on the background of pathology. An aqueous solution of ETP (50 mg/kg) and diclofenac sodium (1% starch suspension, 8 mg/kg) were administered from day 1 of the experiment and for four weeks daily intragastrically once daily. The volume of the affected foot (V) was measured using a LE7500 plethysmometer (PANLAB, Italy) in dynamics – at 1, 5, 10, 15, 20, 25 and 30 days after administration of a permissive dose of PAF. The intensity of inflammation in rats was assessed by peripheral blood parameters, biochemical indicators - markers of the inflammatory process. Statistical analysis of data was performed using the standard software package «Statistica v. 6.0». Differences between groups were considered statistically significant at p <0.05.
 The course of ADA was characterized by the development of systemic inflammation, as evidenced by an increase in the number of leukocytes, increased erythrocyte sedimentation rate (ESR) and the content of C-reactive protein (CRP). A statistically significant increase in the level of LF and sialic acids indicates membrane-destructive processes in connective tissue. Against the background of ETP significantly decreased the level of the main indicator of inflammation CRP 2 times, the content of markers of destruction of joint tissue – sialic acid and LF decreased by 1.9 times relative to PC animals, indicating a positive effect on local and systemic manifestations of inflammation in ADA. The effectiveness of ETP was not inferior to diclofenac sodium (DS).
 Based on the data obtained, it can be concluded that the studied ETP at a dose of 50 mg/kg in the ADA model in rats has a pronounced anti-inflammatory effect and is not inferior to diclofenac sodium, which makes it promising further research as an effective anti-inflammatory agent.

Not So Ordinary Joint Pain - What It Could Be?

Musculoskeletal concerns are a common concern in busy primary care practice. When the musculoskeletal concern is a manifestation of systemic inflammation, as in inflammatory spondyloarthropathy, its early diagnosis is critical in preventing progression to irreversible joint damage, disability, morbidity, and mortality. This case explores an atypical presentation of inflammatory spondyloarthropathy in patients without a significant medical history.

Роль герпетичної інфекції в прогресуванні коморбідної соматичної патології

Мета роботи: визначити особливості клітинної та гуморальної ланок імунної системи у хворих на хронічне обструктивне захворювання легень (ХОЗЛ) груп В та С, GOLD 2–3, які мають ознаки метаболічного синдрому (МС), із наявністю ознак інфікування вірусами групи Herpesviridae. Матеріали та методи. Були обстежені 42 хворі на ХОЗЛ груп В та С, GOLD 2–3, поєднане із МС. 18 осіб мали поєд­нання ХОЗЛ та МС і були інфіковані вірусами Herpesviridae. Середній вік пацієнтів становив 51,3 ± 4,2 роки. У групу порівняння ввійшли 24 пацієнти з ХОЗЛ та МС без герпесвірусної інфекції. Усім хворим було проведене визначення антигенів вірусу простого герпесу (ВПГ) І типу та цитомегаловірусу (ЦМВ) у крові та слині, титру специфічних IgG- та IgM-антитіл до ВПГ І типу та ЦМВ, комплексне імунологічне обстеження з дослідженням показників клітинної та гуморальної ланок імунної системи, цитокінового статусу. Результати. При дослідженні активності вірусів родини герпесу в крові пацієнтів основної групи не було виявлено активної реплікації вірусів ВПГ 1-го типу та ЦМВ, а в слині в 15 хворих (83,3 %) була виявлена активна реплікація ВПГ 1-го типу, а у 12 осіб (66,7 %) — ЦМВ. У всіх пацієнтів основної групи відмічався тяжкий перебіг герпесвірусної інфекції з частотою загострень більше 6 разів на рік. В імунологічному статусі хворих основної групи спостерігалися імунодефіцит переважно Т-клітинної ланки імунної системи та NK-клітин, значне підвищення відносної кількості Т- та В-лімфоцитів із раннім та пізнім маркерами активації на тлі автоімунних проявів та запальних змін у периферичній крові. Висновки. Наявність хронічної персистуючої інфекції ВПГ 1-го типу та ЦМВ обумовлює тяжкий перебіг ХОЗЛ, поєднаного з МС, індукує розвиток інфекційних загострень ХОЗЛ та більш виражені прояви системного запалення при атеросклерозі як морфологічному субстраті МС.

