Significant Differences In TNF-α Research Articles

Effects of light intensity on cleaning away heat property of Viola yedoensis

The current study was conducted to explore the effects of light intensity in cultivating environment on the cleaning away heat property of Viola yedoensis. In the present study, we established the acute inflammation model of ICR mice by injecting carrageenan. We compared the effects of V. yedoensis grown under different light intensities(100%, 80%, 50%, 35% and 5% of full sunlight) on mice body temperature, thermal radiation and the swelling degree of foot tissue before and after modeling observing by thermal infrared imaging technique and weighing method. The changes of energy metabolism related enzymes in liver were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the effects of V. yedoensis grown under different light intensities on human lung cancer cell A549 proliferation were explored with MTT method. The results showed that the body temperature of all groups of mice in V. yedoensis group were significantly lower than that of the blank group, except 5% full sunlight group, and the body temperature declined in positive proportion to light intensity. V. yedoensis group could alleviate foot swelling, reduce SDH activity in liver tissue(especially 100% full sunlight group and 80% full sunlight group were significantly lower than model group), and the degree of alleviating and reducing was positively correlated with light intensity. There was no significant difference in the activity of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase in liver tissue among treatments. The contents of IL-1β, IL-6, TNF-α, PGE_2 in foot tissue of mice in V. yedoensis groups were significantly lower than those in model group. Among them, the lowest levels of IL-1β, IL-6, TNF-α, PGE_2 were found in 80% full sunlight group, and there was no significant difference in TNF-α among different groups. The effects of V. yedoensis aqueous extract on A549 cell line proliferation inhibition rate increased with the light intensities of V. yedoensis cultivating environment. And the effects of V. yedoensis grown under 100% of full sunlight showed significantly higher A549 cell line proliferation inhibition rate compared with other groups(P<0.05). In summary, the light intensity of V. yedoensis cultivating environment is positively correlated with the cleaning away heat property of V. yedoensis, which conforms to the "light-cold and heat property" hypothesis,The V. yedoensis should be planted under full light according.

Immune function and serum vitamin D in shelter dogs: A case-control study

This study sought to establish a baseline understanding of immune function and its association with serum vitamin D in shelter dogs. Ten apparently healthy shelter dogs housed in the Arizona Humane Society for ≥7 days and 10 apparently healthy, age, breed, and sex-matched control dogs were included. Serum 25-hydroxyvitamin D (25[OH]D), the major circulating vitamin D metabolite, was measured using high performance liquid chromatography. Whole blood samples were stimulated with lipopolysaccharide (LPS), lipoteichoic acid, or phosphate buffer solution, and tumor necrosis factor (TNF)-ɑ, interleukin (IL)-6, and IL-10 were measured using a canine-specific multiplex bead-based assay. Phagocytosis of opsonized-Escherichia coli and E. coli-induced oxidative burst were evaluated with flow cytometry.Shelter dogs had decreased percentages of granulocytes and monocytes (GM) that had phagocytized opsonized-E coli (P = 0.019) and performed E. coli-induced oxidative burst (P = 0.011). There were no significant differences in TNF-α, IL-6, IL-10, or 25(OH)D concentrations between shelter and control dogs. Serum 25(OH)D concentrations had a weak positive association with the intensity of GM E. coli-induced oxidative burst (r2 = 0.23, P = 0.03). There was a moderate inverse association between serum 25(OH)D concentration and LPS-stimulated TNF-ɑ production in shelter dogs (r2 = 0.40, P = 0.04). These results demonstrate immune dysregulation in vitro in shelter dogs housed for ≥7 days when compared to age, breed, and sex-matched control dogs. While serum 25(OH)D concentrations did not differ between shelter and control dogs, significant associations between 25(OH)D concentration and immune function parameters in vitro were identified.

Carica pubescens fruit juice reduces tumor necrosis factor-alpha (TNF-α) and fasting blood glucose (FBG) levels in type 2 diabetes mellitus Wistar rats

Chronic inflammation and hyperglycemia in type 2 diabetes mellitus (T2DM) can cause several complications due to organ dysfunctions. Carica pubescens (CP) is a typical fruit from Dieng Plateau, Indonesia which contains some rutin that is kind of flavonoid. It is well known that flavonoid acts as anti-inflammation and anti-hyperglycemic which is useful for T2DM conditions. This study was aimed to investigate the effect of CP fruit juice on tumor necrosis factor-alpha (TNF-α) and fasting blood glucose (FBG) levels in rats induced by HFD-STZ, with rutin as a control. The design of this study was a randomized post-test only control group design. A total of twenty-five male Wistar rats were divided into 5 groups: K- = normal group; K+ = diabetic group; X1 and X2 = diabetic groups that received CP fruit juice 4 mL/200 g BW/day and 8 mL/200 g BW/day; X3 = diabetic group that received rutin 10 mL/200 g BW/day. The treatments were administered orally for 30 days. TNF-α and FBG levels were measured using ELISA and GOD-PAP method respectively. The results showed that TNF-α and FBG levels were significantly decreased in the treatment groups (X1, X2, X3) compared with the K+ group (p<0,05). Also, there was no significant difference in TNF-α and FBG levels between group X2 and X3, indicating that CP fruit juice 8 mL/200 g BW/day has a similar ability with rutin 10 mg/200 g BW/day. It can be concluded that CP fruit juice can be a recommended fruit juice for a diabetic condition by reducing TNF-α and FBG levels.

