Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study.

BACKGROUND: Improving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation. METHODS: This was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22-34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R-4.0.5). RESULTS: SuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19-51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27-84.16) vs. 20.46 ng/mL (IQR, 11.49-36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis. CONCLUSION: Soluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Insights into the Alcyoneusvirus Adsorption Complex.

The structures of the Caudovirales phage tails are key factors in determining the host specificity of these viruses. However, because of the enormous structural diversity, the molecular anatomy of the host recognition apparatus has been elucidated in only a number of phages. Klebsiella viruses vB_KleM_RaK2 (RaK2) and phiK64-1, which form a new genus Alcyoneusvirus according to the ICTV, have perhaps one of the most structurally sophisticated adsorption complexes of all tailed viruses described to date. Here, to gain insight into the early steps of the alcyoneusvirus infection process, the adsorption apparatus of bacteriophage RaK2 is studied in silico and in vitro. We experimentally demonstrate that ten proteins, gp098 and gp526-gp534, previously designated as putative structural/tail fiber proteins (TFPs), are present in the adsorption complex of RaK2. We show that two of these proteins, gp098 and gp531, are essential for attaching to Klebsiella pneumoniae KV-3 cells: gp531 is an active depolymerase that recognizes and degrades the capsule of this particular host, while gp098 is a secondary receptor-binding protein that requires the coordinated action of gp531. Finally, we demonstrate that RaK2 long tail fibers consist of nine TFPs, seven of which are depolymerases, and propose a model for their assembly.

The Significance of Epidermal Growth Factor in Noninvasively Obtained Amniotic Fluid Predicting Respiratory Outcomes of Preterm Neonates.

Preterm premature rupture of membranes (PPROM) interrupts normal lung development, resulting in neonatal respiratory morbidity. Although post-PPROM risks have been researched, only a few studies have investigated noninvasively obtained amniotic fluid (AF) to predict neonatal outcomes. In this study, we aimed to determine whether epidermal growth factor (EGF) in vaginally-collected AF is a significant predictor of neonatal respiratory outcomes after PPROM. We analyzed EGF in vaginally-obtained AF from 145 women with PPROM at 22−34 weeks of gestation. The following neonatal outcomes were included: respiratory distress syndrome, surfactant need, duration and type of respiratory support, and bronchopulmonary dysplasia. We found that EGF concentration was associated with gestational age, and its medians were lower in neonates with respiratory morbidities than unaffected ones. EGF concentrations gradually declined, the lowest being in the most clinically ill patients. EGF < 35 pg/mL significantly predicted the odds of severe respiratory outcomes. EGF in noninvasively collected AF may be a reliable predictor for respiratory outcomes of preterm neonates with PPROM before 34 weeks of gestation. The results of our study may have implications for further research both in noninvasive amniotic fluid analysis and the management of patients after PPROM.

Neutrophil-lymphocyte ratio for the prediction of histological chorioamnionitis in cases of preterm premature rupture of membranes: a case-control study.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is easily calculated blood test parameter, which can be used as marker to predict many inflammatory disorders. The aim of this study was to assess and compare the NLR in maternal blood with the white blood cell (WBC) count and C-reactive protein (CRP) concentration for the prediction of histological chorioamnionitis. METHODS: This was a case-control study of 137 woman with preterm premature rupture of membranes (PPROM) at a gestational age between 22+ 0 and 34+ 6 weeks. Blood samples, collected less than 48 h before delivery and at least 48 h after the administration of corticosteroids, were selected for the analysis. The NLR was calculated by dividing the number of neutrophils by the number of lymphocytes. Chorioamnionitis was diagnosed by the histopathological evaluation of placental membranes and chorionic plate. RESULTS: Patients with diagnosed histological chorioamnionitis (HCA) had significantly higher levels of WBC, CRP and NLR (p-value < 0.001). Levels of WBC, CRP and NLR predicted HCA with an area under the curve (AUC) of 0.81, 0.81 and 0.89, respectively. NLR had statistically significantly higher AUC than WBC, but no significant difference was found between AUCs of NLR and CRP. The cut-off level of NLR was found to be 5,97, which had a sensitivity of 77 % and a specificity of 95 %. CONCLUSION: NLR has a good predictive value for HCA and could be used as an additional diagnostic marker for predicting histological chorioamnionitis in cases with preterm premature rupture of membranes before 34 weeks of gestation.