Microbiota and intestinal permeability as drivers of gastroenterological manifestations of new coronavirus infection (COVID-19)

An important area of effective control of the COVID-19 pandemic is the study of the pathogenetic features of SARSCoV-2 infection, including those based on the assessment of the state of the microbiota and intestinal permeability.Purpose: To study the clinical features of the new coronavirus infection (COVID-19) in patients of mild and moderate severity at the stage of hospitalization, to determine the role of intestinal permeability disorders, changes in the qualitative and quantitative composition of the microbiota in the formation of systemic inflammation in COVID-19 patients.Material and methods: The study was performed in 80 patients with COVID-19, whose average age was 45 years, 19 of them had mild and 61 had moderate severity of the disease. The scope of the examination included traditional clinical, clinical and laboratory, biochemical, instrumental and radiation studies, as well as original methods for studying microbiota and intestinal permeability.Results and conclusions: Clinical features of the course of COVID-19 were studied, clinical and biochemical features, manifestations of systemic inflammation, changes in the intestinal microbiome of patients with mild and moderate severity were identified, concentration levels of proinflammatory cytokines, insulin, fecal calprotectin and zonulin were determined, reflecting the features of intestinal permeability against the background of COVID-19. The role of intestinal permeability and microbiota as the main drivers of the development of gastroenterological manifestations of COVID-19, accompanied by a more severe course of the disease, is emphasized.

Effect of pyrrole derivatives on manifestations of inflammation in rats with chronic ulcerative colitis under prednisolone treatment

Background. Previously, we have detected the antitumor and anti-inflammatory activities of pyrrole-derived protein kinase inhibitors - MI-1 (1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino) -1H-pyrrole-2,5-dione 1) and D1 (5-amino-4-(1,3-benzothiazole-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrole-3-one) using rat colon cancer model. Therefore, pyrrole derivatives was aimed at detecting the anti-inflammatory effect on the model of ulcerative colitis caused by acetic acid in rats. Materials and Methods. Prednisolone was used as a reference anti-inflammatory drug of glucocorticoid nature. It was administered intraperitoneally at a dose of 0.7 mg/kg. The compounds were administered in 2 h after the first administration of acetic acid. Total protein was estimated quantitatively, as described by Lowry et al., 1951. Content of the malonic dialdehyde, protein carbonyl groups, and the activity of antioxidant enzymes as indicators of colon mucosa redox status were measured spectrophotometrically. Statistical analysis of the results was performed using MS Excel-2013. Results and Discussion. In case of chronic colitis, the number of carbonyl groups and lipid peroxidation products in the colonic mucosa are increased, indicating the development of oxidative stress. The injection of pyrrole derivatives separately contributes to the approaching these indicators to normal. Adding prednisolone does not have this effect. Colitis has been shown to have a decrease in superoxide dismutase activity, which is a typical phenomenon for chronic inflammation and may indicate depletion of the enzyme. In case of colitis, alanine aminotransferase activity and the content of direct bilirubin are increased, which indicates a liver injury and are systemic manifestations of inflammation of the colon. Pyrrole derivatives help to reduce the liver injury, which indicates the restoration of normal alanine aminotransferase activity and direct bilirubin content. Conclusion. It has been found that at chronic colitis pyrrole derivatives reduce the manifestations of inflammation, contribute to the normal structure of the mucous membrane (comparative to prednisolone as a standard anti-inflammatory drug). It suggests their anti-inflammatory effectiveness, while an increase in total bilirubin under exposition to pyrrole derivatives may be a sign of the adverse effects on the rat’s liver.