Effect of Moxibustion on HIF-1α and VEGF Levels in Patients with Rheumatoid Arthritis.

Background Moxibustion has a therapeutic effect of reducing swelling and relieving pain in patients with rheumatoid arthritis (RA) but its mechanism is uncertain. Objective To evaluate the effect of moxibustion on serum levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in patients with RA and to explore the possible mechanism of moxibustion. Methods This study involved 46 RA patients who had fulfilled the inclusion criteria and were randomly assigned to a treatment group and a control group in an equal ratio. The control group was treated with methotrexate or leflunomide, while the treatment group received methotrexate or leflunomide and moxibustion at ST 36 (Zusanli), BL 23 (Shenshu), and Ashi points. Patients' clinical symptoms, RA-associated serum markers, and serum levels of TNF-α, IL-1β, HIF-1α, and VEGF were compared in the two groups before and after intervention. Statistical analysis was performed using SPSS 21.0 statistical software. Results 37 of 46 RA patients eventually completed the whole treatment course. Compared with the control group, the treatment group significantly improved the clinical symptoms (P < 0.05) but with no significant differences in RA-associated serum markers (P > 0.05). There were significant differences in TNF-α and IL-1β among the groups after 8 weeks of treatment (P < 0.05). HIF-1α and VEGF were decreased in the treatment group after therapy (P < 0.05). VEGF was reduced in the control group (P < 0.05), while HIF-1α was not significantly improved (P > 0.05). The reductions of HIF-1α and VEGF in the treatment group were superior to the control group (P < 0.05). Conclusions Moxibustion enhanced the anti-inflammatory and analgesic effects of conventional medicine and can enhance the effect of conventional medicine, downregulating HIF-1α/VEGF contents to inhibit angiogenesis.

Physiological and Muscular Stress Associated with Multi-axial Whole-Body Vibration Exposure in Mining Heavy Equipment Vehicle Environment

Whole-body vibration (WBV) is known to be a leading factor for developing musculoskeletal disorders (MSDs). As mining vehicle operators are exposed to frequent transient shocks and substantial non-vertical WBV exposures, they may be at a greater risk than on-road vehicle operators. However, the impact of such exposures is not well understood. Therefore, this study aimed to evaluate how the exposure to WBV affected physiological stress and whether mining vehicles’ vibration with substantial non-vertical WBV components would further increase the level of physiological stress as compared to on-road vehicle vibration (vertical-axis dominant vibration). In a repeated-measures laboratory study, a 6-degree-of-freedom motion platform was used to recreate three different types of field-collected vibration profiles: vertical-axis dominant vibration measured from on-road long-haul trucks (VA), multi-axial vibration measured from mining vehicles (MA), and no vibration (control condition: CC). Subjects were exposed to each vibration condition for 2-hour sessions over three different experimental days. Blood samples were collected before and after each exposure session in order to measure biological markers for inflammation (tumor necrosis factor-α: TNFα), muscle damage (creatine kinase), and physiological stress (cortisol). During the 2-hour WBV exposures, muscle activity in the neck and low back muscles was measured using electromyography. The results showed that there were statistically significant differences in TNFα (inflammatory response) levels between vibration exposure (VA and MA) and the control condition (no vibration) (p = 0.01); however, these differences are not considered as clinically significant changes. No significant changes were found in muscle damage (creatine kinase) and physiological stress (cortisol). The vibration exposure conditions (VA and MA) showed higher low back muscle activity; however, these differences did not reach statistical significance (p’s &gt; 0.08). Neck muscle activity did not differ among exposure conditions. The lack of effect in these results may support previous findings that MSDs develop from prolonged exposure to WBV and not from acute exposure to physical risk factors.

REDUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND INTERFERON-GAMMA CONCENTRATION ON TUBERCULOSIS WITH DIABETES MELLITUS AS A MARKER IN DECREASE IMMUNE SYSTEM

Objective: This study aimed to determine the decreased immune response of tuberculosis (TB) with diabetes mellitus (DM) patients.&#x0D; Methods: A total of 105 TB patients who were undergoing treatment at health centers and hospitals in Banda Aceh and Aceh Besar were included in this study. Data collection was carried out by interviewed to obtained demographic and respondent categories based on the diagnosis. Measurements of height and weight were also conducted to obtain body mass index data. 5 mL peripheral blood was taken from each respondent group into a TB with DM (TB+DM) and TB without DM (TB-DM). The blood tested usage tumor necrosis factor-alpha (TNF-α) level using enzyme-linked immunosorbent assay and interferon-gamma (IFN-γ) using IFN-γ release assay.&#x0D; Results: The average concentration of both TNF-α and IFN-γ was higher in TB-DM group (TNF-a 5.2 pg/mL; IFN-g 1.5 IU/mL) than in TB+DM group (TNF-a 2.06 pg/mL; IFN-g 2.86 IU/mL). There were significant differences in TNF-α between the two groups but no significant differences in IFN-γ protein concentration.&#x0D; Conclusion: The immune response of TB patients with DM symptoms was markedly reduced by the decreased expression of TNF-α and IFN-γ.

P629Voluntary exercise associated with myokine production ameliorates cardiac remodeling and inflammation in a myocardial infarction mouse model

Abstract Background Left ventricular (LV) remodeling, through excessive inflammation, leads to heart failure. Exercise (Ex) training is associated with a risk reduction in heart failure through direct and indirect mechanisms by which Ex contributes an anti-inflammatory effect. During Ex, contracting muscle fibers release myokines, including interleukins (ILs), tumor necrosis factor α (TNF-α), follistatin-like protein 1 (FSTL-1), and fibroblast growth factor 21 (FGF-21), into the bloodstream. These myokines may have beneficial effects on other damaged organs, such as an infarcted myocardium, through anti-inflammatory effects. However, the exact mechanisms of the anti-inflammatory effects of voluntary Ex in myocardial infarction (MI) are poorly understood. Therefore, we investigated the effect of voluntary Ex on cardiac remodeling and inflammation, the relationship between cardiac remodeling and skeletal muscle (SKM) response, and circulating myokine levels in a mouse model of MI. Methods Twelve-week-old male C57BL/6J mice were used and divided into the following 4 groups: sham operation (Sham), MI, Sham+Ex, and MI+Ex. MI was induced by ligation of the left anterior descending coronary artery. Ex groups began voluntary wheel running for 4 weeks after the operation. An echocardiography was performed at baseline and 4 weeks after the operation. The mRNA levels in the LV infarcted area and SKM were measured with RT-PCR and western blot analysis. Plasma levels of myokines were also measured with immunoassays. Results Four weeks after MI induction, echocardiographic evaluation showed that the MI mice had a larger LV end-diastolic diameter (LVEDD) and end-systolic diameter (LVESD) than the Sham mice. The MI mice also showed higher mRNA levels of TNF-α, IL-1β, IL-6, and IL-10 in the LV tissue when compared to the Sham mice. These changes were significantly ameliorated in the MI+Ex mice. Interestingly, in the MI+Ex mice, mRNA levels of IL-6, IL-1β, FSTL-1, and FGF-21 in the SKM were significantly higher than in the MI mice, while there were no significant differences in TNF-α and IL-10 levels in all groups. Similarly, protein expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, sirtuin-1, and mitochondrial transcriptional factor A of mitochondrial function markers in SKM were also significantly higher in the MI+Ex mice than in the MI mice. Furthermore, there were significant correlations between plasma levels of IL-1β, but not other myokines, and LVEDD, and LVESD. In addition, there was also a significant correlation between the SKM IL-1β level and LVESD in the Sham+Ex mice (all, P&lt;0.05). Conclusions Amelioration of cardiac remodeling and inflammation by voluntary Ex is associated with increased myokines, especially IL-1β, in a MI mouse model. These results suggest that increased myokine levels, through voluntary exercise, may play an important role in the prevention of cardiac remodeling after MI.

SUN-282 INCREASE LEVEL OF TNF-α NOT CORRELATED WITH TOTAL ANTIOXIDANT CAPACITY ON CHRONIC KIDNEY DISEASE PATIENTS STAGE 3-5

CKD patients showed higher level of inflammation such as TNF-α and oxidative stress that result in an imbalance between free radical production and antioxidant defenses. Total antioxidant capacity (TAOC) is a parameter of combined antioxidant defenses in biological fluids. There are only few information about association between total antioxidant capacity (TAOC) and TNF-α. This is an observational analytic study on 80 chronic kidney disease patients stage 3-5. CKD staging of eGFR was measured by CKD-EPI. Blood samples was then measured for total antioxidant capacity (TAC) and TNF-α. Correlation between TAOC and TNF-α was measured with Rank-Spearman There were 21 patients on stage 3, 20 patients on stage 4 and 39 patients on stage 5 CKD. There were no significant difference of TAOC among CKD stage 3 to 5 respectively 21,3 ± 10,9;18,3 ± 9,9;20,6 ± 6,9 U/mL with p=0,521 but there were a significant difference of TNF-α among group of CKD stage 3-5 and respectively 2953(1661–9460);3394(1520–8467);3918(1936–17601) pg/mL with p=0,008. TNF-α shows strong negative correlation with eGFR by CKD-EPI (r=-0,383;p=0,000) but there was no correlation between TAC and eGFR (r=-0.119;p=0.146). Statistical analysis using Rank Spearman found that there was no significant correlation between TNF-α level and TAC level (r = 0.127, p = 0.131). Total antioxidant capacity reveals a stagnant level among CKD group 3-5 while the TNF-a level increase among CKD stage 3 to 5 There is no significant correlation between TAC levels and TNF- α. Although there was an increase level of TNF-α but it does not followed by increase capacity of total antioxidant in CKD stage 3-5

