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  1. TNF-Alpha Levels in Tears: A Novel Biomarker to Assess the Degree of Diabetic Retinopathy

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    C. Costagliola

    2013-01-01

    Full Text Available We assess the level of tumour necrosis factor alpha (TNF-alpha in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR and 16 with nonproliferative retinopathy (NDPR, background/preproliferative. Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (. Glycemia in NPDR: 6.6 mmol/L (range: 5.8–6.3; in PDR: 6.7 mmol/L (range: 6.1–7.2; in control: 5.7 mmol/L (range: 4.9–6.1; microalbuminurea in NPDR: 10.6 mg/L (range: 5.6–20; in PDR: 25.2 mg/L (range: 17–40; in control: 5.3 mg/L (range: 2.6–10; Body mass index in NPDR: 26 Kg/m2 (range: 20.3–40; in PDR: 28 Kg/m2 (range 20.3–52; in control: 21 Kg/m2 (range 19–26. The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

  2. [The effect of isoflurane on the secretion of TNF-alpha and IL-1 beta from LPS-stimulated human peripheral blood monocytes].

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    Sato, W; Enzan, K; Masaki, Y; Kayaba, M; Suzuki, M

    1995-07-01

    The cytokines such as tumor necrosis factor and interleukin-1 secreted from macrophages/monocytes proved to play important roles in the pathogenesis of endotoxemia, severe pancreatitis and other surgical injuries. However, it is still unclear how inhalational anesthetic agents influence the secretion of these cytokines from macrophages/monocytes. We investigated the effects of isoflurane on TNF-alpha and IL-1 beta secretions from human peripheral blood monocytes stimulated by lipopolysaccharide. TNF-alpha and IL-1 beta secretions increased after LPS stimulation and this increase was inhibited by isoflurane in dose-dependent fashion. The inhibitory action of isoflurane disappeared between 1 and 3 hours after stopping isoflurane inhalation. We concluded that isoflurane could inhibit TNF-alpha and IL-1 beta secretions from peripheral blood monocytes stimulated by LPS in a dose-dependent fashion and that the inhibitory action of isoflurane was reversible.

  3. Elevated plasma levels of TNF-alpha and Interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders

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    Ellinghaus Peter

    2009-11-01

    Full Text Available Abstract Background Diabetes mellitus (DM has reached epidemic proportions and is an important risk factor for heart failure (HF. Left ventricular diastolic dysfunction (LVDD is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6 and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease. Methods We enrolled 41 consecutive patients (mean age 65+/-10 years submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E transmitral flow velocity was measured. LVDD was defined as E/Em ratio ≥ 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes. Results Patients with E/Em ratio ≥ 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline had significantly higher IL-6 (P = 0,001, TNF-alpha (P Conclusion This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

  4. Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis.

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    Doki, Tomoyoshi; Takano, Tomomi; Kawagoe, Kohei; Kito, Akihiko; Hohdatsu, Tsutomu

    2016-02-01

    Feline infectious peritonitis virus (FIPV) replication in macrophages/monocytes induced tumor necrosis factor (TNF)-alpha production, and that the TNF-alpha produced was involved in aggravating the pathology of FIP. We previously reported the preparation of a feline TNF-alpha (fTNF-alpha)-neutralizing mouse monoclonal antibody (anti-fTNF-alpha mAb). This anti-fTNF-alpha mAb 2-4 was confirmed to inhibit the following fTNF-alpha-induced conditions in vitro. In the present study, we investigated whether mAb 2-4 improved the FIP symptoms and survival rate of experimentally FIPV-inoculated SPF cats. Progression to FIP was prevented in 2 out of 3 cats treated with mAb 2-4, whereas all 3 cats developed FIP in the placebo control group. Plasma alpha1-glycoprotein and vascular endothelial growth factor levels were improved by the administration of mAb 2-4, and the peripheral lymphocyte count also recovered. These results strongly suggested that the anti-fTNF-alpha antibody is effective for the treatment of FIP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

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    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle...... mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body...... to lower ASM and BCM in elderly men both in a univariate regression analysis and a multivariate regression analysis. In conclusion, high plasma levels of TNF-alpha and IL-6 in elderly healthy people and in patients with type 2 diabetes are associated with increased truncal fat mass, suggesting...

  6. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes

    DEFF Research Database (Denmark)

    Pedersen, Maria; Bruunsgaard, Helle; Weis, Nina

    2003-01-01

    The purpose of the current study was to test the hypothesis that an altered fat distribution in elderly healthy subjects and in patients with type-2 diabetes contributes to high circulating levels of interleukin (IL)-6 and tumor necrotic factor (TNF)-alpha, which secondly is related to lower muscle...... mass. Twenty young controls, (20-35 yr), 20 healthy elderly subjects (65-80 yr) and 16 elderly patients with type 2 diabetes (65-80 yr) were included in a cross sectional study. Plasma levels of TNF-alpha and IL-6 were measured after an overnight fast. Dual-energy X-ray absorptiometry and total body...... potassium counting measured truncal fat, appendicular skeletal muscle mass (ASM) and body cell mass (BCM), respectively. TNF-alpha, IL-6 and the relative truncal fat mass were higher in elderly compared with young controls. ASM was lower in diabetic men than in young controls and BCM was lower in elderly...

  7. Serum TNF-Alpha Level Predicts Nonproliferative Diabetic Retinopathy in Children

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    Katarzyna Zorena

    2007-01-01

    Full Text Available The aim of this study was identification of the immunologic markers of the damage to the eye apparatus at early stages of diabetes mellitus (DM type 1 children. One hundred and eleven children with DM type 1 were divided into two groups: those with nonproliferative diabetic retinopathy (NPDR and without retinopathy. All the children had their daily urine albumin excretion, HbA1c, C-peptide measured, 24-hour blood pressure monitoring, and ophthalmologic examination. Levels of TNF-α, IL-6, and IL-12 in serum were measured by ELISA tests (Quantikine High Sensitivity Human by R&D Systems, Minneapolis, Minn, USA. The NPDR children demonstrated a significantly longer duration of the disease in addition to higher HbA1c, albumin excretion rate, C-reactive protein, systolic blood pressure, as well as TNF-α and IL-6 levels than those without retinopathy. The logistic regression revealed that the risk of NPDR was strongly dependent on TNF-α [(OR 4.01; 95%CI 2.01–7.96]. TNF-α appears to be the most significant predictor among the analyzed parameters of damage to the eye apparatus. The early introduction of the TNF-α antagonists to the treatment of young patients with DM type 1 who show high serum activity of the TNF-α may prevent them from development of diabetic retinopathy.

  8. Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

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    Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

    2009-07-01

    Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  9. TNF-alpha, leptin, and lymphocyte function in human aging

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    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...... regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo...

  10. The effect of diode laser and topical steroid on serum level of TNF-alpha in oral lichen planus patients.

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    Othman, Nagwa-Abdelhamid; Shaker, Olfat-Gamil; Elshenawy, Hanaa-Mohamed; Abd-Elmoniem, Wessam; Eldin, Amany-Mohy; Fakhr, Mariam-Yehia

    2016-12-01

    Oral lichen planus (OLP) is a common chronic inflammatory mucosal disease with a multifactorial etiology. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+T cells trigger apoptosis of the basal cells of oral epithelium. Various treatment regimens have been employed for management of symptomatic OLP. This study was carried out to evaluate the effect of topical steroids as well as laser on the clinical signs and symptoms detected by reticular, atrophic, erosive score (RAE score) and tumor necrosis factor- α (TNF-α) level in the serum of patients with symptomatic OLP. The study was conducted on twenty-four patients (18 females and 6 males) with symptomatic OLP that were allocated into two groups. Each included twelve patients. The first group treated either with diode laser (970nm SIROLaser Advance class IIIb, SIRONA The Dental Company, Germany) twice weekly with maximum of ten sessions while the second group were treated with topical corticosteroids (0.1% triamcinolone acetonide orabase, Kenacort-A Orabase Pomad, DEVA HOLDING A.Ș, Istanbul, Turkey) for four weeks. Corticosteroids group showed less clinical signs and symptoms of reticular, atrophic, erosive RAE score ( p =0.02) and TNF-α serum level ( p =0.028) than diode laser group with no reported therapy side effects or complications in any of the treated patients. Topical steroids reduce pain, reticular, atrophic, erosive RAE score and TNF-α serum level more than laser treatment. Moreover, laser treatment can be used as an alternative treatment when steroids are contraindicated for the treatment of symptomatic OLP. Key words: Oral lichen planus, diode laser, topical steroid, RAE score, TNF-α.

  11. Regulation of PPAR{gamma} function by TNF-{alpha}

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    Ye Jianping [Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808 (United States)], E-mail: yej@pbrc.edu

    2008-09-26

    The nuclear receptor PPAR{gamma} is a lipid sensor that regulates lipid metabolism through gene transcription. Inhibition of PPAR{gamma} activity by TNF-{alpha} is involved in pathogenesis of insulin resistance, atherosclerosis, inflammation, and cancer cachexia. PPAR{gamma} activity is regulated by TNF-{alpha} at pre-translational and post-translational levels. Activation of serine kinases including IKK, ERK, JNK, and p38 may be involved in the TNF-regulation of PPAR{gamma}. Of the four kinases, IKK is a dominant signaling molecule in the TNF-regulation of PPAR{gamma}. IKK acts through at least two mechanisms: inhibition of PPAR{gamma} expression and activation of PPAR{gamma} corepressor. In this review article, literature is reviewed with a focus on the mechanisms of PPAR{gamma} inhibition by TNF-{alpha}.

  12. [Polymorphism of TNF-alpha (308 A/G), IL-10 (1082 A/G, 819 C/T 592 A/C), IL-6 (174 G/C), and IFN-gamma (874 A/T); genetically conditioned cytokine synthesis level in children with diabetes type 1].

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    Siekiera, Urszula; Jarosz-Chobot, P; Janusz, J; Koehler, Brygida

    2002-01-01

    Type 1 diabetes is a genetically conditioned autoimmune disease. Genes that account for strong clustering of the disease susceptibility are located within the HLA region. There is also considerable individual variation in the immune response and role of cytokine genes in the disease predisposition. The aim of our research was identification of the genetically controlled TNF-alpha, IL-10, IL-6, IFN-gamma secretion profile in children with diabetes type 1. We have examined 36 children with diabetes type 1 and 36 healthy individuals. DNA was extracted from mononuclear peripheral blood cells. For identification of the cytokine polymorphism PCR-SSP method was used. Patients with diabetes type 1 differ from the group of healthy persons in the cytokine synthesis level and in the cytokine genotypes distribution. Genotype TNF-alpha (A/G) as well as IL-10 (ATA/ATA) was found only in group of children with diabetes but not in the control group. Genotypes IL-10 (GCC/GCC), IL-6 (C/C), IFN-gamma (T/T) were observed with decreased frequency in children with diabetes type 1. No differences between patients and control group in the frequency of IL-10 (GCC/ACC) (GCC/ATA), (ACC/ACC) (ACC/ATA) IL-6 (G/G), (G/C) and IFN-gamma (T/A), (A/A) genotypes were observed. Children with diabetes type 1 were more frequent "high producers" of TNF-alpha and IL-6. It is possible to us molecular method to estimate the genetically controlled immune reactivity. It is a very important immunogenetic factor of the disease predisposition.

  13. [Anti-TNF alpha in dermatology].

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    Mahe, E; Descamps, V

    2002-12-01

    The discovery of the major role of TNF alpha in the physiopathology of certain inflammatory diseases and notably in rheumatoid arthritis and Crohn's disease has led to the development of anti-TNF alpha drugs. These new therapeutic arms issued from bio-technology have rapidly demonstrated their efficacy in the treatment of these two diseases. The anti-TNF alpha arsenal is currently dominated by etanercept, a fusion protein composed of a soluble TNF alpha receptor, and infliximab, a chimeric monoclonal antibody. However, new molecules will soon enrich this arsenal. TNF alpha is a major cytokine of inflammatory diseases of the skin. Many dermatological diseases will probably benefit from these new treatments. Two studies have already demonstrated their interest in cutaneous and articular psoriasis. Encouraging sporadic results suggest other potential indications (Behcet's disease, bullous dermatitis, neutrophilic dermatitis, toxic epidermal necrolysis, systemic vascularitis,.). These promising new treatments, although expensive, and with yet unknown long term side effects, justify rigorous assessment of their efficacy and tolerance in each indication. Here again the dermatologist has a major role to play in post-marketing pharmacovigilance.

  14. The effects of a muscle resistance program on the functional capacity, knee extensor muscle strength and plasma levels of IL-6 and TNF-alpha in pre-frail elderly women: a randomized crossover clinical trial--a study protocol.

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    Lustosa, Lygia P; Coelho, Fernanda M; Silva, Juscelio P; Pereira, Daniele S; Parentoni, Adriana N; Dias, João M D; Dias, Rosangela C; Pereira, Leani S M

    2010-07-28

    With the increase in the elderly population, a growing number of chronic degenerative diseases and a greater dependency on caregivers have been observed. Elderly persons in states of frailty remain more susceptible to significant health complications. There is evidence of an inverse relationship between plasma levels of inflammatory mediators and levels of functionality and muscle strength, suggesting that muscle-strengthening measures can aid in inflammatory conditions. The purpose of this study will be verified the effect of a muscle-strengthening program with load during a ten-week period in pre-frail elderly women with attention to the following outcomes: (1) plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), (2) functional capacity and (3) knee extensor muscle strength. The study design is a randomized crossover clinical trial evaluating 26 elderly women (regardless of their race and/or social condition) who are community residents, older than 65, and classified as pre-frail according to the criteria previously described by Fried et al. (2004). All subjects will be assessed using the Timed up and go and 10-Meter Walk Test functional tests. The plasma levels of IL-6 and TNF-alpha will be assessed by ELISA (enzyme-linked immunosorbent assay) with high sensitivity kits (QuantikineHS, R&D Systems Minneapolis, MN, U.S.). Knee extensor muscle strength will be assessed using the Byodex System 3 Pro(R) isokinetic dynamometer at angular speeds of 60 and 180 degrees/s. The intervention will consist of strengthening exercises of the lower extremities at 50 to 70% of 1RM (maximal resistance) three times per week for ten weeks. The volunteers will be randomized into two groups: group E, the intervention group, and group C, the control group that did not initiate any new activities during the initial study period (ten weeks). After the initial period, group C will begin the intervention and group E will maintain everyday activities without

  15. Infliximab TNF-alpha antagonist decreases intraabdominal adhesions

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    Kurukahvecioglu, O.; Koksal, H.; Yazicioglu, O.; Kerem, M.; Taneri, F.; Gulbahar, O.; Erdem, O.; Engin, D.

    2007-01-01

    Objective was to evaluate the effect of infliximab on adhesion formation and its associated morbidity and complications. This study was performed in the Faculty of Medicine, Gaze University, Turkey between July 2005 and October 2005. Thirty-five rats were randomly divided into 4 groups. Laparotomy was performed in the Sham group (n=5), whereas cecal abrasion was carried out in all other groups. After cecal abrasion 0.9% sodium chloride was administered in the saline group (n=10), infliximab was administered to the study group (n=10) and nothing was administered to the last group (n=10). Adhesion formation was evaluated with macroscopic adhesion scoring systems. Peritoneal fluid samples and mesenteric lymph node biopsies were taken to rule out bacterial peritonitis. Blood and peritoneal irrigation fluids samples were taken to measure the Tumor necrosis factor-alpha (TNF-alpha) levels. Macroscopic adhesion scores showed fewer adhesions in the infliximab group. The infliximab group had significantly fewer adhesions than the abrasion control and saline groups. According to the histological findings, there were no statistically significant differences between the groups. Early blocking of the activity of TNF-alpha after cecal abrasion resulted in lower rates of adhesion formation, macroscopically. The TNF-alpha, a proinflammatory cytokine appears to be an important mediator for postoperative adhesion formation. (author)

  16. Biotin deficiency up-regulates TNF-alpha production in murine macrophages.

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    Kuroishi, Toshinobu; Endo, Yasuo; Muramoto, Koji; Sugawara, Shunji

    2008-04-01

    Biotin, a water-soluble vitamin of the B complex, functions as a cofactor of carboxylases that catalyze an indispensable cellular metabolism. Although significant decreases in serum biotin levels have been reported in patients with chronic inflammatory diseases, the biological roles of biotin in inflammatory responses are unclear. In this study, we investigated the effects of biotin deficiency on TNF-alpha production. Mice were fed a basal diet or a biotin-deficient diet for 8 weeks. Serum biotin levels were significantly lower in biotin-deficient mice than biotin-sufficient mice. After i.v. administration of LPS, serum TNF-alpha levels were significantly higher in biotin-deficient mice than biotin-sufficient mice. A murine macrophage-like cell line, J774.1, was cultured in a biotin-sufficient or -deficient medium for 4 weeks. Cell proliferation and biotinylation of intracellular proteins were decreased significantly in biotin-deficient cells compared with biotin-sufficient cells. Significantly higher production and mRNA expression of TNF-alpha were detected in biotin-deficient J774.1 cells than biotin-sufficient cells in response to LPS and even without LPS stimulation. Intracellular TNF-alpha expression was inhibited by actinomycin D, indicating that biotin deficiency up-regulates TNF-alpha production at the transcriptional level. However, the expression levels of TNF receptors, CD14, and TLR4/myeloid differentiation protein 2 complex were similar between biotin-sufficient and -deficient cells. No differences were detected in the activities of the NF-kappaB family or AP-1. The TNF-alpha induction by biotin deficiency was down-regulated by biotin supplementation in vitro and in vivo. These results indicate that biotin deficiency may up-regulate TNF-alpha production or that biotin excess down-regulates TNF-alpha production, suggesting that biotin status may influence inflammatory diseases.

  17. Patients with Ankylosing Spondylitis and Low Disease Activity because of Anti-TNF-Alpha Therapy Have Higher TRAIL Levels Than Controls: A Potential Compensatory Effect

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    Fernanda Genre

    2014-01-01

    Full Text Available Objective. TRAIL is a potential biomarker of cardiovascular (CV disease. Ankylosing spondylitis (AS is a chronic inflammatory disease associated with metabolic syndrome (MeS and accelerated atherosclerosis. We assessed whether disease activity, systemic inflammation, and MeS features were associated with circulating TRAIL levels in AS patients undergoing TNF-α antagonist infliximab therapy and if infliximab infusion modified TRAIL levels. Methods. We measured TRAIL serum levels in 30 nondiabetic AS patients without CV disease undergoing anti-TNF-α therapy, immediately before and after an infliximab infusion, and in 48 matched controls. Correlations of TRAIL levels with disease activity, systemic inflammation and MeS features, adipokines, and biomarkers of endothelial activation were evaluated. Changes in TRAIL levels following anti-TNF-α infusion were analyzed. Results. TRAIL levels were higher in AS patients than controls. TRAIL levels displayed an inverse correlation with total and LDL cholesterol. We observed an inverse correlation with QUICKI and a marginal association with HOMA-IR. We also found an inverse correlation with resistin and a marginal association with apelin and OPN. Anti-TNF-α infusion did not change TRAIL levels after 120′. Conclusion. Elevated TRAIL levels in AS patients may be the result of a compensatory mechanism to reduce CV risk in these patients.

  18. Deregulated TNF-Alpha Levels Along with HPV Genotype 16 Infection Are Associated with Pathogenesis of Cervical Neoplasia in Northeast Indian Patients.

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    Das, Chandana Ray; Tiwari, Diptika; Dongre, Anita; Khan, Mohammad Aasif; Husain, Syed Akhtar; Sarma, Anirudha; Bose, Sujoy; Bose, Purabi Deka

    2018-05-01

    Multiple factors are associated with human papillomavirus (HPV) infection related cervical anomalies and its progression to cervical carcinoma (CaCx), but data vary with respect to the underlying HPV genotype and with population being studied. No data are available regarding the role of immunological imbalance in HPV infected CaCx pathogenesis from Northeast India, which has an ethnically distinct population, and was aimed to be addressed through this study. The study included 76 CaCx cases, 25 cervical intraepithelial neoplasia (CIN) cases, and 50 healthy female controls. HPV screening and genotyping were performed by PCR. Differential expression of tumor necrosis factor alpha (TNF-α) was studied at serum level by enzyme-linked immunosorbent assay and tissue level by immunohistochemistry and messenger RNA (mRNA) level by real-time PCR. The data were correlated with interferon gamma (IFN-γ) and NF-κβp65 levels at protein level, as well as HPV16 E6 and E7 expression at transcript level statistically. HPV infection and HPV16 genotype were predominant in the studied cohort. TNF-α was found to be downregulated at both mRNA and protein levels in CaCx cases compared to controls; and the gradient downregulation correlated with progression of the disease from normal→CIN→CaCx. TNF-α expression correlated with insufficient modulation of both IFN-γ and NF-κβp65. The HPV16 E6 and E7 transcripts were found to be sharply upregulated in CaCx cases strongly inversely correlated with the TNF-α expression. Significant role of TNF-α downregulation associated with insufficient IFN-γ and total NF-κβp65 modulation and the resulting significant upregulation of viral transcripts E6 and E7 are key to the HPV16 infection mediated CaCx pathogenesis in northeast Indian patients.

  19. Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-alpha in monocyte-derived macrophages.

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    Kim, Sung-Jo

    2010-06-01

    In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha production in differentiated THP-1 cells, a human monocytic cell line. LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-alpha and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Leptin enhanced P. intermedia LPS-induced TNF-alpha production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-alpha expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-alpha production was not mediated by the leptin receptor. The ability of leptin to enhance P. intermedia LPS-induced TNF-alpha production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

  20. Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

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    Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

    2009-11-01

    To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

  1. Ubiquitous hazardous metal lead induces TNF-{alpha} in human phagocytic THP-1 cells: Primary role of ERK 1/2

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    Khan, Mohd Imran [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Islam, Najmul [Department of Biochemistry, J.N Medical College, Aligarh Muslim University, Aligarh (India); Sahasrabuddhe, Amogh A. [Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow (India); Mahdi, Abbas Ali [Department of Biochemistry, C.S.M. Medical University, Lucknow (India); Siddiqui, Huma; Ashquin, Mohd [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Ahmad, Iqbal, E-mail: ahmadi@sify.com [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India)

    2011-05-15

    Induction of tumor necrosis factor-{alpha} (TNF-{alpha}) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-{alpha} is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-{alpha} induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-{alpha} m-RNA and protein secretion. Moreover, the stability of TNF-{alpha} m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-{alpha} m-RNA. However, SB 203580 partially inhibited production and stability of TNF-{alpha} m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-{alpha} m-RNA. Data tends to suggest that expression and stability of TNF-{alpha} induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

  2. Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

    Science.gov (United States)

    Rutault, K; Hazzalin, C A; Mahadevan, L C

    2001-03-02

    Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

  3. Effects of TNF-alpha on Endothelial Cell Collective Migration

    Science.gov (United States)

    Chen, Desu; Wu, Di; Helim Aranda-Espinoza, Jose; Losert, Wolfgang

    2013-03-01

    Tumor necrosis factor (TNF-alpha) is a small cell-signaling protein usually released by monocytes and macrophages during an inflammatory response. Previous work had shown the effects of TNF-alpha on single cell morphology, migration, and biomechanical properties. However, the effect on collective migrations remains unexplored. In this work, we have created scratches on monolayers of human umbilical endothelial cells (HUVECs) treated with 25ng/mL TNF-alpha on glass substrates. The wound healing like processes were imaged with phase contrast microscopy. Quantitative analysis of the collective migration of cells treated with TNF-alpha indicates that these cells maintain their persistent motion and alignment better than untreated cells. In addition, the collective migration was characterized by measuring the amount of non-affine deformations of the wound healing monolayer. We found a lower mean non-affinity and narrower distribution of non-affinities upon TNF-alpha stimulation. These results suggest that TNF-alpha introduces a higher degree of organized cell collective migration.

  4. TNF-{alpha} mediates the stimulation of sclerostin expression in an estrogen-deficient condition

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beom-Jun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Bae, Sung Jin [Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Sun-Young; Lee, Young-Sun; Baek, Ji-Eun; Park, Sook-Young [Asan Institute for Life Sciences, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Lee, Seung Hun [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Koh, Jung-Min, E-mail: jmkoh@amc.seoul.kr [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of); Kim, Ghi Su [Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Poongnap2-Dong, Seoul (Korea, Republic of)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Estrogen deprivation stimulates the bony sclerostin levels with reversal by estrogen. Black-Right-Pointing-Pointer TNF-{alpha} increases the activity and expression of MEF2 in UMR-106 cells. Black-Right-Pointing-Pointer TNF-{alpha} blocker prevents the stimulation of bony sclerostin expression by ovariectomy. Black-Right-Pointing-Pointer No difference in bony sclerostin expression between sham-operated and ovariectomized nude mice. -- Abstract: Although recent clinical studies have suggested a possible role for sclerostin, a secreted Wnt antagonist, in the pathogenesis of postmenopausal osteoporosis, the detailed mechanisms how estrogen deficiency regulates sclerostin expression have not been well-elucidated. Bilateral ovariectomy or a sham operation in female C57BL/6 mice and BALB/c nude mice was performed when they were seven weeks of age. The C57BL/6 mice were intraperitoneally injected with phosphate-buffered serum (PBS), 5 {mu}g/kg {beta}-estradiol five times per week for three weeks, or 10 mg/kg TNF-{alpha} blocker three times per week for three weeks. Bony sclerostin expression was assessed by immunohistochemistry staining in their femurs. The activity and expression of myocyte enhancer factors 2 (MEF2), which is essential for the transcriptional activation of sclerostin, in rat UMR-106 osteosarcoma cells were determined by luciferase reporter assay and western blot analysis, respectively. Bony sclerostin expression was stimulated by estrogen deficiency and it was reversed by estradiol supplementation. When the UMR-106 cells were treated with well-known, estrogen-regulated cytokines, only TNF-{alpha}, but not IL-1 and IL-6, increased the MEF2 activity. Consistently, TNF-{alpha} also increased the nuclear MEF2 expression. Furthermore, the TNF-{alpha} blocker prevented the stimulation of bony sclerostin expression by ovariectomy. We also found that there was no difference in sclerostin expression between ovariectomized

  5. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Nintasen, Rungrat [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Riches, Kirsten; Mughal, Romana S. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa [Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Turner, Neil A. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  6. Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women.

    Science.gov (United States)

    Tsiotra, P C; Tsigos, C; Yfanti, E; Anastasiou, E; Vikentiou, M; Psarra, K; Papasteriades, C; Raptis, S A

    2007-10-01

    Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMIwomen (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (pDM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (pDM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

  7. Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthritis.

    Science.gov (United States)

    Gonzalez-Gay, M A; Garcia-Unzueta, M T; Berja, A; Gonzalez-Juanatey, C; Miranda-Filloy, J A; Vazquez-Rodriguez, T R; de Matias, J M; Martin, J; Dessein, P H; Llorca, J

    2009-01-01

    The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, pghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

  8. Anti-TNF-alpha therapy for sight threatening uveitis.

    NARCIS (Netherlands)

    E.W. Lindstedt (Eric); G.S. Baarsma (Seerp); R.W.A.M. Kuijpers (Robert); P.M. van Hagen (Martin)

    2005-01-01

    textabstractAIM: To describe the effect of additional treatment with anti-TNF-alpha therapy in a case series of 13 patients with serious sight threatening uveitis. METHODS: 13 patients with serious sight threatening uveitis were included, of whom six had Behcet's disease, five had idiopathic

  9. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Plomgaard, P; Nielsen, A R; Fischer, C P

    2007-01-01

    AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle...... and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p ...) uptake (VO2/kg) in the diabetes group (p type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein...

  10. Prolactin, TNF alpha and nitric oxide expression in nitroso-N-methylurea-induced-mammary tumours

    Directory of Open Access Journals (Sweden)

    Vegh Irene

    2007-11-01

    Full Text Available Abstract Background The N-Nitrosomethylurea breast cancer model induced in rats is used for the study of carcinogenesis in mammary cancer, prostate, pancreas, etc. This model is very similar to human neoplastic disease. Methods The present experimental study was designed to assess whether metoclopramide administration has any effect on development of MNU-induced tumours, and evaluate the treatment of goserelin acetate on PRL, TNF alpha and NO expression. NMU was administered to female Wistar rats on 2 occasions (5 mg/100 g body w/rat. PRL and TNF alpha were performed by immune-assay. Nitric Oxide by semi automated-assay and ploidy analyses by flow cytometry. Results The administration of metoclopramide made the induction time shorter and increased the incidence and average of tumours per rat. Tumours development was inhibited by a goserelin chronic administration. The ploidy of adenocarcinoma was polyploid-aneuploid type (average S = 60%. It was higher basal PRL plasma levels in rats with NMU induced tumours than in basal controls without tumour (p Conclusion The increase of blood PRL levels in NMU-induced rats may be an indicator of a poor prognosis of mammary cancer evolution. The metoclopramide administration accelerates tumour growth. However goserelin administration achieves regression in tumour development associated to inhibition PRL, TNF alpha and NO expression.

  11. Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring.

    Science.gov (United States)

    Kačarević, Željka Perić; Grgić, Anđela; Šnajder, Darija; Bijelić, Nikola; Belovari, Tatjana; Cvijanović, Olga; Blažičević, Valerija; Radić, Radivoje

    2017-09-01

    Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages.

    Science.gov (United States)

    Takano, Tomomi; Hohdatsu, Tsutomu; Toda, Ayako; Tanabe, Maki; Koyama, Hiroyuki

    2007-07-20

    The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.

  13. Changes in serum tumor necrosis factor (TNF-alpha) with kami-shoyo-san administration in depressed climacteric patients.

    Science.gov (United States)

    Ushiroyama, Takahisa; Ikeda, Atsushi; Sakuma, Kou; Ueki, Minoru

    2004-01-01

    An herbal medicine (kampo) is widely used to prevent or treat climacteric symptoms. In order to investigate the potential involvement of tumor necrosis factor (TNF)-alpha in susceptibility to mood disorder in climacteric women and to clarify the relationship between immune function and the efficacy of herbal medicine, we compared serum TNF-alpha levels in two treated groups, with and without concurrent use of herbal medicine. This study included 113 consecutive depressed menopausal patients who visited the gynecological and psychosomatic medicine outpatient clinic of the Osaka Medical College Hospital in Japan. Fifty-eight patients were administered kami-shoyo-san according to the definition of above sho. In contrast, 55 patients who were different in sho of kami-shoyo-san were administered antidepressants. Hamilton Rating Scale for depression (HAM-D) scores were determined at baseline and 12 weeks after starting treatment (endpoint). TNF-alpha concentrations were analyzed before and after 12 weeks of treatment. Kami-shoyo-san significantly increased plasma concentrations of TNF-alpha after 12 weeks of treatment, to 17.22 +/- 6.13 pg/ml from a baseline level of 14.16 +/- 6.27 pg/ml (p = 0.048). The percent change in plasma concentration of TNF-alpha differed significantly between the kami-shoyo-san therapy group and the antidepressant therapy group at 4 weeks (12.0 +/- 7.8% and -1.22 +/- 0.25%, respectively, p emotional status via the central nervous system and may be regulated by herbal medicines, although the interactions are very complex.

  14. [Anti-TNF-alpha therapy in ulcerative colitis].

    Science.gov (United States)

    Lakatos, Péter László; Lakatos, László

    2008-05-18

    The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.

  15. Regulation of PGE2 signaling pathways and TNF-alpha signaling pathways on the function of bone marrow-derived dendritic cells and the effects of CP-25.

    Science.gov (United States)

    Li, Ying; Sheng, Kangliang; Chen, Jingyu; Wu, Yujing; Zhang, Feng; Chang, Yan; Wu, Huaxun; Fu, Jingjing; Zhang, Lingling; Wei, Wei

    2015-12-15

    This study was to investigate PGE2 and TNF-alpha signaling pathway involving in the maturation and activation of bone marrow dendritic cells (DCs) and the effect of CP-25. Bone marrow DCs were isolated and stimulated by PGE2 and TNF-alpha respectively. The markers of maturation and activation expressed on DCs, such as CD40, CD80, CD83, CD86, MHC-II, and the ability of antigen uptake of DCs were analyzed by flow cytometry. The proliferation of T cells co-cultured with DCs, the signaling pathways of PGE2-EP4-cAMP and TNF-alpha-TRADD-TRAF2-NF-κB in DCs were analyzed. The results showed that both PGE2 and TNF-alpha up-regulated the expressions of CD40, CD80, CD83, CD86, and MHC-II, decreased the antigen uptake of DCs, and DCs stimulated by PGE2 or TNF-alpha could increase T cell proliferation. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased significantly the expressions of CD40, CD80, CD83, CD86 and MHC-II, increased the antigen uptake of DCs, and suppressed T cell proliferation induced by DCs. PGE2 increased the expressions of EP4, NF-κB and down-regulated cAMP level of DCs. TNF-alpha could also up-regulate TNFR1, TRADD, TRAF2, and NF-κB expression of DCs. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) decreased the expressions of EP4 and NF-κB, increased cAMP level in DCs stimulated by PGE2. CP-25 (10(-5), 10(-6), and 10(-7)mol/l) also could down-regulate significantly TNFR1, TRADD, TRAF2, and NF-κB expression in DCs stimulated by TNF-alpha. These results demonstrate that PGE2 and TNF-alpha could enhance DCs functions by mediating PGE2-EP4-cAMP pathway, TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathway respectively. CP-25 might inhibit the function of DCs through regulating PGE2-EP4-cAMP and TNF-alpha-TNFR1-TRADD-TRAF2-NF-κB pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Expression of POEM, a positive regulator of osteoblast differentiation, is suppressed by TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Tsukasaki, Masayuki [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Aizawa, Ryo [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyazono, Agasa [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Miyamoto, Yoichi; Suzawa, Tetsuo; Takami, Masamichi; Yoshimura, Kentaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan); Morimura, Naoko [Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, 2-1-1 Kitasenzoku, Ohta, Tokyo 145-8515 (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555 (Japan)

    2011-07-15

    Highlights: {yields} TNF-{alpha} inhibits POEM gene expression. {yields} Inhibition of POEM gene expression is caused by NF-{kappa}B activation by TNF-{alpha}. {yields} Over-expression of POEM recovers inhibition of osteoblast differentiation by TNF-{alpha}. -- Abstract: POEM, also known as nephronectin, is an extracellular matrix protein considered to be a positive regulator of osteoblast differentiation. In the present study, we found that tumor necrosis factor-{alpha} (TNF-{alpha}), a key regulator of bone matrix properties and composition that also inhibits terminal osteoblast differentiation, strongly inhibited POEM expression in the mouse osteoblastic cell line MC3T3-E1. TNF-{alpha}-induced down-regulation of POEM gene expression occurred in both time- and dose-dependent manners through the nuclear factor kappa B (NF-{kappa}B) pathway. In addition, expressions of marker genes in differentiated osteoblasts were down-regulated by TNF-{alpha} in a manner consistent with our findings for POEM, while over-expression of POEM recovered TNF-{alpha}-induced inhibition of osteoblast differentiation. These results suggest that TNF-{alpha} inhibits POEM expression through the NF-{kappa}B signaling pathway and down-regulation of POEM influences the inhibition of osteoblast differentiation by TNF-{alpha}.

  17. Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308

    DEFF Research Database (Denmark)

    Skov, Lone; Allen, Michael H; Bang, Bo

    2003-01-01

    secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were...... compared. For the TNF--308 polymorphism there was significant association between the genotype or allele frequencies and having BCC. To determine whether patients with a previous BCC had an increased capacity to secrete TNF-alpha, mononuclear cells were stimulated with lipopolysaccharide. Mononuclear cells...... from patients with a previous BCC (n=15) demonstrated a significantly increased release of TNF-alpha upon stimulation with lipopolysaccharide (Pcells age-matched control subjects (n=16). Further studies of other polymorphisms of the TNF-alpha gene associated...

  18. Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

    Science.gov (United States)

    Merkac, Maja Ivartnik; Tomazic, Janez; Strle, Franc

    2015-12-01

    A 57-year-old woman, receiving TNF-alpha inhibitor adalimumab for psoriasis, presented with early Lyme neuroborreliosis (Bannwarth's syndrome). Discontinuation of adalimumab and 14-day therapy with ceftriaxone resulted in a smooth course and favorable outcome of Lyme borreliosis. This is the first report on Lyme neuroborreliosis in a patient treated with TNF-alpha inhibitor.

  19. [Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients].

    Science.gov (United States)

    Nicolas, P; Hovette, P; Merouze, F; Touze, J E; Martet, G

    1994-01-01

    Authors have studied TNF alpha, IL1 bêta, IL6 and RIL2s in 28 malaria illness patients. Increased levels of TNF, IL1 bêta and RIL2s in serum, are observed on admission to hospital. These cytokine levels are decreased, eight days later, after patients are treated. In discussion, TNF levels as a prognosis component is evocated.

  20. Evaluation of pGL1-TNF-alpha therapy in combination with radiation

    Science.gov (United States)

    Li, J.; Andres, M. L.; Fodor, I.; Nelson, G. A.; Gridley, D. S.

    1998-01-01

    Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. In this study a new plasmid-based human tumor necrosis factor-alpha (TNF-alpha) expression vector was synthesized (pGL1-TNF-alpha) and evaluated together with radiation in the aggressive, rapidly growing C6 rat glioma model. pGL1-TNF-alpha was successfully transfected into C6 cells in vitro using a cationic polyamine method. Expression was detected up to 7 days and averaged 0.4 ng of TNF-alpha in the culture medium from 1x10(5) cells. The expressed protein was biologically functional, as evidenced by growth inhibition of L929, a TNF-alpha-susceptible cell line. Using fluorescence-labeled monoclonal antibodies and laser scanning cytometry, we confirmed that both the P55 and P75 receptors for TNF-alpha were present on the C6 cell membrane. However, the receptors were present at low density and P55 was expressed more than the P75 receptor. These findings were in contrast to results obtained with TNF-alpha-susceptible L929 cells. Tests in athymic mice showed that pGL1-TNF-alpha administered intratumorally 16-18 h before radiation (each modality given three times) significantly inhibited C6 tumor progression (Palpha alone did not slow tumor growth and radiation alone had little effect on tumor growth. These results indicate that pGL1-TNF-alpha has potential to augment the antitumor effects of radiation against a tumor type that is virtually incurable.

  1. TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects.

    Science.gov (United States)

    Kamer, Angela R; Craig, Ronald G; Pirraglia, Elizabeth; Dasanayake, Ananda P; Norman, Robert G; Boylan, Robert J; Nehorayoff, Andrea; Glodzik, Lidia; Brys, Miroslaw; de Leon, Mony J

    2009-11-30

    The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

  2. Evidence for a positive correlation between serum cortisol levels and IL-1beta production by peripheral mononuclear cells in anorexia nervosa.

