Proinflammatory Cytokines In Blood Research Articles

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1β, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

Kinetics of Inflammatory Mediators in the Immune Response to Burn Injury: Systematic Review and Meta-Analysis of Animal Studies

Burns are often accompanied by a dysfunctional immune response, which can lead to systemic inflammation, shock, and excessive scarring. The objective of this study was to provide insight into inflammatory pathways associated with burn-related complications. Because detailed information on the various inflammatory mediators is scattered over individual studies, we systematically reviewed animal experimental data for all reported inflammatory mediators. Meta-analyses of 352 studies revealed a strong increase in cytokines, chemokines, and growth factors, particularly 19 mediators in blood and 12 in burn tissue. Temporal kinetics showed long-lasting surges of proinflammatory cytokines in blood and burn tissue. Significant time-dependent effects were seen for IL-1β, IL-6, TGF-β1, and CCL2. The response of anti-inflammatory mediators was limited. Burn technique had a profound impact on systemic response levels. Large burn size and scalds further increased systemic, but not local inflammation. Animal characteristics greatly affected inflammation, for example, IL-1β, IL-6, and TNF-α levels were highest in young, male rats. Time-dependent effects and dissimilarities in response demonstrate the importance of appropriate study design. Collectively, this review presents a general overview of the burn-induced immune response exposing inflammatory pathways that could be targeted through immunotherapy for burn patients and provides guidance for experimental set-ups to advance burn research.

Senescent-like Blood Lymphocytes and Disease Progression in Amyotrophic Lateral Sclerosis.

Aging is known to exacerbate neuroinflammation, and in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS), an older age is associated with a worse prognosis. We have previously shown the activation of cell senescence pathways in the proteome of peripheral blood mononuclear cells and the increase of proinflammatory cytokines in blood from individuals living with ALS. In this single-center, retrospective study, we investigated the expression of senescent-like blood mononuclear cells in ALS. We first applied multidimensional cytometry by time-of-flight (CyTOF) to study the senescent immunophenotype of blood mononuclear cells from 21 patients with ALS and 10 healthy controls (HCs). We then used targeted flow cytometry (FC) to investigate frequencies of senescent blood lymphocytes in 40 patients with ALS and 20 HCs. Longitudinal analysis included 2 additional time points in 17 patients with ALS. Frequencies of senescent-like lymphocytes were analyzed in relation to survival. Unsupervised clustering of CyTOF data showed higher frequencies of senescent CD4+CD27-CD57+ T cells in patients with ALS compared with those in HCs (p = 0.0017, false discovery (FDR)-adjusted p = 0.029). Moderate to strong negative correlations were identified between CD4 T central memory-cell frequencies and survival (R = -061, p = 0.01; FDR-adjusted p < 0.1) and between CD95 CD8 cells and ALS functional rating scale revised at baseline (R = -0.72, p = 0.001; FDR-adjusted p < 0.1).Targeted FC analysis showed higher memory T regulatory cells (p = 0.0052) and memory CD8+ T cell (M-Tc; p = 0.0006) in bulbar ALS (A-B) compared with those in limb ALS (A-L), while late memory B cells (LM-B) were also elevated in A-B and fast-progressing ALS (p = 0.0059). Higher M-Tc levels separated A-B from A-L (AUC: 0.887; p < 0.0001). A linear regression model with prespecified clinical independent variables and neurofilament light chain plasma concentration showed that higher frequencies of LM-B predicted a shorter survival (hazard ratio: 1.094, CI: 1.026-1.167; p = 0.006). Our data suggest that a systemic elevation of senescent and late memory T and B lymphocytes is a feature of faster progressing ALS and of ALS individuals with bulbar involvement. Lymphocyte senescence and their memory state may be central to the immune dysregulation known to drive disease progression in ALS and a target for biomarkers and therapeutics discovery.

