Azithromycin with scaling and root planing versus scaling and root planing alone in the treatment of periodontitis: A randomized controlled trial.

Background: The growing interest in the possibilities of macrophages modulation with therapeutic purposes promotes new approaches for periodontitis treatment. Aim: The aim of this randomized controlled open clinical study was to evaluate the early clinical and immunological effects of the long-course azithromycin as an adjunct to scaling and root planing in periodontitis. Methods: 50 patients (with stage I-III, grade A/B periodontitis) and 22 periodontally healthy volunteers as the reference group were recruited. Following scaling and root planing (SRP), the patients were randomly assigned to one of two treatment modalities: SRP only (n = 25) and adjunct azithromycin (Az) treatment (n = 25). The patients were monitored at baseline, and 30 ± 5 days after therapy. Clinical attachment loss (CAL), periodontal probing depth (PPD) and bleeding on probing (BoP) were evaluated. Secondary outcome measures included mean changes in single-positive CD68 + and CD163 + macrophages (Mφs) density and ratio, evaluated by immunohistochemistry, and IL1-ß, IL-6, IL-10, TGF-ß levels, detected by ELISA. Results: At 1 month both groups showed significant improvements of CAL, PPD and BoP, without significant added benefit in terms of CAL, PPD and BoP of Az. But Az increased the density of CD68 + and CD163 + Mφs (P < 0.0001), decreased the CD68+/CD163 + ratio (P = 0.043), decreased IL-1ß (P < 0.01), IL-6 (P < 0.001) levels, and increased IL-10 (P < 0.0001) and TGF-ß (P < 0.001) levels compared to SRP and periodontitis at baseline. Conclusion: The long course of Az demonstrated modulation of CD68 + and CD163 + Mφs towards M2 polarization, which may play a significant role in achieving favorable long-term treatment outcomes. ClinicalTrials.gov.

The human toll and humanitarian crisis of the Russia-Ukraine war: the first 162 days.

BACKGROUND: We examined the human toll and subsequent humanitarian crisis resulting from the Russian invasion of Ukraine, which began on 24 February 2022. METHOD: We extracted and analysed data resulting from Russian military attacks on Ukrainians between 24 February and 4 August 2022. The data tracked direct deaths and injuries, damage to healthcare infrastructure and the impact on health, the destruction of residences, infrastructure, communication systems, and utility services - all of which disrupted the lives of Ukrainians. RESULTS: As of 4 August 2022, 5552 civilians were killed outright and 8513 injured in Ukraine as a result of Russian attacks. Local officials estimate as many as 24 328 people were also killed in mass atrocities, with Mariupol being the largest (n=22 000) such example. Aside from wide swaths of homes, schools, roads, and bridges destroyed, hospitals and health facilities from 21 cities across Ukraine came under attack. The disruption to water, gas, electricity, and internet services also extended to affect supplies of medications and other supplies owing to destroyed facilities or production that ceased due to the war. The data also show that Ukraine saw an increase in cases of HIV/AIDS, tuberculosis, and Coronavirus (COVID-19). CONCLUSIONS: The 2022 Russia-Ukraine War not only resulted in deaths and injuries but also impacted the lives and safety of Ukrainians through destruction of healthcare facilities and disrupted delivery of healthcare and supplies. The war is an ongoing humanitarian crisis given the continuing destruction of infrastructure and services that directly impact the well-being of human lives. The devastation, trauma and human cost of war will impact generations of Ukrainians to come.

Effects of l-arginine and l-ornithine supplementations on the treatment of chronic periodontitis: A preliminary randomized short-term clinical trial.

The growing interest in the possibilities of modulating macrophages in inflammatory diseases with therapeutic purpose has prompted the development of new approaches for the treatment of periodontitis. This randomized add-on open preliminary clinical study evaluated the short-term effects of L-arginine or L-ornithine as an adjuvant to scaling and root planing (SRP) in patients with chronic periodontitis. MATERIALS AND METHODS: Seventy-five periodontitis patients were recruited and monitored clinically and immunologically at baseline (before SRP) and 30 ± 5 days after SRP. All patients were assigned by stratified randomization to SRP (SRP only, n = 25), Arg (SRP + L-arginine, n = 25) or Control (SRP + L-ornithine, n = 25) Group. The medicines were used according to available instructions for 10 and 15 days, respectively. During the study, all patients were on a stable diet, without changing their rations and regiments. As immunological monitoring immunohistochemical study of CD68+ and CD163 + single positive gingival macrophages for 5 patients per group in the same time-point was conducted. The data were statistically analyzed. RESULTS: Reduction of periodontal pocket depth (PPD) and bleeding on probing (BoP) was observed in all groups, with significant between-group differences for BoP in the Arg Group (p < 0.0001) at 30 days. The SRP and Arg groups demonstrated nonsignificantly increased density of CD68+ and CD163 + cells. The Orn Group showed an increase in the density of CD68+ and CD163 + macrophages at intragroup (p = 0.0066 and p < 0.0001) and between-group levels (p = 0.001 and p < 0.0001), and these changes corresponded to clinical PPD and BoP reduction. In the Arg and Orn groups at 30 days, CD163 + macrophages significantly predominated over CD68+ (p = 0.013, p < 0.0001). CONCLUSION: The use of L-arginine and L-ornithine as an adjunct to SRP promotes additional limited immunological benefit in the treatment of periodontitis. Metabolic stimulation with L-ornithine, but not L-arginine, is preferable for CD163+ Mφs subpopulation in periodontitis-affected gingiva.