    Science.gov (United States)

    Limone, P; Biglino, A; Bottino, F; Forno, B; Calvelli, P; Fassino, S; Berardi, C; Ajmone-Catt, P; Bertagna, A; Tarocco, R P; Rovera, G G; Molinatti, G M

    2000-01-01

    A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in anorexia nervosa (AN), together with some immunological abnormalities, involving citokine - and particularly Tumor Necrosis-Factor-alpha (TNF-alpha) - production by polymorphonuclear cells. The ability of pro-inflammatory cytokines to activate the HPA axis is well known; however, there are no data demonstrating an interdependence between immunological and endocrine response in AN. To investigate the presence of a correlation between immune response and pituitary-adrenal function, plasma ACTH and serum cortisol concentrations were measured in 13 AN patients and in the same number of controls. TNF-alpha and interleukin (IL)-1beta production by ex-vivo unstimulated and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating cortisol concentrations were higher (p<0.01) in AN (156.7 +/- 45.1 microg/l, mean +/- SD) than in controls (105.9 +/- 25.7 microg/l). Unstimulated IL-1beta release in supernatants of mononuclear cell cultures was slightly but not significantly higher in AN than in controls, while TNF-alpha release was similar in the two groups. A positive correlation was found between IL-1beta concentrations in unstimulated culture supranatants and serum cortisol levels in AN (r=0.782, p=0.002), while in normal subjects there was a trend toward a negative correlation; a slight positive correlation, while not significant, between IL-1beta and plasma ACTH, as well as between TNF-alpha and serum cortisol was also found in AN. These data suggest that the normal relationship between pro-inflammatory cytokines release, particularly IL-1beta, and cortisol secretion is deranged in AN.

  3. TNF-alpha stimulates Akt by a distinct aPKC-dependent pathway in premalignant keratinocytes

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.

    2008-01-01

    , ERK1/2 and p38. The specific peptide blocking the activity of the atypical protein kinase C (aPKC) species zeta and iota/lambda abrogated the effects of TNF-alpha on Akt and ERK1/2 but increased the activation of p38. The TNF-alpha-dependent phosphorylation of Akt-ERK1/2 was slightly decreased by NF...

  4. In vitro secretion of TNF-{alpha} from bone marrow mononuclear cells incubated on amino group modified TiO{sub 2} nano-composite under ultrasound irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Furuzono, T., E-mail: furuzono@ri.ncvc.go.jp [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan); Masuda, M. [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan); Nitta, N.; Kaya, A.; Yamane, T. [Institute for Human Science and Biomedical Engineering, National Institute of Advanced Industrial Science and Technology, 1-2-1 Namiki, Tsukuba, Ibaraki, 305-8564 (Japan); Okada, M. [Department of Bioengineering, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565 (Japan)

    2010-10-15

    It is recently known that titanium dioxide (TiO{sub 2}) can be excited by ultrasound and release of OH radicals on the surface. In this study, secretion of an indirect angiogenic factor, tumor necrosis factor-{alpha} (TNF-{alpha}), from bone marrow mononuclear cells (BM-MNC) incubated on amino group modified TiO{sub 2} nano-particles covalently coated on polyester fabric (TiO{sub 2}/PET) under ultrasonic irradiation was examined in vitro. The cell viability and TNF-{alpha} secretion were measured under ultrasound irradiation condition with 255 mW/cm{sup 2} of intensity, which is below the highest output (1 W/cm{sup 2}) specified in the safety standard for a medical ultrasonic diagnostic apparatus. The living cell number on the TiO{sub 2}/PET and original PET with/without continuous ultrasound irradiation was unchanged statistically by ANOVA test. TNF-{alpha} secretion level from BM-MNC remarkably increased on the TiO{sub 2}/PET under ultrasonic irradiation without cell damage. It was, therefore, thought that the high level of TNF-{alpha} secretion on the TiO{sub 2} nano-composite by ultrasound irradiation was due to oxidative stress induced from OH radicals on TiO{sub 2}.

  5. Benfotiamine alleviates diabetes-induced cerebral oxidative damage independent of advanced glycation end-product, tissue factor and TNF-alpha.

    Science.gov (United States)

    Wu, Shan; Ren, Jun

    2006-02-13

    Diabetes mellitus leads to thiamine deficiency and multiple organ damage including diabetic neuropathy. This study was designed to examine the effect of benfotiamine, a lipophilic derivative of thiamine, on streptozotocin (STZ)-induced cerebral oxidative stress. Adult male FVB mice were made diabetic with a single injection of STZ (200 mg/kg, i.p.). Fourteen days later, control and diabetic (fasting blood glucose >13.9 mM) mice received benfotiamine (100 mg/kg/day, i.p.) for 14 days. Oxidative stress and protein damage were evaluated by glutathione/glutathione disulfide (GSH/GSSG) assay and protein carbonyl formation, respectively. Pro-oxidative or pro-inflammatory factors including advanced glycation end-product (AGE), tissue factor and tumor necrosis factor-alpha (TNF-alpha) were evaluated by immunoblot analysis. Four weeks STZ treatment led to hyperglycemia, enhanced cerebral oxidative stress (reduced GSH/GSSG ratio), elevated TNF-alpha and AGE levels without changes in protein carbonyl or tissue factor. Benfotiamine alleviated diabetes-induced cerebral oxidative stress without affecting levels of AGE, protein carbonyl, tissue factor and TNF-alpha. Collectively, our results indicated benfotiamine may antagonize diabetes-induced cerebral oxidative stress through a mechanism unrelated to AGE, tissue factor and TNF-alpha.

  6. Protective specific immunity induced by doxorubicin plus TNF-alpha combination treatment of EL4 lymphoma-bearing C57BL/6 mice.

    Science.gov (United States)

    Ehrke, M J; Verstovsek, S; Maccubbin, D L; Ujházy, P; Zaleskis, G; Berleth, E; Mihich, E

    2000-07-01

    The therapeutic efficacy of a single (day 8), moderate dose (4 mg/kg, i.v.) of doxorubicin (DOX, Adriamycin) combined with recombinant human TNF-alpha (3 different doses and 5 different schedules, i.v.) was evaluated in C57BL/6 mice bearing an implant (s.c.) of the DOX-sensitive, TNF-alpha-resistant EL4 lymphoma. In parallel to monitoring survival, the levels of several host anti-tumor cytolytic effector functions of splenocytes and thymocytes were evaluated throughout the treatment period and in long-term survivors (LTS). DOX treatment alone resulted in a moderate (approx. 20%) increase in life span but no cures. TNF-alpha alone, at any tested dose or schedule, had little or no positive effect on survival. The combinations of DOX and TNF-alpha were only slightly better than DOX alone with respect to the time to death of mice that died (approx. 29% increase); however, each of the combinations involving 1,000 U TNF-alpha/injection produced a fraction (20% to 80%) of LTS. The host defense activities examined included those of splenic and thymic cytolytic T lymphocytes (CTL) and lymphokine-activated killer cells as well as splenic tumoricidal macrophages. Although most activities were modulated by tumor growth and/or treatment, only CTL responsiveness appeared to correlate with survival. CTL activity in the treated groups with LTS was significantly higher than in control groups late in the treatment period. Finally, ex vivo analyses of splenocytes and thymocytes together with the rejection of implanted tumor at 17 months established that LTS displayed specific long-term immune memory. Copyright 2000 Wiley-Liss, Inc.

  7. Acute moderate elevation of TNF-{alpha} does not affect systemic and skeletal muscle protein turnover in healthy humans

    DEFF Research Database (Denmark)

    Petersen, Anne Marie; Plomgaard, Peter; Fischer, Christian P

    2009-01-01

    -alpha infusion (rhTNF-alpha). We hypothesize that TNF-alpha increases human muscle protein breakdown and/or inhibit synthesis. Subjects and Methods: Using a randomized controlled, crossover design post-absorptive healthy young males (n=8) were studied 2 hours under basal conditions followed by 4 hours infusion...... with the phenylalanine 3-compartment model showed similar muscle synthesis, breakdown and net muscle degradation after 2 hours basal and after 4 hours Control or rhTNF-alpha infusion. Conclusion: This study is the first to show in humans that TNF-alpha does not affect systemic and skeletal muscle protein turnover, when......Context: Skeletal muscle wasting has been associated with elevations in circulating inflammatory cytokines, in particular TNF-alpha. Objective: In this study, we investigated whether TNF-alpha affects human systemic and skeletal muscle protein turnover, via a 4 hours recombinant human TNF...

  8. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  9. TNF-alpha impairs the S-G2/M cell cycle checkpoint and cyclobutane pyrimidine dimer repair in premalignant skin cells: Role of the PI3K-Akt pathway

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.; Calay, D.

    2008-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is induced by UVB radiation and has been implicated in the early stages of skin carcinogenesis. Here, we show that in normal keratinocytes and the transformed keratinocyte cell lines, HaCaT and A431, TNF-alpha stimulates protein kinase B/Akt, which results...... cycling. TNF-alpha enhanced apoptosis less potently and did not increase the level of CPD or stimulate cell cycle progression in normal keratinocytes. Our data suggest that TNF-alpha overrides the G2/M checkpoint in premalignant skin cells and allows for some cells containing unrepaired CPD to enter...... in activation of the survival complex mTORC1 (mammalian target of rapamycin complex 1) and inhibition of the proapoptotic proteins Bad and Fox03a. In UVB-irradiated HaCaT cells (10-20 mJ cm(-2)), TNF-alpha increased the proportion of cycling cells and enhanced the rate of apoptosis. A significantly higher...

  10. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Directory of Open Access Journals (Sweden)

    Nicolaos Vitoratos

    2006-01-01

    Full Text Available The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β, tumor necrosis factor alpha (TNF-alpha, and Th2-type cytokine interleukin 6 (IL-6 were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1 and discharge (group B2 and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  11. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Science.gov (United States)

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome. PMID:17047289

  12. Elevated Circulating IL-1 β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1 β (IL-1 β , tumor necrosis factor alpha (TNF-alpha, and Th2-type cytokine interleukin 6 (IL-6 were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1 and discharge (group B2 and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1 β and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1 β , TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  13. Elevated circulating IL-1beta and TNF-alpha, and unaltered IL-6 in first-trimester pregnancies complicated by threatened abortion with an adverse outcome.

    Science.gov (United States)

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome at admission (group B1) and discharge (group B2) and 22 gestational age-matched women with first-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare differences between groups. IL-1beta and TNF-alpha were detected with significantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels were detected with no significant difference among all the other groups studied. It is concluded that in first-trimester TACP with adverse outcome, a distinct immune response, as reflected by elevated maternal IL-1beta, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome.

  14. Off-label use of TNF-alpha inhibitors in a dermatological university department

    DEFF Research Database (Denmark)

    Sand, Freja Lærke; Thomsen, Simon Francis

    2015-01-01

    (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF-alpha inhibitors. A total of 11 patients (9%) experienced severe adverse......-alpha inhibitors for these conditions....

  15. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Nordgaard-Lassen, Inge; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X...

  16. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

    Science.gov (United States)

    Henness, Sheridan; van Thoor, Eveline; Ge, Qi; Armour, Carol L; Hughes, J Margaret; Ammit, Alaina J

    2006-06-01

    Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

  17. Frequency of distribution of inflammatory cytokines IL-1, IL-6 and TNF-alpha gene polymorphism in patients with obstructive sleep apnea.

    Science.gov (United States)

    Popko, K; Gorska, E; Potapinska, O; Wasik, M; Stoklosa, A; Plywaczewski, R; Winiarska, M; Gorecka, D; Sliwinski, P; Popko, M; Szwed, T; Demkow, U

    2008-12-01

    Obesity is one of the most commonly identified factors for the obstructive sleep apnea syndrome (OSAS). Adipose tissue is the source of many cytokines, among them there are IL-6, IL-1, and TNF-alpha. The level of inflammatory cytokines increases in people with OSAS and obesity. The aim of this study was to evaluate the distribution of genotypes in inflammatory cytokine genes in people with obesity-related OSAS. The examined group consisted of 102 person with obesity related-OSAS and 77 normal weight person without OSAS. Genotyping of DNA sequence variation was carried out by restriction enzyme (IL-1: Taq I, IL-6: Lwe I, TNF-alpha: Nco I) analysis of PCR amplified DNA. The study revealed a significant correlation between polymorphism located in the promoter region of inflammatory cytokine genes and obesity-related OSAS.

  18. Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.

    Science.gov (United States)

    Futaki, M; Watanabe, S; Kajigaya, S; Liu, J M

    2001-02-23

    Fanconi anemia (FA) is a genetic syndrome characterized by bone marrow failure, birth defects, and a predisposition to malignancy. At this time, six FA genes have been identified, and several gene products have been found to interact in a protein complex. FA cells appear to overexpress the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). We therefore examined the effects of TNF-alpha on the regulation of FA complementation group proteins, FANCG and FANCA. We found that treatment with TNF-alpha induced FANCG protein expression. FANCA was induced concurrently with FANCG, and the FANCA/FANCG complex was increased in the nucleus following TNF-alpha treatment. Inactivation of inhibitory kappa B kinase-2 modulated the expression of FANCG. We also found that both nuclear and cytoplasmic FANCG fractions were phosphorylated. These results show that FANCG is a phosphoprotein and suggest that the cellular accumulation of FA proteins is subject to regulation by TNF-alpha signaling.

  19. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    Science.gov (United States)

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  20. Relationship between vagal tone, cortisol, TNF-alpha, epinephrine and negative affects in Crohn's disease and irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Sonia Pellissier

    Full Text Available Crohn's disease (CD and irritable bowel syndrome (IBS involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls. The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients. The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI and depressive symptoms (CES-D. After 30 min of rest, ECG was recorded for heart rate variability (HRV analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r =  -0.48; p<0.05 was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r =  -0.39; p<0.05. No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

  1. TNF-alpha-308G>A polymorphism and the risk of familial CAD in a Pakistani population.

    Science.gov (United States)

    Hussain, Sabir; Iqbal, Tahir; Javed, Qamar

    2015-01-01

    A case-control and trio-families study was performed to establish a potential association between TNF-alpha gene promoter SNPs at -308 and -238, and occurrence of CAD in a Pakistani population. In the first phase, 150 patients and 150 controls were enrolled in the case-control association study. In the second phase, heritability of susceptible alleles was investigated from 88 trio-families with CAD affected offspring. Biochemical analysis of lipids and hs-CRP was carried out spectrophotometrically, while serum TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Genotyping of the TNF-alpha SNPs were determined by PCR-RFLP method. Elevated serum TNF-alpha and hs-CRP were observed from CAD vs. controls (PA polymorphism in case-control study revealed that the said SNP was significantly associated with the increased risk of CAD. The findings demonstrated a significant link between the TNF-alpha variant allele A at -308 and CAD (P=0.0035), whereas the -238 SNP was not associated with the disease. Haplotype A-G of the TNF-alpha gene at -308G>A and -238G>A showed higher frequency in the patient group compared with controls (PA polymorphism is associated with CAD in the study population. Furthermore, for the first time, we showed that the TNF-alpha-308A allele was significantly associated with the familial CAD in our high risk population. Copyright © 2014. Published by Elsevier Inc.

  2. Generation, characterization and therapeutic potential of anti-feline TNF-alpha MAbs for feline infectious peritonitis.

    Science.gov (United States)

    Doki, Tomoyoshi; Takano, Tomomi; Nishiyama, Yuri; Nakamura, Michiyo; Hohdatsu, Tsutomu

    2013-12-01

    Feline infectious peritonitis (FIP) is a lethal infectious disease affecting domestic and wild cats. Several reports suggested that TNF-alpha is related to the progression of FIP. Thus, the administration of a feline TNF-alpha-neutralizing antibody to cats with FIP may reduce the disease progression. In this study, we have prepared nine monoclonal antibodies (MAbs) that recognize feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha were 5-684 ng/ml. MAb 2-4 exhibited high neutralizing activity against natural TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit the following feline TNF-alpha-induced conditions in vitro: (i) an increase in the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN) mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell line. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Suppression of TNF-alpha production by S-adenosylmethionine in human mononuclear leukocytes is not mediated by polyamines

    DEFF Research Database (Denmark)

    Yu, J.; Parlesak, Alexandr; Sauter, S.

    2006-01-01

    precursors or metabolites [phosphatidylcholine, choline, betaine, S-adenosylmethionine (SAM)] have a modulating effect on tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated human mononuclear leukocytes and whether SAM-dependent polyamines (spermidine, spermine) are mediators of SAM......-induced inhibition of TNF-alpha synthesis. Methionine and betaine had a moderate stimulatory effect on TNF-alpha production, whereas phosphatidylcholine (ID(50) 5.4 mM), SAM (ID(50) 131 microM), spermidine (ID(50) 4.5 microM) and spermine (ID(50) 3.9 microM) had a predominantly inhibitory effect. Putrescine did...

  4. In whole blood, LPS, TNF-alpha and GM-CSF increase monocyte uptake of {sup 99m}technetium stannous colloid but do not affect neutrophil uptake

    Energy Technology Data Exchange (ETDEWEB)

    Ramsay, Stuart C. [Townsville Nuclear Medicine, Mater Hospital, Pimlico, Queensland 4812 (Australia) and School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)]. E-mail: stuart.ramsay1@jcu.edu.au; Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Powell, Kellie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia); Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland 4811 (Australia)

    2006-07-15

    Introduction: {sup 99m}Technetium stannous colloid (TcSnC) is used in white cell scanning. It labels neutrophils and monocytes via phagocytosis, with uptake mediated by the phagocytic receptor CD11b/CD18 in neutrophils. Uptake of TcSnC is altered by gram-negative infection, possibly due to the endotoxin component lipopolysaccharide (LPS) or to cytokines released during infection (e.g., TNF-alpha and IFN-gamma). Endotoxemia and increased TNF-alpha levels also occur in inflammatory bowel disease. Another potential confounder in cell labeling is that sepsis patients may be treated with GM-CSF and G-CSF, which alter phagocytic cell function. This study aimed to determine how these factors affect TcSnC cellular uptake. Methods: Whole blood from six healthy volunteers was incubated with LPS, TNF-alpha, IFN-gamma, GM-CSF or G-CSF. Samples were then mixed with TcSnC. Blood was separated across density gradients and imaged using a gamma camera. Three radioactive count peaks were observed in each tube: free plasma activity, mononuclear cell uptake and neutrophil uptake. Results: Compared with controls, significant increases in mononuclear cell uptake were induced by LPS, TNF-alpha and GM-CSF stimulation. It was incidentally noted that exogenous estrogens appear to affect TcSnC labeling and may influence the neutrophil response to stimulation. Neutrophil uptake and plasma activity were not significantly affected. IFN-gamma and G-CSF had no significant effect. Conclusions: In whole blood, the effect of LPS on TcSnC monocyte uptake is different to its effect on neutrophils, consistent with previously reported differences in CD11b/CD18 expression. TNF-alpha response parallels LPS response. GM-CSF also increases TcSnC uptake by monocytes. These effects should be considered when using TcSnC for imaging purposes, as they will tend to increase monocyte labeling. Estrogens may also affect TcSnC labeling. Responses to IFN-gamma and G-CSF are consistent with previously reported effects

  5. The discovery of novel tartrate-based TNF-[alpha] converting enzyme (TACE) inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rosner, Kristin E.; Guo, Zhuyan; Orth, Peter; Shipps, Jr., Gerald W.; Belanger, David B.; Chan, Tin Yau; Curran, Patrick J.; Dai, Chaoyang; Deng, Yongqi; Girijavallabhan, Vinay M.; Hong, Liwu; Lavey, Brian J.; Lee, Joe F.; Li, Dansu; Liu, Zhidan; Popovici-Muller, Janeta; Ting, Pauline C.; Vaccaro, Henry; Wang, Li; Wang, Tong; Yu, W.; Zhou, G.; Niu, X.; Sun, J.; Kozlowski, J.A.; Lundell, D.J.; Madison, V.; McKittrick, B.; Piwinski, J.J.; Shih, N.Y.; Siddiqui, M. Arshad; Strickland, Corey O. (SPRI)

    2010-09-17

    A novel series of TNF-{alpha} convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.

  6. Rocky Mountain Spotted Fever in a patient treated with anti-TNF-alpha inhibitors.

    Science.gov (United States)

    Mays, Rana M; Gordon, Rachel A; Durham, K Celeste; LaPolla, Whitney J; Tyring, Stephen K

    2013-03-15

    Rocky Mountain Spotted Fever (RMSF) is a tick-bourne illness, which can be fatal if unrecognized. We discuss the case of a patient treated with an anti-TNF-alpha inhibitor for rheumatoid arthritis who later developed a generalized erythematous macular eruption accompanied by fever. The clinical findings were suggestive of RMSF, which was later confirmed with serology. Prompt treatment with doxyclycine is recommended for all patients with clinical suspicion of RMSF.

  7. Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

    Science.gov (United States)

    Zou, Jing; Pyykkö, Ilmari; Sutinen, Päivi; Toppila, Esko

    2005-04-01

    Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry. Transcranial vibration caused expression of TNF-alpha, TNF R1 and TNF R2 in the cochlea and the expression of TNF R2 was stronger than that of TNF R1. Vibration also induced VEGF and VEGF R2 expression in the cochlea. The average immediate hearing loss was 62 dB and after three days still 48 dB. It is concluded that transcranial vibration as during temporal bone drilling produces cochlear shear stress that is connected with up-regulation of TNF-alpha and its receptors. Also VEGF and VEGF R2 are up-regulated. These responses may be linked to both the damage and repair process of the cochlea.

  8. Thy-1 attenuates TNF-alpha-activated gene expression in mouse embryonic fibroblasts via Src family kinase.

    Directory of Open Access Journals (Sweden)

    Bin Shan

    Full Text Available Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-alpha. Our study demonstrates distinct profiles of TNF-alpha-activated gene expression in Thy-1 positive (Thy-1+ and negative (Thy-1- subsets of mouse embryonic fibroblasts (MEF. TNF-alpha induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1- MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1- MEFs significantly attenuated TNF-alpha-activated gene expression. Mechanistically, TNF-alpha activated Src family kinase (SFK only in Thy-1- MEFs. Blockade of SFK activation abrogated TNF-alpha-activated gene expression in Thy-1- MEFs, whereas restoration of SFK activation rescued the TNF-alpha response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-alpha-activated gene expression via interfering with SFK- and NF-kappaB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation.

  9. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans

    DEFF Research Database (Denmark)

    Starkie, Rebecca; Ostrowski, Sisse Rye; Jauffred, Sune

    2003-01-01

    and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli...... exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced...

  10. Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome

    OpenAIRE

    Vitoratos, Nicolaos; Papadias, Constantinos; Economou, Emmanuel; Makrakis, Evangelos; Panoulis, Constantinos; Creatsas, George

    2006-01-01

    The purpose of the present study was to examine the profile of selected proinflammatory cytokines in maternal serum of first-trimester pregnancies complicated by threatened abortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1-type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding...

  11. Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

    Science.gov (United States)

    Porter, M H; Hrupka, B J; Altreuther, G; Arnold, M; Langhans, W

    2000-12-01

    Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

  12. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    Science.gov (United States)

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  13. [G-protein potentiates the activation of TNF-alpha on calcium-activated potassium channel in ECV304].

    Science.gov (United States)

    Lin, L; Zheng, Y; Qu, J; Bao, G

    2000-06-01

    Observe the effect of tumor necrosis factor-alpha (TNF-alpha) on calcium-activated potassium channel in ECV304 and the possible involvement of G-protein mediation in the action of TNF-alpha. Using the cell-attached configuration of patch clamp technique. (1) the activity of high-conductance calcium-activated potassium channel (BKca) was recorded. Its conductance is (202.54 +/- 16.62) pS; (2) the activity of BKca was potentiated by 200 U/ml TNF-alpha; (3) G-protein would intensify this TNF-alpha activation. TNF-alpha acted on vascular endothelial cell ECV304 could rapidly activate the activity of BKca. Opening of BKca resulted in membrane hyper-polarization which could increase electro-chemical gradient for the resting Ca2+ influx and open leakage calcium channel, thus resting cytoplasmic free Ca2+ concentration could be elevated. G-protein may exert an important regulation in this process.

  14. Beneficial effects of combined benazepril-amlodipine on cardiac nitric oxide, cGMP, and TNF-alpha production after cardiac ischemia.

    Science.gov (United States)

    Siragy, Helmy M; Xue, Chun; Webb, Randy L

    2006-05-01

    The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3',5'-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-alpha (TNF-alpha) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P Benazepril or amlodipine significantly increased NOX levels (P benazepril significantly increased cGMP (P benazepril-amlodipine further increased CIF NOX and cGMP (P benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-alpha (P benazepril-amlodipine may be beneficial for managing cardiac ischemia.

  15. Early inflammatory response in rat brain after peripheral thermal injury.

    Science.gov (United States)

    Reyes, Raul; Wu, Yimin; Lai, Qin; Mrizek, Michael; Berger, Jamie; Jimenez, David F; Barone, Constance M; Ding, Yuchuan

    2006-10-16

    Previous studies have shown that the cerebral complications associated with skin burn victims are correlated with brain damage. The aim of this study was to determine whether systemic thermal injury induces inflammatory responses in the brain. Sprague Dawley rats (n=28) were studied in thermal injury and control groups. Animals from the thermal injury (n=14) and control (n=14) group were anesthetized and submerged to the neck vertically in 85 degrees C water for 6 s producing a third degree burn affecting 60-70% of the animal body surface area. The controls were submerged in 37 degrees C water for 6 s. Early expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and intracellular cell adhesion molecules (ICAM-1) protein levels in serum were determined at 3 (n=7) and 7 h (n=7) by enzyme-linked immunoabsorbent assay (ELISA). mRNA of TNF-alpha, IL-1beta, and ICAM-1 in the brain was measured at the same time points with a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). An equal animal number was used for controls. Systemic inflammatory responses were demonstrated by dramatic up-regulations (5-50 fold) of TNF-alpha, IL-1beta, and ICAM-1 protein level in serum at 7 h after the thermal injury. However, as early as 3 h after peripheral thermal injury, a significant increase (3-15 fold) in mRNA expression of TNF-alpha, IL-1beta and ICAM-1 was observed in brain homogenates, with increased levels remaining at 7 h after injury. This study demonstrated an early inflammatory response in the brain after severe peripheral thermal injury. The cerebral inflammatory reaction was associated with expression of systemic cytokines and an adhesion molecule.

  16. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  17. ArF excimer laser modulation of TNF-alpha and gelatinase B in NIH 3T3 cells

    International Nuclear Information System (INIS)

    Naudy-Vives, C.; Courant, D.; Perot, J.C.; Garcia, J.; Fretier, P.; Court, L.; Dormont, D.

    1995-01-01

    The effects on TNF-alpha and gelatinase B activity in mammalian cells induced by 193 nm argon fluoride excimer laser have been investigated. The data show that a secretion of 92 kDa type IV collagenase and TNF-alpha were increased in cell culture supernatants. Moreover, the 193 nm laser radiation produces a decrease of cell proliferation and an increase of cell activation 8 hours after irradiation. The total protein amount increases with the delivered dose. Same, but less effects were obtained after exposure to a conventional UV lamp at 254 nm. (author)

  18. CD44 and Bak expression in IL-6 or TNF-alpha gene knockout mice after whole lung irradiation

    International Nuclear Information System (INIS)

    Sakai, Minako; Iwakawa, Mayumi; Ohta, Toshie; Tsujii, Hirohiko; Imai, Takashi; Iwakura, Yoichiro

    2008-01-01

    To understand the molecular mechanisms that underlie radiation pneumonitis, we examined whether knockout of the tumor necrosis factor (TNF) or the interleukin (IL)-6 gene could give mice an inherent resistance to radiation in the acute phase of alveolar damage after thoracic irradiation. The temporal expression of inflammation (CD44) and apoptosis (Bak) markers in lung after thoracic irradiation was measured to determine the degree of alveolar damage. At 4 weeks post-irradiation (10 Gy), small inflammatory foci were observed in all mice, but there were no obvious histological differences between control (C57BL/6JSlc), TNF-alpha knockout (TNF KO), and IL-6 knockout (IL-6 KO) mice. However, immunohistochemical analysis of CD44 and Bak expression over a time course of 2 weeks highlighted significant differences between the three groups. C57BL/6JSlc and TNF KO mice had increased numbers of both CD44-positive and Bak-positive cells after irradiation, while the IL-6 KO mice showed stable levels of CD44 and Bak. In conclusion, the radioresistant status of IL-6 KO mice in the acute phase of alveolar damage after irradiation suggested an important role for IL-6 in radiation pneumonitis. (author)

  19. Role of golimumab, a TNF-alpha inhibitor, in the treatment of the psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Melissa A Michelon

    2010-05-01

    Full Text Available Melissa A Michelon1, Alice B Gottlieb1,21Tufts University School of Medicine, 2Department of Dermatology, Tufts Medical Center, Boston, MA, USAAbstract: Psoriatic arthritis (PsA is an inflammatory arthritis that affects many psoriasis patients and can often have a debilitating disease progression. Golimumab is a new tumor necrosis factor (TNF antagonist recently approved by the FDA for controlling signs and symptoms of psoriatic arthritis. In a Phase III clinical trial in patients with PsA, patients receiving golimumab showed significant improvement in the signs and symptoms of disease. It was usually well tolerated, but adverse events generally occurred more in patients receiving golimumab compared to placebo. Golimumab has also recently shown efficacy in slowing structural damage in PsA. This new biologic therapy provides physicians with another option in the treatment of this inflammatory arthritis while offering patients certain advantages over other TNF antagonists.Keywords: golimumab, psoriatic arthritis, TNF-alpha inhibitor

  20. Drug-Induced Endoplasmic Reticulum and Oxidative Stress Responses Independently Sensitize Toward TNF alpha-Mediated Hepatotoxicity

    NARCIS (Netherlands)

    Fredriksson, Lisa; Wink, Steven; Herpers, Bram; Benedetti, Giulia; Hadi, Mackenzie; de Bont, Hans; Groothuis, Geny; Luijten, Mirjam; Danen, Erik; de Graauw, Marjo; Meerman, John; van de Water, Bob

    Drug-induced liver injury (DILI) is an important clinical problem. Here, we used a genomics approach to in detail investigate the hypothesis that critical drug-induced toxicity pathways act in synergy with the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) to cause cell death of

  1. TNF alpha induces ABCA1 through NF-kappa B in macrophages and in phagocytes ingesting apoptotic cells

    NARCIS (Netherlands)

    Gerbod-Giannone, Marie-Christine; Li, Yankun; Holleboom, Adriaan; Han, Seongah; Hsu, Li-Chung; Tabas, Ira; Tall, Alan R.

    2006-01-01

    Recent evidence suggests that tumor necrosis factor alpha (TNF alpha) signaling in vascular cells can have antiatherogenic consequences, but the mechanisms are poorly understood. TNFa is released by free cholesterol loaded apoptotic macrophages, and the clearance of these cells by phagocytic

  2. Common TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis

    DEFF Research Database (Denmark)

    Jessen, Kirstine Marie; Lindboe, Sarah Bjerre; Petersen, Anncatrine Luisa

    2007-01-01

    consecutive adult patients with culture proven Gram negative bacteremia admitted to a Danish hospital between 2000 and 2002. Analysis for commonly described SNPs of tumor necrosis-alpha, (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator-1 (PAI-1), urokinase plasminogen activator (uPA), CD14...... hazard regression analysis, increasing age, polymicrobial infection and haemoglobin levels were associated with in-hospital mortality. CONCLUSION: We did not find any association between TNF-alpha, IL-1 beta, PAI-1, uPA, CD14 and TLR4 polymorphisms and outcome of Gram negative sepsis. Other host factors...... appear to be more important than the genotypes studied here in determining the severity and outcome of Gram negative sepsis....

  3. Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz; Nielsen, J.; Qvist, N.

    2013-01-01

    BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-alpha) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-alpha agents on post-operative outcomes 30 and 6...

  4. NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1989-01-01

    The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5...

  5. Intratumoral IL-12 and TNF-alpha-loaded microspheres lead to regression of breast cancer and systemic antitumor immunity.

    Science.gov (United States)

    Sabel, Michael S; Skitzki, Joseph; Stoolman, Lloyd; Egilmez, Nejat K; Mathiowitz, Edith; Bailey, Nicola; Chang, Wen-Jian; Chang, Alfred E

    2004-02-01

    Local, sustained delivery of cytokines at a tumor can enhance induction of antitumor immunity and may be a feasible neoadjuvant immunotherapy for breast cancer. We evaluated the ability of intratumoral poly-lactic-acid-encapsulated microspheres (PLAM) containing interleukin 12 (IL-12), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) in a murine model of breast cancer to generate a specific antitumor response. BALB/c mice with established MT-901 tumors underwent resection or treatment with a single intratumoral injection of PLAM containing IL-12, TNF-alpha, or GM-CSF, alone or in combination. Two weeks later, lymph nodes and spleens were harvested, activated with anti-CD3 monoclonal antibodies (mAb) and rhIL-2, and assessed for antitumor reactivity by an interferon gamma (IFNgamma) release assay. Tumor-infiltrating lymphocyte (TIL) analysis was performed on days 2 and 5 after treatment by mechanically processing the tumors to create a single cell suspension, followed by three-color fluorescence-activated cell sorter (FACS) analysis. Intratumoral injection of cytokine-loaded PLAM significantly suppressed tumor growth, with the combination of IL-12 and TNF-alpha leading to increased infiltration by polymorphonuclear cells and CD8+ T-cells in comparison with controls. The induction of tumor-specific reactive T-cells in the nodes and spleens, as measured by IFN-gamma production, was highest with IL-12 and TNF-alpha. This treatment resulted in resistance to tumor rechallenge. A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

  6. Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus

    DEFF Research Database (Denmark)

    Banner, Jytte; Smith, H; Sweet, C

    1993-01-01

    Previous work with a neonatal ferret model for human SIDS had indicated that inflammation caused by a combination of influenza virus and bacterial endotoxin may be a cause of human SIDS. To determine whether cytokines may be involved in this inflammatory response, levels of interleukin (IL)-1 beta......, IL-6 and tumour necrosis factor (TNF)-alpha were examined, using ELISA assays, in culture supernatants of human peripheral blood leucocytes infected with influenza virus and subsequently incubated with endotoxin. Levels of TNF-alpha were increased compared to cells incubated with virus or endotoxin...... alone. Levels of IL-1 beta were also increased whereas levels of IL-6 were generally not enhanced. Cytokines appeared within 1-2 h of stimulation with virus or endotoxin and increased subsequently to reach maximum titres between 16 and 20 h post treatment. While levels of cytokine were much lower when...

  7. Induced expression of mRNA for IL-5, IL-6, TNF-alpha, MIP-2 and IFN-gamma in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A.

    Science.gov (United States)

    Williams, C M; Coleman, J W

    1995-10-01

    We examined the capacity of purified rat peritoneal connective tissue-type mast cells (PMC) to express mRNA for several cytokines. Stimulation of PMC with anti-IgE for 4 hr induced the expression of mRNA encoding interleukin-5 (IL-5), IL-6, tumour necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Unstimulated PMC expressed detectable mRNA for TNF-alpha but not for the other four cytokines. Incubation of PMC with cyclosporin A (CsA) or dexamethasone (DEX), each at 10(-6) M for 24 hr, significantly inhibited the induced expression of mRNA for each of the five cytokines, and also inhibited release of biologically active TNF-alpha. Throughout these experiments mRNA levels of the housekeeping gene G3PDH were not altered by stimulation with anti-IgE or incubation with CsA or DEX. We conclude that immunological activation of rat PMC induces gene expression of several cytokines and that expression of these genes can be inhibited by immunosuppressive drugs.

  8. Impaired CD40L signaling is a cause of defective IL-12 and TNF-alpha production in Sézary syndrome: circumvention by hexameric soluble CD40L.

    Science.gov (United States)

    French, Lars E; Huard, Bertrand; Wysocka, Maria; Shane, Ryan; Contassot, Emmanuel; Arrighi, Jean-François; Piguet, Vincent; Calderara, Silvio; Rook, Alain H

    2005-01-01

    Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma characterized by peripheral blood involvement, impaired cell-mediated immunity, and T-helper 1 (TH1) cytokine production. To understand the mechanism of these defects, we studied the expression and function of CD40L in peripheral blood mononuclear cells (PBMCs) of patients with SzS. We found that PBMCs of patients with SzS have a defect in interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production upon anti-CD3 stimulation and that tumor CD4+ T lymphocytes have a specific defect in CD40L induction after anti-CD3 ligation in vitro. This defect may explain the poor IL-12 production, because IL-12 production by anti-CD3-stimulated PBMCs was dependent on CD40L in healthy donors. The observed defect in tumor cell CD40L expression appears to be due to inappropriate T-cell signaling upon CD3 ligation, because expression of other T-cell activation antigens such as CD25, and to a lesser extent CD69, are also impaired on tumor cells. Importantly however, the inability of SzS PBMCs to appropriately produce IL-12 and TNF-alpha could be restored by recombinant hexameric CD40L. Taken together, our results demonstrate that impaired IL-12 and TNF-alpha production in SzS is associated with defective CD4+ T lymphocyte CD40L induction and indicate that CD40L may have therapeutic potential in SzS.

  9. Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

    Science.gov (United States)

    Pellissier, Sonia; Dantzer, Cécile; Mondillon, Laurie; Trocme, Candice; Gauchez, Anne-Sophie; Ducros, Véronique; Mathieu, Nicolas; Toussaint, Bertrand; Fournier, Alicia; Canini, Frédéric; Bonaz, Bruno

    2014-01-01

    Crohn’s disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8∶00 AM and 10∶00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = −0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = −0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases. PMID

  10. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems.

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    Vassiliou, Evros K; Gonzalez, Andres; Garcia, Carlos; Tadros, James H; Chakraborty, Goutam; Toney, Jeffrey H

    2009-06-26

    Chronic inflammation is a key player in pathogenesis. The inflammatory cytokine, tumor necrosis factor-alpha is a well known inflammatory protein, and has been a therapeutic target for the treatment of diseases such as Rheumatoid Arthritis and Crohn's Disease. Obesity is a well known risk factor for developing non-insulin dependent diabetes melitus. Adipose tissue has been shown to produce tumor necrosis factor-alpha, which has the ability to reduce insulin secretion and induce insulin resistance. Based on these observations, we sought to investigate the impact of unsaturated fatty acids such as oleic acid in the presence of TNF-alpha in terms of insulin production, the molecular mechanisms involved and the in vivo effect of a diet high in oleic acid on a mouse model of type II diabetes, KKAy. The rat pancreatic beta cell line INS-1 was used as a cell biological model since it exhibits glucose dependent insulin secretion. Insulin production assessment was carried out using enzyme linked immunosorbent assay and cAMP quantification with competitive ELISA. Viability of TNF-alpha and oleic acid treated cells was evaluated using flow cytometry. PPAR-gamma translocation was assessed using a PPRE based ELISA system. In vivo studies were carried out on adult male KKAy mice and glucose levels were measured with a glucometer. Oleic acid and peanut oil high in oleic acid were able to enhance insulin production in INS-1. TNF-alpha inhibited insulin production but pre-treatment with oleic acid reversed this inhibitory effect. The viability status of INS-1 cells treated with TNF-alpha and oleic acid was not affected. Translocation of the peroxisome proliferator- activated receptor transcription factor to the nucleus was elevated in oleic acid treated cells. Finally, type II diabetic mice that were administered a high oleic acid diet derived from peanut oil, had decreased glucose levels compared to animals administered a high fat diet with no oleic acid. Oleic acid was found to

  11. Exercise preconditioning reduces brain damage and inhibits TNF-alpha receptor expression after hypoxia/reoxygenation: an in vivo and in vitro study.

