Soluble Receptor Type Research Articles

Soluble interleukin-6 receptor in young adults and its relationship with body composition and autonomic nervous system.

BackgroundThe immune system generates inflammatory responses through cytokines like Interleukin 6 (IL‐6) and the Tumor Necrosis Factor alpha (TNF α); these cytokines mediate cellular responses aided by the presence of soluble receptors such as: Soluble Interleukin 6 Receptor (sIL6R) and Soluble Tumor Necrosis Factor Receptors Type 1 and 2 (sTNFR1, sTNFR2); the literature is limited about the relationship between this cytokines and the role of its soluble receptors.ObjectivesThis study is to determine a possible relationship between specific inflammatory markers and their soluble receptors with the autonomic nervous system's activity and body composition.Methods27 subjects (13 men of 19.3 ± 1.6 years old and 14 women of 19.1 ± 1.7 years old) were evaluated. Body composition, autonomic nervous system activity and plasma concentration of inflammatory markers IL‐6, TNF α, sIL6R, sTNFR1 and sTNFR2 were measured using bio‐impedance, heart rate variability and ELISA respectively.ResultsA positive association between body‐fat percentage and the sIL6R (0.47, p = .013) as well as inverse relationship between muscular mass and the sIL6R (−0.45, p = .019) were found. The sIL6R was also positively correlated with sympathetic activity markers: Relation LF/HF (0.52, p = .006), cardiac sympathetic index (0.45, p = .008), and cardiac vagal index (−0.44, p = .022).ConclusionThis study suggested that the IL‐6 trans‐signaling involving both the soluble receptor, sIL6R, and gp130 membrane co‐receptor could produce inflammatory responses that generate an impact on the autonomic nervous system, possibly due to its direct action on the hypothalamus, the solitary tract nucleus, or the heart.

Correlation between biomarkers of pain in saliva and PAINAD scale in elderly people with cognitive impairment and inability to communicate: descriptive study protocol

IntroductionPain is an under-diagnosed problem in elderly people, especially in those with cognitive impairment who are unable to verbalise their pain. Although the Pain assessment in advanced dementia scale (PAINAD)...

Neuro-Immuno-Endocrine Interactions in Early Life Stress and Heroin Withdrawal Timeline

Both heroin abuse and early life stress (ELS) affect the immune system and the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, accelerated aging due to mild inflammation has been indicated in these conditions. The present study aims to compare plasma levels of apoptosis markers, inflammatory markers, and stress hormones during early heroin abstinence period. Thirty-one individuals with heroin/opioid use disorder who had heroin-ELS and 26 of their siblings who were not abusing substances (ELS), and 32 individuals with heroin/opioid use disorder without a history of ELS (heroin-no ELS) were included in the study. The levels of interleukin-6, C-reactive protein, erythrocyte sedimentation rate, albumin, alanine transaminase, aspartate transaminase, and white blood cell count were assessed as the inflammatory and biochemistry markers. Also, apoptosis markers including tumor necrosis factor (TNF)-related weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, soluble tumor necrosis factor receptor type I as apoptosis markers were detected by enzyme-linked immunosorbent assay. ELS was simultaneously evaluated using the Childhood Trauma Questionnaire, Minnesota Multiphasic Personality Inventory, and beck depression inventory scales. Besides, heroin craving was assessed by Daily Drinking/Drug Questionnaire score in individuals with heroin use disorder. This is the first study to evaluate the inflammatory, stress, and apoptosis markers during heroin abstinence, supporting the association between ELS and peripheral pro-inflammatory markers’ levels and HPA axis.