PATHOGENETIC ROLE OF MACROPHAGE COLONY-STIMULATING FACTOR (CSF-1) IN PREDICTING ENDOMETRIOID DISEASE.

OBJECTIVE: The aim: To assess the CSF - 1 level in peritoneal fluid and menstrual blood of women with endometrioid disease and to investigate its diagnostic and prognostic specificity. PATIENTS AND METHODS: Materials and methods: The study included 80 women of child-bearing age (mean age 30.95 ± 6.49 years) with benign gynaecological pathology of the ovaries and / or fallopian tubes. The women included in the study were divided into two groups: study group (n = 50, mean age 31.04 ± 6.3 years), consisting of patients with confirmed endometrioid disease, and control group (n = 30, mean age 30.8 ± 6.8 years), involving individuals without signs of endometriosis (p> 0.05). RESULTS: Results: We have found significantly higher level of CSF-1 content in the peritoneal fluid in the subjects of the study group (2027.05 ± 732.64 pg / ml) compared with those in the control group (1725.62 ± 466.06 pg / ml) (p = 0.029). There is a tendency towards an increase in CSF-1 level in women with endometriosis in its more severe stages and more severe and extended adhesions. The investigation of CSF-1 content in menstrual blood has demonstrated significant increase in its values in the women of the study group (9431.6 ± 2866.22 pg / ml) compared with the values in the control group (6637.12 ± 954.05 pg / ml), (p = 0.00004). Thus, there is a tendency towards the growth in CSF-1 level in peritoneal fluid and menstrual blood in women with endometriosis and concurrent increase in severity of the disease. CONCLUSION: Conclusions: There has been found significant increase in CSF-1 content in women with endometrioid disease in both peritoneal fluid and menstrual blood (1.2 and 1.4 times, respectively). Thus, macrophage growth factor (CSF-1) can be used as a diagnostic and prognostic criterion in evaluating the progression of endomertioid disease.

THE ROLE OF CIRCADIAN REGULATION OF GHRELIN LEVELS IN PARKINSON'S DISEASE (LITERATURE REVIEW).

The paper is aimed at the analysis of the role of the circadian regulation of ghrelin levels in patients with Parkinson's disease. Based on the literature data, patients with Parkinson's disease have clinical fluctuations in the symptoms of the disease, manifested by the diurnal changes in motor activity, autonomic functions, sleep-wake cycle, visual function, and the efficacy of dopaminergic therapy. Biological rhythms are controlled by central and peripheral oscillators which links with dopaminergic neurotransmission - core of the pathogenesis of Parkinson`s disease. Circadian system is altered in Parkinson`s disease due to that ghrelin fluctuations may be changed. Ghrelin is potential food-entrainable oscillator because it is linked with clock genes expression. In Parkinson`s disease this hormone may induce eating behavior changing and as a result metabolic disorder. The "hunger hormone" ghrelin can be a biomarker of the Parkinson's disease, and the study of its role in the pathogenesis, as well as its dependence on the period of the day, intake of levodopa medications to improve the effectiveness of treatment is promising.

Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes.

INTRODUCTION: Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers. L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method. RESULTS: In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level. CONCLUSIONS: L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.