    Science.gov (United States)

    Ding, Yun-Hong; Mrizek, Michael; Lai, Qin; Wu, Yimin; Reyes, Raul; Li, Jie; Davis, William W; Ding, Yuchuan

    2006-11-01

    Exercise reduces ischemia and reperfusion injury in rat stroke models. We investigated whether gradual increases in tumor necrosis factor-alpha (TNF-alpha) reported during exercise down-regulates expression of TNF-alpha receptors I and II (TNFRI and II) in stroke, leading to reduced brain damage. Adult male Sprague Dawley rats were subjected to 30 minutes of exercise on a treadmill each day for 3 weeks. Then, stroke was induced by a 2-hour middle cerebral artery (MCA) occlusion using an intra-luminal filament. Expressions of TNFRI and II mRNA in the brain were detected using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Protein expressions of TNFRI and II were determined by enzyme-linked immunoabsorbant assay (ELISA) in serum and brain homogenates. Spatial distribution of TNF-alpha receptors in brain regions was determined with immunocytochemistry. In human umbilical vein endothelial cells (HUVEC), we addressed the causal effect of TNF-alpha pretreatment on TNF I and II expression using ELISA and real-time PCR. In exercised rats after stroke, brain infarct was significantly (p<0.01) reduced in the entire MCA supplied regions, associated with a mild expression of TNFRI and II mRNA and protein. The TNF-alpha receptors were restricted to the ischemic core. In contrast, a robust expression of TNFRI and II molecules was found in non-exercised rats subjected to similar ischemia/reperfusion insults. An in vitro study revealed a causal link between TNF-alpha pretreatment and reduced cellular expression of TNF-alpha receptors under hypoxic/reoxygenated conditions. Our results suggest that reduced-brain damage in ischemic rats after exercise preconditioning may be attributable to the reduced expression of TNF-alpha receptors. Chronically increased TNF-alpha expression was also found to reduce TNFI and II responding to acute ischemia/reperfusion insult.

  12. TNF-{alpha} promotes human retinal pigment epithelial (RPE) cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression through activation of Akt/mTORC1 signaling

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    Wang, Cheng-hu; Cao, Guo-Fan [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Jiang, Qin, E-mail: Jqin710@vip.sina.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China); Yao, Jin, E-mail: dryaojin@yahoo.com [The Affiliated Eye Hospital of Nanjing Medical University, Nanjing 210029 (China)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} induces MMP-9 expression and secretion to promote RPE cell migration. Black-Right-Pointing-Pointer MAPK activation is not critical for TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer Akt and mTORC1 signaling mediate TNF-{alpha}-induced MMP-9 expression. Black-Right-Pointing-Pointer SIN1 knockdown showed no significant effect on MMP-9 expression by TNF-{alpha}. -- Abstract: Tumor necrosis factor-alpha (TNF-{alpha}) promotes in vitro retinal pigment epithelial (RPE) cell migration to initiate proliferative vitreoretinopathy (PVR). Here we report that TNF-{alpha} promotes human RPE cell migration by inducing matrix metallopeptidase 9 (MMP-9) expression. Inhibition of MMP-9 by its inhibitor or its neutralizing antibody inhibited TNF-{alpha}-induced in vitro RPE cell migration. Reversely, exogenously-added active MMP-9 promoted RPE cell migration. Suppression Akt/mTOR complex 1(mTORC1) activation by LY 294002 and rapamycin inhibited TNF-{alpha}-mediated MMP-9 expression. To introduce a constitutively active Akt (CA-Akt) in cultured RPE cells increased MMP-9 expression, and to block mTORC1 activation by rapamycin inhibited its effect. RNA interference (RNAi)-mediated silencing of SIN1, a key component of mTOR complex 2 (mTORC2), had no effect on MMP-9 expression or secretion. In conclusion, this study suggest that TNF-{alpha} promotes RPE cell migration by inducing MMP-9 expression through activation of Akt/ mTORC1, but not mTORC2 signaling.

  13. Simulated Microgravity Reduces TNF-Alpha Activity, Suppresses Glucose Uptake and Enhances Arginine Flux in Pancreatic Islets of Langerhans

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.; Paloski, W. H. (Technical Monitor)

    2000-01-01

    The present studies were designed to determine effects of microgravity upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF - alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-117,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS 3) static culture, 4) static culture plus LPS TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV paradigm. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  14. Altered TNF-Alpha, Glucose, Insulin and Amino Acids in Islets Langerhans Cultured in a Microgravity Model System

    Science.gov (United States)

    Tobin, Brian W.; Leeper-Woodford, Sandra K.; Hashemi, Brian B.; Smith, Scott M.; Sams, Clarence F.

    2001-01-01

    The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) activity and indices of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1726+/-1 17,150 u IEU) from Wistar Furth rats were treated as: 1) HARV (High Aspect Ratio Vessel cell culture) , 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity averaged cell culture methods or by three dimensional cell assembly.

  15. TNF-alpha -308G>A polymorphism is associated with suicide attempts in major depressive disorder.

    Science.gov (United States)

    Kim, Yong-Ku; Hong, Jin-Pyo; Hwang, Jung-A; Lee, Heon-Jeong; Yoon, Ho-Kyoung; Lee, Bun-Hee; Jung, Han-Yong; Hahn, Sang-Woo; Na, Kyoung-Sae

    2013-09-05

    Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) -308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) -1082A>G are associated with increased risk for suicide attempts in MDD. Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD. The GG genotype of the TNF-alpha -308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 -1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types. Limitations include a relatively small sample size and a cross-sectional design. TNF-alpha -308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha -308G>A influences suicide in MDD. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha.

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    Sara Leschner

    Full Text Available BACKGROUND: Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy. METHODOLOGY/PRINCIPAL FINDINGS: We describe the initial events of colonization of an ectopic transplantable tumor by Salmonella enterica serovar Typhimurium. Initially, after intravenous administration, bacteria were found in blood, spleen, and liver. Low numbers were also detected in tumors associated with blood vessels as could be observed by immunohistochemistry. A rapid increase of TNF-alpha in blood was observed at that time, in addition to other pro-inflammatory cytokines. This induced a tremendous influx of blood into the tumors by vascular disruption that could be visualized in H&E stainings and quantified by hemoglobin measurements of tumor homogenate. Most likely, together with the blood, bacteria were flushed into the tumor. In addition, blood influx was followed by necrosis formation, bacterial growth, and infiltration of neutrophilic granulocytes. Depletion of TNF-alpha retarded blood influx and delayed bacterial tumor-colonization. CONCLUSION: Our findings emphasize similarities between Gram-negative tumor-colonizing bacteria and tumor vascular disrupting agents and show the involvement of TNF-alpha in the initial phase of tumor-colonization by bacteria.

  17. Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.

    Science.gov (United States)

    Chen, Zhilin; Eadie, Ashley L; Hall, Sean R; Ballantyne, Laurel; Ademidun, David; Tse, M Yat; Pang, Stephen C; Melo, Luis G; Ward, Christopher A; Brunt, Keith R

    2017-01-01

    Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha, in vitro and in vivo . Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.

  18. Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT

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    Mejía Salvador

    2006-02-01

    Full Text Available Abstract Background The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Results Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. Conclusion NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

  19. Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT.

    Science.gov (United States)

    Machuca, Catalina; Mendoza-Milla, Criselda; Córdova, Emilio; Mejía, Salvador; Covarrubias, Luis; Ventura, José; Zentella, Alejandro

    2006-02-21

    The biochemical bases for hormone dependence in breast cancer have been recognized as an important element in tumor resistance, proliferation and metastasis. On this respect, dexamethasone (Dex) dependent protection against TNF-alpha-mediated cell death in the MCF-7 cell line has been demonstrated to be a useful model for the study of this type of cancer. Recently, cytoplasmic signaling induced by steroid receptors has been described, such as the activation of the PI3K/Akt and NF-kappaB pathways. We evaluated their possible participation in the Dex-dependent protection against TNF-alpha-mediated cell death. Cellular cultures of the MCF-7 cell line were exposed to either, TNF-alpha or TNF-alpha and Dex, and cell viability was evaluated. Next, negative dominants of PI3K and IkappaB-alpha, designed to block the PI3K/Akt and NF-kappaB pathways, respectively, were transfected and selection and evaluation of several clones overexpressing the mutants were examined. Also, correlation with inhibitor of apoptosis proteins (IAPs) expression was examined. Independent inhibition of these two pathways allowed us to test their participation in Dex-dependent protection against TNF-alpha-cytotoxicity in MCF-7 cells. Expression of the PI3K dominant negative mutant did not alter the protection conferred by Dex against TNF-alpha mediated cell death. Contrariwise, clones expressing the IkappaB-alpha dominant negative mutant lost the Dex-conferred protection against TNF-alpha. In these clones degradation of c-IAP was accelerated, while that of XIAP was remained unaffected. NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.

  20. NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not induction of intrinsic apoptosis.

    Science.gov (United States)

    Chengedza, Shylet; Benbrook, Doris Mangiaracina

    2010-03-01

    Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also induces intrinsic apoptosis as a single agent. This study tested the hypothesis that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and p-65 NF-kappaB subunit nuclear translocation, but independently of reactive oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF-alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

  1. Equine colostral carbohydrates reduce lipopolysaccharide-induced inflammatory responses in equine peripheral blood mononuclear cells.

    Science.gov (United States)

    Vendrig, J C; Coffeng, L E; Fink-Gremmels, J

    2012-12-01

    Increasing evidence suggests that reactions to lipopolysaccharide (LPS), particularly in the gut, can be partly or completely mitigated by colostrum- and milk-derived oligosaccharides. Confirmation of this hypothesis could lead to the development of new therapeutic concepts. To demonstrate the influence of equine colostral carbohydrates on the inflammatory response in an in vitro model with equine peripheral blood mononuclear cells (PBMCs). Carbohydrates were extracted from mare colostrum, and then evaluated for their influence on LPS-induced inflammatory responses in PBMCs isolated from the same mares, mRNA expression of tumour necrosis factor-alpha, interleukin-6 and interleukin-10 was measured as well as the protein levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10). Equine colostral carbohydrates significantly reduced LPS-induced TNF-alpha protein at both times measured and significantly reduced LPS-induced TNF-alpha, IL-6 and IL-10 mRNA expression by PBMCs. Moreover, cell viability significantly increased in the presence of high concentrations of colostral carbohydrates. Carbohydrates derived from equine colostrum reduce LPS-induced inflammatory responses of equine PBMCs. Colostrum and milk-derived carbohydrates are promising candidates for new concepts in preventive and regenerative medicine.

  2. Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

    Science.gov (United States)

    Ulich, T R; del Castillo, J; Ni, R X; Bikhazi, N

    1989-06-01

    Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the

  3. The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation.

    Science.gov (United States)

    Diuwe, Piotr; Domagala, Piotr; Durlik, Magdalena; Trzebicki, Janusz; Chmura, Andrzej; Kwiatkowski, Artur

    2017-08-01

    One of the most important problems in transplantation medicine is the ischemia/reperfusion injury of the organs to be transplanted. The aim of the present study was to assess the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitor etanercept on the machine perfusion hypothermia of renal allograft kidney function and organ perfusion. No statistically significant differences were found in the impact of the applied intervention on kidney machine perfusion during which the average flow and vascular resistance were evaluated. There were no statistically significant differences in the occurrence of delayed graft function (DGF). Fewer events in patients who received a kidney from the etanercept treated Group A compared to the patients who received a kidney from the control Group B were observed when comparing the functional DGF and occurrence of acute rejection episodes, however, there was no statistically significant difference. In summary, no effect of treatment with etanercept an inhibitor of TNF-alpha in a hypothermic machine perfusion on renal allograft renal survival and its perfusion were detected in this study. However, treatment of the isolated organ may be important for the future of transplantation medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn's Disease: A Comparison of Effectiveness and Safety.

    Science.gov (United States)

    Liu, Jinan; Sylwestrzak, Gosia; Ruggieri, Alexander P; DeVries, Andrea

    2015-07-01

    In recent years, there have been a number of pharmacological innovations for Crohn's disease (CD), a difficult-to-treat condition, including new treatment philosophies (e.g., top-down therapy) and new therapeutic options in terms of the agent and the route of administration. Three anti-tumor necrosis factor (anti-TNF-alpha) agents are available for use among CD patients in the United States: infliximab, an intravenous agent, and adalimumab and certolizumab pegol, 2 newer subcutaneous products. Infliximab is considered the "gold standard" because it has the longest clinical experience, and adalimumab and certolizumab pegol have each gained significant market share. To examine differences in effectiveness and safety between currently available intravenous and subcutaneous anti-TNF-alpha agents used to treat patients with CD. Data for this retrospective, administrative claims analysis were obtained from pharmacy and medical claims from major U.S. health plans geographically dispersed across 14 states during 2007-2011. Patients had at least 1 ICD-9-CM diagnosis for CD, 6 months pre-index eligibility, and initiated anti-TNF-alpha therapy on the index date. Patients in each cohort were propensity score matched on pre-index demographics, clinical characteristics, and baseline health care use. During the post-index period, age-sex adjusted incidence rate ratios (IRRs) of CD-related symptoms, infections, cancers, and hepatic-related conditions were compared using Cox (PH) models. The matched cohorts included 515 patients in each group, with an average age of 39 years. Median follow-up was 17.5 months in the intravenous cohort and 17.7 months in the subcutaneous cohort. In terms of effectiveness outcomes, age-sex adjusted IRRs for the subcutaneous group, with the intravenous cohort as a reference, were as follows: 0.61 (95% CI = 0.32-1.18, P = 0.14) for anal fissures; 0.97 (95% CI = 0.72-1.30, P = 0.85) for abscess; 1.08 (95% CI = 0.79-1.04, P = 0

  5. Evaluation of plasma concentrations of homocysteine, IL-6, TNF-alpha, hs-CRP, and total antioxidant capacity in patients with end-stage renal failure.

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    Mahin Babaei

    2014-12-01

    Full Text Available It has been proved that hyperhomocysteinemia has a high prevalence in patients with end-stage renal disease (ESRD, which may contribute to the high cardiovascular risk in these patients. Cardiovascular disease is the first cause of high mortality rate in ESRD patients. The aim of the present study was to assess five important factors in patients with ESRD (the amount of homocysteine, IL-6, TNF-alpha, hs-CRP, and Total Antioxidant Capacity. These factors were surveyed in ESRD patients to compare with healthy subjects. In a cross-sectional study, we enrolled 80 patients on maintenance hemodialysis and measured the inflammatory and oxidative stress indicators. The plasma samples were assayed for five above mentioned variables using standard protocols. Two-hour post hemodialysis plasma samples were also assayed for TAC. Plasma levels of inflammation markers, IL-6 and hs-CRP, homocysteine were significantly increased in ESRD group versus control group. This increase was also found in TNF-α levels as compared to the controls, but the differences were not statistically significant. Also, the post dialysis samples had significantly lower levels of TAC as compared to predialysis ones.

  6. Immunologic changes in TNF-alpha, sE-selectin, sP-selectin, sICAM-1, and IL-8 in pediatric patients treated for psoriasis with the Goeckerman regimen

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    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University of Prague, Hradec Kralove (Czech Republic). Faculty of Medicine

    2007-11-15

    Psoriasis is a chronic inflammatory skin disease which is often manifested during childhood. The present study investigated changes in the serum levels of proinflammatory cytokines and soluble forms of adhesion molecules in children with psoriasis. The observed patient group of 26 children was treated with the Goeckerman regimen. This therapy combines dermal application of crude coal tar with ultraviolet radiation. The Psoriasis Area Severity Index decreased significantly after treatment by with the Goeckerman regimen (p < 0.001). Serum levels of the proinflammatory cytokine TNF-alpha and adhesion molecules sICAM-1, sP-selectin and sE-selectin decreased after the Goeckerman regimen. The TNF-alpha and sICAM-1 decreased significantly (p < 0.05). Our findings support the complex role of these immune parameters in the immunopathogenesis of psoriasis in children. The serum level of IL-8 increased after the Goeckerman regimen. This fact indicates that the chemokine pathway of IL-8 activity could be modulated by this treatment, most likely by polycyclic aromatic hydrocarbons.

  7. Imbalance between HAT and HDAC activities in the PBMCs of patients with ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors on TNF alpha production.

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    Eric Toussirot

    Full Text Available OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF. We evaluated the balance between histone deacetytlase (HDAC and histone acetyltransferase (HAT in patients with rheumatoid arthritis (RA or ankylosing spondylitis (AS compared to healthy controls (HC and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt- on these enzymatic activities and on the PBMC production of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases.

  8. Adrenergic stimulation promotes T-wave alternans and arrhythmia inducibility in a TNF-alpha genetic mouse model of congestive heart failure.

    Science.gov (United States)

    Shusterman, Vladimir; McTiernan, Charles F; Goldberg, Anna; Saba, Samir; Salama, Guy; London, Barry

    2010-02-01

    T-wave alternans (TWA) is a proarrhythmic repolarization instability that is common in congestive heart failure (CHF). Although transgenic mice are commonly used to study the mechanisms of arrhythmogenesis in CHF, little is known about the dynamics of TWA in these species. We hypothesized that TWA is present in a TNF-alpha model of CHF and can be further promoted by adrenergic stimulation. We studied 16 TNF-alpha mice and 12 FVB controls using 1) in vivo intracardiac electrophysiological testing and 2) ambulatory telemetry during 30 min before and after an intraperitoneal injection of isoproterenol. TWA was examined using both linear and nonlinear filtering applied in the time domain. In addition, changes in the mean amplitude of the T wave and area under the T wave were computed. During intracardiac electrophysiological testing, none of the animals had TWA or inducible arrhythmias before the injection of isoproterenol. After the injection, sustained TWA and inducible ventricular tachyarrhythmias were observed in TNF-alpha mice but not in FVB mice. In ambulatory telemetry, before the isoproterenol injection, the cardiac cycle length (CL) was longer in TNF-alpha mice than in FVB mice (98 +/- 9 and 88 +/- 3 ms, P = 0.04). After the injection of isoproterenol, the CL became 8% and 6% shorter in TNF-alpha and FVB mice (P mice, the magnitude of TWA was 1.5-2 times greater than in FVB mice both before and after the isoproterenol injection. The magnitude of TWA increased significantly after the isoproterenol injection compared with the baseline in TNF-alpha mice (P = 0.003) but not in FVB mice. The mean amplitude of the T wave and area under the T wave increased 60% and 80% in FVB mice (P = 0.006 and 0.009) but not in TNF-alpha mice. In conclusion, TWA is present in a TNF-alpha model of CHF and can be further promoted by adrenergic stimulation, along with the enhanced susceptibility for ventricular arrhythmias.

  9. Obese Mexican American children have elevated MCP-1, TNF-alpha, monocyte concentration, and dyslipidemia

    Science.gov (United States)

    Obesity is an independent risk factor for chronic disease. The prevalence of obesity is especially high among Mexican American children. Peripheral blood monocytes are altered with obesity contributing to elevated systemic inflammation and increased risk of chronic disease. In addition, obesity alte...

  10. The Fps/Fes kinase regulates the inflammatory response to endotoxin through down-regulation of TLR4, NF-kappaB activation, and TNF-alpha secretion in macrophages.

    Science.gov (United States)

    Parsons, Sean A; Greer, Peter A

    2006-12-01

    Fps/Fes and Fer are members of a distinct subfamily of cytoplasmic protein tyrosine kinases that have recently been implicated in the regulation of innate immunity. Previous studies showed that mice lacking Fps/Fes are hypersensitive to systemic LPS challenge, and Fer-deficient mice displayed enhanced recruitment of leukocytes in response to local LPS challenge. This study identifies physiological, cellular, and molecular defects that contribute to the hyperinflammatory phenotype in Fps/Fes null mice. Plasma TNF-alpha levels were elevated in LPS challenged Fps/Fes null mice as compared with wild-type mice and cultured Fps/Fes null peritoneal macrophages treated with LPS showed increased TNF-alpha production. Cultured Fps/Fes null macrophages also displayed prolonged LPS-induced degradation of IkappaB-alpha, increased phosphorylation of the p65 subunit of NF-kappaB, and defective TLR4 internalization, compared with wild-type macrophages. Together, these observations provide a likely mechanistic basis for elevated proinflammatory cytokine secretion by Fps/Fes null macrophages and the increased sensitivity of Fps/Fes null mice to endotoxin. We posit that Fps/Fes modulates the innate immune response of macrophages to LPS, in part, by regulating internalization and down-regulation of the TLR4 receptor complex.

  11. Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2001-01-01

    cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE......, which is characterized by significant inflammation and neuroglial damage. We have recently shown that the exogenous administration of the antioxidant protein zinc-metallothionein-II (Zn-MT-II) significantly decreased the clinical symptoms, mortality, and leukocyte infiltration of the CNS during EAE....... However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce...

  12. High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

    DEFF Research Database (Denmark)

    Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre

    2003-01-01

    BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

  13. Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Møller, Kirsten; Dela, Flemming

    2004-01-01

    Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans.Krogh-Madsen R, Moller K, Dela F, Kronborg G, Jauffred S, Pedersen BK. Professor of Internal Medicine, Dept. of Infectious Diseases 7641, Univ. Hospital Rigshospitalet...

  14. Adalimumab, a fully human anti-TNF-alpha monoclonal antibody, treatment does not influence experimental UV response in the skin of rheumatoid arthritis patients.

    NARCIS (Netherlands)

    Tjioe, M.; Gerritsen, M.J.P.; Broeder, A. den; Hooijdonk, C.A.E.M. van; Kroot, E.J.A.; Riel, P.L.C.M. van; Barrera Rico, P.; Kerkhof, P.C.M. van de

    2003-01-01

    TNF-alpha is known to play an important role in UV-induced immunomodulation and photodamage. It plays a role in UVB-mediated induction of apoptosis and is a strong inducer of the c-Jun N-terminal kinase (JNK) pathway, which eventually leads to the loss of dermal collagen and elastin content.

  15. A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis : a comparison with neutralization of mouse TNF alpha

    NARCIS (Netherlands)

    Mihara, K.; Almansa, C.; Smeets, R. L.; Loomans, E. E. M. G.; Dulos, J.; Vink, P. M. F.; Rooseboom, M.; Kreutzer, H.; Cavalcanti, F.; Boots, A. M.; Nelissen, R. L.

    Background and purpose: The p38 kinase regulates the release of proinflammatory cytokines including tumour-necrosis factor-alpha (TNF alpha) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762-0, we investigated the therapeutic

  16. A fish oil diet does not reverse insulin resistance despite decreased adipose tissue TNF-alpha protein concentration in ApoE-3*Leiden mice

    NARCIS (Netherlands)

    Muurling, Martin; Mensink, Ronald P.; Pijl, Hanno; Romijn, Johannes A.; Havekes, Louis M.; Voshol, Peter J.

    2003-01-01

    Dietary interventions with fish oil have been found to protect against the development of high-fat diet-induced insulin resistance and to decrease the expression of tumor necrosis factor (TNF)-alpha. However, the effect of fish oil administration on preexisting insulin resistance is subject to

  17. ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice.

    NARCIS (Netherlands)

    Selzner, N; Selzner, M; Odermatt, B; Tian, Y; Rooijen, van N.; Clavien, PA

    2003-01-01

    AIMS: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and

  18. Elevated peripheral visfatin levels in narcoleptic patients.

    Directory of Open Access Journals (Sweden)

    Norbert Dahmen

    Full Text Available OBJECTIVE: Narcolepsy is a severe sleep disorder that is characterized by excessive daytime sleepiness, cataplexies and a tendency towards obesity. Recent discoveries indicate that the major pathophysiology is a loss of hypocretin (orexin producing neurons due to immunologically mediated degeneration. Visfatin is a recently described proinflammatory adipokine. It is identical to the immune modulating pre-B-cell colony enhancing factor (PBEF. Our study examines the hypothesis that visfatin levels are altered in narcoleptic patients. METHODS: For the analysis, a total of n = 54 patients (n = 18 males and n = 36 females with the diagnosis of narcolepsy according to DSM-IV and the International Classification of Sleep Disorders were examined (BMI mean 30.3+/-5.5, age mean 52.5+/-16.1 years. As a control group 39 unrelated (n = 12 males and n = 27 females healthy volunteers with no sleep disorder according to DSM-IV were included (BMI mean 28.5+/-4.6, age mean 51.1+/-13.6 years. Peripheral visfatin levels were measured using a commercial enzyme immunoassay kit with a measurement range from 0.1-1000 ng/ml. Narcolepsy symptoms, severity and frequency of symptoms as well as the total duration of various aspects of the symptomatology were assessed by unstructured and structured clinical interviews in including the Stanford Center for Narcolepsy Sleep Inventory. RESULTS: Circulating visfatin was found to be significantly increased in HLA DR2 positive narcoleptic patients compared to controls. CONCLUSION: Taken together, our results add to the evidence of disturbed immunological regulation in patients with narcolepsy.

  19. TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Wenwen; Zheng, Xuexing [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Liu, Shue [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Ouyang, Hongsheng [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Levitt, Roy C.; Candiotti, Keith A. [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Hao, Shuanglin, E-mail: shao@med.miami.edu [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.

  20. Serum concentrations of interleukin (IL-)1alpha, 1beta, 6 and tumor necrosis factor (TNF-) alpha in patients with thyroid eye disease (TED).

    Science.gov (United States)

    Laban-Guceva, Nevenka; Bogoev, Milko; Antova, Magdalena

    2007-01-01

    Serum proinflamatory cytokines were found to be altered in Graves disease (GD) and in TED. Serum values of IL1alpha, IL-1beta, IL-6, TNF-alpha were assessed in 22 patients with TED before and after treatment (aged 46.82 +/- 12.47, M:F=16:6). Free thyroxin was high, TSH low, thyroid ultrasound showed diffuse thyroid enlargement, treatment with antithyroid drugs propylthyouracil (PTU) or methymasol (MMI) resulted in clinical and hormonal remission. Several months after the initiation of the signs of hyperthyroidism, a progression in the ophthalmopathy was observed (Hertel up to 25 mm: normal 15-17 mm) while patients were clinically and hormonally euthyroid. Blood was collected in euthyroid state (with TED signs present, before corticosteroid therapy (CS) treatment) and after 3 months of treatment (patients without TED and without TED treatment). CS resulted in response of 8/22 patients. Ophthalmic irradiation (01) given with CS therapy, resulted in a response in twelve patients (12/12). Lack of response to CS treatment, with rapid increase in proptosis, and loss of visual acuity prompted ophthalmic decompression (OD) in two patients. Both recovered visual acuity, while proptosis fell under 25 mm Hertel. The control group had 29 persons (aged 51.86 +/-10.52, M:F = 16:13). A significant difference was found in the serum levels of IL-1alpha between the groups of controls (0.74+/-0.55 pg/ml) and patients before treatment (1.85 +/- 1.85 pg/ml; p TED treatment its concentration raised to 2.07 +/- 1.82 pg/ml (higher than the pretreatment; NS). For patients with low Clinical Activity Score (CAS) scores (1-5) there was no change in IL-6 concentrations before (1.03+/-o.64 pg/ml) and after treatment (1.07 +/- 0.63 pg/ml). Patients with higher CAS scores (6-10) had a change in IL-6 levels (from 1.32+/-1.00 to 2.67 +/- 4.84; p > 0.05). In addition, patients with pathological VEP had no changes in IL-6 (from 0.93 +/- 0.53 to 0.97 +/- 0.32 pg/ml), while patients with normal VEP had

  1. NIR and MR imaging supported hydrogel based delivery system for anti-TNF alpha probiotic therapy of IBD

    Science.gov (United States)

    Janjic, Jelena M.; Berlec, Ales; Bagia, Christina; Liu, Lu S.; Jeric, Irenej; Gach, Michael; Janjic, Bratislav M.; Strukelj, Borut

    2016-03-01

    Current treatment of inflammatory bowel disease (IBD) is largely symptomatic and consists of anti-inflammatory agents, immune-suppressives or antibiotics, whereby local luminal action is preferred to minimize systemic side-effects. Recently, anti-TNFα therapy has shown considerable success and is now being routinely used. Here we present a novel approach of using perfluorocarbon (PFC) nanoemulsion containing hydrogels (nanoemulgels) as imaging supported delivery systems for anti-TNF alpha probiotic delivery in IBD. To further facilitate image-guided therapy a food-grade lactic acid bacterium Lactococcus lactis capable of TNFα-binding was engineered to incorporate infrared fluorescent protein (IRFP). This modified bacteria was then incorporated into novel PFC nanoemulgels. The nanoemulgels presented here are designed to deliver locally anti-TNFα probiotic in the lower colon and rectum and provide dual imaging signature of gel delivery (MRI) across the rectum and lower colon and bacteria release (NIR). NIR imaging data in vitro demonstrates high IRFP expressing and TNFα-binding bacteria loading in the hydrogel and complete release in 3 hours. Stability tests indicate that gels remain stable for at least 14 days showing no significant change in droplet size, zeta potential and pH. Flow cytometry analyses demonstrate the NIRF expressing bacteria L. lactis binds TNFα in vitro upon release from the gels. Magnetic resonance and near-infrared imaging in vitro demonstrates homogeneity of hydrogels and the imaging capacity of the overall formulation.

  2. ArF excimer laser modulation of TNF-alpha and gelatinase B in NIH 3T3 cells; Modulation de l`expression du TNF-alpha et de la gelatinase B, apres irradiation de fibroblastes NIH 3T3 par un laser a excimeres a 193 NM

    Energy Technology Data Exchange (ETDEWEB)

    Naudy-Vives, C.; Courant, D.; Perot, J.C.; Garcia, J.; Fretier, P.; Court, L.; Dormont, D.

    1995-12-31

    The effects on TNF-alpha and gelatinase B activity in mammalian cells induced by 193 nm argon fluoride excimer laser have been investigated. The data show that a secretion of 92 kDa type IV collagenase and TNF-alpha were increased in cell culture supernatants. Moreover, the 193 nm laser radiation produces a decrease of cell proliferation and an increase of cell activation 8 hours after irradiation. The total protein amount increases with the delivered dose. Same, but less effects were obtained after exposure to a conventional UV lamp at 254 nm. (author). 8 refs.

  3. Changes in the TNF-alpha/IL-10 ratio in hyperglycemia-associated pregnancies.

    Science.gov (United States)

    Moreli, Jusciele B; Corrêa-Silva, Simone; Damasceno, Débora C; Sinzato, Yuri K; Lorenzon-Ojea, Aline R; Borbely, Alexandre U; Rudge, Marilza V C; Bevilacqua, Estela; Calderon, Iracema M P

    2015-03-01

    TNF-α is a diabetogenic cytokine associated with adverse outcomes during pregnancy that can be counterbalanced by IL-10. We have investigated IL-10 and TNF-α balance at maternal and placental levels in hyperglycemia-associated pregnancies. One hundred and ninety-two pregnant women participated, which included normoglycemic women (ND) and women with mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2). Maternal plasma and placental tissue IL-10 and TNF-α levels were measured by ELISA and placental TNF-α was also immunolocalized. Maternal plasma TNF-α levels were highest in GDM (p=0.0190), whereas TNF-α levels were highest in placental tissues in DM2 (p=0.0095). Immunohistochemistry also showed strong reactivity with anti-TNF-α antibody in the villous structures in the DM2 group. Conversely, IL-10 levels were lowest in maternal plasma of the DM2 group (p=0.0228). The TNF-α/IL-10 ratio in maternal plasma progressively increased with the severity of hyperglycemia (pDM2 group (p=0.0150). In both, plasma and placenta, TNF-α/IL-10 ratio were correlated with mean maternal glycemia and HbA1c levels. Alterations of placenta and serum TNF-α/IL-10 balance with predominance of TNF-α were correlated with the severity of hyperglycemia during gestation. This association may offer insight into the pathogenesis of gestational hyperglycemia and associated pregnancy outcomes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Long-term TNF-alpha blockade in patients with amyloid A amyloidosis complicating rheumatic diseases.

    Science.gov (United States)

    Fernández-Nebro, Antonio; Olivé, Alejandro; Castro, María Carmen; Varela, Angela Herranz; Riera, Elena; Irigoyen, Maria V; García de Yébenes, María Jesús; García-Vicuña, Rosario

    2010-05-01

    To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Occupational Exposure to Trichloroethylene and Serum Concentrations of IL-6, IL-10, and TNF-alpha

    Science.gov (United States)

    Bassig, Bryan A.; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Shen, Min; Smith, Martyn T.; Qiu, Chuangyi; Ge, Yichen; Ji, Zhiying; Reiss, Boris; Hosgood, H. Dean; Liu, Songwang; Bagni, Rachel; Guo, Weihong; Purdue, Mark; Hu, Wei; Yue, Fei; Li, Laiyu; Huang, Hanlin; Rothman, Nathaniel; Lan, Qing

    2015-01-01

    To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross-sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL-6, IL-10, and TNF-α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL-10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL-10 was >60% and statistically significant in workers exposed to <12 ppm as well as in workers with exposures ≥ 12 ppm of TCE, compared to unexposed workers. No significant differences in levels of IL-6 or TNF-α were observed among workers exposed to TCE compared to unexposed controls. Given that IL-10 plays an important role in immunologic processes, including mediating the Th1/Th2 balance, our findings provide additional evidence that TCE is immunotoxic in humans. PMID:23798002

  6. Selective targeted delivery of the TNF-alpha receptor p75 and uteroglobin to the vasculature of inflamed tissues: a preliminary report

    Directory of Open Access Journals (Sweden)

    Ventura Elisa

    2011-11-01

    Full Text Available Abstract Background Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects. Results Using uteroglobin (UG, a potent anti-inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consisting of the extracellular ligand-binding portion of the human TNF-alpha receptor P75 (TNFRII and the scFv L19. L19 binds to the ED-B containing fibronectin isoform (B-FN, which is expressed only during angiogenesis processes and during tissue remodeling. B-FN has also been demonstrated in the pannus in rheumatoid arthritis. L19-UG-TNFRII is a stable, soluble homodimeric protein that maintains the activities of both moieties: the immuno-reactivity of L19 and the capability of TNFRII to inhibit TNF-alpha. In vivo bio-distribution studies demonstrated that the molecule selectively accumulated on B-FN containing tissues, showing a very fast clearance from the blood but a very long residence time on B-FN containing tissues. Despite the very fast clearance from the blood, this fusion protein was able to significantly improve the severe symptomatology of arthritis in collagen antibody-induced arthritis (CAIA mouse model. Conclusions The recombinant protein described here, able to selectively deliver the TNF-alpha antagonist TNFRII to inflamed tissues, could yield important contributions for the therapy of degenerative inflammatory diseases.

  7. The effects of TNF-alpha and inhibitors of arachidonic acid metabolism on human colon HT-29 cells depend on differentiation status

    Czech Academy of Sciences Publication Activity Database

    Kovaříková, Martina; Hofmanová, Jiřina; Souček, Karel; Kozubík, Alois

    2004-01-01

    Roč. 72, č. 1 (2004), s. 23-31 ISSN 0301-4681 R&D Projects: GA ČR GA525/01/0419; GA ČR GP524/02/P051; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : colon cancer * cell differentiation * TNF-alpha Subject RIV: BO - Biophysics Impact factor: 4.481, year: 2004

  8. [Study of immunoglobulins, proinflammatory cytokines, lymphoproliferation and phagocytosis in peripheral blood of healthy young people exposed to different levels of atmospheric pollution].

    Science.gov (United States)

    Moreno Ramíez, Everardo; Hernández Urzúa, Miguel Angel; González Villegas, Ana Cecilia; Casas Solís, Josefina; Zaitseva, Galina

    2006-01-01

    Urban environmental pollutants, resulting from the inadequate control in the industries and from the use of vehicles, still represent a great danger for millions of people all around the world. We made a study in healthy young people without family history of atopy that lived in Guadalajara's downtown, as well as in another group of young people who lived in a rural area. According to the census of the year 2000, Guadalajara city has a population of 4 million habitants, and a vehicle number of about a million. The immunological parameters that we studied were: IgG, IgA and IgM immunoglobulins by nephelometry, serum levels of proinflammatory cytokines IL-6, IL-1alpha, IL1-beta and TNF-alpha by ELISAs test, and the phagocytic index in polymorphonuclears. The atmospheric parameters were: NO2, O3, SO2, CO and the suspended particles that were less than 10 micrometers (PM10). These parameters were obtained from a mobile unit found at the Instituto de Astronomia y Meteorología de la Universidad de Guadalajara, and from an automatic station of environmental monitoring. It stands out the high concentrations of NO2 and PM10, which in several occasions were over the standards established by the WHO. IgG, IgA and IgM immunoglobulins were lower in the subjects living in the city that in those who lived in the rural area. Phagocytic index in polymorphonuclears, as well as IL-1alpha levels were higher in the city group, though we did not find a significant difference in the immunological parameters analyzed in the studied groups. Environmental pollution levels found at Guadalajara's downtown does not modify the immunological parameters studied in the peripheral blood of healthy young people. This shows that this group of population is less vulnerable than others to the exposition of moderate levels of urban air pollution.

  9. TNF-alpha

    African Journals Online (AJOL)

    Dr Olaleye Samuel

    Thyroid hormones are essential for normal organ growth, development and function. They ... Hypothyroidism is associated with lower metabolic rate. So, it is ... room temperature. Then the .... skeletal muscles with consequent lipid peroxidative.

  10. Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13

    DEFF Research Database (Denmark)

    Jinquan, T; Frydenberg, Jane; Mukaida, N

    1995-01-01

    receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene...

  11. Ferritin levels, inflammatory biomarkers, and mortality in peripheral arterial disease: a substudy of the Iron (Fe) and Atherosclerosis Study (FeAST) Trial.

    Science.gov (United States)

    Depalma, Ralph G; Hayes, Virginia W; Chow, Bruce K; Shamayeva, Galina; May, Patricia E; Zacharski, Leo R

    2010-06-01

    This study delineated correlations between ferritin, inflammatory biomarkers, and mortality in a cohort of 100 cancer-free patients with peripheral arterial disease (PAD) participating in the Veterans Affairs (VA) Cooperative Study #410, the Iron (Fe) and Atherosclerosis Study (FeAST). FeAST, a prospective, randomized, single-blind clinical trial, tested the hypothesis that reduction of iron stores using phlebotomy would influence clinical outcomes in 1227 PAD patients randomized to iron reduction or control groups. The effects of statin administration were also examined in the Sierra Nevada Health Care (SNHC) cohort by measuring serum ferritin levels at entry and during the 6-year study period. No difference was documented between treatment groups in all-cause mortality and secondary outcomes of death plus nonfatal myocardial infarction and stroke. Iron reduction in the main study caused a significant age-related improvement in cardiovascular disease outcomes, new cancer diagnoses, and cancer-specific death. Tumor necrosis factor (TNF)-alpha, TNF-alpha receptors 1 and 2, interleukin (IL)-2, IL-6, IL-10, and high-sensitivity C reactive protein (hs-CRP) were measured at entry and at 6-month intervals for 6 years. Average levels of ferritin and lipids at entry and at the end of the study were compared. The clinical course and ferritin levels of 23 participants who died during the study were reviewed. At entry, mean age of entry was 67 +/- 9 years for the SNHCS cohort, comparable to FeAST and clinical and laboratory parameters were equivalent in substudy participants randomized to iron reduction (n = 51) or control (n = 49). At baseline, 53 participants on statins had slightly lower mean entry-level ferritin values (114.06 ng/mL; 95% confidence interval [CI] 93.43-134.69) vs the 47 off statins (127.62 ng/mL; 95% CI, 103.21-152.02). Longitudinal analysis of follow-up data, after adjusting for the phlebotomy treatment effect, showed that statin use was associated with

  12. Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women.