A value of soluble Toll-like receptor 2 and 4 in vaginally obtained amniotic fluid for the prediction of histological chorioamnionitis.

INTRODUCTION: This study was conducted to evaluate soluble Toll-like receptor 2 (sTLR-2) and soluble Toll-like receptor 4 (sTLR-4) levels in vaginally obtained amniotic fluid and investigate their value in the prediction of histological chorioamnionitis (HCA). MATERIAL AND METHODS: This prospective case-control study included patients who had been diagnosed with preterm premature rupture of membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free leaking amniotic fluid was obtained vaginally using a sterile speculum up to 48 h before delivery. Amniotic fluid levels of sTLR-2 and sTLR-4 were determined using an enzyme-linked immunosorbent assay. The diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. RESULTS: The study included 156 patients, 65 with (HCA Group) and 91 without (non-HCA Group) HCA. No statistically significant differences were noted in the concentrations of sTLR-2 and sTLR-4 in vaginally obtained amniotic fluid between patients with and without HCA: the median sTLR-2 level was 0.09 ng/mL in the HCA Group vs 0.1 ng/mL in non-HCA Group, and the median sTLR-4 level was 0.23 ng/mL in the HCA Group vs 0.28 ng/mL in non-HCA Group (p > 0.05). A positive correlation between sTLR-2 and sTLR-4 levels was identified (ρ = 0.57, p < 0.001), but no correlation was found between these markers and gestational age. CONCLUSIONS: Concentrations of sTLR-2 and sTLR-4 in vaginally obtained amniotic fluid do not reflect the presence of HCA in pregnancies complicated by preterm premature rupture of membranes before 34 weeks of gestation.

BCG masking phenomena might depend on the species of Mycobacterium.

This study investigated BCG masking dependency on the species of Mycobacterium through the immune response to the mycobacterial region of deletion 1 (RD-1) associated growth affecting proteins (GEP).To evaluate the effects of GEP, 8-week old female BALB/c mice were immunized with either the wild type Mycobacterium bovis (MBGEP) or the ATCC Mycobacterium avium subsp. avium (MAGEP) strain and then subjected to further exposure with Mycobacterium terrae or M. avium sub. avium. Mice immunized with MAGEP and those mice further exposed to M. avium subsp. avium had increased granulocytes (GRA) and monocytes to lymphocytes rate (MLR) compared to control mice. Immunization of mice with GEP induced an antibody response one month after primary immunization, as observed by cross-reactivity. Our findings suggest that MAGEP is related to a latent hypersensitivity reaction and an increased risk of mycobacterial infection susceptibility. According to the results of the present study, previous sensitization with NTM antigens results in varying immune reactions after contact with different NTM argued that masking phenomena may be dependent on the species of Mycobacterium.

Umbilical Blood Levels of IL-6 and TNF-α as Predictors of the Central Nervous System Damage and Retinopathy in Preterm Infants.

OBJECTIVE: The aim was to identify the critical levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A in umbilical cord blood that could be used as markers for predicting the central nervous system (CNS) damage and retinopathy of prematurity (ROP) in preterm infants. STUDY DESIGN: A total of 158 preterm infants, born at 22 to 34 weeks of gestation, were evaluated in the first week after birth and at 36 to 37 weeks of postconceptual age. RESULTS: A significant relationship between CNS changes and concentrations of IL-6 (p < 0.001) and TNF-α (p < 0.001) in umbilical cord blood at 22 to 34 weeks of gestation was determined. The concentration of IL-6 >13.0 pg/mL predicts significant CNS damages in 36 to 37-week infants (p = 0.013). ROP was diagnosed in 24.8% infants (n = 149). It was detected that the levels of TNF-α >116.4 pg/mL (p < 0.001) and IL-6 >13.0 pg/mL (p < 0.05) in umbilical cord blood could predict 2 to 3/3 to 4 stages of ROP. CONCLUSION: Critical values of IL-6 and TNF-α in predicting ≥grade III intraventricular hemorrhage in the early adaptation and in predicting marked CNS damages and severe ROP stages in the later adaptation of preterm infants were determined.

Are cytotoxic effector cells changes in peripheral blood of patients with Sjögren's syndrome related to persistent virus infection: Suggestions and conundrums.