Quantitative assessment of CD68+ AND CD163+ macrophages in the primary focus and metastatic lesions of regional lymph nodes in non-luminal her2-positive invasive breast carcinoma

Introduction: Introduction: Tumor-associated macrophages are an important prognostic factor and have been shown to be associated with invasion and migration of various types of cancer. Unlike M1-macrophages, which have pro-inflammatory and anti-cancer activity, M2-macrophages are immunosuppressive, promoting the restoration of the intracellular matrix, and therefore they contribute to the tumor growth. The aim: To study the quantitative characteristic and localization of CD68+ and CD163+ M2-like TAM that infiltrate non-luminal HER2-enriched carcinomas of BC in the primary focus without metastases and in paired specimens with metastases in the lymph nodes, as well as the pathomorphological characteristics of this type of BC. Material and methods: The material of the study were intraoperative tissues of tumors and ipsilateral lymph nodes at radical removal of mammary glands. Immunohistochemical characteristics of the removed tumors (ER, PR, HER2, Ki67) were used to organize two groups of patients with primary BC according to the N1 / 0 status. Results: The statistical processing of the entire set of digital data confirmed a significant increase in CD68+TAM, but not CD163+M2 under metastatic conditions (p <0.0001), which may suggest an increase in M1-type TAM and their promotion of metastases in non-luminal HER2-enriched BC. Analysis of peculiarities of TAM localization showed that CD68+TAM was localized by clusters within the tumor nests and adjacent stroma, necrotized nests, whereas the typical localization of CD163+TAM M2-like macrophages predominated in the stroma and near the necrotic sites (where their quantitative characteristics coincide with those of CD68+TAM). This may indicate a relative predominance of M1 macrophages precisely in tumor nests. Along with the results on increased CD68+TAM (but not CD163+TAM) in metastases, it is possible to assume the contribution of M1 macrophages to the development / metastasis of BC, as prognosticated for other tumors. Conclusions: A significant decrease in the number of CD68+TAM in metastases of the lymph node as compared with the primary clusters of BC, along with the absence of correlations, may reflect other functions of TAM in the affected lymph nodes or change of the tumor type in the metastasis.

Individual approach to the treatment of obese copd patients can reduce anthropometric indicators, the level of systemic inflammation and improve the quality of life.

OBJECTIVE: Introduction: Chronic obstructive pulmonary disease (COPD) and obesity are major causes of morbidity and mortality worldwide, and according to current estimates, the global burden of these conditions will be even greater. The basis for COPD treatment is bronchodilator therapy and non-pharmacotherapy approaches, such as respiratory rehabilitation and dietary counseling. The aim of this study was to assess the impact of lifestyle modification on anthropometric indices, markers of systemic inflammation, quality of life in patients with COPD and obesity. PATIENTS AND METHODS: Materials and methods: 53 patients with COPD in stable condition with BMI - 30.0-39.9 kg/m2 were included in the study. The patients were divided into 2 groups: the first group - obese COPD patients with lifestyle modification (n=26) and the second group (n=27) -without lifestyle modification. Lifestyle modification involved: nutritional correction and regular physical exercise. The duration of the study was 9 months. We evaluated body mass indices (BMI), waist circumference (WC), actual nutrition, dyspnea by the mMRC scale, quality of life (QL), 6-minute walking distance test (6MWD), spirometry, serum levels of C-reactive protein (CRP) and sputum level of interleukin-26 (IL-26). RESULTS: Results: After 9 months in obese COPD patients with lifestyle modification we found a decrease in body weight and BMI by 1.16 times (p <0.0001), WC by 1.07 times (p<0.0001), the basal metabolic rate by 1.07 times (p=0.02), the actual energy value of consumed food per work day and weekend by 1.19 times and 1.23 times, respectively (p<0.0001), the level of dyspnea by 1.42 times (p <0.0001), systemic inflammation markers decreased - serum CRP by 2.06 times (p < 0.0001), IL-26 level in the induced sputum by 1.65 times (p <0.0001); increased the walked distance by 9.38% (p = 0.0004) and QL (p <0.0001). CONCLUSION: Conclusions: Application of individually developed therapeutic measures incorporating the nutrition correction, taking into account the indicators of the basic metabolism in patients and regular physical activity against the background of inhaled basic therapy, allows us to the reduction of WC, BMI, activity of the inflammatory process, increase tolerance to physical activity and improvement of life quality.

[Iron deficiency reduces systemic inflammation in obese women].