    Science.gov (United States)

    Tsiotra, Panayoula C; Tsigos, Constantine; Anastasiou, Eleni; Yfanti, Eleni; Boutati, Eleni; Souvatzoglou, Emmanouil; Kyrou, Ioannis; Raptis, Sotirios A

    2008-01-01

    Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

  13. Influence of High Aspect Ratio Vessel Cell Culture on TNF-Alpha, Insulin Secretion and Glucose Homeostasis in Pancreatic Islets of Langerhans from Wistar Furth Rats

    Science.gov (United States)

    Tobin, Brian W.a; Leeper-Woodford, Sandra K.

    1999-01-01

    The present studies were carried out to determine the influence of a ground based microgravity paradigm, utilizing the High Aspect Ratio Vessel (HARV) cell culture upon lipopolysaccharide (LPS) stimulated tumor necrosis factor alpha (TNF-alpha) production of pancreatic islets of Langerhans. An additional aim was to elucidate alterations in insulin secretion and glucose utilization using the HARV low shear, gravity averaged vector, cell culture technique. Islets were isolated (1726 +/- 117, 150 micron islet equivalent units) from Wistar Furth rats and assigned to four treatment groups: 1) HARV, 2) HARV plus LPS, 3) static culture, 4) static culture plus LPS. Following 48 hours of culture, insulin concentration was increased in both HARV and static cultures (palpha (L929 cytotoxicity assay) and was measured at selected time points for 48 hours. TNF-alpha was significantly increased in LPS-induced HARV and static cultures, yet the increase was more pronounced in the static culture group (palpha is associated with a decreased insulin secretion is intriguing, both as it relates to in-flight investigations, and as it may provide insight into the pathophysiology of Type I and Type 11 diabetes. Glucose concentration in islet medium was lesser throughout the experiment in static cultures, suggesting a decreased reliance upon glucose as a metabolic substrate in the islets cultured in HARVS. In conclusion, the present studies demonstrate alterations in LPS induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF production in the microgravity HARV paradigm. Additionally, alterations in fuel homeostasis may be promulgated by HARV culture. The clinical and physiological significance of these observations remains to be determined.

  14. Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

    International Nuclear Information System (INIS)

    Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

    2012-01-01

    Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

  15. TNF-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Renno, T; Krakowski, M; Piccirillo, C

    1995-01-01

    in the pathology of multiple sclerosis and its animal model experimental allergic encephalomyelitis (EAE). We used reverse transcriptase (RT)-PCR to study the kinetics, cellular source, and regulation of cytokine gene expression in the central nervous system (CNS) of SJL/J mice with myelin basic protein......, the majority of which were identified as microglia and macrophages by their Mac-1 phenotype. Microglia could be discriminated by their low expression of CD45. Incubation of freshly derived, adult microglia from normal, uninfiltrated, CNS with activated Th1 supernatant induced the production of TNF-alpha m...

  16. Tumour necrosis factor-alpha (TNF-alpha) transcription and translation in the CD4+ T cell-transplanted scid mouse model of colitis

    DEFF Research Database (Denmark)

    Williams, A M; Whiting, C V; Bonhagen, K

    1999-01-01

    The adoptive transfer of activated CD4+ alpha/beta T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from......-labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages...

  17. Cytokine production by oral and peripheral blood neutrophils in adult periodontitis.

    Science.gov (United States)

    Galbraith, G M; Hagan, C; Steed, R B; Sanders, J J; Javed, T

    1997-09-01

    Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) also possess bone-resorptive properties, and are generally considered to play a role in the pathogenesis of periodontal disease. In the present study, TNF-alpha and IL-1 beta production by oral and peripheral blood polymorphonuclear leukocytes (PMN) was examined in 40 patients with adult periodontitis and 40 orally healthy matched controls. Oral PMN released considerable amounts of both cytokines in unstimulated culture, and there was no difference between patients and controls when the cytokine levels were corrected for cell number. However, when the effect of disease activity was examined, cytokine release by oral PMN was found to be greatest in patients with advanced periodontitis. Within the healthy control group, IL-1 beta production by oral PMN was significantly higher in males (Mann-Whitney test, P = 0.0008). Examination of IL-1 beta production by peripheral blood PMN exposed to recombinant human granulocyte-macrophage colony stimulating factor revealed no difference between the patient and control groups. In contrast, IL-1 beta production by peripheral blood PMN was significantly reduced in patients with advanced disease (Mann-Whitney test, P = 0.02), and peripheral PMN IL-1 beta synthesis was greater in female controls (Mann-Whitney test, P = 0.054). No effect of race on cytokine production could be discerned in patients or controls. These results indicate that several factors influence cytokine production in oral health and disease, and that a dichotomy in cytokine gene expression exists between oral and peripheral blood PMN in adult periodontitis.

  18. TNF-alpha 308 SNP Rs3091256 GG Genotype is Strongly Associated with Fibrosis in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Özgür GÜNAL

    2017-12-01

    Full Text Available Objective: We aimed to review the influence of host genetic factors on the clinical course, treatment response as well as fibrosis progression in patients with viral hepatitis C genotype 1. Materials and Methods: Ninety-five patients with chronic hepatitis C virus (HCV infection and 97 controls were enrolled. The patients received pegylated interferon (Peg-IFN+ribavirin therapy for 48 weeks and were followed up for the next 48 weeks. Aspartat aminotransferase/platelet ratio (APRI was used to detect liver fibrosis DNA specimens were extracted from the peripheral blood mononuclear cells and the tumor necrosis factor-alpha (TNF-α 308 rs3091256 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Results: All patients included in the study were infected with HCV genotype 1. of the 95 HCV-positive patients, spontaneous viral clearence was observed in 25.5%, rapid viral response in 44.2%, early viral response in 91.8%, and sustained viral response was found in 73.3% of patients. The allele and genotype were not significant between patients and controls. There was no significant difference in virologic response as well. However, TNF-α-308 single nucleotide polymorphisms (SNP rs3091256 GG genotype was strongly associated with fibrosis and alanine aminotransferase (ALT levels (p=0.006 and p=0.017, respectively. Conclusion: TNF-α-308 polymorphisms may reveal different results among countries. Patients having SNP rs3091256 GG are prone to have higher ALT levels and fibrosis score but have better treatment outcome.

  19. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  20. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  1. Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

    Science.gov (United States)

    De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

    2010-01-01

    The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

  2. Phenotypic, ultra-structural, and functional characterization of bovine peripheral blood dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Janet J Sei

    Full Text Available Dendritic cells (DC are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II+ and CD11c-. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c+ DC, and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle.

  3. Diverging mechanisms for TNF-alpha receptors in normal mouse brains and in functional recovery after injury: From gene to behavior

    DEFF Research Database (Denmark)

    Quintana, Albert; Molinero, Amalia; Florit, Sergi

    2007-01-01

    Cytokines, such as tumour necrosis factor (TNF)-alpha and lymphotoxin-alpha, have been described widely to play important roles in the brain in physiologic conditions and after traumatic injury. However, the exact mechanisms involved in their function have not been fully elucidated. We give some...... to the somatosensorial cortex. The effect of the cryolesion on motor function was evaluated with the horizontal ladder beam test, and the results showed that both TNFR1KO and TNFR2KO mice made fewer errors, suggesting a detrimental role for TNFR1/TNFR2 signaling for coping with brain damage. Expression of approximately...... of TNFR1/TNFR2 receptors may be beneficial after a traumatic brain injury....

  4. Glucose-stimulated prehepatic insulin secretion is associated with circulating alanine, triglyceride, glucagon, lactate and TNF-alpha in patients with HIV-lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Pedersen, S B

    2006-01-01

    with the remaining HIV-infected patients (all Ptriglyceride, alanine, glucagon, lactate and TNF-alpha may be associated with alterations in the first-phase prehepatic insulin secretion response to intravenous glucose in normoglycaemic lipodystrophic HIV-infected patients.......OBJECTIVES: We examined whether insulin-resistant lipodystrophic HIV-infected patients with known high fasting prehepatic insulin secretion rates (FISRs) displayed alterations in first-phase prehepatic insulin response to intravenous glucose (ISREG0-10 min). METHODS: Eighteen normoglycaemic...... lipodystrophic HIV-infected (LIPO) patients and 25 normoglycaemic nonlipodystrophic HIV-infected patients (controls) were included in the study. The prehepatic insulin secretion rate was estimated by deconvolution of C-peptide concentrations, and insulin sensitivity (SIRd) was estimated by the glucose clamp...

  5. Rat hepatocyte invasion by Listeria monocytogenes and analysis of TNF-alpha role in apoptosis Invasão de hepatócitos de rato por Listeria monocytogenes e análise do papel do TNF-alfa na apoptose

    Directory of Open Access Journals (Sweden)

    Sânia Alves dos Santos

    2005-04-01

    Full Text Available Listeria monocytogenes, etiological agent of severe human foodborne infection, uses sophisticated mechanisms of entry into host cytoplasm and manipulation of the cellular cytoskeleton, resulting in cell death. The host cells and bacteria interaction may result in cytokine production as Tumor Necrosis Factor (TNF alpha. Hepatocytes have potential to produce pro-inflammatory cytokines as TNF-alpha when invaded by bacteria. In the present work we showed the behavior of hepatocytes invaded by L. monocytogenes by microscopic analysis, determination of TNF-alpha production by bioassay and analysis of the apoptosis through TUNEL technique. The presence of bacterium, in ratios that ranged from 5 to 50,000 bacteria per cell, induced the rupture of cellular monolayers. We observed the presence of internalized bacteria in the first hour of incubation by electronic microscopy. The levels of TNF-alpha increased from first hour of incubation to sixth hour, ranging from 0 to 3749 pg/mL. After seven and eight hours of incubation non-significant TNF-alpha levels decrease occurred, indicating possible saturation of cellular receptors. Thus, the quantity of TNF-alpha produced by hepatocytes was dependent of the incubation time, as well as of the proportion between bacteria and cells. The apoptosis rate increased in direct form with the incubation time (1 h to 8 + 24 h, ranging from 0 to 43%, as well as with the bacteria : cells ratio. These results show the ability of hepatocyte invasion by non-hemolytic L. monocytogenes, and the main consequences of this phenomenon were the release of TNF-alpha by hepatocytes and the induction of apoptosis. We speculate that hepatocytes use apoptosis induced by TNF-alpha for release bacteria to extracellular medium. This phenomenon may facilitate the bacteria destruction by the immune system.Listeria monocytogenes, agente etiológico de infecção grave de origem alimentar, utiliza mecanismos sofisticados de entrada no citoplasma

  6. The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome.

    Science.gov (United States)

    Ciftci, Tansu Ulukavak; Kokturk, Oguz; Bukan, Neslihan; Bilgihan, Ayse

    2004-10-21

    Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may have a direct effect on glucose and lipid metabolism. On the other hand, it is known that IL-6 and TNF-alpha are important pro-inflammatory cytokines in the pathogenesis of atherosclerosis. The goal of present study was to test whether sleep apnea contributes to the previously reported increases of IL-6 and TNF-alpha independent of obesity. Forty-three obese (body mass index, BMI>27 kg/m2) men with newly diagnosed obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index, AHI> or =5) and age- and BMI-matched 22 obese nonapneic male controls (AHI<5) were enrolled in this study. To confirm the diagnosis, all patients underwent standard polysomnography in the sleep disorders center. Serum samples were taken at 08:00 h in the morning after overnight fasting. Serum IL-6 and TNF-alpha levels were found significantly higher in OSAS patients than in controls (p=0.002, p=0.03). Serum IL-6 and TNF-alpha levels were significantly correlated with AHI in OSAS patients (r=0.03, p=0.046 and r=0.36, p=0.016). There was no significant correlation between serum IL-6, TNF-alpha levels and AHI in controls. Serum IL-6 and TNF-alpha levels were not correlated with BMI both in OSAS patients and controls. In conclusion, circulating IL-6 and TNF-alpha levels in patients with OSAS, as independent of BMI are significantly higher than levels in controls and there is a positive relationship between previously mentioned cytokines' levels and the severity of OSAS. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating IL-6 and TNF-alpha levels.

  7. Differential effects of NF-kappa B and p38 MAPK inhibitors and combinations thereof on TNF-alpha- and IL-1 beta-induced proinflammatory status of endothelial cells in vitro

    NARCIS (Netherlands)

    Kuldo, JM; Westra, J; Asgeirsdottir, SA; Kok, RJ; Oosterhuis, K; Rots, MG; Schouten, JP; Limburg, PC; Molema, G

    Differential effects of NF- kappa B and p38 MAPK inhibitors and combinations thereof on TNF-alpha- and IL- 1 beta- induced proinflammatory status of endothelial cells in vitro. Am J Physiol Cell Physiol 289: C1229 - C1239, 2005. First published June 22, 2005; doi: 10.1152/ ajpcell. 00620.2004.

  8. Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

    Science.gov (United States)

    Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

    2001-06-01

    Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

  9. Toll-like receptor stimulation induces higher TNF-alpha secretion in peripheral blood mononuclear cells from patients with hyper IgE syndrome

    OpenAIRE

    Yeganeh, Mehdi; Henneke, Philipp; Rezaei, Nima; Ehl, Stephan; Thiel, Doerte; Matamoros, Nuria; Pietrogrande, Cristina; Espanol, Teresa; Litzman, Jiri; Franco, Jose L.; Sanal, Ozden; Kilic, Sara S.; Breborowicz, Anna; Plebani, Alessandro; Renner, Ellen

    2008-01-01

    Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with `cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammator...

  10. Application of a TNF-alpha-inhibitor into the scala tympany after cochlear electrode insertion trauma in guinea pigs: preliminary audiologic results.

    Science.gov (United States)

    Ihler, Friedrich; Pelz, Sabrina; Coors, Melanie; Matthias, Christoph; Canis, Martin

    2014-11-01

    Cochlear implantation trauma causes both macroscopic and inflammatory trauma. The aim of the present study was to evaluate the effectiveness of the TNF-alpha inhibitor etanercept applied after cochlear implantation trauma on the preservation of acoustic hearing. Guinea pigs were randomly assigned to three groups receiving cochlear implantation trauma by cochleostomy. In one group, the site was sealed by bone cement with no further treatment. A second group was additionally implanted with an osmotic minipump delivering artificial perilymph into the scala tympani for seven days. In the third group, etanercept 1 mg/ml was added to artificial perilymph. Hearing was assessed by auditory brainstem responses at 2, 4, 6, and 8 kHz prior to and after surgery and on days 3, 5, 7, 14, 28. Fifteen healthy guinea pigs. The trauma led to threshold shifts from 50.3 dB ± 16.3 dB to 68.0 dB ± 19.3 dB. Hearing thresholds were significantly lower in etanercept-treated animals compared to controls on day 28 at 8 kHz and from day 3 onwards at 4 and 2 kHz (p < 0.01; two-way RM ANOVA / Bonferroni t-test). The application of etanercept led to preservation of acoustic hearing after cochlear implantation trauma.

  11. Soluble TNF-Alpha-Receptors I Are Prognostic Markers in TIPS-Treated Patients with Cirrhosis and Portal Hypertension

    DEFF Research Database (Denmark)

    Trebicka, Jonel; Krag, Aleksander; Gansweid, Stefan

    2013-01-01

    TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding...

  12. Cuscuta chinensis Ameliorates Immunosuppression and Urotoxic Effect of Cyclophosphamide by Regulating Cytokines - GM-CSF and TNF-Alpha.

    Science.gov (United States)

    Raju, Nidhi; Sakthivel, Kunnathur Murugesan; Kannan, Narayanan; Vinod Prabhu, Venugopal; Guruvayoorappan, Chandrasekaran

    2015-06-01

    Cancer is the leading cause of death worldwide. Cyclophosphamide (CTX) is commonly used as anticancer drug which causes toxicity by its reactive metabolites such as acroline and phosphoramide mustard. In this study, Cuscuta chinensis (C. chinensis) (family: Convolvulaceae) was assessed for ability to restore mice against CTX-induced toxicity. Coadministration of C. chinensis extract (10 mg/kg BW, IP, daily) for ten consecutive days reduced CTX-induced (25 mg/kg BW, IP, daily) toxicity. Treatment with C. chinensis extract significantly (p < 0.01) increased the relative organ weight and body weight. Moreover, administration of C. chinensis extract significantly increased bone marrow cellulatity and α-esterase activity in CTX-treated mice which suggested its protective role on the hematopoietic system. The GSH content was drastically reduced by CTX administration in urinary bladder which was enhanced by treatment with C. chinensis extract, indicating that preventing acroline-mediated tissue damage or cell toxicity and also the extract decreased the urinary bladder nitric oxide (NO) level which proves recovery over urinary tract injury associated with CTX treatment. The administration of C. chinensis extract decreased serum urea, creatinine, and bilirubin levels when compared to CTX-alone-treated group. Histopathological analysis of the urinary bladder of CTX-alone-treated group showed necrotic damage whereas the C. chinensis-treated group showed normal bladder architecture. The above data clearly demonstrates chemoprotective role of C. chinensis against CTX-induced toxicities by regulating antioxidant and inflammatory mediators.

  13. Anti-TNF-alpha antibody attenuates subarachnoid hemorrhage-induced apoptosis in the hypothalamus by inhibiting the activation of Erk

    Directory of Open Access Journals (Sweden)

    Ma L

    2018-02-01

    Full Text Available Ling Ma,1 Yong Jiang,2 Yanan Dong,2 Jun Gao,2 Bin Du,2 Dianwei Liu2 1Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Background: Subarachnoid hemorrhage (SAH can induce apoptosis in many regions of the brain including the cortex and hippocampus. However, few studies have focused on apoptosis in the hypothalamus after SAH. Although some antiapoptotic strategies have been developed for SAH, such as anti-tumor necrosis factor-alpha (TNF-α antibody, the molecular mechanisms underlying this condition have yet to be elucidated. Therefore, the purpose of this study was to evaluate whether SAH could induce apoptosis in the hypothalamus and identify the potential molecular mechanisms underlying the actions of anti-TNF-α antibody, as a therapeutic regimen, upon apoptosis. Materials and methods: SAH was induced in a rat model. Thirty minutes prior to SAH, anti-TNF-α antibody or U0126, an extracellular signal-regulated kinase (Erk inhibitor, was microinjected into the left lateral cerebral ventricle. In addition, phorbol-12-myristate-13-acetate was injected intraperitoneally immediately after the anti-TNF-α antibody microinjection. Then, real-time polymerase chain reaction, Western blotting and immunohistochemistry were used to detect the expression of caspase-3, bax, bcl-2, phosphorylated Erk (p-Erk and Erk. Finally, anxiety-like behavior was identified by using open field. Results: Levels of caspase-3, bax and bcl-2, all showed a temporary rise after SAH in the hypothalamus, indicating the induction of apoptosis in this brain region. Interestingly, we found that the microinjection of anti-TNF-α antibody could selectively block the elevated levels of bax, suggesting the potential role of anti-TNF-α antibody in the inhibition of SAH

  14. Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During Adipocyte Differentiation and in Mature Adipocytes

    Directory of Open Access Journals (Sweden)

    Sara Palacios-Ortega

    2015-07-01

    Full Text Available Background/Aims: Tumor necrosis factor-α (TNF-α-mediated chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1 is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF-α on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. Methods: 3T3-L1 cells were differentiated (21 days in the presence TNF-α (10 ng/mL and mature adipocytes were also treated with TNF-α for 48 hours. Cav-1 and insulin receptor (IR gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C14]-deoxyglucose uptake assay. Results: TNF-α slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-α did not compromise lipid-storage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. Conclusion: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake.

  15. Decreased proinflammatory cytokine production by peripheral blood mononuclear cells from vitiligo patients following aspirin treatment

    International Nuclear Information System (INIS)

    Zailaie, Mohammad Z.

    2005-01-01

    Limited studies have shown that treatment of cells with aspirin modulates their cytokine production. Consequently, the aim of the present study is to investigate the pattern of important proinflammatory cytokines production by stimulated peripheral blood mononuclear cells (PBMC) from patients with active vitiligo following long-term treatment with low-dose oral aspirin. The study was conducted at the Vitiligo Unit, King Abdul-Aziz University Medical Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Thirty-two patients (18 females and 14 males) with non-segmental vitiligo were divided into 2 equal groups, one group received a daily single dose of oral aspirin (300 mg) and the other group received placebo for a period of 12 weeks. The concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were determined in the supernatant of isolated cultured PMBC after being stimulated with bacterial lipopolysaccharide (LPS), before the start of aspirin treatment and at end of treatment period. Cytokine levels were measured using the quantitative sandwich enzyme-linked immunosorbent assay (ELISA) technique, utilizing commercially available kits. The proinflammatory cytokine production by the PBMC of patients with active vitiligo was significantly increased compared to normal controls. Thus, the relative percentage increase in the production of IL-1beta, IL-6, IL-8 and TNF-alpha was: 39.4%, 110.5% (p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of treatment, proinflammatory cytokine production in the aspirin-treated group of active vitiligo patients was significantly decreased compared to the placebo group. Thus, the relative percentage decrease in the production of IL-1beta IL-6, IL-8 and TNF-alpha was: 42.5%, 45.2% (p<0.05), 30.8% (p<0.01), and 50.6% (p<0.05). The vitiligo activity was arrested in all aspirin-treated patients, while 2 patients demonstrated significant repigmentation.Chronic administration of

  16. Numerical calculation of hemolysis levels in peripheral hemodialysis cannulas

    NARCIS (Netherlands)

    De Wachter, D; Verdonck, P

    Hemolysis in extracorporeal life support systems presents an underestimated problem. In this article, we investigate the hemolytic potential of peripheral hemodialysis cannulas numerically. An axisymmetrical finite element model of 3 cannula sizes was built (13G, 14G, and 16G) that was refined

  17. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-03-28

    To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12

  18. Selected immunological changes in patients with Goeckerman's therapy TNF-alpha, sE-selectin, sP-selectin, sICAM-1 and IL-8

    Energy Technology Data Exchange (ETDEWEB)

    Borska, L.; Fiala, Z.; Krejsek, J.; Andrys, C.; Vokurkova, D.; Hamakova, K.; Kremlacek, J.; Ettler, K. [Charles University, Hradec Kralove (Czech Republic). Faculty of Medicine

    2006-07-01

    Psoriasis is one of the most frequent inflammatory skin diseases in which abnormal individual immune reactivity plays an important role. The aim of the present study was to describe selected immunological changes, concerning pro-inflammatory cytokines (TNF-alpha, IL-8) and adhesion molecules (sE-selectin, sP-selectin, sICAM-1), in 56 patients cured by Goeckerman's therapy (GT). GT includes dermal application of crude coal tar (containing polycyclic aromatic hydrocarbons) and exposure to UV radiation.

  19. [Study on the correlation of the effect of entecavir on Th1/Th2 cytokines level in the treatment of chronic hepatitis].

    Science.gov (United States)

    Li, L; Jing, Y B; Liu, J; Wang, C L; Liu, B

    2017-08-20

    Objective: To explore the expression level of peripheral blood Th1/Th2 type cytokines of chronic hepatitis b (CHB) patients in the entecavir (ETV) antiviral treatment, analyze the relationship between various cytokines, and the correlation among of cytokines and HBV DNA loads. Methods: Luminex Liquid Chip Technology was applied to detect the peripheral blood Th1/Th2 type cytokines expression level of CHB patients; At the same time, liver function was detected by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR Method; Hepatitis b virology markers were detected by Chemiluminescence Method. F-test and Pearson correlation analysis were used for statistical analysis. Results: Before ETV antiviral treatment, peripheral blood Th1 cytokines IFN gamma expression level in patients with CHB increased significantly ( P = 0.010) compared with the healthy control group while TNF alpha expression level having no statistically significant difference ( P = 0.095); Th2 type cytokines IL-4, IL-6, IL-10 levels decreased obviously ( P = 0.039, P = 0.014, P = 0.026) compared with those in the control group. After 48 weeks of treatment, Th1 cytokines IFN gamma and TNF alpha expression levels were reduced significantly (19.2±5.03 pg/ml vs 24.69±6.51 pg/ml, and 6.09±4.99 pg/ml vs 9.50±7.34 pg/ml, P Th1/Th2 type cytokines. And there was no correlation between the various cytokines and HBV DNA loads in patients with CHB. Conclusion: ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads, but also contribute to regulate Th1/Th2 type cytokines expression level in patients with CHB, but there was no correlation between the levels of various cytokines, various cytokines and HBV DNA loads.

  20. Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

    Science.gov (United States)

    Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

    2018-01-01

    AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy

  1. Chemioxyexcitation (delta pO2/ROS)-dependent release of IL-1 beta, IL-6 and TNF-alpha: evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium.

    Science.gov (United States)

    Haddad, J J; Safieh-Garabedian, B; Saadé, N E; Kanaan, S A; Land, S C

    2001-02-07

    The signalling mechanisms in oxidative stress mediated by cytokines in the perinatal alveolar epithelium are not well known. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the profile of cytokines in response to ascending Deltap O(2)regimen (oxyexcitation). The peak of TNF-alpha (4 h) preceded IL-1beta and IL-6 (6-9 h), indicating a positive feedback autocrine loop confirmed by exogenous rmTNF-alpha. Reactive oxygen species (ROS) induced a dose-dependent release of cytokines, an effect specifically obliterated by selective antioxidants of the hydroxyl radical (*OH) and superoxide anion (O(2)-). Actinomycin and cycloheximide blocked the induced production of cytokines, implicating transcriptional and translational control. Whilst the dismutating enzymes superoxide dismutase (SOD) and catalase were ineffective in reducing ROS-induced cytokines, MnP, a cell-permeating SOD mimetic, abrogated xanthine/xanthine oxidase-dependent cytokine release. Desferrioxamine mesylate, which inhibits the iron-catalysed generation of *OH via the Fenton reaction, exhibited a mild effect on the release of cytokines. Dynamic variation in alveolar p O(2)constitutes a potential signalling mechanism within the perinatal lung allowing upregulation of cytokines in an ROS-dependent manner. Copyright 2001 Academic Press.

  2. HORMONE LEVELS IN THE PERIPHERAL BLOOD OF THE ...

    African Journals Online (AJOL)

    , 1972. Plasma oestrogen and progesterone levels after mating, and during late pregnancy and post partum in cows . Endocrinologt, 90, 1336. MARION, G.B. & GIER, H.T., 1968. Factors affecting bovine ovarian activity after parturition. J. Anim.

  3. alpha-MSH in systemic inflammation. Central and peripheral actions.

    Science.gov (United States)

    Catania, A; Delgado, R; Airaghi, L; Cutuli, M; Garofalo, L; Carlin, A; Demitri, M T; Lipton, J M

    1999-10-20

    Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.

  4. Relationship of the Van Herick Grading System with Peripheral Iris Configuration and Level of Iris Insertion.

    Science.gov (United States)

    Khan, Faisal Aziz; Niazi, Shafaq Pervez Khan; Khan, Assad Zaman

    2017-09-01

    To determine the relationship of the van Herick angle grading system with the level of iris insertion and peripheral iris configuration. Observational study. Eye department, Combined Military Hospital, Malir Cantt., Karachi, from May to October 2015. Sixty-five eyes of 65 patients were recruited. Anterior chamber depth at the temporal limbus was measured as a fraction of corneal section thickness using van Herick technique and graded on the standard 4-point scale of the van Herick grading system. Gonioscopy of the temporal quadrant was performed with a Posner 4 mirror goniolens and both the true level of iris insertion and peripheral iris configuration were recorded on a 4-point scale so as to equate with the van Herick 4-point grading system. Spearman's rho test was applied to determine the relationship of the van Herick grading system with level of iris root insertion and peripheral iris configuration. Amoderate positive correlation between van Herick grade and peripheral iris configuration was found which was statistically significant (rs=0.42, p < 0.001). Astatistically significant and moderate positive correlation was also detected between van Herick grade and the level of iris insertion (rs=0.45, p < 0.001). The van Herick grade has a moderately positive relationship with the peripheral iris configuration and true level of iris insertion.

  5. Sex hormone levels in spermatic and peripheral venous blood in patients with varicocele

    International Nuclear Information System (INIS)

    Mai Mang; He Xuejun; Wang Luhua; Fang Lingli; Xi Baoshan; Hong Hanye; Yang Fengtao; She Shaoyi

    2003-01-01

    Objective: To study the mechanism of changes of plasma sex hormone levels in patients with varicocele. Methods: Plasma sex hormones (LH, FSH, T) levels in spermatic and peripheral venous blood in 25 patients with varicocele and 22 patients with inguinal hernia were measured and compared. Results: The plasma T levels of spermatic venous blood in varicocele group were lower than those in inguinal hernia group (p 0.05). Conclusion: The sex hormones concentrations in peripheral blood could be influenced by many factors, making interpretation difficult. The concentration of plasma sex hormone in spermatic venous blood might reflect the truth better

  6. Inflammatory C-reactive protein and cytokine levels in asymptomatic people with chronic spinal cord injury.

    Science.gov (United States)

    Frost, Frederick; Roach, Mary Jo; Kushner, Irving; Schreiber, Peter

    2005-02-01

    To determine the relation between serologic markers of information and clinical characteristics of people with chronic spinal cord injury (SCI). Cross-sectional study. Academic medical center SCI outpatient clinic. Convenience sample of 37 men with chronic SCI and 10 healthy control subjects. Not applicable. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The following results achieved statistical significance at P less than .05. Asymptomatic chronic SCI patients differed from referent controls with respect to serum CRP levels but not IL-6 or TNF-alpha. In SCI patients, higher levels of CRP correlated negatively with hemoglobin and albumin levels. A longer time since injury correlated with lower TNF-alpha values, whereas higher TNF-alpha levels correlated with higher serum albumin. Pressure ulcers and indwelling urinary catheters were associated with higher mean levels of CRP but not of the cytokines TNF-alpha and IL-6. Intermittent urinary catheterization was associated with lower levels of CRP when compared with other methods of bladder management. Asymptomatic people with long-term SCI, especially those with indwelling urinary catheters, showed serologic evidence of a systemic inflammatory state. There was no evidence of an elevation in proinflammatory cytokines. Detection of an ongoing systemic inflammatory response in apparently healthy people with indwelling urinary catheters and small skin ulcers further supports the aggressive pursuit of catheter-free voiding options and pressure ulcer healing.

  7. Endometrial IL-1beta, IL-6 and TNF-alpha, mRNA expression in mares resistant or susceptible to post-breeding endometritis. Effects of estrous cycle, artificial insemination and immunomodulation.

    Science.gov (United States)

    Fumuso, Elida; Giguère, Steeve; Wade, José; Rogan, Dragan; Videla-Dorna, Ignacio; Bowden, Raúl A

    2003-11-15

    Endometrial mRNA expression of the pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) was assessed in mares resistant (RM) or susceptible (SM) to persistent post-breeding endometritis (PPBE). Eight RM and eight SM, were selected based on reproductive records and functional tests out of a herd of 2,000 light cross-type mares. Three experiments were done to study transcription patterns in (i) basal conditions; (ii) after artificial insemination (AI); and (iii) after administration of an immunomodulator at time of artificial insemination. Endometrial biopsies were taken during consecutive cycles: (i) at estrus, when follicles reached 35 mm and at diestrus (7 +/- 1 days after ovulation); (ii) at 24 h post-AI, with dead semen (estrus) and in diestrus; (iii) at 24 h after treatment with a Mycobacterium phlei cell-wall extract (MCWE) preparation and AI (with dead semen), and at diestrus. mRNA expression was quantitated by real time PCR. Under basal conditions, SM had significantly higher mRNA expression of all cytokines in estrus and of IL-1beta and TNF-alpha in diestrus, compared to RM. After AI, there were no differences between RM and SM in estrus; however, mRNA expression for all three pro-inflammatory cytokines was higher than under basal conditions. In diestrus, RM showed significantly lower IL-1beta and TNF-alpha mRNA expression than SM. When MCWE was administered at time of AI, no differences between cytokine induction from RM and SM were found. Globally, mRNA expression for all three cytokines correlated well among themselves when expression was high. The present study showed that (i) in basal conditions RM had lower mRNA expression of pro-inflammatory cytokines than SM with no effect of estrous cycle; (ii) AI upregulated mRNA expression for all three cytokines in both RM and SM, with persistance in diestrus in the latter; (iii) treatment with MCWE at time of AI down-regulated mRNA expression

  8. Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS), and clinical and magnetic resonance imaging measures of disease activity in a 1 year follow-up study of patients with axial spondyloarthritis treated with TNF-{alpha} inhibitors

    DEFF Research Database (Denmark)

    Pedersen, Susanne J; Sørensen, Inge J; Hermann, Kay-Geert A

    2010-01-01

    OBJECTIVES: To investigate construct validity and responsiveness of the novel ankylosing spondylitis disease activity score (ASDAS) in patients with spondyloarthritis (SpA). METHODS: In a 46 weeks prospective, longitudinal multi-center study of 60 SpA patients (80% men, median age 40 years (range...... 21-62)) treated with tumor-necrosis-factor-alpha (TNF-alpha) inhibitors (infliximab (n=41), etanercept (n=13), adalimumab (n=6)) responsiveness of ASDAS, conventional clinical measures of disease activity and treatment response, and the Berlin magnetic resonance imaging (MRI) sacroiliac joint (SIJ......) and lumbar spine inflammation scores were compared. RESULTS: After 22 weeks, 58.3% of the patients were clinical responders (50% or 20mm reduction in BASDAI). At baseline, clinical responders had significantly higher ASDAS (median 4.15 (range 1.98-6.04), p=0.008) compared with non-responders (2.99, 2...

  9. Expression of soluble CD83 in plasma from early-stage rheumatoid arthritis patients is not modified by anti-TNF-alpha therapy

    DEFF Research Database (Denmark)

    Kristensen, Anne-Mette; Stengaard-Pedersen, Kristian; Hetland, Merete Lund

    2017-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases. In RA...... higher in synovial fluid than in plasma, and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid. Finally, confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group...

  10. Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia.

    Science.gov (United States)

    Zhang, L X; Li, X L; Wang, L; Han, J S

    1997-01-16

    Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be endogenous opiate antagonist.

  11. A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

    Science.gov (United States)

    Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

    2017-09-01

    Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, Pmeta-regression analyses showed that age, gender and sample size had no moderating effects on the outcome of the meta-analysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

  12. Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.

    Science.gov (United States)

    Moore, D C; Mather, L E; Bridenbaugh, L D; Balfour, R I; Lysons, D F; Horton, W G

    1976-01-01

    Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.

  13. Peripheral blood and intrathyroidal T cell clones from patients with thyroid autoimmune diseases.

    Science.gov (United States)

    Massart, C; Caroff, G; Maugendre, D; Genetet, N; Gibassier, J

    1999-01-01

    For a better understanding of the pathogenesis of thyroid autoimmune diseases, we have studied morphological and functional properties of T clones from peripheral blood lymphocytes (PBL) and from intrathyroidal lymphocytes (ITL) obtained from 3 patients with Graves' disease or 1 Hashimoto's thyroiditis. Investigations were carried out on clones cultured alone or cocultured with autologous thyrocytes. Clonage efficiency ranged from 30% to 33% for PBL and 10% to 36% for ITL. A predominance of CD4-positive clones was observed whatever the origin of the lymphocytes or the autoimmune pathology. Gamma interferon (IFN-gamma) was detected in the majority (17/19) of the clones tested. Intracytoplasmic interleukin (IL-4) was secreted in 7/19 clones and both cytokines were produced in 5/19 clones. In coculture a proliferative response and tumour necrosis factor (TNF-alpha) production were observed with 6 clones (4 from Graves thyrocytes and 2 from thyroiditis). No cytotoxic clone was derived from Graves or thyroiditis tissues. These data demonstrate that the large majority of T clones are principally CD4-T cells; all the clones secreted TNF-alpha and a large majority produced IFN-gamma. Only a few clones produced IL-4 alone or associated with IFN-gamma. Six T clones induced proliferative response and of TNF-alpha secretion in coculture. Further investigations must be performed on these antigen-reactive T clones to analyse their role in the pathogenesis of the human thyroid autoimmune diseases.

  14. Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Yu, Shuai; Chen, Ying; Hou, Xu; Xu, Donghua; Che, Kui; Li, Changgui; Yan, Shengli; Wang, Yangang; Wang, Bin

    2016-03-01

    Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95% confidence interval [95%CI] 22.14-77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13-3.76, P peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23-3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

  15. Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans

    DEFF Research Database (Denmark)

    Taudorf, Sarah; Krabbe, K.S.; Berg, R.M.

    2008-01-01

    The aim of this study was to investigate to what extent single nucleotide polymorphisms (SNPs) in promoter regions of genes of Toll-like receptor (TLR)-4, tumour necrosis factor (TNF)-alpha, interleukin (IL)-18, interferon (IFN)-gamma, IL-6 and IL-10 affect the cytokine response during a controlled......-607, IFN-gamma+874, IL-6-174, IL-10-592 and IL-10-1082) and endotoxin-induced changes in plasma levels of TNF-alpha, IL-6 and IL-10. IL-18 levels were unaffected by endotoxin. In conclusion, the investigated SNPs did not affect endotoxin-induced low-grade cytokine production of TNF-alpha, IL-6, IL-18 or IL......-10 in healthy young men. Previous reports of a major heritability factor in the inflammatory response may be due to other target genes or effects in older age groups or women Udgivelsesdato: 2008/4...

  16. Impact of Millimeter-Level Margins on Peripheral Normal Brain Sparing for Gamma Knife Radiosurgery

    International Nuclear Information System (INIS)

    Ma, Lijun; Sahgal, Arjun; Larson, David A.; Pinnaduwage, Dilini; Fogh, Shannon; Barani, Igor; Nakamura, Jean; McDermott, Michael; Sneed, Penny

    2014-01-01

    Purpose: To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. Methods and Materials: A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Results: Confirmatory correlation between the nominal target radius (ie, R T ) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/R T , where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R 2 >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/R T values for the target. Conclusions: Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets

  17. Newly identified CpG ODNs, M5-30 and M6-395, stimulate mouse immune cells to secrete TNF-alpha and enhance Th1-mediated immunity.