Randomized controlled trial on immunomodulatory effects of azithromycin in children with steroid-dependent nephrotic syndrome.

Azithromycin (AZM) is a macrolide antibiotic with anti-inflammatory and immunomodulatory effects. Our aim was to compare the immunomodulatory effects of AZM combined with steroid therapy with that of steroid therapy alone in children with steroid-dependent nephrotic syndrome (SDNS). We enrolled 57 patients with SDNS in a multicenter randomized control trial. Patients were classified into two groups: group A (intervention group, N = 29) and group B (control group, N = 28). After achievement of remission with full-dose daily prednisone, patients in group A received AZM in conjunction with steroids which was tapered gradually, while patients in group B received steroids alone. Urine protein creatinine ratio (uPCR) and TNF-α were measured at different points of follow-up throughout the study period (5months after achieving remission). After achievement of remission by full-dose steroids, there were significant differences of TNF-α between the two groups after 1-, 3- and 5-month follow-up (p < 0.001, 0.003, and 0.001, respectively). Also, there was significant difference of TNF-α in both intervention and control groups after exclusion of the relapsed cases at 3- and 5-month follow-up (, p = 0.031 and p = 0.003, respectively). There was significant difference between both groups after 5-month follow-up as regards the number of relapsed patients (group A = 4, group B = 11, p = 0.015). AZM was capable of reducing serum TNF-α which is one of the inflammatory cytokines implicated in the pathogenesis of NS.

Inhibitory effect of tanshinone IIA on inflammatory response in rheumatoid arthritis through regulating β-arrestin 2.

The current study aimed to investigate the inhibitory effect of tanshinone IIA (Tan IIA) on the inflammatory response in patients with rheumatoid arthritis (RA) and explore its mechanism. A total of 50 patients with RA were randomly separated into the control group (15 cases) and the research group (35 cases). The tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in serum were determined, and peripheral blood mononuclear cells (PBMCs) were separated from patients with RA and cultured in vitro. The effects of the β-arrestin 2 small interfering (si)RNA incubation, lipopolysaccharide (LPS) stimulation or Tan IIA incubation on TNF-α and IL-6 levels, and the expression levels of β-arrestin 2, NAD-dependent protein deacetylase sirtuin-1 (SIRT1) and transcription factor p65 (p65) proteins were investigated. Prior to treatment, no significant differences in TNF-α and IL-6 levels in serum of patients with RA were identified between the research and control groups. Following treatment, the TNF-α and IL-6 levels in the serum of patients with RA in the research group were significantly lower compared with those in the research group prior to treatment and those in the control group following treatment (P<0.05). Tan IIA inhibited the LPS-induced secretion of TNF-α and IL-6, upregulated the LPS-inhibited expression of the β-arrestin 2 and SIRT1 proteins, and downregulated the LPS-induced expression of the p65 protein in the PBMCs of patients with RA. The β-arrestin 2 small interfering (si)RNA significantly upregulated the secretion of TNF-α and IL-6, inhibited the expression of the SIRT1 protein and upregulated the expression of the p65 protein in PBMCs of patients with RA. Tan II A effectively increased the weight of rats with rheumatoid arthritis, and reduced the circumference of the left posterior ankle, the posterior plantar metatarsal thickness, and the content of serum TNF-α and IL-6. Tan IIA did not significantly reverse these β-arrestin 2 siRNA-induced changes. Tan IIA inhibited the inflammatory response in PBMCs of patients with RA by upregulating β-arrestin 2 expression.