AB0487 HEPSIDINE LEVEL IN PATIENTS WITH ANKYLOSING SPONDYLITIS, RELATIONSHIP WITH HEMOPOESIS AND FERROKINETICS

Background:Hypoferimia, as a manifestation of systemic inflammation, is quite common in patients with ankylosing spondylitis (AS). Anemic syndrome can be represented by anemia of chronic disease (ACD), iron deficiency anemia (IDA) and their combination. Its frequency of occurrences ranges from 18.5 to 45.8 %. The discovery of the hormone hepcidin in 2001 changed the perception of iron metabolism disorders and demonstrated its association with the inflammatory component. Over the last decade, scientific databases have accumulated a lot of information about hepcidin and its role in the development of anemia and the response to inflammation. However, in the context of the AS, such data are contradictory and therefore need further study.Objectives:To determine the level of hepcidin in patients with ankylosing spondylitis and to assess its relationship with hematopoiesis and ferrokinetics.Methods:The hepcidin levels of 76 patients with ankylosing spondylitis (13 women and 63 men with a mean age of 43.67±0.97 years). The diagnosis of AS was made according to the New York modified criteria of 1984. All patients were divided into three groups: without anemia (n=47), with anemia (n=29) and the control group, representative by age and sex (n=26). According to the percentile analysis, all patients were divided into a group with an optimal <25 ng/ml, extremely high - 25-35 ng/ml and a high level of hepcidin > 35 ng/ml. In addition to hepcidin, hematopoiesis and ferrokinetic parameters were measured in each patient: hemoglobin (Hb), erythrocyte, MCV, serum iron, total serum iron-binding capacity (TIBC), serum ferritin, transferrin saturation (TS). Statistical processing of the obtained results was performed with the use of statistical software package “Microsoft Office Excel 2007”.Results:When conducting a percentile comparison in 95 % of people in the control group, the level of hepcidin was in the range of 17.97-38.8 ng/ml (P5 - P95), and in patients with AS in 95 % - 14.62-87.38 ng/ml. At P95, the level of hepcidin in patients with AS was 2.3 times higher than in P95 control group. Comparing the mean values of hepcidin, a significant difference was found between the group of patients without anemia, where it was 36.08±2.57 ng/ml and the group of patients with anemia, where the level of hepcidin was 51.77±4.62 ng/ml. The lowest level of hepcidin was in patients with IDA (35.8 ±7.50 ng/ml), and the highest (62.78±5.94 ng/ml) - among patients with ACD. The group of patients with ACD and iron deficiency, according to the levels of hepcidin (48.53±9.50 ng/ml) took an intermediate place.In terms of hematopoiesis and ferrokinetics, the level of hemoglobin and erythrocytes did not differ significantly between the groups of optimal, extremely high and high levels of hepcidin. According to the levels of serum iron, TS and ferritin in the group of patients with anemia, a significant association with hepcidin was established (with increasing levels of hepcidin, the values of serum iron, TS and ferritin also increased). In contrast,sTfR levels were the highest in the group with optimal hepcidin levels (6.02±0.71 mg/l) and decreased to 4.88±0.64 mg/l in the group with high hepcidin levels. Such changes in hematopoiesis and ferrokinetics were explained by the accumulation of mostly people with symptoms of ACD in the group with high levels of hepcidin, and the group with optimal levels of hepcidin consisted mainly of patients with IDA.Conclusion:Patients with AS have elevated serum hepcidin levels, it is higher in individuals with anemic syndrome than in patients without anemia and is associated with serum iron, TS and ferritin levels.Disclosure of Interests:None declared.

Вплив додаткової нейропротекції Гліатиліном на перебіг септичного процесу і вираженість енцефалопатії в структурі синдрому поліорганної недостатності