OBJECTIVE: Introduction: Iron plays an important role in the functioning of immunological monitoring due to its stimulating and differentiating effect on the immune system. Obesity is accompanied by chronic low grade inflammation and may be accompanied by a change in the concentration of iron in the blood serum. The aim of the study was to determine the level of systemic inflammation in iron deficiency anemia in patients with obesity. PATIENTS AND METHODS: Materials and methods: 40 women with iron deficiency anemia (30 with obesity and 10 without obesity) and 10 with obesity of a similar age (control group) participated in the study. We evaluated hemogram parameters, indicators of iron exchange (serum iron, ferritin, hepcidin, total iron binding capacity, transferrin saturation) and inflammatory markers: C-reactive protein and interleukin-6 in the blood serum. RESULTS: Results: All patients were females with an average age of 40.3 ± 7.59 years. In the distribution of patients by the cause and the severity degree of iron deficiency anemia, there is no probable difference between the groups. C-reactive protein was significantly higher in women in the control group as compared with the groups of women with iron deficiency anemia (p <0.05). Meanwhile, the groups with iron deficiency anemia had insignificant differences (p> 0.05). Interleukin-6 also had a higher level in the control group as compared with the groups of women who had iron deficiency anemia (p <0.05) and, in contrast to the C-reactive protein of the group with iron deficiency anemia, had a significant divergence (p <0.05). Hepcidin of blood serum was higher in women with iron deficiency anemia without obesity (p<0.05) as compared to women with obesity and control group who did not have a significant difference (p> 0.05). CONCLUSION: Conclusions: The level of systemic inflammation in iron deficiency anemia in patients with obesity is lower than in patients with iron deficiency anemia, which was determined by levels of interleukin-6 and C-reactive protein in the blood serum.

Effect of pioglitazone on insulin resistance, progression of atherosclerosis and clinical course of coronary heart disease.

INTRODUCTION: Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues. THE AIM: Our aim was to study the effect of pioglitazone on insulin resistance, the clinical course of atherosclerosis and coronary heart disease (CHD). MATERIALS AND METHODS: The study included 43 patients with coronary artery disease. Patients were divided into the main group - 20 patients, in whom pioglitazone (Pioglar, Ranbaxy, India) was included in the combined therapy at a dose of 15 mg 1 time per day in the morning, and the comparison group - 23 patients receiving standard complex drug therapy over 6 months. Patients underwent clinical examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism. RESULTS: Joining pioglitazone to standard therapy resulted in the reduction of systolic (p<0.05) and diastolic (p<0.05) blood pressure; decrease in the duration of pain attacks (p<0.05); reduction in the frequency of angina attacks (p<0.05); regression of atherosclerosis of the carotid vessels (p<0.05), decrease in the thickness of the intima-media complex (p<0.05). The decline in oral glucose tolerance test (p<0.05), hyperglycemic factor (p<0.05), total cholesterol (p<0.05), and low density lipoproteins (p<0.05) were observed, as well as increased high-density lipoprotein (p<0.05). CONCLUSION: Long-term treatment with pioglitazone at low doses against the background of standard therapy contributes to functional and clinical condition of patients, promotes the prevention of atherosclerosis and reduction of insulin resistance, thereby improving the clinical manifestations of coronary heart disease.

Anti-inflammatory and endothelium protective effect of long-term pioglitazone intake in patients suffering from bronchial asthma concurrent with ischemic heart disease.

INTRODUCTION: Treatment of co-morbidities, including bronchial asthma (BA) and coronary heart disease (CHD), is a relevant issue of modern therapy. The aim of the research is to study the impact of long-term intake of pioglitazone on the development of inflammation and ED in patients with BA concurrent with CHD. MATERIAL AND METHODS: The clinical study involved 50 people aged 40-75 who suffered from asthma concurrent with CHD. On the first day of the study, blood samples were collected and clinical examinations were performed, after which patients were randomized and divided into the control group who continued to receive only the standard therapy, and the study group, who received pioglitazone (Pioglar, Ranbaxy, India) 15 mg once a day along with comprehensive therapy. Re-examination was carried out in 6 months. RESULTS: It has been found that inclusion of pioglitazone in the course of standard therapy in patients with asthma concurrent with coronary heart within 6 months is a more efficient scheme than the course of standard therapies. According to the data obtained from the patients, there was a significant decrease in respiratory rate (p<0.01), levels of systolic blood pressure (p<0.001) and diastolic blood pressure (p<0.001). Administering pioglitazone contributed to the improvement of respiratory function and airflow obstruction, increased FEV1 performance (p<0.01) and Tiffeneau index (p<0.05). In patients of the study group, intake of pioglitazone helped to reduce angina. Intake of pioglitazone showed a significant decrease in the frequency of angina pectoris FC II (p<0.05) and a significant increase in the frequency of angina FC I (p<0.05), increase in the rate of threshold load power (p<0.05). In assessing endothelium-dependent vasodilation of the brachial artery, it has been noted that intake of pioglitazone by patients with asthma concurrent with coronary heart disease resulted in a statistically significant increase in the diameter of the brachial artery by an average of 4% (p<0.0001), the maximum blood flow velocity (TAMX) by an average of 40 % (p<0.0001), Δ% diameter increase in the brachial artery (p<0.0001), and achieved positive indicators of RI (p<0.0001). In assessing endothelium-dependent vasodilation of brachial artery in patients treated with pioglitazone, there was a significant increase in the diameter of brachial artery on average by 5% (p<0.0001) after taking nitroglycerin, an increase in ?% diameter of brachial artery (p<0.0001) and RI (p<0.0001). Inclusion of pioglitazone in the complex therapy for 6 months resulted in a significant decrease in the index of systemic inflammation hs-CRP (p<0.0001) and adhesion marker sVCAM-1 (p<0.0001), total cholesterol (p<0.001), triglycerides (p<0.001). CONCLUSION: Thus, these data demonstrate the anti-inflammatory and endothelium protective effects of pioglitazone against the background of standard therapy in patients with BA concurrent with CHD within 6 months, which may enhance the clinical efficacy in the treatment of these diseases.