Evaluation of tumor necrosis factor: Alpha in the saliva of oral cancer, leukoplakia, and healthy controls – A comparative study

Aims: The survival of oral squamous-cell carcinoma (OSCC) patients remains poor despite recent treatment advances. A sensitive and specific biomarker is important in screening high-risk patients. The present study was undertaken to test a hypothesis whether salivary tumor necrosis factor-alpha (TNF-α) can be used as a biomarker for OSCC. The study aimed to assess salivary TNF-α in OSCC, leukoplakia, and whether it can be used as a biomarker for the early diagnosis of OSCC. The objectives are as follows: (1) To evaluate salivary TNF-α and compare with histological grades of OSCC. (2) To evaluate salivary TNF-α in leukoplakia and compare with different grades of dysplasia. (3) To compare TNF-α levels in the saliva of oral cancer patients with leukoplakia patients and with healthy control group. Materials and Methods: The study was conducted in 90 participants, of which 30 healthy individuals, 30 leukoplakia, and 30 OSCC patients. Whole unstimulated saliva was collected and analyzed using an ELISA test. Results: TNF-α was significantly elevated in leukoplakia, further elevated in OSCC as compared to controls. There was a significant difference in TNF-α between the different histopathological grades of OSCC and leukoplakia (P ≤ 0.01). There were also statistically significant differences in TNF-α level between different clinical stages in OSCC (P ≤ 0.05). ROC curve analysis and area under curve values showed high specificity and sensitivity in differentiating OSCC from leukoplakia and healthy controls. Conclusion: The present study shows that salivary TNF-α can be used as a marker for predicting leukoplakia and oral cancer. The study also showed a significant correlation between clinical staging and histopathological grading of OSCC and TNF-α level.

IL-6, TNF-α levels and periodontal status changes during the menstrual cycle.

Sex steroid hormones are thought to affect periodontal tissues. A clear understanding of the effect of the menstrual cycle on oral tissues would be an important milestone in the timing of dental interventions in the future. The aim of this longitudinal, prospective study was to evaluate clinical periodontal parameters and levels of interleukin-6 IL-6 and tumour necrosis factor alpha (TNF-α) in gingival crevicular fluid (GCF) during the menstrual cycle. Forty-five patients were included in this study. Clinical periodontal parameters and levels of IL-6 and TNF-α were evaluated at three points of the menstrual cycle: menstruation day MD, ovulation day (OD) and premenstruation day (PmD). Levels of IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay. There were no statistically significant changes in plaque indexes or probing depths during the menstrual cycle (p>0.006) The differences between OD and PmD for gingival index and bleeding on probing were significant (OD>MD) (p<0.006). Statistically significant differences in TNF-α and IL-6 levels in the GCF were observed during the menstrual cycle (PmD>OD>MD) (p<0.006). Periodontal tissues did not exhibit evident changes, but this study demonstrated that the menstrual cycle affected the periodontium and induced inflammatory situations during the menstrual cycle.

Difference in proinflammatory cytokines produced by monocytes between patients with major depressive disorder and healthy controls

BackgroundImmune activation and suppression in patients with major depressive disorders (MDD) have been both reported in different studies. We assume that these findings may indicate innate immunological tolerance in MDD, with subclinical elevated level of proinflammatory cytokines and the decrease in innate immune response while encountering pathogens. MethodsPeripheral monocytes of 50 untreated patients with MDD and 40 healthy controls were isolated and cultured, with or without 10 ng/ml lipopolysacchride (LPS) for 6 h (6 h, LPS+/-), and with LPS for 18 h (18, LPS+). The cell culture supernatants were collected to measure concentrations of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1β). ResultsThe baseline concentrations of IL-6 and IL-1β (6 h, LPS-) were significantly higher in the MDD group than those in the control group. There was no significant difference of TNF-α between the two groups. The fold changes of LPS-induced secretion of IL-6 and TNF-α from monocytes cultured for 6 and 18 h were all lower in the patient groups, and that was true for IL-1β as monocytes cultured for 18 h. LimitationsGiven the gap between the results of in vitro experiments and the actual response that happens in vivo when the immune system encounters pathogens from the external world, future research should include in vivo methods to test the results of the current study. ConclusionsPatients with MDD may have subclinical inflammation during a depressive episode, and the reduced response to LPS in monocytes indicates innate immunological tolerance.

Risk factors and impacts on prognosis of ultrasound lung comets in patients undergoing hemodialysis

Objective: To investigate the risk factors of ultrasound lung comets and its impact on the survivals of patients undergoing hemodialysis. Methods: One hundred and forty-two patients on hemodialysis (Male 76, female 66) were divided into three groups according to the score of lung comets (mild: ≤14 comets; moderate: 15 to 30 comets; severe: >30 comets). Seventy-two healthy subjects examined by lung ultrasound serve as a control. Pulmonary artery systolic pressure and left ventricular ejection fraction (LVEF) were assessed by Doppler ultrasonography. High-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α were measured by the automatic analyzer and enzyme-linked immunosorbent assay. Results: With the increasing age of the patients, lung comets scores increased (P<0.05). There were significant differences in TNF-α (P<0.05), interdialytic weight gain (IDWG) (P<0.05), pulmonary artery systolic pressure and LVEF (P<0.05) among three groups. In multivariate linear regression, the lung comets score was positively related to multiple clinical variables including New York Heart Association (NYHA) classification (P=0.023), hsCRP (P=0.042), TNF-α (P<0.001), IDWG (P=0.031), and pulmonary artery systolic pressure (P<0.001). In the multivariate Cox proportional hazards models, lung comets score was independent risk factor for death (P=0.001). In Kaplan-Meier survival analysis, the risk of all-cause mortality increased in parallel with lung comets score, and patients with lung comets score (>30 comets) were at highest risk of death among all three groups (log-rank test χ(2)=12.73, P=0.001). Conclusion: Lung comets is associated with inflammation, pulmonary artery systolic pressure/volume overload and heart function. Lung comets score represents the alterations of heart function and it may serve as a powerful predictor of all-cause mortality for hemodialysis patients.