Актуальність. Сепсис, як реакція організму на інфекцію, включає такий етап розвитку, як синдром поліорганної недостатності (СПОН). Мозкова дисфункція в 70 % випадків є одним з перших симптомів сепсис-асоційованого СПОН, ще до клінічних проявів в інших системах життєзабезпечення. Сепсис-асоційована енцефалопатія — мультифокальне порушення функцій головного мозку за умови наявності інфекції, що супроводжується проявами системного запалення, але без клінічних і лабораторних доказів прямої причетності інфекції до пошкодження головного мозку. Залежно від критеріїв, покладених в основу діагностики, церебральна дисфункція-недостатність може бути виявлена в усіх хворих із сепсисом. Ступінь її вираженості корелює зі зростанням тяжкості септичного процесу. Сепсис-асоційована дисфункція-недостатність може бути незалежним предиктором летального кінця. Тяжкість церебральної дисфункції-недостатності коливається від летаргії і/або дезорієнтації до коми. Мета: вивчення впливу терапії відповідно до головних положень «Міжнародного керівництва з інтенсивної терапії сепсису та септичного шоку: 2016» із додатковою нейропротекцією Гліатиліном на перебіг септичного процесу й вираженість енцефалопатії в структурі синдрому поліорганної недостатності. Матеріали та методи. За період 2010–2015 рр. нами проведено контрольоване проспективне рандомізоване когортне дослідження на клінічній базі кафедри анестезіології та інтенсивної терапії ДЗ «Дніпропетровська медична академія МОЗ України» і на базі відділення інтенсивної терапії сепсису КП «Дніпропетровська обласна клінічна лікарня ім. І.І. Мечникова» ДОР». У дослідження було включено 22 пацієнти. У всіх хворих було проведено рутинні лабораторні дослідження для визначення рівня клінічних і біохімічних маркерів системного запалення й органних дисфункцій за шкалами SOFA і LIFE. Для оцінки стану свідомості використовували шкалу коми Глазго. Концентрацію цитокінів (фактор некрозу пухлини α, інтерлейкін-1, інтерлейкін-4, інтерферон α) у сироватці крові вивчали імуноферментним методом. Базисна інтенсивна терапія здійснювалася відповідно до основних положень «Міжнародного керівництва з інтенсивної терапії сепсису та септичного шоку: 2016» з додатковим використанням нейропротекторного препарату Гліатиліну (холіну альфосцерат) 1000–3000 мг на добу внутрішньовенно, розчиненого в 0,9% розчині натрію хлориду, протягом 5–10 днів. Дослідження показників проводилося в чотири етапи: на 1-шу, 3-тю, 5-ту, 7-му добу. Результати. Узагальнюючи результати дослідження, можливо сказати, що на п’яту й сьому добу були відсутні клінічні прояви синдрому системної запальної відповіді в понад 75 % хворих; зменшилася тяжкість стану за APACHE II на 72,5 і 74,5 % (p < 0,001) і ступінь вираженості синдрому поліорганної недостатності за SOFA в 9 разів (p < 0,001) відповідно до етапів дослідження. Церебральна недостатність, оцінена за шкалою коми Глазго, становила 15 балів на п’яту й сьому добу дослідження, що відповідало стану ясної свідомості в понад 75 % хворих. Зазначене спостерігалося на тлі тенденції до збалансованості активності прозапальних і протизапальних ланок цитокінової системи, про що свідчили максимальні значення фактора некрозу пухлини α та інтерферону α на п’яту добу спостереження при зниженні концентрації інтерлейкіну-1 на 55,8 % щодо фону. Прогнозована летальність у пацієнтів другої групи становила 51 %, фактична летальність — 7,5 %. Отже, шляхом проведення даного варіанта інтенсивної терапії вдалося знизити передбачувану летальність на 43,5 %.

USE OF HERBAL IMMUNOTROPIC MEDICINES FOR COMPLEX TREATMENT OF GENERALIZED PERIODONTITIS IN PATIENTS WITH CONCOMITANT CORONARY ARTERY DISEASE

The aim: Of this study was to improve the efficiency of complex medicamental treatment of generalized periodontitis (GP) in patients with concomitant CAD using of differentiated immunotropic therapy, especially herbal medicine «Immuno-ton». Material and methods: 130 patients with GP were observed (43 without and 81 with chronic CAD - stable angina, functional classes II-III (CCS)) with detection of oral hygiene indices for Green-Vermillion, inflammation of gums PMA, bleeding of gums PBI, depth of periodontal pockets (determined by direct method). The levels of TNF-α and sPECAM-1 in gingival fluid were detected by ELISA method. Results: The following article is dedicated to studying on the effectiveness of the proposed method of GP I and II degree of development treatment in patients with a concomitant coronary artery disease (CAD) using of herbal medicines with immunomodulating effect. The offered methods provide disappearance of clinical signs of inflammation in the periodontal tissues and prevention of inflammation recurrence in the long terms. Also, it was proved that usage of the forward method of the GP immunotropic therapy with including of herbal immunomodulators leads to normalization of dynamics of tumor necrosis factor -alfa (TNF-α) and soluble platelet-endothelial cell adhesion molecule -1 (sPECAM-1) in oral fluid of abovementioned contingent of patients. Conclusions: The progression of generalized periodontitis in patients with stable coronary heart disease is accompanied with manifestation of systemic inflammation, which have been reduced by immunomodulator Immuno-Ton and extratemporal gel with "Enterosgel" and herbal concentrate "Dzherelo".