Resveratrol more effectively than quercetin reduces endothelium degeneration and level of necrosis factor α in patients with coronary artery disease.

INTRODUCTION: endothelial dysfunction (ED) is one of the most important links in the pathogenesis of atherosclerosis (ASVD) - morphological basis of coronary artery disease (CAD). OBJECTIVE: to study the effect of polyphenolic antioxidants, resveratrol and quercetin, on endothelial degeneration factors in CAD patients. MATERIALS AND METHODS: the study involved 93 patients with coronary artery disease: stable angina pectoris, FC II. The cytofluorometric technique was applied to define the level of circulating endothelial microparticles (EMP) CD32+CD40+ in peripheral blood in order to identify ED. The content of tumor necrosis factor α (TNF-α), fibrinogen, hemocoagulation and lipid profile parameters were being determined in the blood, as well. Patients were divided into 3 groups. Basic therapy (ß-blockers, statins, aspirin) was prescribed to 33 persons of the comparison group, patients of the study group 1 (30 persons) additionally received resveratrol at a dose of 100 mg daily, patients of the study group 2 (30 persons) got quercetin at a dose of 3 g per day. In 2 months, the second examination of the patients was performed in the amount indicated. RESULTS: under the influence of resveratrol a significant reduction of the level of TNF-α and the number of EMP in peripheral blood was shown, in contrast to the results of other study groups. All groups showed a decrease in total cholesterol and low-density lipoprotein cholesterol, statistical differences between data of groups were not found. Indicators of coagulogramma in all study groups did not change significantly, however, there was a statistically significant reduction of fibrinogen in the blood. CONCLUSIONS: resveratrol, unlike quercetin, has a positive effect on the endothelial function and systemic inflammation, which may be the result of its influence on intracellular molecular cascades associated with the nuclear transcription factor of NF-kB.

Resveratrol more effectively than quercetin reduces endothelium degeneration and level of necrosis factor α in patients with coronary artery disease.

INTRODUCTION: endothelial dysfunction (ED) is one of the most important links in the pathogenesis of atherosclerosis (ASVD) - morphological basis of coronary artery disease (CAD). OBJECTIVE: to study the effect of polyphenolic antioxidants, resveratrol and quercetin, on endothelial degeneration factors in CAD patients. MATERIALS AND METHODS: the study involved 93 patients with coronary artery disease: stable angina pectoris, FC II. The cytofluorometric technique was applied to define the level of circulating endothelial microparticles (EMP) CD32+CD40+ in peripheral blood in order to identify ED. The content of tumor necrosis factor α (TNF-α), fibrinogen, hemocoagulation and lipid profile parameters were being determined in the blood, as well. Patients were divided into 3 groups. Basic therapy (ß-blockers, statins, aspirin) was prescribed to 33 persons of the comparison group, patients of the study group 1 (30 persons) additionally received resveratrol at a dose of 100 mg daily, patients of the study group 2 (30 persons) got quercetin at a dose of 3 g per day. In 2 months, the second examination of the patients was performed in the amount indicated. RESULTS: under the influence of resveratrol a significant reduction of the level of TNF-α and the number of EMP in peripheral blood was shown, in contrast to the results of other study groups. All groups showed a decrease in total cholesterol and low-density lipoprotein cholesterol, statistical differences between data of groups were not found. Indicators of coagulogramma in all study groups did not change significantly, however, there was a statistically significant reduction of fibrinogen in the blood. CONCLUSIONS: resveratrol, unlike quercetin, has a positive effect on the endothelial function and systemic inflammation, which may be the result of its influence on intracellular molecular cascades associated with the nuclear transcription factor of NF-kB.