Utility of cytokine, adhesion molecule and acute phase proteins in early diagnosis of neonatal sepsis.

Background and Aim:Neonatal infection, including bacterial sepsis, is a major health care issue with an annual global mortality in excess of one million lives. Therefore, this study aimed to evaluate the potential diagnostic value of C-reactive protein (CRP), E-selectin, procalcitonin (PCT), interleukins-6 (IL-6), and tumor necrosis factor-α (TNF-α) both independently and in combination for the diagnosis of neonatal sepsis in its earliest stages.Materials and Methods:A total of 320 subjects were included in this study. A prospective cross-sectional study was conducted among neonates admitted to Neonatal Intensive Care Unit at King Abdulaziz Medical City, Riyadh, KSA during January 2013 to August 2015, the study based on three study groups categorized according to clinical symptoms and blood culture result. Study groups include healthy control neonates (n = 80), clinical sepsis (CS) group (n = 80) with clinical signs of sepsis but their blood culture was negative, and sepsis group with clinical signs of sepsis and their blood culture was positive.Results:The study observed significant difference in plasma levels of CRP, IL-6, TNF-α, E-selectin, and PCT in patients group when compared with control group (P < 0.001). Furthermore, the levels are significantly different between patient groups including CS and neonatal sepsis group. Moreover, result observed significant difference in CRP and IL-6 in early onset sepsis (EOS) when compared with late onset sepsis (LOS) neonates (P < 0.001 and 0.01), respectively, while there were no significant difference in TNF-α, E-selectin, and PCT between EOS and LOS (P = 0.44, 0.27 and 0.24), respectively. Regarding biomarkers accuracy, the result showed that CRP has the best diagnostic accuracy with cutoff value of 3.6 ng/ml (sensitivity 78% and specificity of 70%). The best combination is shown with CRP and IL-6 in which sensitivity increased to 89% and specificity to 79%.Conclusion:It was concluded that infected new-born babies have a higher E-selectin, PCT, IL-6, TNF-α, and CRP compared with the neonates with CS and control. IL-6, TNF-α, and CRP should be measured in combination for mare diagnostic accuracy in neonatal sepsis. Likewise, PCT should be investigated as a part of sepsis screening for all suspected neonates.

ИЗМЕНЕНИЕ УРОВНЯ ЦИТОКИНОВ ПРИ ОБОСТРЕНИИ ХРОНИЧЕСКОГО ПРОСТОГО БРОНХИТА, ОБУСЛОВЛЕННОМ ВИРУСОМ ПАРАГРИППА 3 ТИПА, У ЖЕНЩИН В ПЕРВОМ ТРИМЕСТРЕ БЕРЕМЕННОСТИ

The contents of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the blood serum were studied in 89 women in the first trimester of pregnancy. The first group (control) was made out of 25 women with uncomplicated pregnancy; the second had 23 women with the exacerbation of chronic simple bronchitis caused by parainfluenza of the 3rd type with antibody titer 1:16-1:64; the third one consisted of 21 patients with the exacerbation of chronic simple bronchitis induced by parainfluenza infection with antibody titers 1:32-1:128; the fourth group had 20 women with exacerbation of chronic simple bronchitis of parainfluenza etiology with antibody titer 1:64-1:256 at early stages of gestation. In the second group in comparison with the first one there were higher contents of IL-4: 21.1±2.00 pg/ml and INF-γ: 29.5±2.31 pg/ml than in the control group: 12.9±1.16 pg/ml (р&amp;#60;0.001) and 22.3±2.08 pg/ml (р&amp;#60;0.05), respectively. In the third group in comparison with the first one there were higher values of IL-4 (the growth by 132.6%, р&amp;#60;0.001), TNF-α (by 36%, p&amp;#60;0.01) and IFN-γ (by 43%, p&amp;#60;0.01). The patients in the fourth group in comparison with the third one did not have significant differences in TNF-α and IFN-γ. Buy there was the decrease of the level of IL-4 by 11.3% (р&amp;#60;0.05) that shows the imbalance of cytokines in women with exacerbation of chronic simple bronchitis caused by parainfluenza of the third type with antibody titer 1:64-1:256 at early stages of gestation. This may lead to persistent course of infectious-inflammatory process as well as to autoimmune damage of vital organs and the formation of initial placental insufficiency.