Pathogenesis of pulmonary complications COVID-19

Basically, COVID-19 is a coronavirus SARS-CoV-2 infection. COVID-19-associated pneumonia is a heterogeneous dis-ease (tracheobronchitis, diffuse alveolar injury and vas-cular injury) that leads to unusual clinico-pathological manifestations such as early-onset chest pain, pulmonary infarction, pulmonary and systemic thromboembolism, pathogenetically linked to extensive capillary, arteriolar and venular thrombosis. Platelet and/or fibrin capillary microthrombi were present in most cases. Early ground glass opacities, detected by computed tomography, re-sembling lung infarctions associated with pulmonary embolism, indicate new vascular pathology in COVID-19. Although most COVID-19 patients recover, a significant number of patients develop serious complications. Bilateral pneumonia, with prevailing acute respiratory distress syndrome, is a sign of severe COVID-19 disease, but the involvement of other organ systems, namely the cardiovascular system, kidneys, liver and central nervous system, occurs in at least half of fatal COVID-19 cases. Besides respiratory failure requiring mechanical ventilation, patients with severe COVID-19 often have intravascular coagulopathy, manifestations of systemic inflammation, and diffuse microvascular lesions found postmortem. In this review, the authors analyze the pathophysiological mechanisms that may explain how the virus when entering the body can cause COVID-19-associated pneumonia, systemic inflammation, thrombosis, and vascular dysfunction. The authors also review the role of the renin-angiotensin-aldosterone system in the context of COVID-19. All these observations highlight the high complexity of COVID-19 disease, involving several compartments, from upper airways (trachea, bronchi) to lung parenchyma, and the vascular bed. A tricompartmental model of pulmonary and systemic pathology in severe COVID-19 is proposed, which covers the known pathological and clinical features of severe COVID-19. A deeper understanding and better knowledge of the pathogenetic changes in COVID-19 will lead to more appropriate diagnostic and therapeutic approaches for clinical management.

The effect of a systemic inflammatory response on adaptive mechanisms and the state of homeostasis in patients with respiratory tuberculosis in combination with chronic obstructive pulmonary disease

The influence of the systemic inflammatory response on the adaptive mechanisms and the state of homeostasis of the body in patients with respiratory tuberculosis against the background of chronic obstructive pulmonary disease is considered. It has been established that respiratory tuberculosis and chronic obstructive pulmonary disease are widespread among the population and are important causes of bronchopulmonary morbidity and mortality. Chronic obstructive pulmonary disease is determined in one third of newly diagnosed patients with respiratory tuberculosis. The combined course of respiratory tuberculosis and chronic obstructive pulmonary disease is a mutually aggravating condition. Comorbid pathology is much more difficult, accompanied by severe intoxication, disintegration of lung tissue and bacterial excretion. Biomarkers and the severity of the systemic inflammatory response are of great clinical and diagnostic value in chronic obstructive pulmonary disease. It was determined that the systemic inflammatory response in chronic obstructive pulmonary disease is characterized by endothelial dysfunction of the vascular wall, significant changes in white blood cells, changes in the protein spectrum of the blood, and lipid metabolism disorders. The manifestations of systemic inflammation and endothelial dysfunction, characteristic of chronic obstructive pulmonary disease, in patients with respiratory tuberculosis, aggravate the course of both diseases. The comorbid state is also characterized by a change in the lipid profile of patients, an increase in the content of total cholesterol and atherogenic fractions. These changes are interrelated with the state of adaptive mechanisms, homeostasis and reactivity of the organism. The state of homeostasis largely determines the development, course and outcome of pathological processes characteristic of tuberculous inflammation and inflammation in chronic obstructive pulmonary disease, and the increase in the effectiveness of the treatment is closely related to the restoration of homeostatic balance and reactivity of the body. The availability of methods for determining the homeostatic balance of the body in clinical practice, with their high information content, allows a personalized approach to the management of patients with comorbidity.