Biomimetic anti-inflammatory and osteogenic nanoparticles self-assembled with mineral ions and tannic acid for tissue engineering

Bone healing involves complex processes including inflammation, induction, and remodeling. In this context, anti-inflammatory and osteoconductive multi-functional nanoparticles have attracted considerable attention for application in improved bone tissue regeneration. In particular, nanoparticles that promote suppression of inflammatory response after injury and direction of desirable tissue regeneration events are of immense interest to researchers. We herein report a one-step method to prepare multi-functional nanoparticles using tannic acid (TA) and simulated body fluid (SBF) containing multiple mineral ions. Mineral-tannic acid nanoparticles (mTNs) were rapidly fabricated in 10 min, and their size (around 250–350 nm) and chemical composition were controlled through the TA concentration. In vitro analysis using human adipose derived stem cells (hADSCs) showed that mTNs effectively scavenged reactive oxygen species (ROS) and enhanced osteogenesis of hADSCs by inducing secretion of alkaline phosphatase. mTNs also increased osteogenic marker gene expression even in the presence of ROS, which can generally arrest osteogenesis (OPN: 1.74, RUNX2: 1.90, OCN: 1.47-fold changes relative to cells not treated with mTNs). In vivo analysis using a mouse peritonitis model revealed that mTNs showed anti-inflammatory effects by decreasing levels of pro-inflammatory cytokines in blood (IL-6: 73 ± 4, TNF-α: 42 ± 2%) and peritoneal fluid (IL-6: 78 ± 2, TNF-α: 21 ± 6%). We believe that this one-step method for fabrication of multi-functional nanoparticles has considerable potential in tissue engineering approaches that require control of complex microenvironments, as required for tissue regeneration.

Nebulized Non-Immunogenic Staphylokinase in the Mice Acute Lung Injury Model.

Acute lung injury (ALI) as a model of acute respiratory distress syndrome is characterized by inflammation, complex coagulation, and hematologic abnormalities which result in the formation of fibrin-platelet microthrombi in the pulmonary vessels with the rapid development of progressive respiratory dysfunction. We hypothesize that a nebulized fibrinolytic agent, non-immunogenic staphylokinase (nSta), may be useful for ALI therapy. First, the effect of the nebulized nSta (0.2 mg/kg, 1.0 mg/kg, or 2.0 mg/kg) on the coagulogram parameters was studied in healthy rats. ALI was induced in mice by nebulized administration of lipopolysaccharide (LPS) at a dose of 10 mg/kg. nSta (0.2 mg/kg, 0.4 mg/kg or 0.6 mg/kg) was nebulized 30 min, 24 h, and 48 h after LPS administration. The level of pro-inflammatory cytokines was determined in the blood on the 8th day after LPS and nSta administration. The assessment of lung damage was based on their weighing and microscopic analysis. Fibrin/fibrinogen deposition in the lungs was determined by immunohistochemistry. After nSta nebulization in healthy rats, the fibrinogen blood level as well as activated partial thromboplastin time and prothrombin time did not change. In the nebulized ALI model, the mice showed an increase in lung weight due to their edema and rising fibrin deposition. An imbalance of proinflammatory cytokines was also found. Forty percent of mice with ALI without nSta nebulization had died. Nebulized nSta at a dose of 0.2 mg/kg reduced the severity of ALI: a decrease in interstitial edema and inflammatory infiltration was noted. At a dose of 0.4 mg/kg of nebulized nSta, the animals showed no peribronchial edema and the bronchi had an open clear lumen. At a dose of 0.6 mg/kg of nebulized nSta, the manifestations of ALI were completely eliminated. A significant dose-dependent reduction of the fibrin-positive areas in the lungs of mice with ALI was established. Nebulized nSta had a normalizing effect on the proinflammatory cytokines in blood— interleukin (IL)-1α, IL-17A, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). These data showed the effectiveness of nebulized nSta and the perspectives of its clinical usage in COVID-19 patients with acute respiratory distress syndrome (ARDS).