    Science.gov (United States)

    Choi, Sun-Shim; Chung, Eunkyung; Jung, Yu-Jin

    2010-08-01

    Bacterial CpG motifs are known to induce both innate and adaptive immunity in infected hosts via toll-like receptor 9 (TLR9). Because small oligonucleotides (ODNs) mimicking bacterial CpG motifs are easily synthesized, they have found use as immunomodulatory agents in a number of disease models. We have developed a novel bioinformatics approach to identify effective CpG ODN sequences and evaluate their function as TLR9 ligands in a murine system. Among the CpG ODNs we identified, M5-30 and M6-395 showed significant ability to stimulate TNF-alpha and IFN-gamma production in a mouse macrophage cell line and mouse splenocytes, respectively. We also found that these CpG ODNs activated cells through the canonical NF-kappa B signaling pathway. Moreover, both CpG ODNs were able to induce Th1-mediated immunity in Mycobacterium tuberculosis (Mtb)-infected mice. Our results demonstrate that M5-30 and M6-395 function as TLR9-specific ligands, making them useful in the study of TLR9 functionality and signaling in mice.

  18. Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

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    Chong Wang

    Full Text Available BACKGROUND: Peripheral blood Apolipoprotein E (ApoE levels have been proposed as biomarkers of Alzheimer's disease (AD, but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews for case-control studies measuring ApoE levels in serum or plasma from AD subjects and healthy controls. The pooled weighted mean difference (WMD and 95% confidence interval (CI were used to estimate the association between ApoE levels and AD risk. RESULTS: Eight studies with a total of 2250 controls and 1498 AD cases were identified and analyzed. The pooled WMD from a random-effect model of AD participants compared with the healthy controls was -5.59 mg/l (95% CI: [-8.12, -3.06]. The overall pattern in WMD was not varied by characteristics of study, including age, country, assay method, publication year, and sample type. CONCLUSIONS: Our meta-analysis supports a lowered level of blood ApoE in AD patients, and indicates its potential value as an important risk factor for AD. Further investigation employing standardized assay for ApoE measurement are still warranted to uncover the precise role of ApoE in the pathophysiology of AD.

  19. Central attention is serial but mid-level and peripheral attention are parallel—a hypothesis

    Science.gov (United States)

    Marois, Rene

    2016-01-01

    In this brief review, we will argue that attention falls along a hierarchy from peripheral through central mechanisms. We further argue that these mechanisms are distinguished not just by their functional roles in cognition, but also by a distinction between serial mechanisms (associated with central attention) and parallel mechanisms (associated with mid-level and peripheral attention). In particular, we suggest that peripheral attentional deployments in distinct representational systems may be maintained simultaneously with little or no interference, but that the serial nature of central attention means that even tasks that largely rely on distinct representational systems will come into conflict when central attention is demanded. We go on to review both behavioral and neural evidence for this prediction. We conclude that even though the existing evidence mostly favors our account of serial central and parallel non-central attention, we know of no experiment that has conclusively borne out these claims. As such, this paper offers a framework of attentional mechanisms that will aid in guiding future research on this topic. PMID:27388496

  20. Effects of snake venom from Saudi cobras and vipers on hormonal levels in peripheral blood.

    Science.gov (United States)

    Abdel-Galil, Khidir A; Al-Hazimi, Awdah M

    2004-08-01

    Knowledge about the effects of snake venoms on endocrine glands in the Kingdom of Saudi Arabia (KSA) is meager. The aim of the present study is to investigate the acute and chronic envenomation from 4 snakes out of 8 species of Saudi Cobras and Vipers on the tissues of endocrine glands and peripheral hormonal levels in male rats. The peripheral blood levels of 4 hormones mainly testosterone, cortisol, insulin and thyroxin were investigated in male Wistar rats following acute and chronic treatment of the rats with poisonous snake venoms at the Department of Physiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Kingdom of Saudi Arabia between September 2000 to May 2001. Using radio immunoassay for hormonal analysis, a rise in testosterone levels in peripheral blood was obtained following acute treatment, which is due to the effect of the venoms on vascular permeability and increased blood flow. In contrast, the chronic treatment with venoms resulted in a delayed effect on vascular permeability and testicular degeneration resulting in a decreased blood flow and a significant drop in testosterone concentration. Cortisol levels were no different from the controls during acute treatment but it demonstrates gradual rise following chronic treatment to withstand the stress imposed on the animals. Similar results were obtained for insulin, which showed normal values with acute treatment but decreased levels of chronic treatment suggesting insulin insufficiently. Likewise, the thyroxin levels were decreased with chronic treatment suggesting a toxic effect of the poison on the rich blood supply of the thyroid follicles with a subsequent decrease in blood flow to the tissues and therefore, decreased thyroid hormone levels. The effects of venom toxicity on testosterone levels were either normal or stimulatory with acute treatment or inhibitory with chronic treatment depending on the vascular blood flow and testicular degeneration. Cortisol levels were normal at

  1. A feasibility study of the Xpert MTB/RIF test at the peripheral level laboratory in China

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    Xichao Ou

    2015-02-01

    Conclusions: The introduction of MTB/RIF could increase the accuracy of detection of MTB and rifampin resistance in peripheral-level TB laboratories in China. One single specimen is adequate for TB diagnosis by MTB/RIF.

  2. Up-regulation of p55 TNF alpha-receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats.

    Science.gov (United States)

    Sakuma, Yoshihiro; Ohtori, Seiji; Miyagi, Masayuki; Ishikawa, Tetsu; Inoue, Gen; Doya, Hideo; Koshi, Takana; Ito, Toshinori; Yamashita, Masaomi; Yamauchi, Kazuyo; Suzuki, Munetaka; Moriya, Hideshige; Takahashi, Kazuhisa

    2007-08-01

    The rat L5/6 facet joint is multisegmentally innervated from the L1 to L6 dorsal root ganglia (DRG). Tumor necrosis factor (TNF) is a known mediator of inflammation. It has been reported that satellite cells are activated, produce TNF and surround DRG neurons innervating L5/6 facet joints after facet injury. In the current study, changes in TNF receptor (p55) expression in DRG neurons innervating the L5/6 facet joint following facet joint injury were investigated in rats using a retrograde neurotransport method followed by immunohistochemistry. Twenty rats were used for this study. Two crystals of Fluorogold (FG; neurotracer) were applied into the L5/6 facet joint. Seven days after surgery, the dorsal portion of the capsule was cut in the injured group (injured group n = 10). No injury was performed in the non-injured group (n = 10). Fourteen days after the first application of FG, bilateral DRGs from T13 to L6 levels were resected and sectioned. They were subsequently processed for p55 immunohistochemistry. The number of FG labeled neurons and number of FG labeled p55-immunoreactive (IR) neurons were counted. FG labeled DRG neurons innervating the L5/6 facet joint were distributed from ipsilateral L1 to L6 levels. Of FG labeled neurons, the ratio of DRG neurons immunoreactive for p55 in the injured group (50%) was significantly higher than that in the non-injured group (13%). The ratio of p55-IR neurons of FG labeled DRG neurons was significantly higher in total L1 and L2 DRGs than that in total L3, 4, 5 and 6 DRGs in the injured group (L1 and 2 DRG, 67%; L3, 4, 5 and 6 DRG, 37%, percentages of the total number of p55-IR neurons at L1 and L2 level or L3-6 level/the total number of FG-labeled neurons at L1 and L2 level or L3-6 level). These data suggest that up-regulation of p55 in DRG neurons may be involved in the sensory transmission from facet joint injury. Regulation of p55 in DRG neurons innervating the facet joint was different between upper DRG innervated

  3. Blood concentrations of the cytokines IL-1beta, IL-6, IL-10, TNF-alpha and IFN-gamma during experimentally induced swine dysentery

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    Jensen-Waern Marianne

    2008-08-01

    Full Text Available Abstract Background Knowledge of the cytokine response at infection with Brachyspira hyodysenteriae can help understanding disease mechanisme involved during swine dysentery. Since this knowledge is still limited the aim of the present study was to induce dysentery experimentally in pigs and to monitor the development of important immunoregulatory cytokines in blood collected at various stages of the disease. Methods Ten conventional pigs (~23 kg were orally inoculated with Brachyspira hyodysenteriae B204T. Eight animals developed muco-haemorrhagic diarrhoea with impaired general body condition. Blood was sampled before inoculation and repeatedly during acute dysentery and recovery periods and cytokine levels of IL-1β, IL-6, Il-10, TNF-α and IFN-γ were measured by ELISA. Results IL-1β was increased at the beginning of the dysentery period and coincided with the appearance of Serum amyloid A and clinical signs of disease. TNF-α increased in all animals after inoculation, with a peak during dysentery, and IL-6 was found in 3 animals during dysentery and in the 2 animals that did not develop clinical signs of disease. IL-10 was found in all sick animals during the recovery period. IFN-γ was not detected on any occasion. Conclusion B. hyodysenteriae inoculation induced production of systemic levels of IL-1β during the dysentery period and increased levels of IL-10 coincided with recovery from dysentery.

  4. Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes

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    Chu Chih-Sheng

    2012-03-01

    Full Text Available Abstract Background Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD. Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM. Methods Serial changes of plasma glucose (PG, tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6 and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years before coronary angiography. Patients were classified as normal (NGT; 42%, impaired (IGT; 34% and diabetic (T2DM; 24% glucose tolerance by 75 g-OGTT. Results Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; P μmol/l; P P Conclusions These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia per se, are associated with CAD in patients without previous recognized diabetes.

  5. The short-term effects of treatment of chronic periodontitis on circulating levels of endotoxin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6.

    Science.gov (United States)

    Ide, Mark; Jagdev, Daljit; Coward, Paula Y; Crook, Martin; Barclay, G Robin; Wilson, Ron F

    2004-03-01

    The acute-phase response involves molecules including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). This study aimed to determine whether subgingival scaling resulted in rapid changes in plasma concentrations of these molecules. Twenty-three non-smoking adults with chronic periodontitis received subgingival scaling for 60 minutes. Venous blood samples were taken at 0, 15, 30, 60, and 120 minutes. TNF-alpha and IL-6 were assayed from all samples and CRP from the baseline and final samples. Lipopolysaccharide (LPS) was assayed at 0, 15, and 30 minutes using limulus lysate assay (LAL) and EndoCAb Ig assays. LPS assays were suggestive of a transient low-grade bacteremia, but changes in LPS approaching significance (P=0.061) were seen with LAL only. There was a significant increase in circulating TNF-alpha (P=0.0387) and IL-6 (Pperiodontal breakdown (P=0.001). There was also a significant correlation between levels of IL-6 and TNF-alpha (Pperiodontitis patients undergoing an episode of subgingival scaling show a significant elevation in circulating TNF-alpha and IL-6. This may account for anecdotal reports of pyrexia following treatment and may be significant in terms of the relationship between periodontal disease, bacteremia, and cardiovascular disease.

  6. Elevated Levels of Peripheral Kynurenine Decrease Bone Strength in Rats with Chronic Kidney Disease

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    Bartlomiej Kalaska

    2017-10-01

    Full Text Available The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD. The animals were sacrificed 1 and 3 months after 5/6 Nx or sham operation. Nephrectomized rats presented higher concentrations of serum creatinine, urea nitrogen, and parathyroid hormone both 1 and 3 months after nephrectomy. These animals revealed higher concentrations of kynurenine and 3-hydroxykynurenine in the serum and higher gene expression of aryl hydrocarbon receptor (AhR as a physiological receptor for kynurenine and AhR-dependent cytochrome in the bone tissue. Furthermore, nephrectomy significantly increased the number of osteoclasts in the bone without affecting their resorptive activity measured in serum. These changes were particularly evident in rats 1 month after 5/6 Nx. The main bone biomechanical parameters of the tibia were unchanged between nephrectomized and sham-operated rats but were significantly increased in older compared to younger animals. A similar trend was observed for geometrical parameters measured with calipers, bone mineral density based on Archimedes' method and image of bone microarchitecture obtained from micro-computed tomography analyses of tibial cortical bone. In nephrectomized animals, peripheral kynurenine levels correlated negatively with the main parameters of bone biomechanics, bone geometry, and bone mineral density values. In conclusion, our data suggest that CKD-induced elevated levels of peripheral kynurenine cause pathological changes in bone

  7. Production of TNF-alpha by skin explants of dinitrochlorobenzene-challenged ears in rats: A model for the evaluation of contact hypersensitivity

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    Kataranovski Milena

    2002-01-01

    Full Text Available Background. Contact hypersensitivity (CHS is a local inflammatory response of the skin following challenge of hapten-sensitized animals. It is the consequence of cell infiltration of derm and the release of inflammation mediators, among which Tumor necrosis factor-alpha (TNF-α is one of the most important factors. The intensity of the inflammation could be quantified by ear swelling which is the classical manifestation of the reaction. This study was testing the working hypothesis that levels of TNF-α in skin organ culture medium should correlate with the intensity of CHS reaction measured in vivo by ear swelling assay, and with the density of dermal infiltrate in ear skin samples. In order to test the working hypothesis, the intensity of inflammatory reaction following challenge was evaluated by classical measurements of ear swelling, by the determination of TNF-α levels in culture fluids of ear skin following epicutaneous application of dinitrochlorobenzene (DNCB into the ears of sensitized animals. Methods. Animal model of CHS reaction to DNCB in Albino Oxford rats was used as described. Ear swelling was quantified in percentage terms as the difference in thickness between the challenged and nontreated ears of the same animal. Dermal infiltrate density in histopathologically analyzed samples of ear skin was evaluated by computer-assisted image analysis. Ear skin samples were cultured in standard medium for 24 h, and TNF-α concentration in the conditioned medium was subsequently determined with ELISA test. Results. Dose-dependent increase in the density of the dermal infiltrate and in TNF-α in CM were noted following the application of 0.65%, 1.3% and 2.6% of DNCB to the ears of previously sensitized rats. The correlation between ear swelling and the levels of TNF-α (r=0.933, p<0.001 in CM, and between ear swelling and dermal infiltrate density (r=0.916, p<0.001 was found. Correlation was also found between the density of the dermal

  8. CARCINOEMBRYONIC ANTIGEN LEVELS IN THE PERIPHERAL AND MESENTERIC VENOUS BLOOD OF PATIENTS WITH RECTAL CARCINOMA

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    Herminio Cabral de REZENDE JUNIOR

    2013-12-01

    Full Text Available Context The serum carcinoembryonic antigen (CEA is an important prognostic factor in colorectal cancer, however the rectum presents different routes of venous drainage, stating that the level of CEA in peripheral and mesenteric rectal tumors may be different, depending on the location of the tumor in the rectal segment. Objective The goal of this study was to evaluate the relationship between the peripheral and mesenteric venous levels of CEA and the association between these levels and the tumour location in the rectums of patients successfully operated on for rectal carcinoma. Methods Thirty-two patients who were surgically treated for rectal carcinoma were divided into patients with tumours located in the upper rectum (n = 11 or lower rectum (n = 21. The CEA values were assessed by electrochemiluminescence immunoassay. Serum and mesenteric CEA levels were associated with the tumour anatomopathological characteristics: location, histological type, cellular differentiation grade, depth of invasion into the rectal wall, angiolymphatic invasion, tumour, node, and metastasis staging; and the CEA index (≤1.0 or ≥1.0 ng /mL. Results Analysis of the serum CEA values using clinical and anatomopathological parameters revealed no significant association with tumour location, histological type, cellular differentiation grade, depth of invasion into the intestinal wall, and tumour, node, and metastasis staging. The mesenteric CEA levels were significantly associated with the tumour location (P = 0.01. The CEA values in the mesenteric venous blood and the presence of angiolymphatic invasion (P = 0.047 were significantly different. A significant relationship was found between the CEA index value and the rectal tumour location (P = 0.0001. Conclusions The CEA levels were higher in the mesenteric vein in tumours located in the upper rectum and in the presence of angiolymphatic invasion. CEA drainage from lower rectum adenocarcinomas preferentially occurs

  9. Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction.

    Science.gov (United States)

    Kim, Nahyun; Hughes, Tonda L; Park, Chang G; Quinn, Laurie; Kong, In Deok

    2016-03-01

    The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, χ(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents.

  10. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

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    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  11. Correlation between increasing tissue ischemia and circulating levels of angiogenic growth factors in peripheral artery disease.

    Science.gov (United States)

    Jalkanen, Juho; Hautero, Olli; Maksimow, Mikael; Jalkanen, Sirpa; Hakovirta, Harri

    2018-04-21

    The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades. The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements. The levels of VEGF (P = 0.009) and HGF (P correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements. Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. In vitro secretion profiles of interleukin (IL-1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes

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    Maida-Claros Rolando

    2007-12-01

    Full Text Available Abstract Background Chorioamniotic membranes infection is a pathologic condition in which an abnormal secretion of proinflammatory cytokines halts fetal immune tolerance. The aim of the present study was to evaluate the functional response of human chorioamniotic membranes, as well as the individual contribution of the amnion and choriodecidua after stimulation with Escherichia coli, a pathogen associated with preterm labor. Methods Explants of chorioamniotic membranes from 10 women (37–40 weeks of gestation were mounted and cultured in a Transwell system, which allowed us to test the amnion and choriodecidua compartments independently. Escherichia coli (1 × 10 6 CFU/mL was added to either the amniotic or the choriodecidual regions or both; after a 24-h incubation, the secretion of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10 in both compartments was measured using a specific ELISA. Data were analyzed by Kruskal-Wallis one-way analysis of variance. Results After stimulation with Escherichia coli, the choriodecidua compartment showed an increase in the secretion of IL-1beta (21-fold, IL-6 (2-fold, IL-8 (6-fold, and IL-10 (37-fold, regardless of which side of the membrane was stimulated; TNFalpha secretion augmented (22-fold also but only when the stimulus was applied simultaneously to both sides. When the amnion was stimulated directly, the level of IL-1beta (13-fold rose significantly; however, the increase in IL-8 secretion was larger (20-fold, regardless of the primary site of infection. TNFalpha secretion in the amnion compartment rose markedly only when Escherichia coli was simultaneously applied to both sides. Conclusion Selective stimulation of fetal membranes with Escherichia coli results in a differential production of IL-1beta, IL-6, TNFalpha, IL-8, and IL-10. These tissues were less responsive when the amnion side was stimulated. This is in agreement with the hypothesis that the choriodecidua may play a primary role during an ascending

  13. Evaluation of Serum Levels of Pregnancy Associated Plasma Protein-A, Tumor Necrosis Factor-alpha and Highly Sensitive C-Reactive Protein in Diabetic Children

    International Nuclear Information System (INIS)

    Abdel-Messeih, PH.L.; El-safie, A.I.; Said, A.I.

    2011-01-01

    Recent evidence favours the primary role of cellular auto immunity and its humoral mediators in the pathogenesis and follow up of children with type 1 diabetes mellitus (type 1 DM). The present study is carried out to investigate serum levels of pregnancy associated plasma protein-A (PAPP-A), tumor necrosis factor-alpha (TNF-alpha ) and highly sensitive C-reactive protein (hs-CRP) in children with type 1 DM. Potential role of body mass index (BMI) was evaluated. Circulating levels of TNF-alpha, PAPP-A and hs-CRP are significantly increased in children with type 1 DM as compared with healthy subjects suggesting activation of inflammatory immune response system. A significant negative correlation was obtained between TNF-alpha and BMI in diabetic patients. This is highly suggestive of the availability of these non invasive indices to help further examining type 1 DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.

  14. Variation of DNA damage levels in peripheral blood mononuclear cells isolated in different laboratories

    DEFF Research Database (Denmark)

    Godschalk, Roger W L; Ersson, Clara; Stępnik, Maciej

    2014-01-01

    This study investigated the levels of DNA strand breaks and formamidopyrimidine DNA glycosylase (FPG) sensitive sites, as assessed by the comet assay, in peripheral blood mononuclear cells (PBMC) from healthy women from five different countries in Europe. The laboratory in each country (referred...... to as 'centre') collected and cryopreserved PBMC samples from three donors, using a standardised cell isolation protocol. The samples were analysed in 13 different laboratories for DNA damage, which is measured by the comet assay. The study aim was to assess variation in DNA damage in PBMC samples that were......%) by standardisation of the primary comet assay endpoint with calibration curve samples. The level of DNA strand breaks in the samples from two of the centres (0.56-0.61 lesions/10(6) bp) was significantly higher compared with the other three centres (0.41-0.45 lesions/10(6) bp). In contrast, there was no difference...

  15. Hormone levels in peripheral plasma of the Afrikaner cow: Pt. 1

    International Nuclear Information System (INIS)

    Coetzer, W.A.; Van Niekerk, C.H.; Morgenthal, J.C.; Van der Westhuizen, J.M.

    1978-01-01

    Concentration of progesterone and luteinizing hormone were determined in peripheral blood plasma during the oestrus cycle of three non-lactating Afrikaner cows. Blood samples were drawn daily during the luteal phase (Day 3-16) and every 8 hours from Day 17 to 2 days after oestrus. Progesterone was measured by radioimmunoassay and LH by a double antibody radioimmunoassay. Progesterone levels increased gradually from Day 3, reaching maximum values of 6,3-13,3 ng/ml on Day 16-17. A temporary decrease in the progesterone concentration was found between Day 11 and 14 of the cycle. Progesterone levels dropped from peak values to less than 1 ng/ml within 48 hours and were followed by oestrus 50,7 hours later. Progesterone concentrations were lowest at oestrus ( [af

  16. The investigation of cytokine level in peripheral blood of patients with thyroid eye disease

    International Nuclear Information System (INIS)

    Yuan Wenhong; Zhang Yi; Luo Zhihang

    2008-01-01

    Objective: To detect the level of serum interleukin-6 (IL-6) and insulin-lide growth factor-1 (IGF-1) in patients with thyroid eye disease and to seek the relationship between serum level and the outbreak as well as the condition variety. Methods: To measure the level of serum IL-6 and IGF-1 by radioimmunoassay in 30 patients with thyroid eye disease after their clinical expression and activity score have been assessed, 30 patients with hyperthyroidism but without ophthalmopathy, 30 healthy subjects. Results: The level of serum IL-6 and IGF-1 in patients with thyroid eye disease were higher than that of patients with hyperthyroidism but without ophthalmopathy (t=4.20, t=4.00, P<0.01) and healthy subjects (t=4.20, t=4.05, P<0.01). IL-6 and IGF-1 levels tend to elevate with the increase of severity of eye disease. There were significant differences among them. Conclusion: The leve of IL-6, IGF-1 and the cause of thyroid eye disease are closely related, and IL-6 and IGF-1 levels in peripheral blood might reflect the severity of eye disease. (authors)

  17. An observational study of vitamin b12 levels and peripheral neuropathy profile in patients of diabetes mellitus on metformin therapy.

    Science.gov (United States)

    Gupta, Kamesh; Jain, Anand; Rohatgi, Anurag

    A descriptive, observational study was completed in a tertiary care hospital between November 2014 and March 2016. Fifty consecutive patients of Type 2-Diabetes Mellitus who had been on metformin therapy for at least three months were included in our study. Several Parameters were compared with vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS) and Nerve Conduction Velocity). These included the duration of diabetes, duration of metformin usage, dietary history, and HbA1c levels. Definite B12 deficiency was defined as B12peripheral neuropathy (r=0.40). The mean TCSS score was 6.8. The percentage of patients with mild neuropathy was 28%, with moderate neuropathy was 20% and severe neuropathy in 12% of the patients. The average duration of metformin use in patients without peripheral neuropathy was 5.5yrs whereas the average length of metformin use in patients with peripheral neuropathy was 10.4 yrs. Patients on long-term metformin therapy are at a high risk for Vitamin B12 deficiency and peripheral neuropathy. Interval Screening for peripheral neuropathy is recommended for patients on metformin even if Vitamin B12 levels appear to be normal. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  18. TNF-alpha inhibitors: Current indications

    OpenAIRE

    Sharma Rashmi; Sharma Chaman

    2007-01-01

    Advances in the DNA hybrid technology led to the development of various biologicals that specifically target TNF-α. There are currently three anti- TNF- α drugs available- etanercept, infliximab and adalimumab. Etanercept is approved by FDA for rheumatoid arthritis (RA) in 2000 followed by its approval for ankylosing spondylitis, psoriasis and psoriatic arthritis. Infliximab and adalimumab are approved by FDA in 2002 for RA. Infliximab is also approved for ankylosing spondylitis, ps...

  19. Association between Free Triiodothyronine Levels and Peripheral Arterial Disease in Euthyroid Participants.

    Science.gov (United States)

    Wang, Po; DU, Rui; Lin, Lin; Ding, Lin; Peng, Kui; Xu, Yu; Xu, Min; Bi, Yu Fang; Wang, Wei Qing; Ning, Guang; Lu, Jie Li

    2017-02-01

    This current cross-sectional study investigates the relationship between thyroid hormones and peripheral artery disease (PAD) among euthyroid Chinese population aged 40 years and above. Serum free triiodothyronine (FT3), free thyroxin (FT4), thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. PAD was defined as ankle-brachial index (ABI) triiodothyronine-to-free-thyroxin (FT3/FT4 ratio) had a decreased risk of prevalent PAD (multivariate-adjusted odds ratio, 95% confidence interval: 0.32, 0.15-0.62, P for trend = 0.01 and 0.31, 0.13-0.66, P for trend = 0.004, respectively) compared to those in the lowest quartile. To conclude, FT3 levels and the FT3/FT4 ratio was inversely associated with prevalent PAD in euthyroid Chinese population aged 40 years and above. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  20. Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

    Directory of Open Access Journals (Sweden)

    Scalerta Romano

    2009-12-01

    Full Text Available Abstract Background The detection of circulating tumor cells (CTC is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR for the expression of four CTC related genes: carcinoembryonic antigen (CEA, cytokeratin-19 (CK19, vascular endothelial growth factor (VEGF and Survivin (BIRC5. Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients.

  1. APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

    Science.gov (United States)

    Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

    2013-11-01

    To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

  2. Elevated levels of tumor necrosis factor alpha and mortality in centenarians

    DEFF Research Database (Denmark)

    Bruunsgaard, Helle; Andersen-Ranberg, Karen; Hjelmborg, Jacob v B

    2003-01-01

    BACKGROUND: Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-alpha was also a prognostic marker for all......-cause mortality in these persons. METHODS: We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during...... the subsequent 5 years. RESULTS: Only 9 subjects were alive after 5 years. Elevated levels of TNF-alpha were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C...

  3. Study of p53 protein expression levels from irradiated peripheral blood lymphocytes for biodosimetry

    International Nuclear Information System (INIS)

    Cavalcanti, M.B.; Fernandes, T.S.; Melo, J.A.; Neves, M.A.B.; Machado, C.G.F

    2005-01-01

    Biodosimetry can be defined as the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. Scoring of unstable chromosomal aberrations and micronuclei, from in vitro irradiated peripheral blood lymphocytes, is commonly used for biodosimetry based on cytogenetic analysis. However, this method of analysis is time-consuming, which may represent a pitfall when fast investigation of a possible exposure to ionizing radiation (IR) is needed. The interaction of IR with the living cell can cause injuries in the DNA molecules. However, normal cells possess mechanisms of repair that are capable to correct those damages. During the repair process of the DNA various proteins are expressed. Among these proteins, p53 plays an important role. This protein is a transcription factor that helps in the maintenance of the genomic integrity. p53 protein is found into the cytoplasm in reduced concentrations and has a short average life. However, expression of p53 protein can be induced by DNA harmful radioinduced, which increases the concentration and the average life of this protein, making possible its detection. Thus, the correlation between the increasing of p53 expression and the irradiation may constitute a fast and reliable method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the objective of this research was to evaluate the p53 protein expression levels from lymphocytes of the human peripheral blood after in vitro irradiation. For this, samples of peripheral blood from healthy individuals were irradiated with known doses. Lymphocytes were separated on ficoll gradient by centrifugation and re-suspended at 1x 10 6 /mL in RPMI medium enriched with fetal calf serum. Hence, lymphocytes were incubated in 5% CO 2 at 37 deg C prior to the methodology of flow cytometry, using intranuclear antigens for the quantification of p53. In this report, the methodology performed and the results obtained

  4. Study of p53 protein expression levels from irradiated peripheral blood lymphocytes for biodosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti, M.B.; Fernandes, T.S. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Amaral, A. [Universite Paris XII (UPXII) (France); Melo, J.A. [Centro de Radioterapia de Pernambuco (CERAPE), PE (Brazil); Neves, M.A.B.; Machado, C.G.F, E-mail: maribrayner@yahoo.com.br [Fundacao de Hematologia e Hemoterapia de Pernambuco, PE (Brazil)

    2005-07-01

    Biodosimetry can be defined as the investigation of radioinduced biological effects in order to correlate them with the absorbed dose. Scoring of unstable chromosomal aberrations and micronuclei, from in vitro irradiated peripheral blood lymphocytes, is commonly used for biodosimetry based on cytogenetic analysis. However, this method of analysis is time-consuming, which may represent a pitfall when fast investigation of a possible exposure to ionizing radiation (IR) is needed. The interaction of IR with the living cell can cause injuries in the DNA molecules. However, normal cells possess mechanisms of repair that are capable to correct those damages. During the repair process of the DNA various proteins are expressed. Among these proteins, p53 plays an important role. This protein is a transcription factor that helps in the maintenance of the genomic integrity. p53 protein is found into the cytoplasm in reduced concentrations and has a short average life. However, expression of p53 protein can be induced by DNA harmful radioinduced, which increases the concentration and the average life of this protein, making possible its detection. Thus, the correlation between the increasing of p53 expression and the irradiation may constitute a fast and reliable method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the objective of this research was to evaluate the p53 protein expression levels from lymphocytes of the human peripheral blood after in vitro irradiation. For this, samples of peripheral blood from healthy individuals were irradiated with known doses. Lymphocytes were separated on ficoll gradient by centrifugation and re-suspended at 1x 10{sub 6}/mL in RPMI medium enriched with fetal calf serum. Hence, lymphocytes were incubated in 5% CO{sub 2} at 37 deg C prior to the methodology of flow cytometry, using intranuclear antigens for the quantification of p53. In this report, the methodology performed and the results

  5. The effect of orbital implantation on peripheral blood melatonin and sex hormone levels in child patients with congenital eyeball dysplasia.

    Science.gov (United States)

    Ma, Junze; Liu, Tao; Qu, Jianqiang

    2017-09-01

    The aim of the study was to examine the effect of orbital implantation on peripheral blood melatonin and sex hormone levels in pediatric patients with congenital eyeball dysplasia. A total of 28 cases of pediatric patients with congenital eyeball dysplasia diagnosed in the Second Affiliated Hospital of Xi'an Jiaotong University from June 2014 to December 2014 were selected for the study. The patients included those that received orbital implantation, and the melatonin levels in the peripheral blood in patients before and after operation was observed. In addition, the sex hormone levels and T lymphocytes, plasma reactive oxygen species (ROS) and VEGF levels, urine 8-OHdG and 8-isoPGF2α levels in patients before and after treatment were detected, followed by statistical analysis. As a result, after 3 months of orbital implantation, the sex hormone levels in peripheral blood in child patients fluctuated significantly, and differences were not statistically significant (P>0.05). The peripheral blood T lymphocytes and ROS levels were significantly lower than those before treatment, and the differences were statistically significant (Peyeball dysplasia. The hydroxyapatite orbital implantation can achieve more satisfactory curative effects, and there are fewer postoperative complications. It does not affect the appearance of the eye, and therefore, it is suitable for patients with congenital eyeball dysplasia.

  6. Ethanol affects acylated and total ghrelin levels in peripheral blood of alcohol-dependent rats.

    Science.gov (United States)

    Szulc, Michal; Mikolajczak, Przemyslaw L; Geppert, Bogna; Wachowiak, Roman; Dyr, Wanda; Bobkiewicz-Kozlowska, Teresa

    2013-07-01

    There is a hypothesis that ghrelin could take part in the central effects of alcohol as well as function as a peripheral indicator of the changes which occur during long-term alcohol consumption. The aim of this study was to determine a correlation between alcohol concentration and acylated and total form of ghrelin after a single administration of alcohol (intraperitoneal, i.p.) (experiment 1) and prolonged ethanol consumption (experiment 2). The study was performed using Wistar alcohol preferring (PR) and non-preferring (NP) rats and rats from inbred line (Warsaw High Preferring, WHP; Warsaw Low Preferring, WLP). It was found that ghrelin in ethanol-naive WHP animals showed a significantly lower level when compared with the ethanol-naive WLP or Wistar rats. After acute ethanol administration in doses of 1.0; 2.0 and 4.0 g/kg, i.p., the simple (WHP) or inverse (WLP and Wistar) relationship between alcohol concentration and both form of ghrelin levels in plasma were found. Chronic alcohol intake in all groups of rats led to decrease of acylated ghrelin concentration. PR and WHP rats, after chronic alcohol drinking, had lower levels of both form of ghrelin in comparison with NP and WLP rats, respectively, and the observed differences in ghrelin levels were in inverse relationship with their alcohol intake. In conclusion, it is suggested that there is a strong relationship between alcohol administration or intake, ethanol concentration in blood and both active and total ghrelin level in the experimental animals, and that ghrelin plasma concentration can be a marker of alcohol drinking predisposition. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  7. Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1.

    Science.gov (United States)

    Mitrović, Milena; Ilić, Tatjana; Stokić, Edita; Paro, Jovanka Novaković; Naglić, Dragana Tomić; Bajkin, Ivana; Icin, Tijana

    2011-09-01

    Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

  8. Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation?

    Science.gov (United States)

    Serra-Millàs, Montserrat

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in central nervous system development, neurogenesis and neuronal plasticity. BDNF is also expressed in several non-neuronal tissues, and it could play an important role in other processes, such as cancer, angiogenesis, etc. Platelets are the major source of peripheral BDNF. However, platelets also contain high amounts of serotonin; they express specific surface receptors during activation, and a multitude of pro-inflammatory and immunomodulatory bioactive compounds are secreted from the granules. Until recently, there was insufficient knowledge regarding the relationship between BDNF and platelets. Recent studies showed that BDNF is present in two distinct pools in platelets, in α-granules and in the cytoplasm, and only the BDNF in the granules is secreted following stimulation, representing 30% of the total BDNF in platelets. BDNF has an important role in the pathophysiology of depression. Low levels of serum BDNF have been described in patients with major depressive disorder, and BDNF levels increased with chronic antidepressant treatment. Interestingly, there is an association between depression and platelet function. This review analyzed studies that evaluated the relationship between BDNF and platelet activation and the effect of treatments on both parameters. Only a few studies consider this possible confounding factor, and it could be very important in diseases such as depression, which show changes in both parameters. PMID:27014600

  9. Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats.

    Science.gov (United States)

    Eamlamnam, Kallaya; Patumraj, Suthiluk; Visedopas, Naruemon; Thong-Ngam, Duangporn

    2006-04-07

    To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. Male Spraque-Dawley rats (n=48) were divided into four groups. Group1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-alpha and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05) increased in the ulcer groups when compared to the control group. The level of TNF-alpha was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-alpha had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-alpha were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-alpha level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-alpha level and reduce

  10. Peripheral blood mononuclear cells HIV DNA levels impact intermittently on neurocognition.

    Directory of Open Access Journals (Sweden)

    Lucette A Cysique

    Full Text Available To determine the contribution of peripheral blood mononuclear cells' (PBMCs HIV DNA levels to HIV-associated dementia (HAD and non-demented HIV-associated neurocognitive disorders (HAND in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART.Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03. Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05. Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 106 PBMC. Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04, and higher in those with no ART treatment during HIV infection 1st year (p = .03. Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03, and motor-coordination (p = .02-.12 to a lesser extent.PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.

  11. Relationship of peripheral blood TLRs and Tespa1 expression levels with cytokines and oxidative stress in patients with chronic urticarial

    Directory of Open Access Journals (Sweden)

    Yun Xu

    2017-05-01

    Full Text Available Objective: To study the relationship of peripheral blood TLRs and Tespa1 expression levels with cytokines and oxidative stress in patients with chronic urticaria. Methods: A total of 68 patients who were diagnosed with chronic urticaria and treated in Songzi People’s Hospital clinic between June 2014 and April 2017 were selected as the CU group of the research, and 80 healthy volunteers who received physical examination were selected as the control group. TLR2, TLR7 and Tespa1 mRNA expression in peripheral blood mononuclear cells as well as the levels of Th1/Th2 cytokines and oxidative stress indexes in serum were detected. Results: TLR2 and TLR7 mRNA expression in peripheral blood mononuclear cells of CU group were significantly higher than those of control group while Tespa1 mRNA expression was significantly lower than that of control group. Serum IFN-γ, IL-2, TNF-α, T-AOC, SOD and GSH-Px levels of CU group were significantly lower than those of control group, negatively correlated with peripheral blood TLR2 and TLR7 mRNA expression, and positively correlated with Tespa1 mRNA expression; serum IL-4, IL-5, IL-10, IL-31 and MDA levels were significantly higher than those of control group, positively correlated with peripheral blood TLR2 and TLR7 mRNA expression, and negatively correlated with Tespa1 mRNA expression. Conclusions: The changes in peripheral blood TLR2, TLR7 and Tespa1 expression in patients with chronic urticaria can cause the changes in Th1/Th2 immune response and the activation of oxidative stress.

  12. Blood Glucose Levels in Portal and Peripheral Circulation and Their Relation to Food Intake in the Rat

    NARCIS (Netherlands)

    Strubbe, J.H.; Steffens, A.B.

    1977-01-01

    Rats weighing about 450 g were provided with permanent catheters in the portal vein and the right auricle. This method allows blood sampling from the portal and peripheral circulation at the same moment in the nondisturbed unanesthetized rat. In the ad lib condition the portal glucose level was

  13. Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep.

    Science.gov (United States)

    Herrmann-Hoesing, Lynn M; Noh, Susan M; White, Stephen N; Snekvik, Kevin R; Truscott, Thomas; Knowles, Donald P

    2009-04-01

    Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.

  14. Interaction of rotavirus with human peripheral blood mononuclear cells: plasmacytoid dendritic cells play a role in stimulating memory rotavirus specific T cells in vitro.

    Science.gov (United States)

    Mesa, Martha C; Rodríguez, Luz-Stella; Franco, Manuel A; Angel, Juana

    2007-09-15

    We studied the interaction of RV with human peripheral blood mononuclear cells (PBMC) from adult volunteers. After exposure of PBMC to rhesus RV (RRV), T and B lymphocytes, NK cells, monocytes, and myeloid and plasmacytoid dendritic cells expressed RV non-structural proteins, at variable levels. Expression of these RV proteins was abolished if infection was done in the presence of anti-VP7 neutralizing antibodies or 10% autologous serum. Supernatants of RRV exposed PBMC contained TNF-alpha, IL-6, IFN-alpha, IFN-gamma, IL-2 and IL-10. Plasmacytoid DC were found to be the main source of IFN-alpha production, and in their absence the production of IFN-gamma and the frequency of RV specific T cells that secrete IFN-gamma diminished. Finally, we could not detect RV-antigen associated with the PBMC or expression of RV non-structural proteins in PBMC of acutely RV-infected children. Thus, although PBMC are susceptible to the initial steps of RV infection, most PBMC of children with RV-gastroenteritis are not infected.