Ligands and receptors of the TNF superfamily are decreased in major depression and during early antidepressant therapy

BackgroundThe up-regulation of pro-inflammatory agents, amongst them tumor necrosis factor (TNF), may represent low-grade inflammation in major depression. To further elucidate inflammatory mechanisms related to TNF in depression, the aim of the current study was to investigate the involvement of ligands and receptors of the TNF/TNF-receptor-superfamily yet un- or little explored in major depression. MethodsSerum levels of ligands (TNF, TNF-related weak inducer of apoptosis [TWEAK], B-cell activating factor [BAFF], tumor necrosis factor superfamily member 14 [TNFSF14; LIGHT], A proliferation-inducing ligand [APRIL]) and receptor molecules (TNF receptor superfamily member 8 [TNFRSF8; sCD30], soluble TNF receptor type 1 [sTNFR1] and type 2 [sTNFR2]) of the TNF/TNF-receptor-superfamily were measured in 50 unmedicated patients suffering from major depression and 48 healthy controls and were reassessed in 37 of the depressed patients two weeks after the initiation of antidepressive treatment. ResultsIn comparison to the healthy controls, the interrelated serum levels of TWEAK, BAFF, TNFSF8, sTNFR1 and sTNFR2 were reduced both in the unmedicated and medicated depressed patients. Serum levels of BAFF and TNF significantly increased during the initiation of antidepressive treatment. In the combined sample of unmedicated depressed and healthy controls, but not the separate groups, scores of the BDI-II inversely correlated with levels of TWEAK, BAFF, sTNFR1, sTNFR2 and TNFSF8. ConclusionThe current findings give evidence for a role of the TNF/TNF-receptor-superfamily in the pathophysiology of major depression that may involve reduced tissue regeneration and neurogenesis rather than an acceleration of pro-inflammatory pathways.

Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Our study aimed to compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Serum cytokine levels (neopterin, IL-18, and CXCL9 and soluble tumor necrosis factor receptor type I (sTNFR-I) and II) were determined by enzyme-linked immunosorbent assay in 78 patients with s-JIA, including 21 with MAS. Receiver operating characteristic curve analysis revealed area under the curve values and cut off values of neopterin, IL-18, CXCL9, sTNFR-II/I ratio and ferritin were 0.9465/19.5 nmol/l, 0.8895/69250 ng/ml, 0.9333/3130 pg/ml, 0.9395/3.796 and 0.8671/2560 ng/ml, respectively. Serum neopterin levels were significantly elevated in patients with MAS and those were correlated positively with disease activity. In conclusion, serum neopterin levels may be used as a promising indicator of disease activity in s-JIA and MAS and for evaluating it. It may also be a useful marker to diagnose the transition to MAS from active-phase s-JIA.

Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition.

SummaryCancer stem cells (CSCs) are defined by their ability to regenerate a tumor upon transplantation. However, it is not yet clear whether tumors contain a single CSC population or different subsets of cells with mixed capacities for initiating primary and secondary tumors. Using two different identification strategies, we studied the overlap between metastatic stem cells and tumor-initiating cells (TICs) in the MMTV-PyMT model. Our results show that in the MMTV-PyMT model, Lin−CD90−ALDHhigh cells retained a high tumor-initiating potential (TIP) in orthotopic transplants, in contrast to Lin−CD24+CD90+, which retained higher metastatic capacity. Interestingly, suppression of TGFβ signaling increased TIC numbers. We here describe the existence of distinct populations of CSCs with differing capacities to initiate tumors in the primary or the secondary site. Inhibiting TGFβ signaling shifts the balance toward the former, which may have unanticipated implications for the therapeutic use of TGFβ/TGFBR1 inhibitors.

Changes in soluble tumor necrosis factor receptor type1 levels and early renal function decline in patients with diabetes.