Lunasin protease inhibitor concentrate decreases pro-inflammatory cytokines and improves histopathological markers in dextran sodium sulfate-induced ulcerative colitis

Lunasin protease inhibitor concentrate (LPIC) is a novel combination of soy bioactive peptide lunasin, Kunitz and Bowman-Birk protease inhibitors. The reported anti-inflammatory and anticancer properties of each one of them suggest LPIC as a promising candidate for the treatment of inflammatory-related diseases. Our objective was to assess the in vivo anti-inflammatory properties of LPIC. First, an in vitro test was performed in lipopolysaccharide (LPS)-activated RAW264.7 murine macrophages by measuring the production of nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) as inflammatory markers. For the in vivo model, ulcerative colitis (UC) was induced in mice via oral administration of dextran sodium sulfate (DSS). LPIC treatment was performed via daily intraperitoneal injection of 50 mg/kg body weight. Body weight, visible blood in stool and stool consistency were scored daily as macroscopic indicators of disease progression. Occult blood was evaluated by the presence of hemoglobin in stool every third day. Colon length, caecum weight, colonic myeloperoxidase activity (MPO), presence of pro-inflammatory cytokines in blood and colon, changes in the architecture, and expression of inducible nitric oxide synthase (iNOS) in colonic tissue were evaluated. In vitro, LPIC induced production of NO and maintained cytokine levels in comparison to activated untreated macrophages. In vivo, LPIC increased colonic bleeding and did not improve macroscopic markers of the disease, but reduced colonic IL-1β and IL-6, decreased systemic circulation of TNF-α, attenuated neutrophils infiltration and iNOS expression in colonic tissue, and diminished the damage in colonic architecture. Our results suggest that combinations of peptides in LPIC may counteract the anti-inflammatory properties in vitro; while in vivo, LPIC can significantly reduce the histopathological damage, hence is a possible therapeutic strategy to attenuate UC.

Some aspects of application glucocorticoid drugs in the complex treatment of new coronaviral infection

The aim of the study was to evaluate the clinical and lab- oratory parameters of the effectiveness of low-dose glu- cocorticoid therapy in the complex treatment of patients with lung disease caused by a new coronavirus infection (COVID-19). Methods. The study included 40 hospitalized patients aged 37 to 68 years (mean age 52.2 years) with a confirmed diagnosis of medium severe to severe COVID- 19 pneumonia and CT-2 or CT-3 lung tissue involvement. All patients received standard therapy. Patients were randomized into two groups: the main group (n=20) and the control group (n=20). The main group additionally received MPS, according to the protocol: 4 mg tablets, 7 tablets per day, divided into 2 doses (4 tablets in the morning and 3 at lunchtime) in the course of 10 days. On admission to hospital, all patients demonstrated clinical symptoms of the disease, fever and decline in oxygen saturation. Based on the dynamics of clinical, radiological, and la boratory parameters, the additional effectiveness of oral glucocorticoids in the pathogenetic therapy of COVID-19 in comparison with control group was assessed. Results. According to laboratory test re- sults, the screened patients on hospital admission had an increased level of acute phase indicators and proin- flammatory cytokines. Correlation analysis revealed the credible link between the vo lume of lung involvement (based on CT-scans), oxygen sa turation, body mass index (BMI), and interleukin-10 levels (anti-inflammatory cy- tokine activation marker). Credible correlation between concentration of acute-phase parameters and proinflam- matory cytokines (IL-1, IL-6) in blood was detected. The use of methylprednisolone in the comprehensive treat- ment of patients with severe pneumonia associated with COVID-19 has been accompanied by reliable increase in ferritin, C-reactive protein, and interleukin-1, interleu- kin-6, interleukin-10. Less time was needed for symptom resolution and recovery of oxygen saturation in patients who took methylprednisolone. Meanwhile, a timeframe for reaching positive CT dynamics and the total duration of treatment hadn’t changed significantly. Conclusion. Prescribing cycles of oral glucocorticoid therapy helps to reduce proinflammatory cytokines in blood and accel- erate oxygen saturation recovery, however, it does not influence the duration of hospitalization and the time frame of resolution of inflammatory changes in lungs du ring the period of hospitalization.

5α,6α-Epoxyphytosterols and 5α,6α-Epoxycholesterol Increase Nitrosative Stress and Inflammatory Cytokine Production in Rats on Low-Cholesterol Diet.