  15. Global levels of histone modifications in peripheral blood mononuclear cells of subjects with exposure to nickel.

    Science.gov (United States)

    Arita, Adriana; Niu, Jingping; Qu, Qingshan; Zhao, Najuan; Ruan, Ye; Nadas, Arthur; Chervona, Yana; Wu, Fen; Sun, Hong; Hayes, Richard B; Costa, Max

    2012-02-01

    Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro. This study was conducted in a Chinese population to determine whether occupational exposure to Ni is associated with alterations of global histone modification levels and to evaluate the inter- and intraindividual variance of global histone modification levels. Forty-five subjects with occupational exposure to Ni and 75 referents were recruited. Urinary Ni and global H3K4 trimethylation, H3K9 acetylation, and H3K9 dimethylation levels were measured in peripheral blood mononuclear cells (PBMCs) of subjects. H3K4me3 was elevated in Ni-exposed subjects (0.25% ± 0.11%) compared with referents (0.15% ± 0.04%; p = 0.0004), and H3K9me2 was decreased (Ni-exposed subjects, 0.11% ± 0.05%; referents, 0.15% ± 0.04%; p = 0.003). H3K4me3 was positively (r = 0.4, p = 0.0008) and H3K9ac was negatively (r = 0.1, p = 0.01) associated with urinary Ni. Interindividual variances of H3K4me3, H3K9ac, and H3K9me2 were larger compared with intraindividual variance in both exposure test groups, resulting in reliability coefficients (an estimate of consistency of a set of measurements) of 0.60, 0.67, and 0.79 for H3K4me3, H3K9ac, and H3K9me2, respectively, for Ni-exposed subjects and of 0.75, 0.74, and 0.97, respectively, for referent subjects. The results of this study indicate that occupational exposure to Ni is associated with alterations of global histone modification levels and that measurements of global levels of histone modifications are relatively stable over time in human PBMCs.

  16. [The comparison of blood levels between peripheral vein and tooth extraction wound after the oral administration of antibiotics (author's transl)].

    Science.gov (United States)

    Hashimoto, T; Ookawa, H; Morishita, M; Takeyasu, K; Shiiki, K; Imoto, T

    1981-06-01

    The oral administration of 300 mg of clindamycin was undertaken on 23 patients, of 500 mg of cefadroxil on 11 patients and of 250 mg of talampicillin on 12 patients, and then tooth extraction was performed under local anesthesia. Blood samples were taken from the extraction wound and the peripheral vein at the same time and assayed by the bioassay method. The blood levels of clindamycin and cefadroxil indicated a similar pattern between the extraction wound and the peripheral vein, but the blood level of talampicillin reached peek level rapider than clindamycin and cefadroxil. The blood levels of the extraction wound were 60 - 80% as compared with the venous blood levels with each antimicrobial agent.

  17. LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

    Science.gov (United States)

    Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina

    2015-08-01

    Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

  18. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  19. CD28-, CD45RA(null/dim) and natural killer-like CD8+ T cells are increased in peripheral blood of women with low-grade cervical lesions.

    Science.gov (United States)

    Pita-Lopez, Maria Luisa; Ortiz-Lazareno, Pablo Cesar; Navarro-Meza, Monica; Santoyo-Telles, Felipe; Peralta-Zaragoza, Oscar

    2014-01-01

    In response to antigen naive CD8+, T cells differentiate into effector cells, which express Natural killer (NK) receptors, lose CD28 expression, and die by apoptosis. However, in smaller quantities, the cells are retained for subsequent exposure to the same antigen. Knowledge is limited regarding whether the percentages of CD28-, Effector memory (EMRA(null/dim)), and the CD16+/CD56 + CD8+ T cells of women with low-grade cervical lesions are altered at a systemic level. We enrolled in this study women controls and women with Human papilloma virus infection (HPV-I) without associated cellular neoplastic changes and with Cervical Intraepithelial Neoplastic-I (CIN-I). Flow cytometry (FC) was performed for measurement of CD28-, memory subset, and NK-like CD8 + T cells, and IL-17, IFN-gamma, Tumor necrosis factor (TNF)-alpha, Interleukin (IL)-10, IL-6, IL-4, and IL-2. Finally, we genotyped the HPV. The CIN-I group increased the CD8 + CD28- and CD16+/56+ T cell percentage compared with that of HPV-I and controls (p levels among all groups. Increased levels of CD28-, EMRA(null/dim), and CD16+/CD56 + CD8+ T cells of peripheral blood in women with CIN-I may be associated with persistent HPV infection and could exert an influence on progression to cervical cancer.

  20. Peripheral Signals of Food Intake in Response to Low Leptin Levels Induced by Centrifugation

    Science.gov (United States)

    Moran, M. M.; Wade, Charles E.; Stein, T. P.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    The focus of the study was to examine leptin and other peripheral signals of energy balance, following hypergravity. The study was conducted in two experiments. In experiment 1 rats were centrifuged at either 1.5, 2, or remained at 1 G. During days 8 to 14 of experiment 1, mean body mass of the 1.5 and 2 G groups was significantly (p<0.05) lower than controls. No differences were found in food intake (g/day/100 g body mass). Epididymal fat in the 2 G group was 21% lower than controls and 14% lower than the 1.5 G group. Plasma leptin was reduced from controls in the 1.5 and 2 G groups by 45 and 63%, respectively. A significant correlation was found between G load and urinary catecholamines. In experiment 2, rats were centrifuged at either 1.25, 1.5, or remained at 1 G. During days 8 to 14, body mass and food intake were similar between the 1, 1.25, and 1.5 G groups. Epididymal fat was reduced from controls in the 1.25 (14%) and 1.5 (19%) G groups. Leptin was reduced from controls in the 1.25 (45%) and 1.5 (46%) G groups. No differences were found in urinary epinephrine. Urinary norepinephrine levels were significantly higher than controls in each centrifuge group. During hypergravity exposure, food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  1. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    Science.gov (United States)

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

  2. Analysis of changes of serum leptin, C-peptide levels and peripheral fat tissue leptin receptor expression in obesity

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Shukui; Fu Lei

    2002-01-01

    Objective: To explore the mechanism of obesity and obesity accompanied type two diabetes mellitus by investigating changes of serum leptin, C-peptide (C-P) levels and leptin receptor expression in peripheral adipose tissues. Methods: Peripheral leptin receptor density was measured via radio-ligand binding method, serum leptin and C - P levels were measured via radioimmunoassay in 91 cases (38 in obesity group, 23 in over weight, and 30 in normal controls). Results: With the increase of body mass index (BMI), the peripheral leptin receptor density of the over weight and obese cases decreased and was mash less than that of normal cases (both p<0.01, respectively). There was no statistical differences for Kd value among the three groups, suggesting no associated change between the binding ability of leptin receptor to its ligand. There was a negative correlation between BMI and leptin receptor density (r = -0.70, p < 0.01). The serum leptin and C-P levels in weight excess and obese subjects with type two DM were both increased, but significantly higher in obese group than those in weight excess group (p < 0.01). The increase of C-P was much marked than that of leptin. Serum C-P level was positively correlated with BMI. Conclusion: Changes of serum leptin, C-P levels and peripheral leptin receptor expression in cases with simple obesity and obesity accompanied with type two DM were related closely with BMI. Type 2 DM in obese subjects was related with leptin resistance and insulin resistance

  3. Dengue viral RNA levels in peripheral blood mononuclear cells are associated with disease severity and preexisting dengue immune status.

    Directory of Open Access Journals (Sweden)

    Anon Srikiatkhachorn

    Full Text Available Infection with dengue viruses (DENV causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF, to dengue hemorrhagic fever (DHF. The in vivo targets of DENV and the relation between the viral burden in these cells and disease severity are not known.The levels of positive and negative strand viral RNA in peripheral blood monocytes, T/NK cells, and B cells and in plasma of DF and DHF cases were measured by quantitative RT-PCR.Positive strand viral RNA was detected in monocytes, T/NK cells and B cells with the highest amounts found in B cells. Viral RNA levels in CD14+ cells and plasma were significantly higher in DHF compared to DF, and in cases with a secondary infection compared to those undergoing a primary infection. The distribution of viral RNA among cell subpopulations was similar in DF and DHF cases. Small amounts of negative strand RNA were found in a few cases only. The severity of plasma leakage correlated with viral RNA levels in plasma and in CD14+ cells.B cells were the principal cells containing DENV RNA in peripheral blood, but overall there was little active DENV RNA replication detectable in peripheral blood mononuclear cells (PBMC. Secondary infection and DHF were associated with higher viral burden in PBMC populations, especially CD14+ monocytes, suggesting that viral infection of these cells may be involved in disease pathogenesis.

  4. {gamma}-radiation of excited nuclear discrete levels in peripheral heavy ion collisions

    Energy Technology Data Exchange (ETDEWEB)

    Korotkikh, V.L.; Chikin, K.A. [Scobeltsyn Institute of Nuclear Physics, Moscow State University (Russian Federation)

    2002-06-01

    A new process of a nuclear excitation to discrete states in peripheral heavy ion collisions is studied. High-energy photons are emitted by the exited nuclei with energies up to a few tens of GeV at angles of a few hundred microradians with respect to the beam direction. We show that a two-stage process, where an electron-positron pair is produced by virtual photons emitted by nuclei and then the electron or positron excites the nucleus, has a large cross-section. It is equal to about 5 b for CaCa collisions. On the one hand, it produces a significant {gamma}-rays background in the nuclear fragmentation region but, on the other hand, it could be used for monitoring the nuclear beam intensity at the LHC. These secondary nuclear photons could be a good signal for triggering peripheral nuclear collisions. (orig.)

  5. γ-radiation of excited nuclear discrete levels in peripheral heavy ion collisions

    Science.gov (United States)

    Korotkikh, V. L.; Chikin, K. A.

    A new process of a nuclear excitation to discrete states in peripheral heavy ion collisions is studied. High-energy photons are emitted by the exited nuclei with energies up to a few tens of GeV at angles of a few hundred microradians with respect to the beam direction. We show that a two-stage process, where an electron-positron pair is produced by virtual photons emitted by nuclei and then the electron or positron excites the nucleus, has a large cross-section. It is equal to about 5 b for CaCa collisions. On the one hand, it produces a significant γ-rays background in the nuclear fragmentation region but, on the other hand, it could be used for monitoring the nuclear beam intensity at the LHC. These secondary nuclear photons could be a good signal for triggering peripheral nuclear collisions.

  6. γ-radiation of excited nuclear discrete levels in peripheral heavy ion collisions

    International Nuclear Information System (INIS)

    Korotkikh, V.L.; Chikin, K.A.

    2002-01-01

    A new process of a nuclear excitation to discrete states in peripheral heavy ion collisions is studied. High-energy photons are emitted by the exited nuclei with energies up to a few tens of GeV at angles of a few hundred microradians with respect to the beam direction. We show that a two-stage process, where an electron-positron pair is produced by virtual photons emitted by nuclei and then the electron or positron excites the nucleus, has a large cross-section. It is equal to about 5 b for CaCa collisions. On the one hand, it produces a significant γ-rays background in the nuclear fragmentation region but, on the other hand, it could be used for monitoring the nuclear beam intensity at the LHC. These secondary nuclear photons could be a good signal for triggering peripheral nuclear collisions. (orig.)

  7. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  8. PERIPHERAL PARASITAEMIA AND ITS ASSOCIATION WITH PLASMA CYTOKINES LEVELS IN MALARIA-INFECTED PREGNANT WOMEN IN ABA, ABIA STATE, NIGERIA.

    Science.gov (United States)

    Ifeanyichukwu, M O; Okamgba, O C; Amilo, G I; Nwokorie, E A

    2017-01-01

    Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls. Blood samples were aseptically collected from each subject and tested for HIV and malaria parasites using standard methods. Also, plasma levels of cytokines were measured using Th1/Th2 human cytokine ELISA kits (Abcam, UK). Analysis of Variance and Student's t-test were used for Comparison of groups while Pearson's Correlation Coefficient was used for tests of association. The results revealed a mean parasite density of 685.56±484.55 parasites/µl of blood. Malaria infected pregnant subjects showed significantly higher levels of IFN-γ, TNF-α, IL-4, IL-6 and IL-10 when compared with their non-infected counterparts (P< 0.05). The cytokines evaluated were higher in moderate parasitaemia than mild parasitaemia. Positive correlation existed between peripheral parasite density (PPD) and IL-4 (r= 0.24, P=0.004), PPD and IL-6 (r = 0.35, P = 0.001) as well as PPD and IL-10 (r = 0.29, P = 0.001). This study showed that increase in peripheral parasitaemia increased levels of some plasma cytokines (IL-4, IL-6 and IL-10) but not IFN-γ and TNF-α in the malaria infected pregnant women studied.

  9. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 may help downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70) in the neurogenic bladder of spinal cord injured patient with urinary tract infections: a two-case study.

    Science.gov (United States)

    Anukam, Kingsley C; Hayes, Keith; Summers, Kelly; Reid, Gregor

    2009-01-01

    The management of urinary tract infection (UTI) in individuals with spinal cord injury (SCI) continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P = .015) in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

  10. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 May Help Downregulate TNF-Alpha, IL-6, IL-8, IL-10 and IL-12 (p70 in the Neurogenic Bladder of Spinal Cord Injured Patient with Urinary Tract Infections: A Two-Case Study

    Directory of Open Access Journals (Sweden)

    Kingsley C. Anukam

    2009-01-01

    Full Text Available The management of urinary tract infection (UTI in individuals with spinal cord injury (SCI continues to be of concern, due to complications that can occur. An emerging concept that is a common underlying pathophysiological process is involved, wherein pathogens causing UTI have a role in inflammatory progression. We hypothesized that members of the commensal flora, such as lactobacilli, may counter this reaction through anti-inflammatory mediation. This was assessed in a pilot two-patient study in which probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri were administered to one patient and placebo to another, both along with antibiotics to treat acute UTI. Urinary TNF-alpha was significantly downregulated (P=.015 in the patient who received the probiotic and who used intermittent catheterization compared with patient on placebo and using an indwelling catheter. The extent to which this alteration resulted in improved well-being in spinal cord injured patients remains to be determined in a larger study.

  11. Efficiencies of Low-Level Laser Therapy (LLLT) and Gabapentin in the Management of Peripheral Neuropathy: Diabetic Neuropathy.

    Science.gov (United States)

    Abdel-Wahhab, Khaled G; Daoud, Eitedal M; El Gendy, Aliaa; Mourad, Hagar H; Mannaa, Fathia A; Saber, Maha M

    2018-03-12

    Diabetic neuropathy (DN) is the highly occurred complication of diabetes mellitus; it has been defined as an event of peripheral nerve dysfunction characterized by pain, allodynia, hyperalgesia, and paraesthesia. The current study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) in the management of neuropathy in diabetic rats. The used animals were divided into the following groups: negative control, streptozotocin-induced diabetic rats, and diabetic rats with peripheral neuropathy (DNP) and DNP treated with gabapentin or with LLLT. Behavioral tests were carried out through hotplate test for the determination of pain sensations and the Morris water maze test for spatial reference memory evaluation. Blood samples were collected at the end of treatment for biochemical determinations. In the current study, the latency of hind-paw lick decreased significantly when DNP are treated with gabapentin or LLLT. The Morris water maze test showed that LLLT treatment improved memory that deteriorated in DNP more than gabapentin do. The results of the biochemical study revealed that LLLT could not affect the level of beta-endorphin that decreased in DNP but significantly decreased S100B that rose in DNP. PGE2 and cytokines IL-1β, IL-10, and TNF-α showed significant increase in DNP compared with control group. The gabapentin administration or LLLT application significantly reversed the levels of the mentioned markers towards the normal values of the controls. Levels of serum MDA and nitric oxide increased significantly in the DNP but rGSH showed significant decrease. These markers were improved significantly when the DNP were treated with gabapentin or LLLT. The treatment with gabapentin or LLLT significantly decreased the raised level in total cholesterol in DNP but could not decrease the elevated level of triglycerides, while LDL cholesterol decreased significantly in DNP treated with gabapentin but not affected by LLLT. Values of serum alanine

  12. [Influence of diet and behavior related factors on the peripheral blood triglyceride levels in adults: a cross-sectional study].

    Science.gov (United States)

    Liang, M B; Wang, H; Zhang, J; He, Q F; Fang, L; Wang, L X; Su, D T; Zhao, M; Zhang, X W; Hu, R Y; Cong, L M; Ding, G G; Ye, Z; Yu, M

    2017-12-10

    Objective: To study the influence of diet and behavior related factors on the peripheral blood triglyceride levels in adults, through a cross-sectional survey. Methods: The current study included 13 434 subjects without histories of major chronic diseases from a population-based cross-sectional survey: the 2010 Metabolic Syndrome Survey in Zhejiang Province. A generalized linear model was used to investigate the influence of diet/behavior-related factors on the peripheral blood triglyceride levels. Results: Mean TG of the sample population appeared as (1.36±1.18) mmol/L. The proportions of elevated TG and marginally elevated TG were 10.3% and 11.0% respectively, with statistically significant difference seen between males and females ( χ (2)=44.135, P smoking, alcohol-intake, meat, fruit and water intake in male population from this study. However, in females, the intake of aquatic product and physical exercise showed statistically significant differences. After controlling for other variables, factors as age, drinking, staple food and aquatic products showed positive influence on TG, while milk presented negative influence on TG. Through interaction analysis, fruit and meat intake in males and staple food in females showed positive influence on TG, when compared to the reference group. Conclusion: Hyperglyceridemia appeared as one of the major metabolic abnormities in Zhejiang province. Programs on monitoring the alcohol, staple food and meat intake should be priority on intervention, in the communities.

  13. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    Science.gov (United States)

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The effect of heparin administration on the FT4-levels and on an unspecific peripheral thyroid parameter

    International Nuclear Information System (INIS)

    Eber, B.; Borkenstein, J.; Leb, G.

    1984-01-01

    Heparin produces changes in FT 4 -levels both in vivo and in vitro as determined by commercial kits. Methods utilising the principle of equilibrium dialysis show significant increases whereas methods using T 4 -tracer analogue techniques reveal marked decreases in FT 4 -values. Possible clinical side-effects of heparin administration such as heparin-induced hyperthyroidism and tachyarrhythmias are discussed. The present results confirm the FT 4 -decreasing effect of in vivo and in vitro administration of heparin with FT 4 -RIAs based on the tracer analogue technique; however, the unspecific peripheral thyroid parameter of systolic time-intervals did not reveal any tendency towards hyperthyroidism. Also the discrepant results dependent on the method used, indicate that, following heparin administration FT 4 -levels do not reflect that hormone concentration is relevant to the metabolism of the whole body. (orig.) [de

  15. Influence of orlistat therapy on serum insulin level and morphological and functional parameters of peripheral arterial circulation in obese patients

    Directory of Open Access Journals (Sweden)

    Hajduković Zoran

    2005-01-01

    Full Text Available Background/Aim. Insulin resistance is related to accelerated atherosclerosis, whereas weight loss is associated with the increasing insulin sensitivity, the improvement of functional and the morphological parameters of arterial circulation, and the reduction of cardiovascular morbidity and mortality. The aim of our study was to evaluate the influence of orlistat treatment on serum insulin level and functional and morphologic parameters of peripheral arterial circulation. Methods. We conducted a prospective, randomized, double − blind, placebo − controlled study. Thirty patients with body mass index over 30 kg/m2 normotensive, nonsmokers, without clinically manifested cardiovascular disease or diabetes were randomly assigned either orlistat (120 mg, 3 times daily; n = 20 or placebo (n = 10 in a double − blind manner. All of the patients were on individually calculated hypocaloric diet. The follow-up period was 24 weeks. Arterial pressure, fasting serum glucose and insulin level, triglycerides, total cholesterol and low density lipoprotein-cholesterol were determined at the beginning, following 3 and 6 months. Also, the intima − media thickness of right superficial femoral artery and the mean blood flow velocity were determined with ultrasonography. Results. Inside the period of 3 and 6 months, there were the greater reductions of body mass index, arterial pressure, fasting glucose and insulin level, total cholesterol, low density lipoproteins, as well as the greater reductions of mean velocity blood flow and peripheral pulse pressure in the orlistat group vs the placebo group (p < 0.01. Greater reductions in the waist circumference and intima − media thickness were registered following 6 months in the orlistat vs the placebo group (p < 0.01. Conclusion. In the group of obese patients orlistat therapy reduced risk factors, serum insulin level and improved early arterial functional changes as assessed with the reductions of the mean

  16. Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors.

    Directory of Open Access Journals (Sweden)

    Jae-Sung Park

    Full Text Available Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF, brain derived neurotrophic factor (BDNF and insulin-like growth factor-1 (IGF-1, in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

  17. Proinflammatory cytokine levels in fibromyalgia patients are independent of body mass index.

    Science.gov (United States)

    Hernandez, Maria E; Becerril, Enrique; Perez, Mayra; Leff, Philippe; Anton, Benito; Estrada, Sergio; Estrada, Iris; Sarasa, Manuel; Serrano, Enrique; Pavon, Lenin

    2010-06-03

    Fibromyalgia (FM) is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1beta, TNF-alpha, and IL-6) may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure the circulatory levels of proinflammatory cytokines to determine the influence of BMI on these levels in FM patients and healthy volunteers (HVs). In Spanish FM patients (n = 64) and HVs (n = 25), we measured BMI and serum concentrations of proinflammatory cytokines by capture ELISA. There were significant differences in BMI levels between FM patients (26.40 +/- 4.46) and HVs (23.64 +/- 3.45) and significant increase in IL-6 in FM patients (16.28 +/- 8.13 vs 0.92 +/- 0.32 pg/ml) (P BMI and TNF-alpha (F = 0.098, p = 0.75) or IL-6 (F = 0.221, p = 0.63) levels in FM patients. Our analysis in FM patients of BMI as a covariate of proinflammatory cytokines levels showed that serum TNF-alpha and IL-6 levels are independent of BMI. Further studies are necessary to dissect these findings and their implication in future therapeutic approaches for FM patients.

  18. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2015-10-01

    ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion. J...D, Apap-Bologna A, Kemp G. A dye-photosensitized reaction that generates stable protein-protein crosslinks. Analytical biochemistry . 1989 May 15;179(1

  19. The clinical significance of determination of peripheral blood TXA2, PGI2, TNF-α levels in patients with acute pancreatitis

    International Nuclear Information System (INIS)

    Hong Guangqiu; Ye Fei; Lin Hao

    2010-01-01

    Objective: To investigate the clinical significance of changes of peripheral blood TXA 2 , PGI 2 , TNF-α levels on assessment of the severity and prognosis of patients with acute pancreatitis (AP). Methods: Peripheral blood levels of TXA 2 , PGI 2 (plasma with RIA) and TNF-α (serum with ELISA) were detected in 30 patients with severe AP (SAP group), 56 patients with mild AP(MAP group) and 40 controls. Results: The peripheral blood levels of TXA 2 , TNF-α in the SAP group were significantly higher than those in the MAP group (P 2 levels were significantly lower (P 2 , PGI 2 and TNF-α levels were closely related to the severity and prognosis of AP and were important clinical indicators. (authors)

  20. Effect of menstrual cycle on HIV-1 levels in the peripheral blood and genital tract. WHS 001 Study Team.

    Science.gov (United States)

    Reichelderfer, P S; Coombs, R W; Wright, D J; Cohn, J; Burns, D N; Cu-Uvin, S; Baron, P A; Coheng, M H; Landay, A L; Beckner, S K; Lewis, S R; Kovacs, A A

    2000-09-29

    To assess the variation in HIV-1 over the menstrual cycle, including RNA levels in the female genital tract, plasma HIV-1-RNA levels, CD4 cell counts, and culturable virus. A prospective analysis of 55 HIV-1-infected women. Blood and genital tract specimens were collected weekly over 8 weeks, spanning two complete menstrual cycles. Applying repeated-measures models that used menses as the reference level, the variation in viral RNA levels was compared in endocervical canal fluid and cells (collected by Sno-strips and cytobrush, respectively) and ectocervicovaginal lavage (CVL) fluid. Repeated-measures models were also used to assess the variation in plasma CD4 cell counts and viral load. Shedding patterns differed among the three sampling methods, independent of genital tract co-infections. Genital tract HIV-1-RNA levels from CVL fluid and endocervical canal cytobrush specimens were highest during menses and lowest immediately thereafter (P = 0.001 and P = 0.04). The HIV-1-RNA level in endocervical canal fluid was highest in the week preceding menses (P = 0.003). The menstrual cycle had no effect on blood levels of RNA (P = 0.62), culturable virus (P = 0.34), or CD4 cell counts (P = 0.55). HIV-1-RNA levels were higher in endocervical canal fluid than in peripheral blood plasma during the late luteal phase (P = 0.03). HIV-1-RNA levels vary with the menstrual cycle in the female genital tract but not the blood compartment. HIV-1-RNA levels are higher in endocervical canal fluid than in blood plasma. These findings may have important implications for sex-specific pathogenesis, heterosexual transmission, and contraceptive hormone interventions in HIV-1-infected women.

  1. Association of Serum Uric Acid Levels with Leg Ischemia in Patients with Peripheral Arterial Disease after Treatment.

    Science.gov (United States)

    Sotoda, Yoko; Hirooka, Shigeki; Orita, Hiroyuki; Wakabayashi, Ichiro

    2017-07-01

    We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearson's correlation coefficient, -0.292 (p<0.01)] and leg exercise-induced decrease in ABI [Pearson's correlation coefficient, 0.236 (p< 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45-13.65, p<0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34-13.82, p<0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD.

  2. Functional characterization of neotropical snakes peripheral blood leukocytes subsets: Linking flow cytometry cell features, microscopy images and serum corticosterone levels.

    Science.gov (United States)

    de Carvalho, Marcelo Pires Nogueira; Queiroz-Hazarbassanov, Nicolle Gilda Teixeira; de Oliveira Massoco, Cristina; Sant'Anna, Sávio Stefanini; Lourenço, Mariana Mathias; Levin, Gabriel; Sogayar, Mari Cleide; Grego, Kathleen Fernandes; Catão-Dias, José Luiz

    2017-09-01

    Reptiles are the unique ectothermic amniotes, providing the key link between ectothermic anamniotes fish and amphibians, and endothermic birds and mammals; becoming an important group to study with the aim of providing significant knowledge into the evolutionary history of vertebrate immunity. Classification systems for reptiles' leukocytes have been described by their appearance rather than function, being still inconsistent. With the advent of modern techniques and the establishment of analytical protocols for snakes' blood by flow cytometry, we bring a qualitative and quantitative assessment of innate activities presented by snakes' peripheral blood leukocytes, thereby linking flow cytometric features with fluorescent and light microscopy images. Moreover, since corticosterone is an important immunomodulator in reptiles, hormone levels of all blood samples were measured. We provide novel and additional information which should contribute to better understanding of the development of the immune system of reptiles and vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The relationship between periodontal status and peripheral levels of neutrophils in two consanguineous siblings with severe congenital neutropenia: case reports.

    Science.gov (United States)

    Tözüm, Tolga Fikret; Berker, Ezel; Ersoy, Fügen; Tezcan, Iihan; Sanal, Ozden

    2003-03-01

    Congenital neutropenia is characterized by a severe reduction in absolute neutrophil counts, resulting in an almost total absence of neutrophils. It is well known that severe neutropenia affects periodontal status. Oral manifestations include ulcerations, gingival desquamation, gingival inflammation, attachment loss, and alveolar bone loss which may result in tooth loss. Treatment with granulocyte-colony stimulating factor (G-CSF) may improve this periodontal condition. This article reports the relationship between periodontal disease status and peripheral neutrophil levels in two consanguineous siblings with severe congenital neutropenia who did not receive routine G-CSF for 2 years prior to examination. Both siblings were given scaling, root planing, and periodontal prophylaxis in regular follow-up visits. This report demonstrates that periodontal therapy supported by adequate oral hygiene may result in restoration of neutrophil counts in siblings with congenital neutropenia.

  4. Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels

    Science.gov (United States)

    Dalle Molle, R; Portella, A K; Goldani, M Z; Kapczinski, F P; Leistner-Segala, S; Salum, G A; Manfro, G G; Silveira, P P

    2012-01-01

    Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena. PMID:23168995

  5. Influence of disease activity on steroid hormone levels in peripheral blood of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van den Brink, H. R.; Blankenstein, M. A.; Koppeschaar, H. P.; Bijlsma, J. W.

    1993-01-01

    The steroid hormone status of 27 female patients (15 premenopausal and 12 postmenopausal) and 11 male patients with rheumatoid arthritis (RA) was investigated before and after a clinically significant deterioration in disease activity. In postmenopausal patients the serum level of cortisol decreased

  6. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Directory of Open Access Journals (Sweden)

    Mario Rivera-Meza

    2017-07-01

    Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

  7. Dynamic movement of cytochrome c from mitochondria into cytosol and peripheral circulation in massive hepatic cell injury.

    Science.gov (United States)

    Kobayashi, Yoshinori; Mori, Masaaki; Naruto, Takuya; Kobayashi, Naoki; Sugai, Toshiyuki; Imagawa, Tomoyuki; Yokota, Shumpei

    2004-12-01

    In the process of apoptosis, it is known that the transition of cytochrome c from mitochondria into the cytosol occurs, and tumor necrosis factor (TNF)-alpha is one of the molecules responsible for this event. But in the state of hypercytokine induced by D-galactosamine (D-GaIN)/Lipopolysaccharide (LPS), the localization of cytochrome c is little known. Rats were administrated with D-GaIN(700 mg/kg)/LPS(200 microg/kg). Blood and tissue samples were collected and examined for levels of pro-inflammatory cytokines, the apoptosis of liver cells, and the localization of cytochrome c. Before administration of D-GaIN/LPS, cytochrome c was definitely localized in the mitochondria. At 2 h after simultaneous administration of D-GaIN/LPS, cytochrome c had accumulated in the cytosol following abrupt increases of plasma TNF-alpha. Massive cell destruction due to apoptosis proved by Terminal deoxynucleo-tidyl transferase-mediated dUTP nick end labeling staining was observed in liver tissue 4 h later and markedly increased levels of cytochrome c were detected in the plasma 12 h after D-GaIN/LPS administration. Liver injury induced by simultaneous administration of D-GaIN/LPS was closely associated with the production of TNF-alpha, and also with the dynamic movement of cytochrome c from the mitochondria into the cytosol, and then into the systemic circulation. The detection of plasma cytochrome c levels may be a useful clinical tool for the detection of apoptosis in vivo.

  8. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level

    OpenAIRE

    CADIOU , Hervé; AOUDE , Imad; Tazir , Bassim; Molinas , Adrien; Forbes Fenech , Claire; Meunier , Nicolas; Grosmaitre , Xavier

    2014-01-01

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of...

  9. Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

    Science.gov (United States)

    Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

    2014-04-02

    Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

  10. Endocan Levels in Peripheral Blood Predict Outcomes of Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Ling Tang

    2014-01-01

    Full Text Available Purpose. To investigate the prognostic significance of endocan, compared with procalcitonin (PCT, C-reactive protein (CRP,white blood cells (WBC, neutrophils (N, and clinical severity scores in patients with ARDS. Methods. A total of 42 patients with ARDS were initially enrolled, and there were 20 nonsurvivors and 22 survivors based on hospital mortality. Plasma levels of biomarkers were measured and the acute physiology and chronic health evaluation II (APACHE II was calculated on day 1 after the patient met the defining criteria of ARDS. Results. Endocan levels significantly correlated with the APACHE II score in the ARDS group (r=0.676, P=0.000, n=42. Of 42 individuals with ARDS, 20 were dead, and endocan was significantly higher in nonsurvivors than in survivors (median (IQR 5.01 (2.98–8.44 versus 3.01 (2.36–4.36 ng/mL, P=0.017. According to the results of the ROC-curve analysis and COX proportional hazards models, endocan can predict mortality of ARDS independently with a hazard ratio of 1.374 (95% CI, 1.150–1.641 and an area of receiver operator characteristic curve (AUROC of 0.715 (P=0.017. Moreover, endocan can predict the multiple-organ dysfunction of ARDS. Conclusion. Endocan is a promising biomarker to predict the disease severity and mortality in patients with ARDS.

  11. Effects of Endovascular Interventions on vWF and Fb Levels in Type 2 Diabetic Patients with Peripheral Artery Disease.

    Science.gov (United States)

    Yao, Hua-Qiang; Wang, Fu-Jun; Kang, Zhen

    2016-05-01

    von Willebrand Factor (vWF) and fibrinogen (Fb) are associated with hypercoagulability and thrombosis, which are the pathology and symptom of arterial disease. This research aims to study the effects of endovascular interventions on blood vWF and Fb levels in patients with diabetic peripheral artery disease (PAD). Totally, 66 type 2 diabetic patients with PAD (intervention group) and 26 type 2 diabetic patients without PAD (control group) were enrolled. These patients are matched at gender, age, and diabetes duration. For PAD patients, percutaneous interventions (balloon dilation or stent implantation) were performed, and blood samples were collected before, during, and after interventions. Then, enzyme-linked immunosorbent assay and prothrombin time-derived method were used to detect the levels of vWF and Fb, respectively. For intervention group, vWF and Fb levels in distal ischemic regions (vWF: 231.3%, Fb: 4.97 g/L) were significantly higher than that in nonischemic regions (vWF: 147.6%, Fb: 3.91 g/L, P value Fb levels were significantly increased (vWF: 299.2%, Fb: 5.69 g/L, P value Fb levels reached a peak (vWF: 199.3%, Fb: 4.96 g/L) and then decreased gradually to lower than the preinterventional levels (vWF: 148.3%, Fb: 3.88 g/L, P value Fb in the first week postintervention, leading to endothelial dysfunction and blood hypercoagulability. It suggested endothelial function protection and anticoagulant therapies should be applied to diabetic PAD patients after interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The relationship between typhoons' peripheral circulation and ground-level ozone concentrations in central Taiwan.

    Science.gov (United States)

    Cheng, Wan-Li; Lai, Li-Wei; Den, Walter; Wu, Meng-Ting; Hsueh, Chao-An; Lin, Pay-Liam; Pai, Chueh-Ling; Yan, Yeou-Lih

    2014-02-01

    Surface data of meteorological parameters (wind speed, wind direction, and mixing height) and air pollutant concentrations (O3, NO, and NO2) were collected for a 92-day period associated with typhoon formation in 2005. The influence of typhoons on O3 concentration were defined by azimuth and distance from Taiwan, and Types A, B, and C correspond to typhoons less than 1,500 km from Taiwan and located between azimuths 45° and 135°, 135° and 225°, and 225° and 45°, respectively. Type D corresponds to typhoons more than 1,500 km from Taiwan. Titration reactions were conducted at three temporal phases: 2000-0700, 0800-1100, and 1200-1400 LST (Local Standard Time). The air pollution model (TAPM) was used to simulate wind fields and trajectories of air masses. It was determined that typhoon position affected O3 concentration, temporal and spatial patterns of O3 titration and vertical meteorological characteristics, which were not all at the statistically significant level.

  13. Modification of hemoglobin level and hematocrit value in the peripheral blood of mice after 45Ca internal irradiation by MPG (2-mercaptopropionylglycine)

    International Nuclear Information System (INIS)

    Bhagat, R.M.; Kumar, A.

    1986-01-01

    Radioprotective effect of MPG has been studied on the hemoglobin level and hematocrit value of peripheral blood of Swiss albino mice against radiation-induced changes after injecting radiocalcium ( 45 Ca) at the dose level of 37 kBq/g body weight. MPG was injected 15-30 minutes before 45 Ca injection at dose of 20 mg/kg body weight intraperitoneally and also MPG was injected at various repeated doses. It has been observed that MPG in repeated doses is effective in reducing the radiation-induced changes in the hemoglobin and hematocrit value of peripheral blood of Swiss albino mice following 45 Ca internal irradiation. (author)

  14. T lymphocytes in the lesional skin and the levels of peripheral blood cytokines in patients with psoriasis

    Directory of Open Access Journals (Sweden)

    İbrahim Kökçam

    2011-03-01

    Full Text Available In the current study, it was aimed to investigate the roles of tissue cellular immunity and serum levels of cytokines in the patients with plaque psoriasis treated with calcipotriol-betamethasone dipropionate.Materials and methods: The study included 20 patients with psoriasis. Peripheral blood and biopsy samples were collected from lesional and normal skins before and after treatment. The results were compared with each other.Results: Immunohistochemical examination revealed significant elevations of CD4+, CD8+ and CD25+ T lymphocytes in the lesional tissues when compared to that in the healthy tissues and post treatment tissue (p0.05. The levels of IL–4, IL–10, TNF-α, IFN-γ and TGF-β1 in serum were not significantly different between before and after treatment periods (p>0.05.Conclusion: Our study demonstrated that there were infiltration of CD4+ and CD8+ cell in the lesional skin and CD8+ T-lymphocytes were the dominant cell types. The improvement of the lesions and significant decreases in CD4+ and CD8+ T-cells in accordance with the treatment strongly support the hypothesis that Th lymphocytes may have prominent roles in the immunopathogenesis of the disease. However, our findings showed that sufficient T-cells still remains in the tissue, which is consistent with the chronic characteristic of the disease, and the topical treatment could not be able to prevent the activation of the disease.

  15. Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

    Science.gov (United States)

    Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

    2013-11-01

    CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

  16. Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

    Science.gov (United States)

    Rao, Sambasiva P.; Sancho, Jose; Campos-Rivera, Juanita; Boutin, Paula M.; Severy, Peter B.; Weeden, Timothy; Shankara, Srinivas; Roberts, Bruce L.; Kaplan, Johanne M.

    2012-01-01

    Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact. PMID:22761788

  17. Human peripheral blood mononuclear cells exhibit heterogeneous CD52 expression levels and show differential sensitivity to alemtuzumab mediated cytolysis.

    Directory of Open Access Journals (Sweden)

    Sambasiva P Rao

    Full Text Available Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs display the highest number while natural killer (NK cells, plasmacytoid dendritic cells (pDCs and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact.

  18. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Tatiana Lauxen Peruzzolo

    2015-01-01

    Full Text Available Pediatric bipolar disorder (PBD is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder. We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  19. Reduction in high blood tumor necrosis factor-alpha levels after manipulative therapy in 2 cervicogenic headache patients.

    Science.gov (United States)

    Ormos, Gábor; Mehrishi, J N; Bakács, Tibor

    2009-09-01

    This case report discusses the treatment of 2 patients with cervicogenic headache (CHA) attending the Outpatient Clinic of the Hungarian National Institute for Rheumatology and Physiotherapy (Budapest, Hungary) and reviews the pathophysiology, therapeutic strategy, and problems associated with the treatment of CHA. Patient 1 was a 27-year-old female who sustained a whiplash injury. A sharp, shooting headache developed, readily induced, and aggravated by just bending the neck backward or by turning her head. Magnetic resonance imaging revealed a disk protrusion at C4-C5 pressing the anterior cerebrospinal space. Patient 2 was a 62-year-old female who sustained a whiplash injury; her cervical movements became restricted, which precipitated headaches. Magnetic resonance imaging revealed a paramedian disk hernia between the C4 and C5 vertebrae that intruded into the right ventral cerebrospinal space. After 4 weeks of manipulative therapy for patient 1, both active and passive range of motion returned to normal, and the high tumor necrosis factor-alpha (TNF-alpha) level (63 pg/mL) was substantially reduced (28 pg/mL). Patient 2 was started on manipulative therapy twice a week for 4 weeks; after 2 months, the patient became symptom-free, and high TNF-alpha level (72 pg/mL) was reduced greatly (35 pg/mL). Two patients with whiplash injury and disk herniation developed CHA associated with very high TNF-alpha levels. After manipulative therapy, these patients became symptom-free, and their TNF-alpha levels decreased substantially.