Effectiveness of atorvastatin application in patients with chronic obstructive lung disease with concomitant diabetes type 2

The aim of the study was to study the efficacy of using atorvastatin in patients with chronic obstructive pulmonary disease (COPD) with concomitant type 2 diabetes mellitus (DM). Material and methods. 49 COPD patients with concomitant type 2 diabetes were examined. Patients were prescribed atorvastatin 20-40 mg once daily for 6 months in addition to standard therapy. In the examination of patients used the CAT-test, the test with a 6-minute walk, the integral BODE index, spirometry, bio-impedance analysis. The dynamics of treatment also evaluated the lipid spectrum of the blood, carbohydrate metabolism, functional state of the endothelium, the level of leptin, adiponectin, resistin, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1) and C-reactive protein (SRB) blood. Results. In the analysis of bioimpedansometry indicators in the dynamics of atorvastatin treatment in patients with COPD with concomitant type 2 diabetes, a significant decrease in the percentage of fat, visceral fat and BMI was found. When evaluating spirometry, there was a tendency for an increase in FEV1, but no confidence (p> 0.05). Six months of atorvastatin treatment in COPD patients with concomitant diabetes mellitus type 2 showed a significant decrease in shortness of breath by 61.8% (p> 0.05), a decrease in the SAT score by 40.7% (p 0.05). The levels of adipocytokines (leptin and resistin), TNFα, TGFβ1, and CRP in serum when using atorvastatin in COPD patients with concomitant type 2 diabetes significantly decreased in the absence of significant changes in adiponectin (p> 0.05). Analysis of endothelial functional status indicators at the end of treatment showed a probable 35.3% increase in nitrate / nitrite level, a 2-fold decrease in CCEE (p <0.001), and a 2.3-fold increase in ET-1 (p <0.001). According to the study, atorvastatin had no significant effect on carbohydrate metabolism, but did improve blood lipid spectrum. Therefore, in patients with COPD with concomitant type 2 diabetes, the use of atorvastatin does not impair the course of diabetes, but may possibly reduce cardiovascular risk by improving carbohydrate metabolism. Given that statins improve the functional state of the endothelium, the effect of atorvastatin on endothelial dysfunction in patients with COPD with concomitant type 2 diabetes has been investigated. Conclusions. Thus, the six-month application of atorvastatin in the complex treatment of patients with COPD with concomitant type 2 diabetes improves body composition, exercise tolerance, quality of life, prognosis and reduces the severity of comorbid pathology against the backdrop of manifestations of systemic inflammation.

New coronavirus infection COVID-19: clinical and prognostic significance of plasma fibrinogen level

COVID-associated coagulopathy is currently widely discussed in the medical press. There are no unambiguous ideas about its mechanisms and significance at the present time. One of the manifestations is hyperfibrinogenemia. The study of specific changes in this laboratory indicator is of interest from the point of view of evaluating the prognosis of the course of coronavirus infection and selecting therapy. Objectives. Analysis of plasma fibrinogen dynamics in patients with COVID-19, assessment of clinical and prognostic significance of the indicator. Materials and methods. The retrospective study included 350 patients undergoing inpatient treatment for SARS-CoV-2 infection. At the time of analysis, 49 patients (14 %) died, and the rest were discharged from the hospital. The dynamics of fibrinogen content was evaluated, compared with the outcomes of the disease, clinical complications of a thrombotic or hemorrhagic nature, and other laboratory indicators. Results and conclusion. A characteristic feature of COVID-associated coagulopathy is hyperfibrinogenemia (the maximum value of fibrinogen is 6.2 ± 1.7 g/l) as a manifestation of systemic inflammation with a transition in 14 % of patients to hypofibrinogenemia (the minimum value is 1.57 ± 0.29) due to hepatic dysfunction and consumption coagulopathy. In the context of pharmacological antithrombotic prevention, hyperfibrinogenemia did not show clinical significance as a risk factor for thrombosis, while a decrease in fibrinogen less than 2.0 g/l was associated with a 9-fold increase in the risk of hemorrhagic complications in patients with coronavirus infection (OR 9.913 СI 95 % [1.613–60.931]). A decrease in fibrinogen below normal values and an excess of 9.0 g/l are equally predictors of an adverse outcome in patients with COVID-19. The relative risk of death was 3.263 СI 95 % (1.970–5.407) and 2.574 СI 95 % (1.265–5.237), respectively.