The relationship between serial changes in soluble tumor necrosis factor receptor type 1 (TNFR1) levels and an early decline in estimated glomerular filtration rate (eGFR) decline remains to be defined. We found that in patients with an early decline in renal function (n = 30), soluble TNFR1 values increased (2,595 ± 683 vs 3,596 ± 1,203 pg/mL, P < 0.001) as eGFR decreased (89 ± 1 vs 51 ± 2 mL/min/1.73m2, P < 0.001) over an 8‐year period. In contrast, there were no significant changes in soluble TNFR1 levels in patients with stable renal function (n = 17). In a multilevel mixed effects regression model, changes in soluble TNFR1 levels were found to be independently associated with eGFR decline (Z = −4.31, P < 0.001). An early decline in eGFR is associated with an increase in soluble TNFR levels; however, the factors driving this increase and the possible pathological role that soluble TNFR1 plays in progressive diabetic kidney disease remain to be determined.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease

BackgroundEndothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. Patients80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. ResultsAfter adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1–3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. ConclusionAmong novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Soluble anti-müllerian hormone receptor type 2 (SAMHR2): A new biomarker for diagnosis of fertility disorders

Soluble anti-müllerian hormone receptor type 2 (SAMHR2): A new biomarker for diagnosis of fertility disorders

Kinetics of inflammatory biomarkers in plasma predict the occurrence and features of cytomegalovirus DNAemia episodes in allogeneic hematopoietic stem cell transplant recipients.

Cytomegalovirus (CMV) DNAemia occurs frequently in CMV-seropositive allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, and usually results from reactivation of latent infection established in the recipient. Predicting the occurrence of CMV DNAemia may be helpful in managing CMV infection in allo-HSCT recipients. Here, the kinetics of several inflammatory biomarkers in plasma were characterized and assessed for their potential value in anticipating the development and features of active CMV infection in allo-HSCT recipients, as documented using real-time PCR assays. The cohort consisted of 46 non-consecutive adult patients who underwent T-cell replete allo-HSCT at our center. Plasma levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor type 2 (sTNF-R2), transforming growth factor-β1 (TGF-β1), and interferon-inducible protein 10 (IP-10/CXCL10) were measured in consecutive specimens obtained from conditioning either by nephelometry (CRP) or by specific immunoassays (the rest). Of the 46 patients, 22 had a first episode of CMV DNAemia at a median of 34 days after allo-HSCT (range, day 19-day 50). We found that both the TGF-β1 area under a curve (AUC) and peak levels were significantly lower in patients who subsequently developed CMV DNAemia than in patients with no CMV DNAemia. Interestingly, CRP but not TGF-β1 AUC and peak levels predicted the occurrence of CMV DNAemia episodes requiring preemptive antiviral therapy. The data presented herein suggest that kinetics of inflammatory biomarkers in plasma might be useful to anticipate post-engraftment CMV DNAemia episodes and predict the need for preemptive antiviral therapy in allo-HSCT recipients.

Cytokine profile of macrophage activation syndrome associated with Kawasaki disease

The present study aimed to assess the kinetics of cytokine release and compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) associated with Kawasaki disease (KD). Serum neopterin, interleukin (IL)-18, IL-6 and soluble tumour necrosis factor receptor type I (sTNFR-I) and sTNFR-II levels were determined using enzyme-linked immunosorbent assay in 78 patients with KD, including five with MAS. Results were compared to the clinical features of MAS. Serum neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were significantly elevated in KD patients with MAS compared to those in the acute phase. Receiver operating characteristic curve analysis revealed areas under the curve and cutoff values of neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were 0.9750/30.0 nmol/L, 0.9813/1165 ng/mL, 0.9969/16,600 pg/mL and 0.9875/4.475, respectively. Serum sTNFR-II levels correlated positively with disease activity. These findings indicate that overproduction of interferon (IFN)–γ and TNF-α reflected by increased serum levels of neopterin and sTNFR-II are closely associated with the pathogenesis of MAS associated with KD. Serum sTNFR-II levels might be a useful marker to diagnose the transition to MAS.

Procalcitonin levels predicting the infliximab response of immunoglobulin resistant Kawasaki disease

ObjectiveTo search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients.Study design.Twenty-seven patients with KD who received infliximab after 4–5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. ResultsSerum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00–5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32–1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. ConclusionSerum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment.