Etiology of Sjögren's syndrome (SS) is still unknown, but there is strong evidence that certain pathogens of bacterial or viral origin can incite autoimmune response. The aim of this study was to quantitatively evaluate changes of the main cell populations (dendritic cells, natural killer, natural killer T and cytotoxic T lymphocytes) presumably participating in virus clearance in peripheral blood of patients with primary SS (pSS). In analyzing cytotoxic T lymphocytes (CTL) populations we observed alterations in the frequency of highly cytotoxic effector CD8high/57+/27-/45RA+, less cytotoxic CD8high/57-/27-/45RA+ effector cells and cytotoxic memory CD8high/57+/27+/45RA- effector cells. We found a decrease of conventional dendritic cells (cDC) population in peripheral blood of pSS patients. It is possible that, a decrease of effector CTL and cDC, accompanied by increase of transitory phenotype memory CTL in peripheral blood of pSS patients may be associated with viral etiopathogenesis of Sjögren's syndrome.

Significance of C-reactive protein in predicting fetal inflammatory response syndrome.

OBJECTIVES: The aim of the study was to identify and evaluate a possible correlation between C-reactive protein (CRP) concentration in maternal blood and the risk of developing fetal inflammatory syndrome (FIRS). MATERIAL AND METHODS: The study included 158 infants born at 22-34 weeks of gestation and their mothers. Umbilical cord blood cytokines were evaluated in immunoassay tests and maternal blood was tested for CRP concentration. RESULTS: The period of gestation was significantly shorter in the FIRS group as compared to the control group (29.5 ± 3.1 vs. 32.2 ± 2.4 weeks, p < 0.001). Gestational age was ≤ 30 weeks for 53.8% of the newborns in the FIRS group and 15.8% of the newborns in the control group (p < 0.001). Maternal CRP before, during and after labor was significantly higher in the FIRS group as compared to the control group (p < 0.001). Our study investigated the correlation between CRP in maternal blood and IL-6 concentration during the entire perinatal period (p < 0.001). CONCLUSION: CRP concentration in the FIRS group was significantly higher than in controls before, during, and after labor. Thus, it seems safe to conclude that changing concentration of inflammatory factors in maternal blood are closely related to FIRS. Elevated CRP in maternal blood might signify a progressing intrauterine infection and herald the development of FIRS.

Could the complement component C4 or its fragment C4d be a marker of the more severe conditions in patients with primary Sjögren's syndrome?

Our aim is to evaluate the complement component C4 (C4) and its fragment C4d (C4d) levels, focusing on their associations with other markers of B cells' activity in patients with primary Sjögren's syndrome (pSS). Humoral factors C4, C4d, B cell-activating factor (BAFF), κ and λ free light chains (FLCs) and IgG (by immunoassay) were investigated in 58 patients with pSS and in 28 healthy controls. We observed significantly higher levels of BAFF, κ and λ FLC and IgG, and significantly lower level of C4 in pSS patients, while the level of C4d was similar in the both groups. Significantly higher levels of BAFF, κ and λ FLCs, IgG, and significantly lower C4 level were found in anti-SSA/SSB antibodies (Abs) seropositive pSS patients' group comparing with healthy controls. Level of C4d was significantly lower in anti-SSA/SSB Abs seropositive pSS patients comparing with seronegative pSS patients and healthy controls. C4d correlated with C4, anti-SSB Abs level and κ/λ ratio. Significantly higher κ FLC and IgG levels were found in anti-SSA/SSB Abs seronegative pSS patients comparing with healthy controls. Anti-SSA/SSB seropositivity in pSS patients is associated with the decreased level of C4d. These results show that C4d can be an appropriate marker of antibody response and complement activation in pSS patients with Abs, and possibly may show the more severe condition-exhaustion of C4. Further studies are required to determine whether C4d assessment could be a relevant biomarker for the more severe condition and the worse prognosis of pSS.

The significance of TNF-α and MMP-8 concentrations in non-invasively obtained amniotic fluid predicting fetal inflammatory response syndrome.