Objective Oxidized cholesterol derivatives are compounds with proven atherogenic and mutagenic effects. However, little is known about the effect of oxidized plant sterol derivatives (oxyphytosterols), whose structure is similar to the one of oxycholesterols. Our previous studies indicate that they have a similar profile of action, e.g., both exacerbate disorder of lipid metabolism and oxidative stress in experimental animals. The aim of the present study was to assess the effect of epoxycholesterol and epoxyphytosterols (mainly sitosterol) on the severity of nitrosative stress and the concentration of selected proinflammatory cytokines in blood and liver tissue of rats on a low-cholesterol diet. Material and Methods. Forty-five male Wistar rats were fed with feed containing 5α,6α-epoxyphytosterols (ES group, n: 15), 5α,6α-epoxycholesterol (ECh group, n: 15), and oxysterol-free feed (C group, n: 15) for 90 days (daily dose of oxysterols: 10 mg/kg). At the end of the experiment, nitrotyrosine, TNF-α, IL-1β, IL-6, and lipid metabolism parameters were determined in blood serum. Furthermore, nitrotyrosine, TNF-α, cholesterol, and triglyceride content were determined in liver homogenates. Results Serum nitrotyrosine, IL-1β, and TNF-α concentrations as well as TNF-α content in the liver were significantly higher in both groups exposed to oxysterols (ECh and ES groups) as compared to the C group. The serum IL-6 level and nitrotyrosine content in the liver were significantly higher in the ECh group, as compared to the C and ES groups. There was evidence to support the dyslipidemic effect of studied compounds. Conclusions The results indicate that oxidized plant sterols have a similar toxicity profile to that of oxycholesterols, including nitrosative stress induction, proinflammatory effect, and impaired lipid metabolism.

The non-saponin fraction of Korean Red Ginseng (KGC05P0) decreases glucose uptake and transport in vitro and modulates glucose production via down-regulation of the PI3K/AKT pathway in vivo

BackgroundThe non-saponin fraction of Korean Red Ginseng has been reported to have many biological activities. However, the effect of this fraction on anti-diabetic activity has not been elucidated in detail. In this study, we investigated the effects of KGC05P0, a non-saponin fraction of Korean Red Ginseng, on anti-diabetic activity in vitro and in vivo. MethodsWe measured the inhibition of commercially obtained α-glucosidase and α-amylase activities in vitro and measured the glucose uptake and transport rate in Caco-2 cells. C57BL/6J mice and C57BLKS/Jdb/db (diabetic) mice were fed diets with or without KGC05P0 for eight weeks. To perform the experiments, the groups were divided as follows: normal control (C57BL/6J mice), db/db control (C57BLKS/Jdb/db mice), positive control (inulin 400 mg/kg b.w.), low (KGC05P0 100 mg/kg b.w.), medium (KGC05P0 200 mg/kg b.w.), and high (KGC05P0 400 mg/kg b.w.). ResultsKGC05P0 inhibited α-glucosidase and α-amylase activities in vitro, and decreased glucose uptake and transport rate in Caco-2 cells. In addition, KGC05P0 regulated fasting glucose level, glucose tolerance, insulin, HbA1c, carbonyl contents, and proinflammatory cytokines in blood from diabetic mice and significantly reduced urinary glucose excretion levels. Moreover, we found that KGC05P0 regulated glucose production by down-regulation of the PI3K/AKT pathway, which inhibited gluconeogenesis. ConclusionOur study thereby demonstrated that KGC05P0 exerted anti-diabetic effects through inhibition of glucose absorption and the PI3K/AKT pathway in in vitro and in vivo models of diabetes. Our results suggest that KGC05P0 could be developed as a complementary food to help prevent T2DM and its complications.

Vascular Leak and Hypercytokinemia Associated with Severe Fever with Thrombocytopenia Syndrome Virus Infection in Mice.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever (VHF) endemic to China, South Korea, Japan, and Vietnam. Here we characterize the pathogenesis and natural history of disease in IFNAR-/- mice challenged with the HB29 strain of SFTS virus (SFTSV) and demonstrate hallmark features of VHF such as vascular leak and high concentrations of proinflammatory cytokines in blood and tissues. Treatment with FX06, a natural plasmin digest product of fibrin in clinical development as a treatment for vascular leak, reduced vascular permeability associated with SFTSV infection but did not significantly improve survival outcome. Further studies are needed to assess the role of vascular compromise in the SFTS disease process modeled in IFNAR-/- mice.

Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is highly effective against relapsed or refractory acute lymphoblastic leukemia (ALL), but is hindered by neurotoxicity. In 53 adult patients with ALL, we found a significant association of severe neurotoxicity with high pretreatment disease burden, higher peak CAR T-cell expansion, and early and higher elevations of proinflammatory cytokines in blood. Patients with severe neurotoxicity had evidence of blood-cerebrospinal fluid (CSF) barrier disruption correlating with neurotoxicity grade without association with CSF white blood cell count or CAR T-cell quantity in CSF. Proinflammatory cytokines were enriched in CSF during severe neurotoxicity with disproportionately high levels of IL6, IL8, MCP1, and IP10, suggesting central nervous system-specific production. Seizures, seizure-like activity, myoclonus, and neuroimaging characteristics suggested excitatory neurotoxicity, and we found elevated levels of endogenous excitatory agonists in CSF during neurotoxicity.Significance: We detail the neurologic symptoms and blood, CSF, and neuroimaging correlates of neurotoxicity associated with CD19 CAR T cells and identify neurotoxicity risk factors. Our findings implicate cellular components other than T cells and suggest novel links between systemic inflammation and characteristic neurotoxicity symptoms. Cancer Discov; 8(8); 958-71. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 899.

Level of proinflammatory cytokines in blood of patients with chronic nonbacterial prostatitis

It was studied a level of proinflammatory cytokines concentration in blood of 120 patients with chronic nonbacterial prostatitis. It was found, that in patients with chronic nonbacterial prostatitis concentration of interleukin-6, 8 and tumor necrosis factor-alpha in blood was higher, comparing to healthy men. Higher level of proinflammatory cytokines concentration was ascertained in patients with inflammatory chronic pelvic pain syndrome (category IIIA), which indicates on practicability of use of medication with immunomodulating action in treatment of such patients.

Long Dan Xie Gan Formula Granule Promotes Pro-Inflammatory Cytokine Expression in Female Guinea Pigs with Recurrent Genital Herpes

ABSTRACT Objective To explore the effects of Long Dan Xie Gan formula granule (LDXGFG) on regulation of pro-inflammatory cytokines in female guinea pigs with recurrent genital herpes (herpes simplex virus 2, HSV-2). Methods Levels of pro-inflammatory cytokines in blood of HSV-2-infected guinea pigs, including IL-6, IL-8, IL-10, IL-12, IFN-α, IFN-β, IFN-γ, and TNF-α, were detected by ELISA; corresponding gene expression levels in tissues were detected by real-time PCR. Results IL-6, IL-10, IL-12, IFN-α, IFN-γ and TNF-α decreased significantly in both blood and diseased tissues after infection with recurrent genital herpes. Upon feeding LDXGFG to HSV-2-infected guinea pigs, IL-6, IL-10, IL-12, IFN-α, IFN-γ and TNF-α demonstrated significant increases, similar to the effects of acyclovir (ACV). LDXGFG promoted the expression of pro-inflammatory cytokines in blood and tissue, with a stronger effect than ACV. Moreover, LDXGFG demonstrated broader effects than ACV. Conclusion The present results suggest that LDXGFG can serve as an alternative, inexpensive, and long-term treatment for HSV-2 infection.

The Influence of Various Drags on Mortality of Mice and the Concentration of Proinflammatory Cytokines in Blood at Sepsis Caused by E. Coli

The Influence of Various Drags on Mortality of Mice and the Concentration of Proinflammatory Cytokines in Blood at Sepsis Caused by E. Coli

Study of treatment effectiveness of patients with chronic nonbacterial prostatitis