The Effects of CFTR and Mucoid Phenotype on Susceptibility and Innate Immune Responses in a Mouse Model of Pneumococcal Lung Disease.

Recent studies have reported the isolation of highly mucoid serotype 3 Streptococcus pneumoniae (Sp) from the respiratory tracts of children with cystic fibrosis (CF). Whether these highly mucoid Sp contribute to, or are associated with, respiratory failure among patients with CF remains unknown. Other mucoid bacteria, predominately Pseudomonas aeruginosa, are associated with CF respiratory decline. We used a mouse model of CF to study pneumococcal pneumonia with highly mucoid serotype 3 and non-mucoid serotype 19A Sp isolates. We investigated susceptibility to infection, survival, and bacterial counts from bronchoaviolar lavage samples and lung homogenates, as well as associated inflammatory cytokines at the site of infection, and lung pathology. Congenic CFTR–/– mice and wild-type (WT)-mice were infected intranasally with CHB756, CHB1126, and WU2 (highly mucoid capsular serotype 3, intermediately mucoid serotype 3, and less mucoid serotype 3, respectively), or CHB1058 (non-mucoid serotype 19A). BAL, lung homogenates, and blood were collected from mice 5 days post-infection. Higher CFU recovery and shorter survival were observed following infection of CFTR–/– mice with CHB756 compared to infection with CHB1126, WU2, or CHB1058 (P≤0.001). Additionally, CFTR–/– mice infected with CHB756 and CHB1126 were more susceptible to infection than WT-mice (P≤0.05). Between CFTR–/– mice and WT-mice, no significant differences in TNF-α, CXCL1/KC concentrations, or lung histopathology were observed. Our results indicate that highly mucoid type 3 Sp causes more severe lung disease than non-mucoid Sp, and does so more readily in the lungs of CFTR–/– than WT-mice.

BIOMARCADORES DE INFLAMACIÓN SUBCLÍNICA EN PACIENTES INFANTO-JUVENILES CON DIABETES TIPO 1

La diabetes tipo 1 (DT1) se asocia a un riesgo incrementado de complicaciones vasculares. Las citoquinas proinflamatorias IL-6, MCP-1 y TNF-α han sido implicadas en el desarrollo de estas complicaciones.El objetivo de este trabajo fue determinar los niveles plasmáticos de IL-6, MCP-1, TNF-α, PCRus y fibrinógeno (Fg) en pacientes infanto-juveniles con DT1 y su asociación con el grado de control glucémico y tiempo de evolución de la enfermedad.Se estudiaron 45 pacientes con DT1 (24 M/21 F), edad 11,2±1,8 años, con tiempo de evolución de la enfermedad de 3,1±3,0 años, sin complicaciones vasculares, que se compararon con 20 sujetos sanos. Se determinaron los niveles plasmáticos de IL-6, MCP-1 y TNF-α, Fg, PCRus, recuento de leucocitos, glucemia en ayunas y HbA1c. Se descartó la presencia de retinopatía y nefropatía Los datos fueron analizados con el programa SPSS 15 para Windows. Los niños diabéticos presentaron niveles mayores de IL-6 (1,10±0,74 vs 0,68±0,19 pg/ml; p=0,005), MCP-1 (130±49 vs 95±18 pg/ml; p=0,02), PCRus (1,02±1,07 vs 0,43±026 mg/l; p=0,007), Fg (299±59 vs 246±18 mg/dl, p=0,0001), respecto de los controles. No se observaron diferencias significativas de TNF-α entre ambos grupos. Al agrupar a los diabéticos según el grado de control glucémico (HbA1c &lt;8% y ≥8%) y el tiempo de evolución de la enfermedad (≤3 y &gt;3 años), no se encontraron diferencias significativas en las moléculas estudiadas. En los diabéticos la HbA1c se correlacionó con IL-6, MCP-1 y PCRus.Estos resultados reflejan un estado proinflamatorio en la población diabética estudiada.

The Effects of Ozurdex® (Dexamethasone Intravitreal Implant) on Experimental Proliferative Vitreoretinopathy

Purpose: To investigate a new sustained-release formulation of dexamethasone (Ozurdex®) for inhibiting proliferative vitreoretinopathy (PVR) and its effect on the expression of retinal glial reaction and inflammation in experimental PVR eyes. Methods: We used 30 pigmented rabbits for this study. One week after gas compression, the eyes were injected with 5 × 10⁴ retinal pigment epithelial cells into the vitreous cavity to induce PVR. Concurrently, one eye also received an intravitreal injection of Ozurdex; the other eye was used as a control. PVR was graded by indirect ophthalmoscopy on days 1, 3, 7, 14, 21, and 28. The expression of the retinal glial reaction and inflammation in experimental PVR eyes were evaluated by Western blot analysis. Results: PVR severity increased gradually and peaked after 14 days, and no differences in PVR severity between the study and control groups were observed at any time point. The expression of glial fibrillary acid protein (GFAP) increased on days 7 and 14 in both the PVR control and study groups. While the use of Ozurdex in the study group showed less GFAP expression, this difference was not significant. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 significantly increased on days 7 and 14 in PVR control eyes. There was a significant difference in TNF-α between PVR control eyes and Ozurdex-treated eyes on days 7 (p < 0.001) and 14 (p = 0.019). Ozurdex in the study group showed lower IL-6 expression; however, this difference was not significant on days 7 (p = 0.063) and 14 (p = 0.052). Conclusions: The intravitreal injection of Ozurdex suppressed the expression of inflammatory markers; however, it did not mitigate the severity of experimental PVR in this animal model.