OBJECTIVE: To determine the significance of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-8 (MMP-8) in vaginally obtained amniotic fluid predicting fetal inflammatory response syndrome (FIRS) after preterm premature rupture of membranes (PPROM). METHODS: In this prospective case-control study, TNF-α and MMP-8 concentrations were evaluated in vaginally obtained amniotic fluid from women with PPROM at 22-34 weeks of pregnancy. Biomarkers' concentrations were determined using an enzyme-linked immunosorbent assay. Patients were divided into two groups: the FIRS group (cord blood interleukin-6 > 11 pg/ml or histological funisitis) and the non-FIRS group (without these findings). The data were analyzed using R package (R-4.0.5). RESULTS: The median TNF-α and MMP-8 concentrations in amniotic fluid from the 145 women included in the study were higher in the FIRS group than in the non-FIRS group. The area under the curve of TNF-α and MMP-8 was 0.77 and 0.75, respectively. The TNF-α concentration cut-off predicting FIRS was 89.20 pg/ml and was 170.76 pg/ml for MMP-8. In regression analysis, MMP-8 concentration was an independent predictor for FIRS. An MMP-8 concentration greater than 170 ng/ml and a TNF-α concentration greater than 89 pg/ml increased the odds of FIRS 7.62 and 14.92 times, respectively. CONCLUSIONS: MMP-8 and TNF-α concentrations in vaginally obtained amniotic fluid may be good predictors for FIRS after PPROM before 34 weeks of pregnancy. The non-invasive amniotic fluid analysis could be an alternative method to invasive amniocentesis.

Expression of IL-17, IL-23 and their receptors in minor salivary glands of patients with primary Sjögren's syndrome.

The main purpose of this study was to determine the expression of interleukins-17/-23 (ILs-17/-23) and receptors of interleukins-17/-23 (IL-17R, IL-23R) in minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS). Expression of IL-17, IL-23 and receptors of IL-17/-23 was analyzed in MSGs from 25 patients with pSS, 25 patients with probable preclinical pSS, and 25 patients with nonautoimmune sicca syndrome by immunohistochemistry. Comparison of the expression of IL-17, IL-23 and receptors of IL-17, IL-23 in MSG of patients with pSS with probable preclinical pSS, and with nonautoimmune sicca syndrome showed significant differences between three groups. However, the expression of IL-17, IL-23 and receptors of IL-17/-23 in MSG was comparable in pSS and probable preclinical pSS patients. We did not find correlation between the expression of IL-17 and IL-23 and of IL-17R and IL-23R in patients with pSS. These results demonstrate an involvement of IL-17/-23 system in the early pSS pathogenesis.

Melatonin secretion in children with epilepsy.

This study examined melatonin (MLT) system in children with epilepsy. Diurnal patterns of salivary MLT, urinary metabolite 6-sulphatoxymelatonin, core body temperature, pulse and blood pressure were measured in 51 children with epilepsy (6.6-17.9 years) and 29 comparison children (5.5-17.3 years). The children with epilepsy preserved MLT and other circadian rhythms. In nine children with epilepsy (17.6%), peak salivary MLT concentrations were very high. There were no associations between MLT secretion/excretion parameters (diurnal profile, peak nocturnal concentrations, area under the time curve, duration of elevated concentrations, acrophase) and seizure characteristics (time, type of seizures, antiepileptic medications). The study observations are important for understanding of the MLT system in epilepsy and for exploring the potential for seizure treatment with melatonin.

Prognostic Markers for Chorioamnionitis: IL-6, TNF-α, and MMP-8 in Vaginally Obtained Amniotic Fluid.

BACKGROUND: Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value and to determine the most appropriate cut-off values for the prediction of chorioamnionitis. METHODS: This case control study included women who were diagnosed with preterm premature rupture of the membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free-leaking amniotic fluid was obtained vaginally with a sterile speculum less than 48h before delivery. Amniotic fluid IL-6, TNF-α, and MMP-8 levels were determined by the Enzyme Linked Immunosorbent Assay. Diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. RESULTS: The study included 156 women, 65 patients in the histological chorioamnionitis group (Group I) and 91 in a group without diagnosed histological chorioamnionitis (Group II). The median concentrations of IL-6, MMP-8, and TNF-α in amniotic fluid were statistically significantly higher in Group I than in Group II (p-value < 0.001). The area under the curve of TNF-α and MMP-8 were higher than the area under the curve of IL-6 (0.91, 0.89, and 0.81, respectively). No statistically significant difference was found when comparing the receiver operating characteristic (ROC) curves of TNF-α and MMP-8. The optimum cut-off values for the prediction of chorioamnionitis were found to be 1389.82 pg/mL for IL-6, 21.17 pg/mL for TNF-α, and 172.53 ng/mL for MMP-8. The sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV) of the IL-6 cut-off for chorioamnionitis were 88%, 70%, 67%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of the TNF-α cut-off were 88%, 84%, 79%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of the MMP-8 cut-off were 80%, 87%, 81%, and 86%, respectively. CONCLUSIONS: The vaginally obtained amniotic fluid IL-6, MMP-8, and TNF-α seem to be good predictors for chorioamnionitis of patients with preterm premature rupture of membranes before 34 weeks of gestation. The noninvasive technique of sampling amniotic fluid could be alternative method to invasive amniocentesis.