MORPHO-FUNCTIONAL CHANGES OF THYMUS AND CONTENTS OF BLOOD LYMPHOCYTE SUBPOPULATIONS IN FEMALE WISTAR RATS WITH DIFFERENT RESISTANCE TO HYPOXIA IN SYSTEMIC INFLAMMATORY RESPONSE

Hypoxia and immune reactions are closely interrelated at molecular, cellular and organism levels, and the individuals differ in resistance to oxygen deficiency. Animals with high and low resistance to hypoxia have different adaptive capabilities and predisposition to the development of inflammatory diseases. Data on the individual characteristics of hypoxia resistance in female laboratory animals and humans, and its relationship to immune system reactions in both normal conditions and inflammatory diseases are not available in the literature. It is known, however, that acute infectious and inflammatory diseases develop at lesser rates and are less severe in women and female laboratory animals than in males, which can be explained by higher resistance of females to hypoxia. The aim of our study is to reveal the features of morpho-functional thymus changes, and subpopulation of peripheral blood lymphocytes in systemic inflammatory response induced by LPS administration to female Wistar rats with different resistance to hypoxia. Resistance of mature female Wistar rats to hypoxia was determined as a survival period in a ventilated lowpressure chamber simulating high altitude condition (11 500 m). The rats with a lifetime “at high altitude” of &gt; 180 s have been classified as highly resistant to hypoxia, and the animals surviving for &lt; 20 seconds were designated low-resistant. One month after determining the hypoxia resistance, the females were injected intraperitoneally with E. coli O26:B6 lipopolysaccharide (LPS) at a dose of 1.5 mg/kg during the dioestrus phase. The animals were withdrawn from the experiment by i/m Zoletyl injection (15 mg/kg) one day after LPS administration. The relative volume fractions of thymic cortex and medulla were evaluated; the areas of necrosis were determined in the liver, and the number of neutrophils in the interalveolar septa was counted in the lungs. The serum contents of corticosterone, testosterone, TGF-β were determined. A flow cytometry evaluation of the relative and absolute numbers was performed for major subpopulations of lymphocytes in peripheral blood. The number of apoptotically dying cells of the thymus was assessed. For statistical processing of the obtained data, the Statistica 8.0 software was applied, using criteria of multiple comparisons by Kruskal–Wallis and Dann. The differences were considered statistically significant at p &lt; 0.05.In both high- and low-resistant to hypoxia females, the development of a systemic inflammatory -response was accompanied by a moderately severe thymic involution, apoptosis of thymocytes, an increase in the absolute number of NK, and rise of testosterone and corticosterone contents. LPS injection into low-resistant rats, if compared to females highly resistant to hypoxia, led to more severe manifestations of systemic inflammation, i.e., a pronounced inflammatory reaction in the lungs and a more extensive liver necrotic area accompanied by increased absolute numbers of regulatory T lymphocytes and T helper cells, and more pronounced thymic accidental involution with apoptotic death of thymocytes. Systemic manifestations of inflammation were less pronounced in hypoxia-resistant female rats, which was apparently associated with activation of lymphocyte migration from the thymus and blood to the inflammation focus, and development of more effective immune response.Conclusion: immune reactions in the systemic inflammatory response induced by LPS in female Wistar rats depend on individual resistance to hypoxia. These data should be used to develop approaches to personalized therapy of infectious and inflammatory diseases in women.

An Empirical Approach Leveraging Tumorgrafts to Dissect the Tumor Microenvironment in Renal Cell Carcinoma Identifies Missing Link to Prognostic Inflammatory Factors.