The objective: Studying of level of essential microelements (Zinc, Copper, Magnesium, Iron) in blood and ejaculate, specialty of antioxidant and immune defense of the patients with chronic nonbacterial prostatitis and reasoning of polymicroelemental and immunomodulat ing medication use.Materials and methods. Under supervision were 120 patients with chronic nonbacterial prostatitis, among them 60 patients with inflammatory chronic pelvic pain syndrome (ICPPS – category IIIA) and 60 patients with noninflammatory chronic pelvic pain syndrome (NCPPS – IIIB). Microelements in whole blood and ejaculate were determined using atomic absorption spectrophotometry on C 115 PC. State of antioxidant defense was judged considering quantification of Catalase after A. Bach and S.Zubkova and Superoxide Dismutase. Immune status was analyzed in accordance to the results of determination of the interleukins-6, -8 (IL-6, IL-8) concentration and quantification of tumor necrosis factor-alpha (α-TNF) in blood serum, using the set of company “VECTOR-BEST”, by immunoassay analysis. Correction of violations of bioelemental status and immune defense was conducted by prescription except the standard therapy the polyelemental complex and interferon alpha-2b.Results. A certain decrease of microelements Zn, Fe, Mg and Cu increase were observed in both groups of patients with chronic nonbacterial prostatitis. Also it was noted that with long duration of chronic nonbacterial prostatitis takes place the antioxidant enzymes level decrease. It was noted a visible concentrations increase of proinflammatory cytokines in blood of both groups of patients with chronic nonbacterial prostatitis. Especially significant increase in serum was IL-8. Under influence of treatment was noted positive dynamics of improve ment of bioelemental consist of blood and ejaculate, increase of antioxidant enzymes level and decrease of proinflammatory cytokines concentration in blood of patients with chronic nonbacterial prostatitis.Conclusion. With chronic nonbacterial prostatitis was observed decrease of Zinc, Iron, Magnesium and increase of Copper level in blood as well as in ejaculate of the patients. Metabolic changes with shortage of Zn and excess of Cu correlate with antioxidant system disbalance , that is with antioxidant defense level decrease. With chronic nonbacterial prostatitis was observed increase of proinflammatory cytokines concentration, especially in patients with inflammatory chronic pelvic pain syndrome.Inclusion of polyelemental complex and interferon alpha-2b in complex treatment of the patients with nonbacterial chronic prostatitis improves macro and microelemental status of blood and ejaculate, thereby strengthens antioxidant and immune defense.

Cognitive dysfunction and content of inflammatory markers in patients after coronary artery bypass graft

To study the relationship between the content of inflammatory biomarkers and cognitive function in patients after coronary artery bypass graft (CABG) performed in condition of artificial blood circulation (ABC) or open-heart surgery (OHS). Twenty-nine patients with ischemic heart disease who survived CABG, mean age 62.4±6.2 years, were studied. The ABC group (n=18) and OHS group (n=11) were matched for age and sex. Patients underwent standard clinical examination as well as neurological examination and neuropsychological testing. Concentrations of pro- and anti-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IL-1RA, IFN-γ, IP-10; MCP-1, MIP-1α, MIP-1β, RANTES, TNF) were determined in blood plasma obtained 24 h before and 2h after surgery using multiplex immunofluorescence assay. In both groups, an increase in concentrations of IL-6, IL-8, IL-10, IL-12, IP-10, MCP-1, MIP-1β and RANTES was observed at point T1. Concentration of IL-1RA was significantly higher only in the ABC group but not in the OHS group. After CABG, an increase in concentrations of IL-8, IP-10, MIP-1β, IL-1RA was significantly higher in the ABC group. The Montreal scale was the most sensitive test for assessment of cognitive functions in post CABG patients. A significant decrease in scores (>3) was noted in 8 out of 18 patients in the ABC group and in one patient of the OHS group. The correlations between the decrease in cognitive functioning in the 7th day after surgery and plasma cytokine concentration 2 h after surgery were identified for IL-6 (r=0.472; p=0.01); IL-8 (r=0.403; p=0.03); IP-10 (r=0.372; p=0.047); MCP-1 (r=0.470; p=0.01). CABG is accompanied by the systemic inflammatory reaction, with the more marked inflammatory effect in patients operated under condition of extracorporeal circulation. CABG with ABC causes an impairment of cognitive functions during the first week in many patients. Impaired cognitive status was associated with the increase in concentrations of proinflammatory cytokines in blood plasma.