sICAM-1 as potential additional parameter in the discrimination of the Sjögren syndrome and non-autoimmune sicca syndrome: a pilot study.

OBJECTIVE: Both Sjögren's syndrome (SS) and non-autoimmune sicca syndrome (nSS) can show symptoms of dry eyes and a dry mouth, and objective reductions in tear and saliva production. Dry eyes and dry mouth are frequent but they are distinct pathological entities that require diagnostic discrimination. METHODS: The aim of present study was to compare the serum levels of sICAM-1, TFF3, RANTES, adiponectin, and FGF in primary (pSS), secondary due to rheumatoid arthritis (sSS), non-autoimmune sicca syndrome (nSS), and healthy groups. The serum levels of selected molecules were determined by enzyme-linked immunosorbent assay (ELISA) in 29 patients with pSS, 30 with sSS, 17 with nSS, and 15 healthy subjects. RESULTS: sICAM-1 was significantly elevated in pSS and sSS patients compared with nSS group. Levels of FGF, TFF3, and RANTES were significantly increased in pSS, sSS, and nSS patients compared with healthy controls. No significant correlations were found between the levels of measured molecules and the clinical parameters. CONCLUSIONS: Our study showed that sICAM-1 might be useful as an additional parameter for differential diagnosis of SS and nSS, and TFF could be additional diagnostic marker for SS diagnosis. KEY POINTS: • sICAM-1 was significantly elevated in Sjögren syndrome patients compared with non-autoimmune sicca syndrome group. • TFF was significantly elevated in Sjögren syndrome patients compared with healthy controls. • They might be useful as additional parameters for differential diagnosis.

Sjögren's Syndrome: Concerted Triggering of Sicca Conditions.

AIM: The aim of this study was to evaluate the expression of persistence of mumps virus and some cells that interact with viral infection in the focus of the autoimmune epithelitis and peripheral blood of Sjögren's syndrome patients in comparison to patients with rheumatoid arthritis (RA) and nonautoimmune sicca syndrome (nSS). MATERIALS AND METHODS: 126 patients (119 women and 7 men) were grouped into four groups: (1) patients with primary Sjögren's syndrome (pSS), (2) patients with secondary Sjögren's syndrome due to rheumatoid arthritis (sSS), (3) patients with rheumatoid arthritis (RA), and (4) patients with nonautoimmune sicca syndrome (nSS). Immunohistochemical analysis of immune response to the suggested silent persistence of mumps virus in the minor labial salivary gland biopsies and flow cytometric analysis of blood cells was done. RESULTS: Immunohistochemical signs of mumps virus persistence were found in the minor salivary glands of all study groups. Also, a significantly different immune response to virus infection (protein IFI16, interferons gamma and beta, dendritic cells, and receptor for natural killers) was revealed in the minor salivary glands of the study groups. Cytometric analysis of the blood cells revealed a dropping amount of circulating natural killers and dendritic cells in patients with SS. Significant correlations between immunohistochemical staining and serological findings were revealed. CONCLUSIONS: Abundant immunohistochemical signs of mumps virus protein in the salivary glands and depletion of circulating immune cells make a background for thought of presumable mumps or/and other virus participation in epithelial damage causing sicca syndrome in predisposed patients.

Distribution of Peripheral Lymphocyte Populations in Primary Sjögren's Syndrome Patients.