  20. Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns.

    Science.gov (United States)

    Pertyńska-Marczewska, Magdalena; Głowacka, Ewa; Grodzicka, Alicja; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jacek R; Wilczyński, Jan

    2010-02-01

    Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. of study These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. Neutrophil-derived secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes.

  1. Cardiac valve evaluation and adipokine levels in obese women treated with sibutramine.

    Science.gov (United States)

    Saraç, Sefa; Saraç, Fulden

    2010-06-01

    The aims of present study were 1) to evaluate cardiac valve characteristics, 2) to determine the plasma concentrations of fibrinogen, high sensitivity C-reactive protein (hsCRP), adiponectin, and tumor necrosis factor-alpha (TNF-alpha) in the obese women before and after 19 months sibutramine treatment in the obese women. Sixty obese women were enrolled in this prospective, randomized study. Thirty women received 10 mg once daily dose of sibutramine for 19 months. The rest of the obese women received 15 mg once daily dose of sibutramine for 19 months. All patients were evaluated with echocardiography. Plasma levels of adiponectin and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA) and hsCRP by immunoturbimetric assay. Student paired and unpaired t tests were used to compare the 10 mg or 15 mg dose sibutramine effects either in groups or between the groups. There were no signs of significant regurgitation or thickening of the mitral and aortic valves on echocardiographic evaluation performed after 19 months of treatment. Parameters of systolic function after 10 or 15 mg treatment were not different from pretreatment characteristics. Minimal tricuspid regurgitation was found in one (1/27) patient treated with 10 mg sibutramine after 19 months. Among obese patients treated with 15 mg sibutramine one patient (1/28) had minimal mitral valve regurgitation and 2 patients (2/28) had minimal aortic insufficiency. Stage II diastolic dysfunction in the 15 obese treated with 15 mg regressed to stage I diastolic dysfunction (50%). Stage II diastolic dysfunction in the 10 obese treated with 10 mg regressed to stage I diastolic dysfunction (33.3%). Mean levels of TNF-alpha(p=0.04), fibrinogen (p=0.03) and hsCRP (p=0.04)i decreased and adiponectin (p=0.03) levels increased in the obese treated with 10 mg sibutramine. Likewise, in the patients treated with 15 mg sibutramine, mean levels of TNF- alpha(p=0.01), fibrinogen (p= 0.02), and hsCRP (p= 0.04) decreased

  2. Magnetic resonance enterography changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s disease: correlation with SES-CD and clinical-biological markers

    International Nuclear Information System (INIS)

    Stoppino, Luca Pio; Della Valle, Nicola; Rizzi, Stefania; Cleopazzo, Elsa; Centola, Annarita; Iamele, Donatello; Bristogiannis, Christos; Stoppino, Giuseppe; Vinci, Roberta; Macarini, Luca

    2016-01-01

    In recent years, the use of MRI in patients with Crohn’s disease (CD) has increased. However, few data are available on how MRI parameters of active disease change during treatment with anti-TNF and whether these changes correspond to symptoms, serum biomarkers, or endoscopic appearance. The aim of this study was to determine the changes over time in MRI parameters during treatment with anti-TNF in patients with CD, and to verify the correlation between MRI score, endoscopic appearance and clinical-biological markers. We performed a prospective single centre study of 27 patients with active CD (18 males and 9 females; median age of 27,4 ys; age range, 19–49). All patients underwent ileocolonoscopy and MRI at baseline and 26 weeks after anti-TNF therapy. Endoscopic severity was graded according to the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Magnetic Resonance Index of Activity (MaRIA) was calculated. Patients underwent clinical evaluation (CDAI) and the C-reactive protein (CRP) level was measured. The associations between variables were assessed with Pearson’s bivariate correlation analysis. A total of 135 intestinal segments were studied. The median patient age was 27,4 years, 67 % were male and the mean disease duration was 6,1 years. For induction of remission, 18 patients were treated with infliximab and 9 with adalimumab. The mean SES-CD and MaRIA scores significantly changed at week 26 (SES-CD: 14,7 ± 8,9 at baseline vs. 4,4 ± 4,6 at 26 weeks - p < 0.001; MaRIA: 41,1 ± 14,8 at baseline vs. 32,8 ± 11,7 at 26 weeks - p < 0.001). Also the CDAI and serum levels of CRP decreased significantly following treatment (p < 0.001). The overall MaRIA correlated with endoscopic score and with clinical activity (CDAI) both at baseline and at week 26 (p < 0.05). The correlation between overall MaRIA and CRP was significant only at week 26 (p < 0.001). The MaRIA has a good correlation with SES-CD, a high accuracy for prediction of endoscopic

  3. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral......AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were...... included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed...

  4. Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression.

    Science.gov (United States)

    Tortarolo, Massimo; Vallarola, Antonio; Lidonnici, Dario; Battaglia, Elisa; Gensano, Francesco; Spaltro, Gabriella; Fiordaliso, Fabio; Corbelli, Alessandro; Garetto, Stefano; Martini, Elisa; Pasetto, Laura; Kallikourdis, Marinos; Bonetto, Valentina; Bendotti, Caterina

    2015-10-01

    Changes in the homeostasis of tumor necrosis factor α (TNFα) have been demonstrated in patients and experimental models of amyotrophic lateral sclerosis (ALS). However, the contribution of TNFα to the development of ALS is still debated. TNFα is expressed by glia and neurons and acts through the membrane receptors TNFR1 and TNFR2, which may have opposite effects in neurodegeneration. We investigated the role of TNFα and its receptors in the selective motor neuron death in ALS in vitro and in vivo. TNFR2 expressed by astrocytes and neurons, but not TNFR1, was implicated in motor neuron loss in primary SOD1-G93A co-cultures. Deleting TNFR2 from SOD1-G93A mice, there was partial but significant protection of spinal motor neurons, sciatic nerves, and tibialis muscles. However, no improvement of motor impairment or survival was observed. Since the sciatic nerves of SOD1-G93A/TNFR2-/- mice showed high phospho-TAR DNA-binding protein 43 (TDP-43) accumulation and low levels of acetyl-tubulin, two indices of axonal dysfunction, the lack of symptom improvement in these mice might be due to impaired function of rescued motor neurons. These results indicate the interaction between TNFR2 and membrane-bound TNFα as an innovative pathway involved in motor neuron death. Nevertheless, its inhibition is not sufficient to stop disease progression in ALS mice, underlining the complexity of this pathology. We show evidence of the involvement of neuronal and astroglial TNFR2 in the motor neuron degeneration in ALS. Both concur to cause motor neuron death in primary astrocyte/spinal neuron co-cultures. TNFR2 deletion partially protects motor neurons and sciatic nerves in SOD1-G93A mice but does not improve their symptoms and survival. However, TNFR2 could be a new target for multi-intervention therapies. © 2015 International Society for Neurochemistry.

  5. Ghrelin and obestatin levels in rheumatoid arthritis.

    Science.gov (United States)

    Koca, Suleyman Serdar; Ozgen, Metin; Aydin, Suleyman; Dag, Sait; Evren, Bahri; Isik, Ahmet

    2008-10-01

    Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (pghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, pghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

  6. Level of cytogenetic damage and morphological abnormalities in peripheral blood erythrocytes of fish from the Techa river

    Energy Technology Data Exchange (ETDEWEB)

    Tryapitsina, G. [Urals Research Center for Radiation Medicine - URCRM, Chelyabinsk State University (Russian Federation); Shaposhnikova, I. [Urals Research Center for Radiation Medicine - URCRM (Russian Federation); Rudolfsen, G. [Norwegian Radiation Protection Authority - NRPA, and University of Tromsoe (Norway); Obvintseva, N.; Pryakhin, E. [Urals Research Center for Radiation Medicine (Russian Federation); Akleyev, A. [Urals Research Center for Radiation Medicine and Chelyabinsk State University (Russian Federation)

    2014-07-01

    Low-level radioactive waste had been releasing to the Techa River from 1949 to 1956. Now it is a suitable water system to study the potential effect of chronic low level exposure of radiation. During that period over 76 million m{sup 3} of waste water was released into the river with total activity of 1.1 *10{sup 17} Bq. In 2012 we examined the erythrocytes in peripheral blood of fish (roach, perch, pike), inhabiting different part of the Techa River (Russia, Chelyabinsk region). Sampling was conducted twice a year (in May during spawning, and in August during feeding) at three stations with various levels of radioactive contamination: Station RT1 in the upper reach of the Techa River, station RT2 in the middle reach and station RT3 in the lower reach of the river. Determination of radionuclide concentrations in water, bottom sediments and fish was performed. An average above-background content of {sup 90}Sr in the body of fish inhabiting the Techa River is given in the table. Fish from the nearby Miass River was used as a control group. Blood was taken from the tail vein of live fish for the preparation of smears for determination of cytogenetic damage levels. 3,000 erythrocytes were analyzed for each fish on microscope Axioskop 50 (Carl Zeiss). Regression analyses found out significant dependency of the frequency of erythrocytes with micronuclei in blood on the burden of {sup 90}Sr in the body of roach in the summer period (F{sub 1,32}=4.6; p=0.04). The given data do not allow excluding the genotoxic influence of radiation on fish. Another important effect is an increase in the frequency of erythrocytes with cell division pathology: with an increase of the burden of {sup 90}Sr in the body, an increase in the frequency of amitoses and the sum of division pathologies are noted in the body. Regression analyses indicated a significant dependency of these parameters on the burden of {sup 90}Sr in the body of fish (for the frequency of amitoses F{sub 1,199}=6.3, p=0

  7. [Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa].

    Science.gov (United States)

    Jiskra, J; Haluzík, M; Svobodová, J; Haluzíková, D; Nedvídková, J; Parízková, J; Kotrlíková, E

    2000-10-25

    Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

  8. Lymphocutaneous Sporotrichosis during Treatment with Anti-TNF-Alpha Monotherapy

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    2015-01-01

    Full Text Available Sporotrichosis is an infectious disease caused by Sporothrix schenckii, a dimorphic fungus isolated for the first time in 1896 by Benjamin Schenck from a 36-year-old male patient presenting lesions on the right hand and arm. The infection generally occurs by traumatic inoculation of soil, plants, and organic matter contaminated with the fungus. Different clinical syndromes are described as a direct consequence of S. schenckii infection, including lymphocutaneous and disseminated forms, although extracutaneous presentations are reported most frequently in AIDS patients. Here we describe the case of a 57-year-old Caucasian male diagnosed in 2004 with ankylosing spondylitis under stable treatment with adalimumab monotherapy (40 mg every other week. During a routine follow-up visit in March 2013, he presented with multiple nodular lesions arranged in a linear fashion along the left hand and forearm. After diagnostic aspiration of the lesions, lymphocutaneous sporotrichosis was diagnosed and appropriate therapy started.

  9. TNF alpha drives mitochondrial stress in POMC neurons in obesity

    NARCIS (Netherlands)

    Yi, Chun-Xia; Walter, Marc; Gao, Yuanqing; Pitra, Soledad; Legutko, Beata; Kälin, Stefanie; Layritz, Clarita; García-Cáceres, Cristina; Bielohuby, Maximilian; Bidlingmaier, Martin; Woods, Stephen C.; Ghanem, Alexander; Conzelmann, Karl-Klaus; Stern, Javier E.; Jastroch, Martin; Tschöp, Matthias H.

    2017-01-01

    Consuming a calorically dense diet stimulates microglial reactivity in the mediobasal hypothalamus (MBH) in association with decreased number of appetite-curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC neuronal function is secondary to the microglial activation is unclear.

  10. Polimorfismo del TNF-alpha en autoinmunidad y tuberculosis.

    Directory of Open Access Journals (Sweden)

    Paula A. Correa

    2004-06-01

    Full Text Available El factor de necrosis tumoral alfa (TNF-a está incriminado tanto en enfermedades autoinmunes como en infecciosas. En el presente estudio se examinó el polimorfismo de la región promotora -308 del gen del TNF-a en enfermedades autoinmunes [lupus eritematoso sistémico (LES, artritis reumatoidea (AR, síndrome de Sjögren primario (SSp] y en tuberculosis. La genotipificación del polimorfismo -308 del TNF-a se realizó en ADN de pacientes con AR (N=165, LES (N=118, SSp (N=67, tuberculosis (N=138 y controles sanos (N=419, mediante reacción en cadena de la polimerasa con polimorfismos en los tamaños de los fragmentos de restricción (PCR-RFLP. El alelo TNF2 se asoció con la AR (OR=1,6; IC95% 1,2-2,3, p=0,008, el LES (OR=2,3; IC95% 1,6-3,3, p

  11. Study on serum TNF-α level, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Shi Buqing

    2006-01-01

    Objective: To study the changes of serum TNF-α levels, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis. Methods: Serum TNF-α levels (with RIA), B cell as well as T cell subsets distribution type (with monoclonal antibody technique) were examined in 37 patients with rheumatoid arthritis and 30 controls. Results Serum TNF-α levels and B lymphocytes count were significantly higher in the patients than those in controls (P 3 , CD 4 and CD 4 /CD 8 were obviously lower (P<0.01). Conclusion: Rheumatoid arthritis is an autoimmune disease with abnormal immunoregulation. (authors)

  12. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  13. [Effects of Electroaupuncture Stimulation of "Xiajuxu" (ST 39), etc. on Duodenal Mucosal Injury, Serum Pro-inflammatory Factors Levels and Duodenal Nicotinic Acetylcholine Receptor alpha 7 Expression in Duodenal Ulcer Rats].

    Science.gov (United States)

    Ling, Xi; Zhang, Hong; Yi, Xi-qin; Wu, Jin-feng

    2016-04-01

    To observe the relatively specific effect of electroacupuncture (EA) of "Xiajuxu" (ST 39, the lower hesea paint of the small intestine), etc. on the level of serum TNF-alpha, lnterleukin-1 P (IL-1 P) and high mobility group protein B 1 (HMGB 1) contents, and duodenum a7 nicotinic acetyicholine receptor (nAchR) expression in duodenal ulcer rats, so as to explore its mechanisms underlying improving duodenal ulcer. Sixty SD rats were randomly divided into 6 groups: normal control, model, Xiajuxu (ST 39), Zusanli (ST 36), Shangjuxu (ST 37) and Yanglingquan (GB 34). The duodenal ulcer model was established by subcutaneous injection of 10% Cysteamine Hydrochloride (300 mg/kg), following by giving the rats with access to water containing Cysteamine. EA (10 Hz/50 Hz, 1- 3 mA) was applied to bilateral ST 39, ST 36, ST 37 and GB 34 for 30 min, once daily for 10 days. The ulcer scores (0-5 points) of the duodenal mucosa were assessed according to modified Moraes' methods. Serum TNF-alpha, IL-1 beta and HMGB 1 levels were assayed by ELISA and the expression of neuronal a7 nAchR in the duodenal tissue was detected by Western blot. After modeling, the ulcer score, serum TNF-alpha, IL-i p and HMGB 1 contents were significantly increased (P0.05). EA stimulation of ST 36, ST 37 and ST 39 can reduce ulcer injury in duodenal ulcer model rats, which may be associated with their effects in down-regulating serum TNF-alpha, IL-1 beta and HMGB 1 contents and up-regulating alpha7 nAchR expression of the duodenal tissue, possibly by suppressing immune and inflammatory reactions and regulating nicotinic activity.

  14. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  15. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high......) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P...

  16. Modification of postnatal hemoglobin level and hematocrit value in the peripheral blood of mice after gamma radiation in utero by MPG (2-mercaptopropionylglycine)

    International Nuclear Information System (INIS)

    Goyal, P.K.; Kumar, S.; Dev, P.K.

    1980-01-01

    Pregnant Swiss albino mice were irradiated with oamma radiation at post-conception days 14.5, 16.25 and 18.25. Hemoglobin level and hematocrit value in the peripheral blood of the male offsprings were found to be below normal during the early postnatal development. The value became normal from 4 week onwards. However these values were found to be significantly elevated in the early postnatal development of the male offsprings of the mice which were administered MPG before irradiation. The possible radioprotective mechanism of MPG is discussed. (M.G.B.)

  17. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

    Science.gov (United States)

    Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

    2015-10-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

  18. The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells

    Science.gov (United States)

    Kwiatkowska, Marta; Jarosiewicz, Paweł; Michałowicz, Jaromir; Koter-Michalak, Maria; Huras, Bogumiła; Bukowska, Bożena

    2016-01-01

    The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide—glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01–10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances. PMID:27280764

  19. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

    Science.gov (United States)

    Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

    2015-01-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

  20. The mRNA level of MLH1 in peripheral blood is a biomarker for the diagnosis of hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Yu, Hong; Li, Hui; Cui, Yongan; Xiao, Wei; Dai, Guihong; Huang, Junxing; Wang, Chaofu

    2016-01-01

    Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by functional defects in mismatch repair (MMR) genes, including mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2). This study aimed to assess whether the mRNA expression of MLH1 in peripheral blood could be used as a biomarkers for the diagnosis of HNPCC. The mRNA level of MLH1 was determined in 19 HNPCC families (46 members) using real-time quantitative polymerase chain reaction (qPCR). The mRNA levels of MLH1 in HNPCC were significantly lower than controls (P MLH1 for the diagnosis of HNPCC with the area under curve of 0.858. At an optimal cut-off value (0.511), the mRNA level of MLH1 had a sensitivity of 81.3% and a specificity of 86.7% for distinguishing HNPCC from controls. In conclusion, the mRNA expression of MLH1 in peripheral blood may serve as a biomarker for the diagnosis of HNPCC.

  1. Cytochrome P450 1B1 mRNA levels in peripheral blood cells and exposure to polycyclic aromatic hydrocarbons in Chinese coke oven workers

    Energy Technology Data Exchange (ETDEWEB)

    Hanaoka, Tomoyuki; Tsugane, Shoichiro [Epidemiology and Biostatistics Division, National Cancer Center Research Institute East, 6-5-1 Kashiwanoha, Kashiwa-shi, 277-8577 Chiba (Japan); Yamano, Yuko; Kagawa, Jun [Tokyo Womens' Medical University, 8-1 Kawadacho, Shinjuku-ku, 162-8666 Tokyo (Japan); Pan, Guowei; Zhang, Shujuan [Liaoning Provincial Center for Disease Prevention and Control, 42-1 Jixian Street, 110005 Shenyang (China); Hara, Kunio [Institute for Science of Labour, 2-8-14 Miyamae-ku, 216-8501 Kawasaki (Japan); Ichiba, Masayoshi; Zhang, Jiusong [Saga Medical School, 5-1 Nabeshima, Saga-shi, 849-8501 Saga (Japan); Liu, Tiefu; Li, Landi [Angang Public Health and Anti-epidemic Station Lishan District, 23 Shengoushi Yutian Street, 114034 Anshan (China); Takahashi, Ken [University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, 807-8555 Kitakyushu (Japan)

    2002-09-16

    Cytochrome P450 1B1 (CYP1B1) is induced through the Ah receptor and is involved in the activation of polycyclic aromatic hydrocarbons (PAHs). To determine the validity of a quantitative analysis of CYP1B1 mRNA in peripheral human blood cells for the estimation of PAH exposure, a real-time quantitative polymerase chain reaction method was used to measure the relative levels of CYP1B1 mRNA in 37 Chinese coke oven workers and 13 control workers. A large inter-individual difference in the levels was observed. The average level of the CYP1B1 mRNA in workers at the top work site, where the PAH exposure level from the coke ovens was highest, was significantly higher than in workers at the middle site (P<0.01) or the controls (P=0.02). A non-significant positive correlation was found between the CYP1B1 mRNA levels and urinary 1-hydroxypyrene (R=0.22, P=0.13), and a significant correlation between these mRNA levels and urinary cotinine (R=0.33, P=0.02). It was interesting that a significant positive correlation between CYP1B1 mRNA and 1-hydroxypyrene was observed in subjects with the Leu/Leu type of CYP1B1 Leu432Val polymorphism (R=0.33, P=0.02, n=38) and a non-significant correlation in subjects with the Leu/Val and Val/Val types (R=-0.36, P=0.25, n=12), although the number of subjects in this strata analysis was small. Our preliminary study suggests that PAH exposure in coke ovens and smoking maybe associated with CYP1B1 mRNA levels in peripheral blood cells although mRNA is generally unstable and could be expressed following exposure to other agents.

  2. Serum levels of TGF-β1 in patients of diabetic peripheral neuropathy and its correlation with nerve conduction velocity in type 2 diabetes mellitus.

    Science.gov (United States)

    Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

    2016-01-01

    To correlate serum levels of TGF-β1 with motor and sensory nerve conduction velocities in patients of type 2 diabetes mellitus The study was conducted in diagnosed type 2 diabetes mellitus patients which were divided in patients with clinically detectable peripheral neuropathy of shorter duration (n=37) and longer duration (n=27). They were compared with patients without clinical neuropathy (n=22). Clinical diagnosis was based on neuropathy symptom score (NSS) and Neuropathy disability score (NDS) for signs. Blood samples were collected for baseline investigations and estimation of serum TGF-β1. Nerve conduction velocity was measured in both upper and lower limbs. Median, Ulnar, Common Peroneal and Posterior Tibial nerves were selected for motor nerve conduction study and Median and Sural nerves were selected for sensory nerve conduction study In patients of type 2 diabetes mellitus with clinically detectable and serum TGF-β1 showed positive correlation with nerve conduction velocities High level of TGF-β1 in serum of T2DM patients with neuropathy show possible contribution in development of neuropathy. Due to its independent association this cytokine might be used as biomarker for diabetic peripheral neuropathy. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Combination of signal intensity measurements of lesions in the peripheral zone of prostate with MRI and serum PSA level for differentiating benign disease from prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Engelhard, K.; Kreckel, M. [Department of Radiology, Martha-Maria Hospital Nuernberg (Germany); Hollenbach, H.P.; Deimling, M. [Siemens Medical Engineering Group, Erlangen (Germany); Riedl, C. [Dept. of Urology, University of Erlangen-Nuernberg, Erlangen (Germany)

    2000-12-01

    The aim of this study was to predict the benign or malignant nature of a prostatic lesion by defining a threshold value of signal intensity ratio and a limiting value of serum prostate-specific antigen (PSA) in patients with elevated PSA level. Twenty-six patients with elevated PSA level and no hypoechogenic lesions at endosonography underwent MR imaging using an endorectal body phased-array coil at 1.5 T (Siemens Magnetom Symphony). A T2-weighted turbo-spin-echo (TSE) pulse sequence was applied in a transverse orientation. Two radiologists evaluated the images. In the presence of a pathological finding they defined regions of interest (ROI) in the suspicious pathological area of the peripheral zone and in muscle for reference. The quotient of the two ROIs was calculated and then correlated with the actual PSA level. Diagnosis was confirmed by prostate biopsy. Ten of 12 patients with quotients smaller than 4 showed cancer at histology. Nine of 12 men with cancer proven by biopsy had PSA levels higher than 10 ng/ml. A significant difference (p < 0.001) was found between the quotients of cancer and quotients of chronic prostatitis, fibrosis, or glandular atrophy. The accuracy of tumor differentiation of the method was 77 %. Measurement of signal intensity quotients in the peripheral zone of the prostate in combination with knowledge of defined limits of PSA levels the technique could be helpful in detecting additional cancer areas for prostate biopsy. False-negative tumor results of standard sextant biopsy can be reduced. In men with high PSA values the method has a role in differentiating between patients who require prostate biopsy and those of clinical observation. (orig.)

  4. Association of plasma fetuin-a levels with peripheral arterial disease and lower extremity arterial calcification in subjects with type 2 diabetes mellitus.

    Science.gov (United States)

    Eleftheriadou, Ioanna; Grigoropoulou, Pinelopi; Kokkinos, Alexander; Mourouzis, Iordanis; Perrea, Despoina; Katsilambros, Nicholas; Sfikakis, Petros P; Tentolouris, Nikolaos

    2017-03-01

    Fetuin-A is a hepatic glycoprotein that is involved in insulin resistance and atherosclerosis. Herein we examined the association of plasma fetuin-A levels with peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM). A total of 71 patients with T2DM and 57 non-diabetic individuals were recruited. Diagnosis of PAD was based on the absence of triphasic waveform at pedal arteries, while ankle-brachial index (ABI) was calculated. Radiographs of both feet and ankles were taken for the assessment of lower extremity arterial calcification (LEAC). Plasma fetuin-A levels were measured using ELISA. Patients with T2DM had higher fetuin-A levels than non-diabetic participants. Participants with diabetes and PAD had lower fetuin-A levels than non-PAD diabetic patients. In subjects with T2DM fetuin-A levels were associated with ABI. Multivariate analysis demonstrated that in patients with T2DM the odds of PAD increased with long diabetes duration, smoking, presence of arterial hypertension and dyslipidemia, as well as with lower fetuin-A levels. A trend towards higher fetuin-A levels in subjects with less severe LEAC was found. Plasma fetuin-A levels are lower in patients with T2DM and PAD and are associated with PAD, irrespective of traditional cardiovascular risk factors. Moreover, fetuin-A may be involved in arterial calcification. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Influence of an irregular surface and low light on the step variability of patients with peripheral neuropathy during level gait.

    Science.gov (United States)

    Thies, Sibylle B; Richardson, James K; Demott, Trina; Ashton-Miller, James A

    2005-08-01

    Patients with peripheral neuropathy (PN) report greater difficulty walking on irregular surfaces with low light (IL) than on flat surfaces with regular lighting (FR). We tested the primary hypothesis that older PN patients would demonstrate greater step width and step width variability under IL conditions than under FR conditions. Forty-two subjects (22 male, 20 female: mean +/- S.D.: 64.7 +/- 9.8 years) with PN underwent history, physical examination, and electrodiagnostic testing. Subjects were asked to walk 10 m at a comfortable speed while kinematic and force data were measured at 100 Hz using optoelectronic markers and foot switches. Ten trials were conducted under both IL and FR conditions. Step width, time, length, and speed were calculated with a MATLAB algorithm, with the standard deviation serving as the measure of variability. The results showed that under IL, as compared to FR, conditions subjects demonstrated greater step width (197.1 +/- 40.8 mm versus 180.5 +/- 32.4 mm; P < 0.001) and step width variability (40.4 +/- 9.0 mm versus 34.5 +/- 8.4 mm; P < 0.001), step time and its variability (P < 0.001 and P = 0.003, respectively), and step length variability (P < 0.001). Average step length and gait speed decreased under IL conditions (P < 0.001 for both). Step width variability and step time variability correlated best under IL conditions with a clinical measure of PN severity and fall history, respectively. We conclude that IL conditions cause PN patients to increase the variability of their step width and other gait parameters.

  6. EARLY IDENTIFICATION OF SWINE INFLUENZA A (H1N1- BASING ONEPIDEMIOLOGIC CLUE, CLINICAL PRESENTATION, IMAGING FINDINGS, PERIPHERAL LEUCOCYTE COUNTS AND SPO2 LEVELS

    Directory of Open Access Journals (Sweden)

    Venkateswararao Kopparti

    2017-11-01

    Full Text Available BACKGROUND The present study is a retrospective study of 22 cases of RT-PCR positive swine influenza spanning from 2014 to 20-09-2017 with main objective of early identification of influenza A H1N1 basing on epidemiological clue, clinical presentation, imaging findings and lab parameters as early antiviral therapy and judicious management of ARDS brings good outcome as per available literature. 1,2,3 MATERIAL AND METHODS 22 confirmed adult cases of swine influenza by throat/nasopharyngeal swab RT-PCR for H1N1 were studied in terms of clinical presentation, imaging findings, lab manifestations and SpO2 levels4 with particular emphasis on imaging findings. RESULTS 95% presented with symptoms of Influenza-Like Illness (ILI. Nearly, 80% of patients belonged to fourth to fifth decades. Leucocyte count was normal in 75% and 25% had low leucocyte count (<4000, SpO2 levels were normal in 25% and low in 75% cases. CXR was abnormal in 82% of cases of which 83% had mid/lower zone peripheral, patchy, pleural-based consolidations and 17% showed all lung zone opacities. HRCT chest done in 32% of cases showed similar features of chest xray findings with dominant mid/lower zone pleural-based consolidations to ground-glass haziness without pleural effusions and no mediastinal nodal involvement. CONCLUSION As intermittent outbreaks of swine influenza are still continuing in India with recent spurt in incidence in the months of April/May 2017, early diagnosis of H1N1 A is necessary for improved outcome. Early diagnosis is feasible by ILI presentation, normal or low leucocyte count, low SpO2 levels and characteristic radiologic findings of bilateral mid/lower zone pleural-based peripheral patchy opacities to consolidations. As this can be done at peripheral level, primary care physicians need to be sensitised in early diagnosis and treatment and prompt referral to higher centres when needed. Since, the present study is a retrospective one and of public health

  7. Study on the relationship between peripheral blood red blood cells immunofunction status and serum TNF-α levels in pediatric patients with Henoch-Schoenlein purpura

    International Nuclear Information System (INIS)

    Feng Yue; He Haoming

    2005-01-01

    Objective: To investigate the relationship between changes of peripheral RBC immuno-function and serum TNF-α levels in pediatric patients with Henoch-Schoenlein purpura. Methods: RBC immuno-function status was studied with immunologic methods and serum TNF-α levels were measured with RIA in 31 pediatric patients with Henoch-Schoenlein purpura and 35 controls, Results: Levels of RBC-C3bRR were significantly lower and levels of serum TNF-α were significantly higher in the patients than those in controls (P<0.01). These two variables were significantly negatively correlated (r=-0.3018, P<0.05). On the contrary, the RBC-ICRRR levels were significantly higher in the patients (P<0.01) and were positively correlated with levels of TNF-α (r=0.3588, P<0.05). Conclusion: There were disturbances of RBC immuno-regulation with suppressed immuno-function in the purpura patients, which were related to the high levels of TNF-α. (authors)

  8. Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Farrelly, Cormac, E-mail: farrellycormac@gmail.com [Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Lal, Priti [University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine (United States); Trerotola, Scott O.; Nadolski, Gregory J.; Watts, Micah M. [Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Gorrian, Catherine Mc. [Mater Misericordiae University Hospital, University College Dublin School of Medicine & Medical Science (Ireland); Guzzo, Thomas J. [University of Pennsylvania Perelman School of Medicine, Department of Urology and Surgery (United States)

    2016-05-15

    PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

  9. Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study

    International Nuclear Information System (INIS)

    Farrelly, Cormac; Lal, Priti; Trerotola, Scott O.; Nadolski, Gregory J.; Watts, Micah M.; Gorrian, Catherine Mc.; Guzzo, Thomas J.

    2016-01-01

    PurposeTo correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA.Materials and MethodsIn this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1–7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens.ResultsMean PVS PSA was 4.29, range 2.3–6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left–sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events.ConclusionfPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

  10. Correlation of Peripheral Vein Tumour Marker Levels, Internal Iliac Vein Tumour Marker Levels and Radical Prostatectomy Specimens in Patients with Prostate Cancer and Borderline High Prostate-Specific Antigen: A Pilot Study.

    Science.gov (United States)

    Farrelly, Cormac; Lal, Priti; Trerotola, Scott O; Nadolski, Gregory J; Watts, Micah M; Gorrian, Catherine Mc; Guzzo, Thomas J

    2016-05-01

    To correlate prostate-specific antigen (PSA), free to total PSA percentage (fPSA%) and prostatic acid phosphatase (PAP) levels from peripheral and pelvic venous samples with prostatectomy specimens in patients with prostate adenocarcinoma and borderline elevation of PSA. In this prospective institutional review board approved study, 7 patients with biopsy proven prostate cancer had a venous sampling procedure prior to prostatectomy (mean 3.2 days, range 1-7). Venous samples were taken from a peripheral vein (PVS), the right internal iliac vein, a deep right internal iliac vein branch, left internal iliac vein and a deep left internal iliac vein branch. Venous sampling results were compared to tumour volume, laterality, stage and grade in prostatectomy surgical specimens. Mean PVS PSA was 4.29, range 2.3-6 ng/ml. PSA and PAP values in PVS did not differ significantly from internal iliac or deep internal iliac vein samples (p > 0.05). fPSA% was significantly higher in internal iliac (p = 0.004) and deep internal iliac (p = 0.003) vein samples compared to PVS. One of 7 patients had unilateral tumour only. This patient, with left-sided tumour, had a fPSA% of 6, 6, 6, 14 and 12 in his peripheral, right internal iliac, deep right internal iliac branch, left internal iliac and deep left internal iliac branch samples respectively. There were no adverse events. fPSA%, unlike total PSA or PAP, is significantly higher in pelvic vein compared to peripheral vein samples when prostate cancer is present. Larger studies including patients with higher PSA values are warranted to further investigate this counterintuitive finding.

  11. Study on the relationship between peripheral blood red blood cells imuno-function status and serum gastrin level in patients with peptic ulcer

    International Nuclear Information System (INIS)

    Li Qin; Fan Rong; Luo Honglai; Wang Ying; Tao Liangliang; Wang Zhenkai

    2011-01-01

    Objective: To explore the relationship between changes of peripheral blood red blood cells immuno-function status and serum gastrin level in patients with peptic ulcer. Methods: RBC immuno-function status was studied with immune methods and serum gastrin level was measured with RIA in 51 patients with peptic ulcer and compared with 35 healthy control group. Results: RBC-C3bRR percentage was significantly lower in patients with peptic ulcer than that in controls (P<0.01), while serum gastrin level was significantly higher (P<0.01). RBC-C3bRR was significantly nagatively correlated to serum gastrin (r=-0.3828, P<0.01). RBC-ICRRR percentage was prominently higher than that in healthy controls (P<0.01), and RBC-ICRRR was positively correlated to serum gastrin level (r=0.4185, P<0.01). Conclusion: There were disturbance of RBC immune-regulation with suppressed immune function and higher gastrin levels in patients with peptic ulcer. (authors)

  12. Radioimmunological studies on the level of progesterone in the peripheral blood of pregnant rabbits with special respect to season and number of living newborn

    International Nuclear Information System (INIS)

    Enbergs, H.

    1979-01-01

    The progesterone concentrations in the peripheral blood have been measured radioimmunologically in 12 white Newzealand rabbits 10 times during pregnancy. The results were examined especially in respect to season and number of living newborn. The progesterone concentrations reached their peak values at the 7th (7.0 ng/ml) resp. 11th day (7.4 ng/ml). The progesterone niveau was in October only a little lower than in May. The progesterone levels of 5 rabbits with diameter 10 newborn were nearly identical with those of 5 rabbits with only diameter 6.2 newborn. This shows, that the progesterone niveau does not depend mainly on the number of the newborn in the observed range. (orig.) [de

  13. Peripheral Blood CD64 Levels Decrease in Crohn’s Disease following Granulocyte and Monocyte Adsorptive Apheresis

    Directory of Open Access Journals (Sweden)

    Toshimi Chiba

    2011-12-01

    Full Text Available Granulocyte and monocyte adsorptive apheresis (GMA is reportedly useful as induction therapy for Crohn’s disease (CD. However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI. The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.

  14. Correlation between base-excision repair gene polymorphisms and levels of in-vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes.

    Directory of Open Access Journals (Sweden)

    Hongping Yu

    Full Text Available In vitro benzo[a]pyrene diol epoxide (BPDE-induced DNA adducts in cultured peripheral lymphocytes have been shown to be a phenotypic biomarker of individual's DNA repair phenotype that is associated with cancer risk. In this study, we explored associations between genotypes of base-excision repair genes (PARP1 Val762Ala, APEX1 Asp148Glu, and XRCC1 Arg399Gln and in vitro BPDE-induced DNA adducts in cultured peripheral blood lymphocytes in 706 cancer-free non-Hispanic white subjects. We found that levels of BPDE-induced DNA adducts were significantly higher in ever smokers than in never smokers and that individuals with the Glu variant genotypes (i.e., Asp/Glu and Glu/Glu exhibited lower levels of BPDE-induced DNA adducts than did individuals with the common Asp/Asp homozygous genotype (median RAL levels: 32.0 for Asp/Asp, 27.0 for Asp/Glu, and 17.0 for Glu/Glu, respectively; P(trend = 0.030. Further stratified analysis showed that compared with individuals with the common APEX1-148 homozygous Asp/Asp genotype, individuals with the APEX1-148Asp/Glu genotype or the Glu/Glu genotype had a lower risk of having higher-level adducts (adjusted OR = 0.60, 95% CI: 0.36-0.98 and adjusted OR = 0.47, 95% CI: 0.26-0.86, respectively; P(trend = 0.012 among smokers. Such an effect was not observed in non-smokers. However, there was no significant interaction between the APEX1 Asp148Glu polymorphism and smoking exposure in this study population (P = 0.512. Additional genotype-phenotype analysis found that the APEX1-148Glu allele had significantly increased expression of APEX1 mRNA in 270 Epstein-Barr virus-transformed lymphoblastoid cell lines, which is likely associated with more active repair activity. Our findings suggest that the functional APEX1-148Glu allele is associated with reduced risk of having high levels of BPDE-induced DNA adducts mediated with high levels of mRNA expression.

  15. Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

    Science.gov (United States)

    Roh, Hee-Tae; So, Wi-Young

    2017-01-01

    Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

  16. Correlation of the severity of atopic dermatitis with absolute eosinophil counts in peripheral blood and serum IgE levels

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    Dhar Sandipan

    2005-01-01

    Full Text Available BACKGROUND: Although a number of epidemiological studies, showing incidence and prevalence of atopic dermatitis, were available, scant attention has been paid to the correlation between the parameters of the disease like severity, absolute eosinophil count and IgE level, which has been known to be associated inconsistently. Hence this study was undertaken. METHODS: A total of 102 patients of atopic dermatitis, both children and adults, and 107 age matched controls were studied at the Pediatric Dermatology clinic, Institute of Child Health and department of Dermatology, AMRI-Apollo hospitals, Kolkata. RESULTS: The average age of onset of atopic dermatitis was observed to be 4.55 years. Both the average absolute eosinophil count and IgE levels in patients of atopic dermatitis were significantly higher than that of the controls. Each of these parameters showed significant correlation with severity of the disease and showed a nonhomogeneous distribution reflected by significant association with personal history of bronchial asthma and family history of atopy, when both parents were atopic. CONCLUSIONS: Our study shows that clinical activity of the disease as recorded by the "SCORAD" index can be used as an indicator of the hematological abnormalities as well as to some extent as a prognostic indicator. Family history of atopy correlates with the hematological abnormalities only if both parents are involved and bronchial asthma is the only associated atopic condition which correlates with the parameters of the disease .

  17. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotide

    DEFF Research Database (Denmark)

    Kamstrup, Søren; Verthelyi, D.; Klinman, D.M.