Are the Cognitive Alterations Present in Children Born From Preeclamptic Pregnancies the Result of Impaired Angiogenesis? Focus on the Potential Role of the VEGF Family.

Evidence from clinical studies has proposed that children born from preeclamptic women have a higher risk of suffering neurological, psychological, or behavioral alterations. However, to date, the mechanisms behind these outcomes are poorly understood. Here, we speculate that the neurodevelopmental alterations in the children of preeclamptic pregnancies result from impaired angiogenesis. The pro-angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) are key regulators of both vascular and neurological development, and it has been widely demonstrated that umbilical blood of preeclamptic pregnancies contains high levels of soluble VEGF receptor type 1 (sFlt-1), a decoy receptor of VEGF. As a consequence, this anti-angiogenic state could lead to long-lasting neurological outcomes. In this non-systematic review, we propose that alterations in the circulating concentrations of VEGF, PlGF, and sFlt-1 in preeclamptic pregnancies will affect both fetal cerebrovascular function and neurodevelopment, which in turn may cause cognitive alterations in post-natal life.

Post-mortem in situ stability of serum markers of cerebral damage and acute phase response.

The aim of the given study was to test the in situ stability of biochemical markers of cerebral damage and acute phase response in the early post-mortem interval to assess their usability for forensic pathology. A monocentric, prospective study investigated post-mortem femoral venous blood samples at four time points obtained within 48h post-mortem starting at the death of 20 deceased, using commercial immunoassays for the ten parameters: S100 calcium-binding protein B (S100B), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), ferritin, soluble tumor necrosis factor receptor type 1 (sTNFR1), and lactate dehydrogenase (LDH). Significant changes in serum levels were observed only later than 2h after death for all markers. Inter-laboratory comparability was high, and intra-assay precision was sufficient for most markers. Most of the biomarker levels depended on the severity of hemolysis and lipemia but were robust against freeze-thaw cycles. Serum levels increased with longer post-mortem intervals for S100B, NSE, ferritin, sTNFR1, and LDH (for all p < 0.001) but decreased over this period for CRP (p = 0.089) and PCT (p < 0.001). Largely unchanged median values were found for GFAP (p = 0.139), BDNF (p = 0.106), and IL-6 (p = 0.094). Serum levels of CRP (p = 0.059) and LDH (p = 0.109) did not differ significantly between the final ante-mortem (resuscitation) and the first post-mortem sample (moment of death). Collecting the post-mortem blood sample as soon as possible will reduce the influence of post-mortem blood changes. Serum GFAP for detection of cerebral damage as well as serum IL-6 and CRP as proof of acute phase response seemed to be preferable due to their in situ stability in the first 2days after death.

Plasma inflammatory cytokines and survival of pancreatic cancer patients.

ObjectivesInflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome.MethodsWe measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models.ResultsOverall mortality was significantly increased in patients in the top quartile of CRP (HR = 2.52, 95% CI: 1.82–3.49), IL-6 (HR = 2.78, 95% CI: 2.03–3.81), sTNF-RII (HR = 2.00, 95% CI: 1.46–2.72), and MIC-1 (HR = 2.53, 95% CI: 1.83–3.50), compared to those in the bottom quartile (P-trend <0.0001 for all four comparisons). Furthermore, patients with higher circulating concentrations of all four cytokines had a median survival of 3.7 months; whereas, those with lower levels had a median survival of 19.2 months (HR = 4.55, 95% CI: 2.87–7.20, P-trend <0.0001).ConclusionIndividual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted.

Acute phase response after fatal traumatic brain injury.