Purpose of this study was to evaluate the lymphocyte populations' distribution changes in peripheral blood of patients with primary Sjögren's syndrome (pSS). Lymphocyte populations' distribution changes in peripheral blood of pSS patients were investigated in 52 patients with pSS and in 28 healthy controls by flow cytometry. We found decreased absolute count of CD3(+) T cell population in pSS patients. Analysis of CD4(+) T cell population showed significant proportion and absolute count differences in pSS patient's blood with SSA/SSB antibodies (Abs) in comparison to controls. No significant differences were observed analyzing CD4(+) and CD8(+) Treg subpopulation. Proportion and absolute counts of Th17 cells were significantly lower in pSS patient's blood. Absolute counts of CD8(+) T cells were significantly lower in pSS patients in comparison to controls and also impaired proportion and absolute counts of CD8(+) subpopulations according to CD27(+) and CD57(+) were observed. Absolute counts of NKT and NK cells were decreased in pSS with Abs. B cells proportion was increased only in blood of pSS with Abs. Lymphocyte distribution impairment can be due to genetically determined lymphopenia or lymphocyte migration from periphery to inflammatory sites or/and increased susceptibility to apoptosis.

Activity of T-helper cells in patients with primary Sjogren's syndrome.

AIM: To investigate the T-helper (Th1, Th2 and Th17) cell activity in the peripheral blood of patients with primary Sjögren's syndrome (pSS), non-Sjögren's sicca syndrome (nSS) and healthy controls. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 34 pSS, 13 nSS patients and 13 healthy controls were stimulated, labeled for cluster of differentiation-4 (CD4), interferon-γ (IFN-γ), interleukin-4 (IL-4) and IL-17A and analyzed by flow cytometry. RESULTS: The activities of Th1 and Th17 cells in patients with pSS were similar to those of the control group. The percentage of both IFN-γ- and IL-17-producing Th17/Th1-like cells was significantly higher in the pSS, as compared to the control group, whereas that of Th2 cells was lower. A significant correlation was found between all Th-subset activities in the control group. However, in the pSS group, a correlation was found only between Th1 with Th2 and Th17 and Th17 with Th17/Th1-like. CONCLUSION: The imbalance in Th-subset activities in peripheral blood may play a role in the pathogenesis of pSS.

Leukocytosis as a prognostic marker in the development of fetal inflammatory response syndrome.

OBJECTIVE: To identify and evaluate the correlation between leukocyte count in maternal blood and the risk of developing fetal inflammatory response syndrome (FIRS). PATIENTS AND METHODS: The study involved 158 infants born at 22 - 34 weeks of gestation and their mothers. Umbilical cord blood cytokines were evaluated in immunoassay tests and maternal blood was tested for the leukocyte formula. RESULTS: The period of gestation was significantly shorter in the FIRS group compared to the control group (29.5±3.1 vs. 32.2±2.4 weeks, p<0.001). Gestational age was ≤30 weeks for 53.8% of the newborns in the FIRS group and 15.8% of the newborns in the control group (p<0.001). The number of leukocytes in maternal blood before and during labor was significantly higher in the FIRS group than in the control group (p=0.034 and 0.004, respectively). The study determined the correlation between the total leukocyte count in maternal blood and IL-6 concentration during labor (p=0.05) and tumor necrosis factor (TNF-α) concentration in umbilical cord blood before and during labor (p=0.02 and 0.007, respectively). CONCLUSION: Leukocytosis in the FIRS group was significantly higher than in the control group before and during labor. According to our data, one of the possible indicators of intrauterine infection could be the number of leukocytes in maternal blood.

Diurnal melatonin patterns in children: ready to apply in clinical practice?

Experimental and clinical studies suggest that endogenous melatonin plays an important role in pediatric sleep regulation. This finding led to the introduction of exogenous melatonin to treat sleep disturbances. Optimizing the treatment algorithm involves a review of melatonin measurements and interpretations in clinical practice. Diurnal patterns of salivary melatonin and urinary metabolite 6-sulfatoxymelatonin were investigated in 29 children and adolescents (age, 5.5-17.3 years) by measuring concentrations every 3 hours. Relationships between melatonin parameters (peak concentrations and area under the time curve) and anthropometric measures (height, weight, and body mass index), age, and sleep scores (Sleep Disturbance Scale for Children) were investigated. High interindividual variability was evident in melatonin diurnal profiles. Melatonin production (adjusted to body weight) decreased with age and sexual maturation (P < 0.00). Both salivary melatonin and its urinary metabolite measurements can be used to evaluate the melatonin system in children. However, the high interindividual variability of diurnal melatonin concentrations challenges clinical applications in regard to diagnostic purposes and the criteria for initiating exogenous melatonin therapy. Further investigations and the development of criteria for clinical evaluations of the pediatric melatonin system are needed.