By leveraging tumorgraft (patient-derived xenograft) RNA-sequencing data, we developed an empirical approach, DisHet, to dissect the tumor microenvironment (eTME). We found that 65% of previously defined immune signature genes are not abundantly expressed in renal cell carcinoma (RCC) and identified 610 novel immune/stromal transcripts. Using eTME, genomics, pathology, and medical record data involving >1,000 patients, we established an inflamed pan-RCC subtype (IS) enriched for regulatory T cells, natural killer cells, TH1 cells, neutrophils, macrophages, B cells, and CD8+ T cells. IS is enriched for aggressive RCCs, including BAP1-deficient clear-cell and type 2 papillary tumors. The IS subtype correlated with systemic manifestations of inflammation such as thrombocytosis and anemia, which are enigmatic predictors of poor prognosis. Furthermore, IS was a strong predictor of poor survival. Our analyses suggest that tumor cells drive the stromal immune response. These data provide a missing link between tumor cells, the TME, and systemic factors.Significance: We undertook a novel empirical approach to dissect the renal cell carcinoma TME by leveraging tumorgrafts. The dissection and downstream analyses uncovered missing links between tumor cells, the TME, systemic manifestations of inflammation, and poor prognosis. Cancer Discov; 8(9); 1142-55. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 1047.

The Role Of IL-6 In TMPD-Treated Lupus Arthritis Mice

Lupus or systemic lupus erythematosus is a chronic autoimmune disease with systemic inflammation manifestations mainly in targeted organs. The appropriate animal model for lupus is necessary. The induction method by using 2,6,10,14 tetramethylpentadecane (TMPD) reveals more complex manifestations than other hydrocarbons. However, the autophagy of macrophages as an effect of TMPD makes differences to make the decision in lupus biomarker as a targeted therapy in lupus arthritis. Thus, this research focused on the role of CD68+IL-6 produced by macrophages and total IL-6 in lupus in correlation to the arthritis severity. The naïve and TMPD-treated groups (n=3) were induced by means of 0.5 ml TMPD i.p. After 6 months, the mice were sacrificed then the fresh spleens were prepared as isolated cells to be measured by using flow cytometry method. The knee joints were prepared for histology observation. The statistical analysis was performed by using T-test SPSS 22 version. The results showed the relative percentage of CD68+IL-6+ in the TMPD-treated group increased significantly (P&lt;0.05) with the value of 62.38±9.97 %, compared to naïve group 49.70±2.34 %. Moreover, the total IL-6 did not increase significantly (P&gt;0.05). Meanwhile, the arthritis severity score of the TMPD-treated group revealed severe erosion with the grade of 3.7±1.06, higher significantly (P&lt;0.05) than the naïve group (0.5±0.71). The joint spaces in both groups were not significantly different. Finally, the observations gave the clear information that despite the autophagy potency, the CD68+IL-6 and the arthritis severity score were good markers in lupus preclinical study. Keywords: CD68+IL-6; inflammation; lupus arthritis; TMPD

Neutrophil extracellular traps contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS.

BackgroundAcute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a manifestation of systemic inflammation in the lungs, but the factors that trigger inflammation in ALI/ARDS are unclear. We hypothesized that neutrophil extracellular traps (NETs) contribute to the pathogenesis of acid aspiration-induced ALI/ARDS.ResultsAnalysis of bronchial aspirates from ARDS patients showed that NETs were significantly correlated with the degree of ARDS (r = –0.5846, p = 0.0359). NETs in bronchoalveolar lavage fluid of acid-aspiration mice were significantly higher (141.6 ± 23.08) at 3 h after injury than those in the sham group (1234 ± 101.9; p = 0.003, n = 5 per group). Exogenous NETs aggravated lung injury, while alvelestat and DNase markedly attenuated the intensity of ARDS.Materials and MethodsWe investigated whether NETs are involved in the severity of gastric aspiration-induced ARDS. Then, a hydrochloric acid aspiration-induced ALI murine model was used to assess whether NETs are pathogenic and whether targeting NETs is protective. Exogenous NETs were administered to mice. Alvelestat can inhibit neutrophil elastase (NE), which serves an important role in NET formation, so we investigated whether alvelestat could protect against ALI in cell and mouse models.ConclusionsNETs may contribute to ALI/ARDS by promoting tissue damage and systemic inflammation. Targeting NETs by alvelestat may be a potential therapeutic strategy.