An inflammatory response occurring after fatal traumatic brain injury (TBI) initiates time-dependent cascades of acute phase response. This may offer the potential to monitor postmortem biomarker levels of several pro-inflammatory cytokines to gain information about the cause of death and the trauma survival time. Cerebrospinal fluid (CSF) and serum samples were collected from forensic autopsies of 95 adult cadavers after postmortem intervals up to 6days. The cases were divided according to their cause of death into fatal TBI (n = 46) with different survival times and age- and gender-matching non-TBI fatalities as controls (n = 49). Quantitative marker levels of interleukin-6 (IL-6), ferritin, soluble tumor necrosis factor receptor type 1, C-reactive protein, and lactate dehydrogenase were analyzed using immunoassays. Standardized statistical tests were performed to differentiate causes of death and survival time of TBI cases. The CSF IL-6, ferritin, and LDH levels after TBI were significantly higher than those in the controls (p < 0.001). Only serum IL-6 values showed comparable differences (p < 0.05). Both CSF and serum ferritin levels were discriminative between early and delayed death after TBI (p < 0.05). There were partly distinctive correlations between marker levels in both fluids with rising values after longer survival. There were up to moderate correlation between the marker levels and the postmortem interval due to postmortem hemolysis. However, neither CSF nor serum level ranges were affected by the age or gender of the subjects. This study is the first to measure all five proteins systematically in postmortem trauma cases. Ferritin and IL-6 proved themselves to be interesting postmortem biomarkers to provide specific information on the injury pattern and the survival time of traumatic fatalities. Such forensic investigations could serve as inexpensive and fast laboratory tests.

Endothelial immune activation and functional state in patients with hypertensive disease

To investigate the nitric oxide (NO) system, the activity of endothelial NO synthase (e-NOS) and inducible NO synthase (i-NOS) in relation to the levels of tumor necrosis factor-α (TNF- α) and its soluble receptor type I (sTNFRI) depending on the grade of hypertensive disease (HD). A total of 317 patients, including 284 patients aged 30 to 65 years (mean age 54.7±0.58 years) with Grades 1-3 HD who had not previously received regular antihypertensive therapy and 33 apparently healthy individuals, were examined at Kharkov City Clinical Hospital Eleven. Immune activation was judged by the serum levels of the proinflammatory cytokine TNF-α in all the examinees and y those of sTNFRI, which were measured by enzyme immunoassay. To study the endothelial functional state, the level of stable end metabolites of nitric oxide, that of S-nitrosothiol and the activity of NO synthases were biochemically determined in 100 patients from this group. A control group consisted of 16 apparently healthy individuals. There were increases in the circulating levels of proinflammatory cytokines (TNF-α, sTNFRI), the content of S-nitrosothiol and the activity of i-NOS. At the same time, there were decreases in the activity of e-NOS and the level of end nitric oxide metabolites, such as nitrites and nitrates. In patients with HD, the end metabolites of nitric oxide decrease, which indirectly shows a reduction in its vasoactive part, and the stable NO metabolite S-nitrosothiol increases. This is associated with enhanced NO oxidation under conditions of oxidative stress and endothelial dysfunction. The higher amount of S-nitrosothiol in the examinees may be associated with increased i-NOS. The immunoinflammatory activation mediated by the proinflammatory cytokines, particularly by the enhanced activity of TNF-α and sTNFRI, has been proven to play a role.

Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses

BackgroundSeveral studies have described an association between childhood maltreatment and inflammatory markers in the psychotic disorders (schizophrenia [SZ] and bipolar disorder [BD]). Previous studies have been relatively small (<50 participants), and the severity of abuse and the putative influence of body mass index (BMI) have not been properly investigated. MethodsThe combined effects of childhood abuse severity and clinical diagnosis on inflammatory markers were investigated in a large sample (n=483) of patients with a disorder on the psychosis spectrum and in healthy controls (HCs). Plasma levels of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], soluble tumor necrosis factor receptor type 1 [TNFR-R1], glycoprotein 130 [gp130]) were analyzed, and BMI and data on childhood trauma events, on the basis of the Childhood Trauma Questionnaire (CTQ), were obtained from all participants. ResultsPatients had increased levels of hs-CRP (P<0.001, Cohens d=0.4), lower levels of gp130 (P<0.001, Cohens d=0.5), higher BMI (P<0.001, Cohens d=0.5) and reported more childhood maltreatment experiences (P<0.001, Cohens d=1.2) than the HC group. The severity of childhood abuse (up to three types of abuse: sexual abuse, physical abuse, and emotional abuse) was associated with elevated BMI (f=8.46, P<0.001, Cohen’s d=0.5) and hs-CRP (f=5.47, P=0.001, Cohen’s d=0.3). Combined effects of patient status and severity of childhood abuse were found for elevated hs-CRP (f=4.76, P<0.001, Cohen’s d=0.4). Differences among the groups disappeared when BMI was added to the model. DiscussionTrauma-altered immune activation via elevated hs-CRP in patients with SZ and BD may be mediated by higher BMI; however, the direction of this association needs further clarification.

The problem of fatigue in patients suffering from neoplastic disease.

Modern therapeutic management of patients with cancer is associated with many adverse side effects, including fatigue defined as weariness, burnout, lassitude, malaise, apathy, impatience, and/or inability to perform daily activities. It occurs frequently before the diagnosis of cancer and may persist for a long time after the end of cancer therapy. It is a common problem that occurs regardless of the type of cancer and applied therapeutic procedure. The appearance of this symptom significantly affects the quality of life of patients and often reduces the effectiveness of implemented treatment. The symptom of fatigue occurs among approximately 80% of patients treated with chemotherapy and/or radiotherapy, as well as among more than 75% of patients with metastatic disease. Causes of fatigue include metabolic and immune system disorders as well as increased level of tumour necrosis factor α (TNF-α). Recent studies also indicate a significant contribution of other cytokines, especially pro-inflammatory ones, i.e. interleukin-1 (IL-1), interleukin-6 (IL-6), soluble tumour necrosis factor receptor type II (sTNF type II) and C-reactive protein (CRP). A patient reporting fatigue should be properly diagnosed and thoroughly interviewed by doctors. Patients are mostly treated non-pharmacologically (by means of physical exercise and psychotherapy) and pharmacologically (by applying methylphenidate and methylprednisolone). What is also extremely important is proper education of the patient and their closest family/friends on the symptoms, which significantly reduces anxiety and stress. On the other hand therapeutic management hinders the subjectivity of feeling and lack of standardised scales to rate symptoms.

Early changes in adipokines from overweight to obesity in children and adolescents

ObjectiveChildhood obesity has been associated with metabolic syndrome and cardiovascular diseases. This study aimed to compare plasma levels of traditional metabolic markers, adipokines and soluble tumor necrosis factor receptor type 1 (sTNFR1) in overweight, obese and lean children. We also assessed the relationships of these molecules with classical metabolic risk factors. MethodsThis study included 104 children and adolescents, which were grouped as: lean (n=24), overweight (n=30), and obese subjects (n=50). They were subjected to anthropometrical, clinical and laboratorial measurements. All measurements were compared between groups. Correlation analyses were also performed to evaluate the association between clinical data, traditional metabolic markers, adipokines and sTNFR1. ResultsFasting glucose, insulin, homeostatic model assessment of insulin resistance (HOMA‐IR), LDL‐cholesterol and triglycerides were comparable in lean, overweight and obese subjects. Plasma levels of sTNFR1 were similar in lean and overweight subjects, but significantly increased in obese group. Leptin, adiponectin and resistin levels did not differ when overweight were compared to obese subjects. However, all adipokines differed significantly when lean subjects were compared to overweight and obese individuals. Plasma levels of adiponectin were negatively correlated with body mass index (BMI), whereas leptin, resistin and sTNFR1 concentrations positively correlated with BMI. ConclusionOur results showed significant differences in circulating levels of the evaluated markers when lean, overweight and obese individuals were compared, suggesting that these biomarkers may change from lean to overweight and from overweight to obesity.