Endoplasmic Reticulum Stress and Obesity.

In recent years, the world has seen an alarming increase in obesity and closely associated with insulin resistance which is a state of low-grade inflammation, the latter characterized by elevated levels of proinflammatory cytokines in blood and tissues. A shift in energy balance alters systemic metabolic regulation and the important role that chronic inflammation, endoplasmic reticulum (ER) dysfunction, and activation of the unfolded protein response (UPR) play in this process.Why obesity is so closely associated with insulin resistance and inflammation is not understood well. This suggests that there are probably other causes for obesity-related insulin resistance and inflammation. One of these appears to be endoplasmic reticulum (ER) stress.The ER is a vast membranous network responsible for the trafficking of a wide range of proteins and plays a central role in integrating multiple metabolic signals critical in cellular homeostasis. Conditions that may trigger unfolded protein response activation include increased protein synthesis, the presence of mutant or misfolded proteins, inhibition of protein glycosylation, imbalance of ER calcium levels, glucose and energy deprivation, hypoxia, pathogens or pathogen-associated components and toxins. Thus, characterizing the mechanisms contributing to obesity and identifying potential targets for its prevention and treatment will have a great impact on the control of associated conditions, particularly T2D.

MECHANISMS OF INCREASED RESISTANCE TO INFECTION IN THE EARLY PHASE OF SEPSIS IN MICE AFTER ACUTE INTOXICATION WITH ORGANOPHOSPHORUS COMPOUNDS

It was established in experiments on random-bred albino mice that the reduction of mortality of mice from sepsis and decrease of pro-inflammatory cytokines (TNF- , IL-1 , IL-6 ) concentrations in blood after acute intoxication with organophosphorus compounds (OPCs) is due to the implementation of the cholinergic antiinflammatory pathway: activation of muscarinic acetylcholine receptors m1 and 7n-acetylcholine receptors of the monocyte macrophage system. The anti-inflammatory effect after acute intoxication with OPCs is also associated with excitation of the sympathetic nervous system, 2 adrenergic receptors on T-lymphocytes, macrophages and monocytes and the subsequent reduction of pro-inflammatory cytokines in blood.

Cardiovascular system diseases in patients with polycystic ovary syndrome – the role of inflammation process in this pathology and possibility of early diagnosis and prevention

Polycystic ovary syndrome is a disorder which affects 5-10% of women in reproductive age. PCOS is a cause of hyperandrogenism, menstrual disorders and infertility. The most common clinical symptoms are hirsutism, acne and obesity. Patients often suffer from metabolic disorders: insulin resistance, hyperinsulinemia, dislipidemia, leading to atherosclerosis and others irregularities of the metabolic syndrome. Patients are in the high risk group for cardiovascular diseases (CVD) development because of the metabolic abnormalities. Obesity is observed in 35-60% of women with PCOS. Lean women with PCOS are also exposed to a greater risk of glucose intolerance development and abnormalities in lipid profile than women without PCOS with comparable BMI. Adipocytes are the source of many compounds of the paracrine and endocrine activity. Some of them are also markers and mediators of inflammation. Increased levels of proinflammatory cytokines in blood can promote atherosclerosis and cardiovascular disease. Markers: IL-18, TNF, IL-6 and hs-CRP are often elevated in patients with polycystic ovary syndrome. An increase in inflammatory markers may be an early indicator of the risk of developing insulin resistance and atherosclerosis, and may become a useful prognostic and therapeutic tool for monitoring patients with PCOS: lean and those with overweight and obesity. Assessment of the concentrations of inflammatory markers may become a very useful test in evaluating the risk of developing atherosclerosis and cardiovascular disease, long before their clinical manifestation. It will also allow for the appropriate prophylaxis.

Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.

SUMMARYBACKGROUND: Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined.OBJECTIVE: To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB.DESIGN: Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA.RESULTS: More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median < 3%, range 0–32.6) in both patient groups. The proportion with IDA and hepcidin concentration ⩽ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median < 3%, range 0–15.1).CONCLUSIONS: ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.