Effects of agmatine on excessive inflammatory reaction and proliferation of splenic cells in mice with trauma

To observe protective effects of agmatine (AGM) on inflammatory response and spleen immune function in mice with trauma. Forty-eight adult male C57BL/6 mice were randomly divided into three groups (n = 16 each), including control group, model group (bilateral femoral fracture and removal of 35% of the total blood volume), and AGM group (trauma/hemorrhage and AGM 200 mg/kg). Eight mice in each group were sacrificed at 3 hours and 24 hours, respectively, after modeling, and blood samples and tissue homogenate of spleen and liver were collected. The contents of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-1β) in serum and liver tissue were determined with enzyme linked immunosorbent assay (ELISA). Serum aspartate transaminase (AST), alanine aminotransferase (ALT) and lactic dehydrogenase (LDH) were determined with automatic biochemistry analyzer. Spleen proliferation response stimulated with concanavalin A (ConA) was evaluated with methyl thiazolyl tetrazolium colourimetry (MTT). γ-interferon (IFN-γ) and IL-2 releases were determined with ELISA. Compared with control group, 3 hours after trauma/hemorrhage, the levels of serum TNF-α, IL-6, and IL-1β in model group were significantly elevated [TNF-α (ng/L): 145.38±31.50 vs. 23.06±11.14, IL-6 (ng/L): 496.94±50.76 vs. 47.13±17.47, IL-1β (ng/L): 321.31±43.02 vs. 29.25±16.24,all P < 0.01]. It was found that AGM treatment could alleviate the increase in serum pro-inflammatory mediators induced by trauma/hemorrhage, such as TNF-α (ng/L: 111.56±25.47 vs. 145.38±31.50), IL-6 (ng/L: 412.56±44.33 vs. 496.94±50.76), IL-1β (ng/L: 273.38±45.25 vs. 321.31±43.02, P < 0.05 or P < 0.01). Twenty-four hours after trauma/hemorrhage, serum pro-inflammatory mediators were recovered to the levels in control group. There was no significant difference in TNF-α and IL-6 levels at 3 hours after trauma/hemorrhage among groups. Compared with control group, the expressions of liver TNF-α and IL-6 in model group were increased at 24 hours following trauma [TNF-α (ng/mg): 32.93±4.90 vs. 26.58±2.33,IL-6 (ng/mg): 11.20±1.66 vs. 8.38±0.89,both P < 0.01]. However, AGM inhibited the level of TNF-α (ng/mg: 28.92±3.16 vs. 32.93±4.90) and IL-6 (ng/mg: 9.03±1.28 vs. 11.20±1.66) in the liver as induced by trauma/hemorrhage (P < 0.05 and P < 0.01). At 24 hours after modeling, model group and AGM group had distinctly higher serum AST, ALT, LDH levels than those of control group [AST (U/L): 405.9±31.2, 245.7±22.1 vs. 128.2±15.9; ALT (U/L): 92.1±6.3, 51.6±5.0 vs. 30.1±3.2; LDH (U/L): 606.7±36.3, 478.7±25.3 vs. 384.0±16.6, all P < 0.01]. Nevertheless,the increase in serum AST, ALT and LDH was alleviated in AGM group (all P < 0.01). Meantime, trauma/hemorrhage produced a noticeable depression of proliferation of splenic cells and IFN-γ and IL-2 release stimulated with ConA compared with control group [proliferation rate: (40.97±4.13)% vs. (89.99±7.76)%, IFN-γ (ng/L): 91.6±12.3 vs. 353.2±21.5,IL-2 (ng/L): 53.4±6.4 vs. 91.0±12.2,all P < 0.01]. In contrast, AGM notably restored the capacity of proliferation response of splenic cells [proliferation rate: (74.86±5.75)% vs. (40.97±4.13)%,P < 0.01],enhanced the release of IFN-γ and IL-2 stimulated with ConA [IFN-γ (ng/L): 327.8±23.6 vs. 91.6±12.3, IL-2 (ng/L): 74.8±10.4 vs. 53.4±6.4, both P < 0.01]. AGM can dramatically alleviate spleen immunosuppression, excessive inflammation and organ damage induced by trauma/hemorrhage.