    2001-01-01

    Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found in bacter......Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found...... in bacterial but not vertebrate DNA. Different motifs are optimally stimulatory in different species. This work examines whether oligodeoxynucleotides (ODNs) containing CpG motifs stimulate peripheral blood mononuclear cells from pigs. Results show that pigs respond to CpG ODN by proliferating and secreting IL......-6, IL-12 and TNF-alpha. By screening a large panel (>100) of ODNs, the palindromic hexamer 'ATCGAT' was identified as being optimally active in all animals examined (N = 10). These findings are the first to establish the immunostimulatory activity of CpG ODN in pigs, and suggest that the therapeutic...

  18. Evaluation of angiopoietin 1 and 2, vascular endothelial growth factor, and tumor necrosis factor alpha levels in asthmatic children.

    Science.gov (United States)

    Köksal, Burcu Tahire; Ozbek, Ozlem Yilmaz; Bayraktar, Nilufer; Yazici, Ayse Canan

    2014-01-01

    Asthma is characterized by chronic airway inflammation that is associated with structural changes termed airway remodeling. Recently, cytokines/mediators that augment inflammation have been attracting attention in this field. The aim of this study was to evaluate serum angiopoietin (Ang)-1, Ang-2, vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) alpha values, which have important roles in inflammation, angiogenesis, and remodeling in asthmatic children. We also documented correlations between demographic features, duration of asthma, and pulmonary function test (PFT) parameters. Randomly selected 40 children (20 male and 20 female children, aged 6-16 years) with mild or moderate persistent asthma and 32 healthy children (15 male and 17 female children, aged 6-16 years) enrolled in the study. All asthmatic children had been using inhaled corticosteroids at least for the last 3 months. Serum Ang-1 levels were significantly lower in asthmatic children than those in normal controls. The Ang-1/Ang-2 ratio was also significantly lower in asthmatic children compared with those in normal controls (p < 0.01). However, serum Ang-2, VEGF, and TNF-alpha levels were similar in the two groups. A significant positive correlation was found between VEGF and duration of asthma. No correlation between serum Ang-1, Ang-2, VEGF values, and PFT parameters was obtained. On the other hand, significant negative correlation was detected between serum TNF-alpha and forced expiratory volume in 1 second. We have shown that serum Ang-1 levels and Ang-1/Ang-2 ratio were significantly reduced and balance was toward Ang-2 in asthmatics children. This process may lead to inflammation, destabilization of blood vessels, and trigger remodeling.

  19. Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients

    Directory of Open Access Journals (Sweden)

    Xu Zhuwei

    2009-06-01

    Full Text Available Abstract Background As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226 levels in sera, and membrane CD226 (mCD226 expression on peripheral blood mononuclear cells (PBMC from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy. Results Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (P P Conclusion These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.

  20. Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults.

    Science.gov (United States)

    Maass, Anne; Düzel, Sandra; Brigadski, Tanja; Goerke, Monique; Becke, Andreas; Sobieray, Uwe; Neumann, Katja; Lövdén, Martin; Lindenberger, Ulman; Bäckman, Lars; Braun-Dullaeus, Rüdiger; Ahrens, Dörte; Heinze, Hans-Jochen; Müller, Notger G; Lessmann, Volkmar; Sendtner, Michael; Düzel, Emrah

    2016-05-01

    Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n=21) or to a control group (indoor progressive-muscle relaxation/stretching, n=19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. Copyright © 2015 The Authors

  1. High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality

    DEFF Research Database (Denmark)

    Johansen, J. S.; Pedersen, Agnes Nadelmann; Schroll, M.

    2007-01-01

    YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We...... studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n...

  2. Low BMI is correlated with increased TGF-β and IL-10 mRNA levels in the peripheral blood of breast cancer patients.

    Science.gov (United States)

    Liu, Chao; Wang, Qian; Sun, Bing; Meng, Xiangying; Li, Lan; Yang, Liuchun; Cong, Yang; Liu, Jiannan; Xuan, Liang; Huang, Yan; Wu, Shikai

    2018-03-01

    Transforming growth factor-β (TGF-β), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-β, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-β, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF-β mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (BMI (BMI BMI ≥ 25), respectively (P BMI, may strongly affect systematic immune function in patients with breast cancer. © 2018 IUBMB Life, 70(3):237-245, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  3. No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation.

    Science.gov (United States)

    Kuypers, Kim P C; de la Torre, Rafael; Farre, Magi; Yubero-Lahoz, Samanta; Dziobek, Isabel; Van den Bos, Wouter; Ramaekers, Johannes G

    2014-01-01

    The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.

  4. No evidence that MDMA-induced enhancement of emotional empathy is related to peripheral oxytocin levels or 5-HT1a receptor activation.

    Directory of Open Access Journals (Sweden)

    Kim P C Kuypers

    Full Text Available The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg, with or without pindolol (20 mg, oxytocin nasal spray (40 IU+16 IU or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18-26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial registration: MDMA & PSB NTR 2636.

  5. Large-area irradiated low-level laser effect in a biodegradable nerve guide conduit on neural regeneration of peripheral nerve injury in rats.

    Science.gov (United States)

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2011-08-01

    This study used a biodegradable composite containing genipin-cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT), developed in a previous study, as a nerve guide conduit. The aim of this study was to analyse the influence of a large-area irradiated aluminium-gallium-indium phosphide (AlGaInP) diode laser (660 nm) on the neural regeneration of the transected sciatic nerve after bridging the GGT nerve guide conduit in rats. The animals were divided into two groups: group 1 comprised sham-irradiated controls and group 2 rats underwent low-level laser (LLL) therapy. A compact multi-cluster laser system with 20 AlGaInP laser diodes (output power, 50mW) was applied transcutaneously to the injured peripheral nerve immediately after closing the wound, which was repeated daily for 5 min for 21 consecutive days. Eight weeks after implantation, walking track analysis showed a significantly higher sciatic function index (SFI) score (Pguide conduit in rats. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. No Evidence that MDMA-Induced Enhancement of Emotional Empathy Is Related to Peripheral Oxytocin Levels or 5-HT1a Receptor Activation

    Science.gov (United States)

    Kuypers, Kim P. C.; de la Torre, Rafael; Farre, Magi; Yubero-Lahoz, Samanta; Dziobek, Isabel; Van den Bos, Wouter; Ramaekers, Johannes G.

    2014-01-01

    The present study aimed at investigating the effect of MDMA on measures of empathy and social interaction, and the roles of oxytocin and the 5-HT1A receptor in these effects. The design was placebo-controlled within-subject with 4 treatment conditions: MDMA (75 mg), with or without pindolol (20 mg), oxytocin nasal spray (40 IU+16 IU) or placebo. Participants were 20 healthy poly-drug MDMA users, aged between 18–26 years. Cognitive and emotional empathy were assessed by means of the Reading the Mind in the Eyes Test and the Multifaceted Empathy Test. Social interaction, defined as trust and reciprocity, was assessed by means of a Trust Game and a Social Ball Tossing Game. Results showed that MDMA selectively affected emotional empathy and left cognitive empathy, trust and reciprocity unaffected. When combined with pindolol, these effects remained unchanged. Oxytocin did not affect measures of empathy and social interaction. Changes in emotional empathy were not related to oxytocin plasma levels. It was concluded that MDMA (75 mg) selectively enhances emotional empathy in humans. While the underlying neurobiological mechanism is still unknown, it is suggested that peripheral oxytocin does not seem to be the main actor in this; potential candidates are the serotonin 2A and the vasopressin 1A receptors. Trial Registration MDMA & PSB NTR 2636 PMID:24972084

  7. Relationships between human vitality and mitochondrial respiratory parameters, reactive oxygen species production and dNTP levels in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Maynard, Scott; Keijzers, Guido; Gram, Martin

    2013-01-01

    . Therefore, we measured a number of cellular parameters related to mitochondrial activity in peripheral blood mononuclear cells (PBMCs) isolated from middle-aged men, and tested for association with vitality. These parameters estimate mitochondrial respiration, reactive oxygen species (ROS) production...

  8. Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications.

    Science.gov (United States)

    Blum, Arnon; Pastukh, Nina; Socea, Dorina; Jabaly, Hanin

    2018-06-01

    Proliferative diabetic retinopathy is a devastating complication of diabetes mellitus, developing within 15 years in 50% of patients with type 1 diabetes mellitus (DM) and in 10% of patients with type 2 DM. The correlation between levels of inflammatory markers in the peripheral blood and retinopathy staging has not been studied yet, and the purpose of this prospective study was to find a possible association between inflammation and staging of diabetic retinopathy. A prospective (pilot) study that measured level of adhesion molecules in the peripheral blood of 10 healthy subjects and 30 patients with type 2 diabetes mellitus. Patients were grouped by the degree of retinopathy: 10 without retinopathy, 10 with non-proliferative retinopathy [NPDR] and 10 with proliferative retinopathy [PDR]. After signing the consent form, an ophthalmologic examination was performed, and 10 mL of blood was drawn. In order to assess adhesion molecules' level serum samples were collected, frozen, and stored at a temperature of -80 °C until analysis was performed as one batch. 10 healthy volunteers and 30 patients were enrolled. Healthy volunteers were younger (36.6 ± 7.9 years) compared to patients (no retinopathy 64.5 ± 10.8 years, NPDR 71.4 ± 8.9 years, and PDR 63.3 ± 11.6 years) (p = .0003 for all groups of patients in comparison with the healthy subjects). VCAM-1 levels were increased by retinopathy staging - starting from 81.86 ± 3.80 ng/ml (healthy), 105.55 ± 1.37 ng/ml (no retinopathy), 111.78 ± 4.14 ng/ml (NPDR), and 123.45 ± 3.99 ng/ml (PDR), with a significant difference between healthy and patients without retinopathy (p = .03), between no retinopathy and NPDR (p = .001), and between NPDR and PDR (p < .0001). E selectin was increased in correlation with severity of the retinopathy, with a significant difference between groups of patients (p = .03 between healthy subjects and T2DM patients

  9. Interferon-¿- and tumour necrosis factor-a-producing cells in humans who are immune to cutaneous leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, K; Theander, T G; Hviid, L

    1999-01-01

    Individuals infected with Leishmania major usually acquire immunity to cutaneous leishmaniasis. In this study we have investigated peripheral blood mononuclear cells (PBMC) stimulated by Leishmania antigens in two groups of Sudanese individuals, one with a history of cutaneous leishmaniasis and one...... leishmaniasis produced significantly higher levels of IFN-gamma and TNF-alpha than cells from individuals without a history of the disease. Similar levels of IL-10 were found in the two groups. Flow cytometric analysis revealed high numbers of CD3+ cells producing IFN-gamma and TNF-alpha, and only a few CD3......+ cells containing IL-10, in the PBMC cultures from the individuals with a history of cutaneous leishmaniasis. Interferon-gamma and TNF-alpha were predominantly produced by CD4+ T cells rather than CD8+ T cells. The results suggest that cellular immunity against cutaneous leishmaniasis is mediated...

  10. Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Mortensen, T; Holten-Andersen, M

    2001-01-01

    /ml were inoculated with 1 ml (6 Lf units) of tetanus toxoid vaccine. The anti-tetanus antibody levels were determined in serum obtained before inoculation and after 7, 14 and 28 days, respectively. C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), histamine......, vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or plasma obtained on the same days. RESULTS: After inoculation anti-tetanus antibody levels were equally raised...

  11. Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

    DEFF Research Database (Denmark)

    Nielsen, C H; Hegedüs, L; Rieneck, K

    2007-01-01

    Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood...... appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-alpha, IFN...

  12. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  13. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    International Nuclear Information System (INIS)

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

  14. Effects of flaxseed oil on anti-oxidative system and membrane deformation of human peripheral blood erythrocytes in high glucose level.

    Science.gov (United States)

    Yang, Wei; Fu, Juan; Yu, Miao; Huang, Qingde; Wang, Di; Xu, Jiqu; Deng, Qianchun; Yao, Ping; Huang, Fenghong; Liu, Liegang

    2012-07-08

    The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited. Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy. Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level. The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia.

  15. Study on the correlative analysis between the changes of immunofunction status of peripheral blood red blood cells and plasma thromboxane B2 (TXB2) level in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Liu Ailing; Zhou Dongxia; Wang Yuanyuan

    2011-01-01

    Objective: To explore the relationship between changes of immunofuction status of peripheral blood red blood cells and plasma thromboxane B 2 (TXB 2 ) level in patients with PIH. Methods: RBC immunofunction status was studied with immunologic methods and plasma TXB 2 Level was measured with RIA in 33 patients with PIH and 35 normal controls.Results Level of RBC-C3bRR was significantly lower and level of plasma TXB 2 was markedly higher in the patients than those in controls (P 2 (r=0.4084, P 2 levels in patients with PIH. (authors)

  16. Clinical significance of determination of changes of serum TNF-α levels, peripheral B lymphocyte count and T lymphocyte subsets distribution pattern in patients with pregnancy induced hypertension syndrome

    International Nuclear Information System (INIS)

    Zhao Wenjuan

    2006-01-01

    Objective: To explore the changes of serum TNF-α levels, peripheral B cell count and T subsets distribution pattern in patients with pregnancy induced hypertension syndrome. Methods: Serum TNF-α levels (with RIA), peripheral B cell count as well as T subsets (with monoclonal technique) were examined in 34 patients with pregnancy induced hypertension syndrome and 35 controls. Results: The serum TNF-α levels and B lymphocytes count were significantly higher than those in controls (P 3 , CD 4 , CD4/CD8 ratio were significantly lower than those in controls (P<0.01). Conclusion: Pregnancy induced hY- pertension syndrome is a kind of autoimmune diseases with abnormal immunoregulation. (authors)

  17. Changes in nutritional status, body composition, quality of life, and physical activity levels of cancer patients undergoing autologous peripheral blood stem cell transplantation.

    Science.gov (United States)

    Hung, Yun-Chi; Bauer, Judith; Horsley, Pamela; Waterhouse, Mary; Bashford, John; Isenring, Elisabeth

    2013-06-01

    This pilot exploratory study aimed to describe the changes in nutritional status, body composition, quality of life (QoL), and physical activity levels (PAL) of cancer patients undergoing high-dose conditioning and autologous peripheral blood stem cell transplantation (PBSCT) at pre-admission, hospital discharge, and at 100 days post-transplantation, and to examine if changes in these parameters are interrelated. Twenty-four patients (56.2 ± 12.9 years; 7 females, 17 males) were recruited from an Australian transplant center. Assessment was prospectively conducted at pre-admission, hospital discharge, and 100 days post-transplantation using the scored patient-generated subjective global assessment, air displacement plethysmography, EORTC QLQ-C30 (version 3), and the international physical activity questionnaire. At discharge, nutritional status deteriorated (patient-generated subjective global assessment (PG-SGA) median, +8.0; interquartile range, 6.0-13.0; p body mass (LBM; -2.2 kg, CI 95% -3.0, -1.4; p < 0.001), and decrease in QoL (-10.6, CI 95% -24.1, 2.9; p = 0.117); the proportion of patients with high PAL decreased (p = 0.012). By 100 days post-transplantation, all patients were well-nourished; however, LBM remained lower -1.0 kg (CI 95% -1.9, -0.1; p = 0.028). Change in nutritional status (PG-SGA score) was associated with weight (r = -0.46; p = 0.039) and fat mass (r = -0.57; p = 0.013). Change in QoL was associated with nutritional reservoir (i.e., fat; r = 0.54; p = 0.024); QoL was consistently higher for patients with high PAL. High-dose conditioning and autologous PBSCT is associated with deterioration in nutritional status, QoL and PAL, with LBM remaining below baseline levels at 100 days post-transplantation. A nutrition and exercise intervention program post-hospital discharge may be beneficial for these patients.

  18. Lack of increased DNA double-strand breaks in peripheral blood mononuclear cells of individuals from high level natural radiation areas of Kerala coast in India

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Vinay [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Homi Bhabha National Institute, Anushakti Nagar, Mumbai 400 094 (India); Kumar, P.R. Vivek; Koya, P.K.M.; Jaikrishan, G. [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Das, Birajalaxmi, E-mail: birajalaxmi@yahoo.co.in [Low Level Radiation Research Section, Radiation Biology and Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2016-06-15

    Highlights: • Basal level DNA DSBs was measured in individuals from NLNRA and HLNRA of Kerala. • No significant difference in the gamma-H2AX foci between HLNRA and NLNRA individuals. • Marginal reduction of gamma-H2AX foci in HDG of HLNRA compared to LDG and NLNRA. • A possible threshold dose of 5mGy/year for DSBs observed at chronic low dose exposure in vivo. - Abstract: The high level natural radiation area (HLNRA) of Kerala is a 55 km long and 0.5 km wide strip in south west coast of India. The level of background radiation in this area varies from <1.0 mGy/year to 45.0 mGy/year. It offers unique opportunity to study the effect of chronic low dose/low dose-rate radiation directly on human population. Spontaneous level of DNA double strand breaks (DSBs) was quantified in peripheral blood mononuclear cells of 91 random individuals from HLNRA (N = 61, mean age: 36.1 ± 7.43 years) and normal level natural radiation area (NLNRA) (N = 30, mean age: 35.5 ± 6.35 years) using gamma-H2AX as a marker. The mean annual dose received by NLNRA and HLNRA individuals was 1.28 ± 0.086 mGy/year and 8.28 ± 4.96 mGy/year, respectively. The spontaneous frequency of DSBs in terms of gamma-H2AX foci among NLNRA and HLNRA individuals were 0.095 ± 0.009 and 0.084 ± 0.004 per cell (P = 0.22). The individuals from HLNRA were further classified as low dose group (LDG, 1.51–5.0 mGy/year, mean dose: 2.63 ± 0.76 mGy/year) and high dose group (HDG, >5.0 mGy/year, mean dose: 11.04 ± 3.57 mGy/year). The spontaneous frequency of gamma-H2AX foci per cell in NLNRA, LDG and HDG was observed to be 0.095 ± 0.009, 0.096 ± 0.008 and 0.078 ± 0.004 respectively. Individuals belonging to HDG of HLNRA showed marginally lower frequency of DSBs as compared to NLNRA and LDG of HLNRA. This could be suggestive of either lower induction or better repair of DSBs in individuals from HDG of HLNRA. The present study indicated that 5.0 mGy/year could be a possible threshold dose for DSB induction

  19. Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes

    International Nuclear Information System (INIS)

    Sherman, M.L.; Datta, R.; Hallahan, D.E.; Weichselbaum, R.R.; Kufe, D.W.

    1991-01-01

    Previous studies have demonstrated that ionizing radiation induces the expression of certain cytokines, such as TNF alpha/cachectin. However, there is presently no available information regarding the molecular mechanisms responsible for the regulation of cytokine gene expression by ionizing radiation. In this report, we describe the regulation of the TNF gene by ionizing radiation in human myeloid leukemia cells. The increase in TNF transcripts by x rays was both time- and dose-dependent as determined by Northern blot analysis. Similar findings were obtained in human peripheral blood monocytes. Transcriptional run-on analyses have demonstrated that ionizing radiation stimulates the rate of TNF gene transcription. Furthermore, induction of TNF mRNA was increased in the absence of protein synthesis. In contrast, ionizing radiation had little effect on the half-life of TNF transcripts. These findings indicate that the increase in TNF mRNA observed after irradiation is regulated by transcriptional mechanisms and suggest that production of this cytokine by myeloid cells may play a role in the pathophysiologic effects of ionizing radiation

  20. P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report.

    Science.gov (United States)

    Wu, Hong; Nie, Yijun; Xiong, Huangui; Liu, Shuangmei; Li, Guilin; Huang, An; Guo, Lili; Wang, Shouyu; Xue, Yun; Wu, Bing; Peng, Lichao; Song, Miaomiao; Li, Guodong; Liang, Shangdong

    2015-12-01

    Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1β, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1β levels. TNF-α and IL-1β levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.

  1. Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

    Science.gov (United States)

    Bianchi, M; Moser, C; Lazzarini, C; Vecchiato, E; Crespi, F

    2002-03-01

    Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the

  2. The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

    Science.gov (United States)

    Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

    2010-09-10

    5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

  3. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  4. [Effects of comprehensive therapy on serum SPARC levels in ankylosing spondylitis patients accompanied with osteoporosis].

    Science.gov (United States)

    Xu, Jing-ren; Lin, Yan; Zhang, Chun-Yan; Li, Wei-Min; Guo, Chen-Jun; Ye, Lei

    2013-04-01

    To observe the effects of comprehensive therapy on serum secreted protein acidic and rich in cysteine (SPARC) levels in ankylosing spondylitis (AS) patients accompanied with osteoporosis (OP), and to explore the possible mechanisms for SPARC in AS patients accompanied with osteoporosis. Totally 48 AS patients accompanied with OP (Group A) were treated with massage, intravenous infusion of Cervus and Cucumis Polypeptide Injection, and Bushen Quhan Zhiwang Decoction (BQZD) for 3 months. At the same time, 45 normal healthy subjects were recruited as the normal control group (Group B). Serum SPARC levels were measured by ELISA in Group A before and after comprehensive therapy and in those of Group B. The levels of bone mineral density of femoral neck (FN BMD), bone mineral density of 2 -4 lumbar spine (L2-4 BMD), bone specific alkaline phosphatase (BSAP), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta-1 (TGF-beta1) were detected. Meanwhile, Bath AS disease activity index (BASDAI) and Bath AS functional index (BASFI) were detected in Group A before and after treatment. The correlations between the aforesaid indices and serum SPARC levels were analyzed. Serum SPARC levels were significantly lower in those of Group A than in those of Group B (175. 30 +/- 72.04 micro/L vs 190. 52 +/- 86. 13 microg/ L, P <0. 01). Serum SPARC levels in those of Group A were negatively correlated with TNF-alpha (r = -0.261, P <0.01), positively with L2-4 BMD, TGF-beta1, and BSAP (r =0.437,0.256, 0.385, P <0.05, P <0.01). L2-4BMD and BSAP were independently predictors of serum SPARC in patients of Group A. After comprehensive therapy, the levels of TNF-alpha, BASDAI, and BASFI obviously decreased, TGF-beta1, BSAP, L2-4 BMD, and FN BMD obviously increased (P <0. 05, P <0. 01). The serum SPARC levels also significantly increased (188.32 +/- 87.50 microg/L, P <0. 05). Comprehensive therapy could effectively improve the bone metabolism, clinical symptoms and the

  5. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Science.gov (United States)

    Hernández-Jiménez, Claudia; García-Torrentera, Rogelio; Olmos-Zúñiga, J Raúl; Jasso-Victoria, Rogelio; Gaxiola-Gaxiola, Miguel O; Baltazares-Lipp, Matilde; Gutiérrez-González, Luis H

    2014-01-01

    The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5), mechanical ventilation with dry oxygen dispensation, and Group II (n = 5), mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77). This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05). Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02). Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  6. Respiratory mechanics and plasma levels of tumor necrosis factor alpha and interleukin 6 are affected by gas humidification during mechanical ventilation in dogs.

    Directory of Open Access Journals (Sweden)

    Claudia Hernández-Jiménez

    Full Text Available The use of dry gases during mechanical ventilation has been associated with the risk of serious airway complications. The goal of the present study was to quantify the plasma levels of TNF-alpha and IL-6 and to determine the radiological, hemodynamic, gasometric, and microscopic changes in lung mechanics in dogs subjected to short-term mechanical ventilation with and without humidification of the inhaled gas. The experiment was conducted for 24 hours in 10 dogs divided into two groups: Group I (n = 5, mechanical ventilation with dry oxygen dispensation, and Group II (n = 5, mechanical ventilation with oxygen dispensation using a moisture chamber. Variance analysis was used. No changes in physiological, hemodynamic, or gasometric, and radiographic constants were observed. Plasma TNF-alpha levels increased in group I, reaching a maximum 24 hours after mechanical ventilation was initiated (ANOVA p = 0.77. This increase was correlated to changes in mechanical ventilation. Plasma IL-6 levels decreased at 12 hours and increased again towards the end of the study (ANOVA p>0.05. Both groups exhibited a decrease in lung compliance and functional residual capacity values, but this was more pronounced in group I. Pplat increased in group I (ANOVA p = 0.02. Inhalation of dry gas caused histological lesions in the entire respiratory tract, including pulmonary parenchyma, to a greater extent than humidified gas. Humidification of inspired gases can attenuate damage associated with mechanical ventilation.

  7. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  8. Circulating TNF-alpha and IL-6 concentrations and TNF-alpha -308 G>A polymorphism in children with premature adrenarche

    Directory of Open Access Journals (Sweden)

    Pauliina eUtriainen

    2010-11-01

    Full Text Available Premature adrenarche (PA, the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6. We tested the hypothesis that serum concentrations of TNF-α and IL-6 are increased in PA by studing 73 children with PA and 98 age- and gender-matched controls. Serum TNF-α and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-α gene -308 G>A polymorphism (known to affect TNF-α gene transcription, and genotype-phenotype associations were studied. The mean serum TNF-α concentration was higher in the PA than control children (20.4 vs. 18.4 pg/ml, P=0.048, whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-α was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P=0.038. In the PA group, TNF-α concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-α gene -308 G>A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-α concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-α gene -308 G>A polymorphism does not seem to be associated with the development of PA.

  9. Biofeedback can reduce foot pressure to a safe level and without causing new at-risk zones in patients with diabetes and peripheral neuropathy.

    Science.gov (United States)

    De León Rodriguez, D; Allet, L; Golay, A; Philippe, J; Assal, J-Ph; Hauert, C-A; Pataky, Z

    2013-02-01

    Plantar pressure reduction is mandatory for diabetic foot ulcer healing. Our aim was to evaluate the impact of a new walking strategy learned by biofeedback on plantar pressure distribution under both feet in patients with diabetic peripheral neuropathy. Terminally augmented biofeedback has been used for foot off-loading training in 21 patients with diabetic peripheral sensory neuropathy. The biofeedback technique was based on a subjective estimation of performance and objective visual feedback following walking sequences. The patient was considered to have learned a new walking strategy as soon as the peak plantar pressure (PPP) under the previously defined at-risk zone was within a range of 40-80% of baseline PPP in 70% of the totality of steps and during three consecutive walking sequences. The PPP was measured by a portable in-shoe foot pressure measurement system (PEDAR(®)) at baseline (T0), directly after learning (T1) and at 10-day retention test (T2). The PPP under at-risk zones decreased significantly at T1 (165 ± 9 kPa, p biofeedback leads to a safe and regular plantar pressure distribution without inducing any new 'at-risk' area under both feet. Copyright © 2012 John Wiley & Sons, Ltd.

  10. Study on the changes of serum soluble IL-2 receptor (SIL-2R) levels and distribution pattern of peripheral blood T-cell subsets after treatment in pediatric patients with Bronchopneumonia

    International Nuclear Information System (INIS)

    Chen Chuanbin

    2005-01-01

    Objective:To investigate the significance of changes of serum SIL-2R levels and T-cell subsets distribution type after treatment in pediatric patients with bronchopneumonia. Methods: Serum SIL-2R levels (with ELISA) and peripheral blood T-cell subset distribution pattern (with monoclonal antibody technique) were determined in 33 pediatric patients with broncho-pneumonia and 30 controls. Results: Before treatment, the serum SIL-2R levels in the patients were significantly higher than those in normal controls (P 0.05). Serum SIL-2R levels were positively correlated with CD4/CD8 ratio. Conclusion: Detection of serum SIL-2R levels and CD4/CD8 ratio is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

  11. Mucin gene mRNA levels in broilers challenged with eimeria and/or Clostridium perfringens.

    Science.gov (United States)

    Kitessa, Soressa M; Nattrass, Gregory S; Forder, Rebecca E A; McGrice, Hayley A; Wu, Shu-Biao; Hughes, Robert J

    2014-09-01

    The effects of Eimeria (EM) and Clostridium perfringens (CP) challenges on the mRNA levels of genes involved in mucin (Muc) synthesis (Muc2, Muc5ac, Muc13, and trefoil family factor-2 [TFF2]), inflammation (tumor necrosis factor alpha [TNF-alpha] and interleukin-18 [IL-18]), and metabolic processes (cluster of differentiation [CD]36) in the jejunum of broilers were investigated. Two parallel experiments involving 1) EM challenge and 2) EM and CP challenges were conducted. The first experiment was a 2 X 2 study with 12 birds per treatment (N = 48) involving fishmeal substitution (25%) in the diet (FM) and EM challenge. The treatments were: Control (FM-, EM-), Fishmeal (FM+, EM-), EM challenge (FM-, EM+), and fishmeal substitution and EM challenge (FM+, EM+). The second experiment was a 2 X 2 X 2 experiment with six birds per treatment (N = 48) involving fishmeal (FM-, FM+), Eimeria (EM-, EM+), and C perfringens (CP-, CP+). In both arms of the study, male broilers were given a starter diet for the whole period of 16 days, except those assigned to FM+, where 25% of the starter ration was replaced with fishmeal from days 8 to 14. EM inoculation was performed on day 9 and CP inoculation on days 14 and 15. The EM challenge birds were euthanatized for sampling on day 13; postmortem examination and sampling for the Eimeria plus C perfringens challenge arm of the study were on day 16. In the Eimeria challenge arm of the study, fishmeal supplementation significantly suppressed the mRNA levels of TNF-alpha, TFF2, and IL-18 pre-CP inoculation but simultaneously increased the levels of Muc13 and CD36 mRNAs. Birds challenged with Eimeria exhibited increased mRNA levels of Muc13, Muc5ac, TNF-alpha, and IL-18. In the Eimeria and C. perfringens challenge arm, birds exposed to EM challenge exhibited significantly lower mRNA levels of Muc2 and CD36. The mRNA levels of CD36 were also significantly suppressed by CP challenge. Our results showed that the transcription of mucin synthesis

  12. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

    International Nuclear Information System (INIS)

    Mohseni, Mehran; Mihandoost, Ehsan; Shirazi, Alireza; Sepehrizadeh, Zargham; Bazzaz, Javad Tavakkoly; Ghazi-khansari, Mahmoud

    2012-01-01

    The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT 2 qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

  13. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Mohseni, Mehran [Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan (Iran, Islamic Republic of); Mihandoost, Ehsan, E-mail: mihandoost.e@gmail.com [Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shirazi, Alireza [Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sepehrizadeh, Zargham [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bazzaz, Javad Tavakkoly [Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-khansari, Mahmoud [Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2012-10-15

    The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT{sup 2}qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

  14. High fat diet and inflammation - modulation of Haptoglobin level in rat brain

    Directory of Open Access Journals (Sweden)

    Maria Stefania eSpagnuolo

    2015-12-01

    Full Text Available Obesity and dietary fats are well known risk factors for the pathogenesis of neurodegenerative diseases. The analysis of specific markers, whose brain level can be affected by diet, might contribute to unveil the intersection between inflammation/obesity and neurodegeneration. Haptoglobin (Hpt is an acute phase protein, which acts as antioxidant by binding free Haemoglobin (Hb, thus neutralizing its pro-oxidative action. We previously demonstrated that Hpt plays critical functions in brain, modulating cholesterol trafficking in neuroblastoma cell lines, beta-amyloid (Aβ uptake by astrocyte, and limiting Aβ toxicity on these cells. A major aim of this study was to evaluate whether a long term (12 or 24 weeks high-fat diet (HFD influences Hpt and Hb expression in rat hippocampus. We also assessed the development of obesity-induced inflammation by measuring hippocampal level of TNF-alpha, and the extent of protein oxidation by titrating nitro-tyrosine (N-Tyr. Hpt concentration was lower (p<0.001 in hippocampus of HFD rats than in control animals, both in the 12 and in the 24 weeks fed groups. HFD was also associated in hippocampus with the increase of Hb level (p<0.01, inflammation and protein oxidative modification, as evidenced by the increase in the concentration of TNF-alpha and nitro-tyrosine. In fact, TNF-alpha concentration was higher in rats receiving HFD for 12 (p<0.01 or 24 weeks (p<0.001 compared to those receiving the control diet. N-Tyr concentration was more elevated in hippocampus of HFD than in control rats in both 12 weeks (p=0.04 and 24 weeks groups (p=0.01, and a positive correlation between Hb and N-Tyr concentration was found in each group. Finally, we found that the treatment of the human glioblastoma-astrocytoma cell line U-87 MG with cholesterol and fatty acids, such as palmitic and linoleic acid, significantly impairs (p<0.001 Hpt secretion in the extracellular compartment.We hypothesize that the HFD-dependent decrease of

  15. Subanalysis of the CONFIRM Registries: Acute Procedural Outcomes in Claudicant and Critical Limb Ischemia Patients With Varying Levels of Calcification Treated for Peripheral Arterial Disease With Orbital Atherectomy.

    Science.gov (United States)

    Adams, George L; Das, Tony; Lee, Michael S; Beasley, Robert; Mustapha, Jihad

    2015-11-01

    Patients with peripheral arterial disease (PAD) can be classified into groups based upon the severity of the disease using the Rutherford classification system. This analysis compares the procedural outcomes of PAD patients treated with orbital atherectomy stratified by Rutherford class (1-3 = intermittent claudication; 4-6 = critical limb ischemia [CLI]), and acute angiographic outcomes of these patients stratified by degree of lesion calcification. The CONFIRM registry series was analyzed and included 1697 patients with intermittent claudication (Rutherford class 1-3) and 1320 patients with CLI (Rutherford class 4-6) treated with orbital atherectomy. The composite rate of dissection, perforation, slow-flow, vessel closure, spasm, embolism, and thrombus formation was compared between claudicants and CLI patients with varying degrees of lesion calcification. Patients with CLI were older and had a higher prevalence of diabetes, coronary artery disease, and renal disease (Patherectomy resulted in similar low procedural complication rates in the CLI group compared with the claudicant group. These results suggest that orbital atherectomy is safe and effective for treating calcified lesions in high-risk patients with varying severity of PAD symptoms.

  16. Low Levels of CD36 in Peripheral Blood Monocytes in Subclinical Atherosclerosis in Rheumatoid Arthritis: A Cross-Sectional Study in a Mexican Population

    Directory of Open Access Journals (Sweden)

    Eduardo Gómez-Bañuelos

    2014-01-01

    Full Text Available Patients with rheumatoid arthritis (RA have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC and carotid intima-media thickness (cIMT in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P<0.001. CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, P<0.001, ox-LDL (r = −0.427, P = 0.05, TNFα (r = −0.729, P<0.001, and IL-6 (r = −0.822, P<0.001. Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.

  17. Cytokine profile and nitric oxide levels in sera from patients with brucellosis

    Directory of Open Access Journals (Sweden)

    Refik M.

    2004-01-01

    Full Text Available The aims of this study were to investigate the serum levels of some cytokines [tumor necrosis factor-alpha (TNF-alpha, interleukin 1ß (IL-1ß, IL-2R, IL-6, and IL-8] and nitric oxide (NO levels in patients with untreated brucellosis and to test the correlation of these parameters with each other. The study was conducted on 67 subjects, 37 patients with brucellosis and 30 healthy individuals with no history of Brucella infection. Brucellosis was identified by a positive blood culture and/or increased Brucella antibodies in serological tests in addition to compatible clinical symptoms. Cytokine profile analysis was performed by the immulite chemiluminescent enzyme immunometric assay whose inter- and intra-assay coefficients of variance were 2.6-3.6 and 4.4-8.5%, respectively. The levels of nitrites/nitrates, which are representative of NO levels, were measured by the Griess method. Patients with brucellosis had significantly elevated serum levels of nitrites/nitrates, IL-2R, IL-6 and IL-8 (mean ± SD, 102.8 ± 23.8 µmol/l, 806.1 ± 58.5 U/ml, 21.1 ± 2.3 pg/ml, and 8.8 ± 1.6 pg/ml, respectively compared to healthy controls, whereas TNF-alpha and IL-1ß levels were unchanged. No statistically significant correlation was detected between any of the studied cytokine levels and nitrate/nitrite concentrations according to Pearson's linear correlation test. We conclude that only IL-6, IL-8 and IL-2R are elevated in brucellosis and the extent of elevation depends on the severity and clinical pattern of the disease. Moderate elevation in serum NO was comparable to that observed in previous studies. This explains the absence or very rare occurrence of septic shock in brucellosis.

  18. Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

    Science.gov (United States)

    Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

    2013-06-01

    Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

  19. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  20. Elevated levels of peripheral blood CD14(bright) CD16+ and CD14(dim) CD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes.

    Science.gov (United States)

    Ryba-Stanisławowska, Monika; Myśliwska, Jolanta; Juhas, Ulana; Myśliwiec, Małgorzata

    2015-09-01

    The study aimed to analyze the CD14(bright) CD16(+) and CD14(dim) CD16(+) monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 in the context of their association with microvascular complications. 61 children with type 1 diabetes and 30 healthy individuals were enrolled in a study. CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were quantified in peripheral blood by means of flow cytometry. At the time of sampling blood glucose concentration was taken along with biochemical measurement of renal function, CRP and glycosylated hemoglobin. The Spearman's correlations were used to compare the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict the development of microangiopathies. The flow cytometric analysis of monocyte subsets in peripheral blood of analyzed subjects revealed that the numbers of CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were significantly higher in patients with type 1 diabetes than in the healthy individuals. As to the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict development of microangiopathies, it was shown that both CD16(+) subsets were associated with increased risk of retinopathy development, defined as retinopathy development value. Elevated levels of intermediate CD14(bright) CD16(+) and non-classical CD14(dim) CD16(+) monocytes predict development of diabetic retinopathy in patients with type 1 diabetes. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  1. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  2. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  3. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...... disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro...

  4. Reliability of the discrete choice experiment at the input and output level in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Skjoldborg, Ulla Slothuus; Lauridsen, Jørgen; Junker, Peter

    2009-01-01

    OBJECTIVES: To investigate the issue of conjoint reliability over time. METHODS: A discrete choice experiment was applied using scenarios that describe the effect of treating rheumatoid arthritis patients with TNF-alpha inhibitors, a novel class of highly effective, but expensive antirheumatic...... agents. Respondents participated in three face-to-face interviews over a period of 4 months. Reliability was measured both at the input level, where the consistency of matches made by respondents to the Discrete Choice Experiment (DCE) question between replications was determined, and at the output level...... and the final choice in survey 3. Output level: The confidence intervals for WTP figures in surveys 1 and 2 and 1 and 3 were overlapping, implying that the DCE was reliable at the output level over time. CONCLUSION: The proportion of consistent responses was higher than would be expected by chance. Conjoint...

  5. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected when the doctor sees the affected cornea in a person who also has a severe and/or long- ...

  6. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  7. Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients.

    Science.gov (United States)

    Greten, T F; Slansky, J E; Kubota, R; Soldan, S S; Jaffee, E M; Leist, T P; Pardoll, D M; Jacobson, S; Schneck, J P

    1998-06-23

    Human T lymphotropic virus type 1 (HTLV-1) -associated myelopathy/tropic spastic paraparesis is a demyelinating inflammatory neurologic disease associated with HTLV-1 infection. HTLV-1 Tax11-19-specific cytotoxic T cells have been isolated from HLA-A2-positive patients. We have used a peptide-loaded soluble HLA-A2-Ig complex to directly visualize HTLV-1 Tax11-19-specific T cells from peripheral blood and cerebrospinal fluid without in vitro stimulation. Five of six HTLV-1-associated myelopathy/tropic spastic paraparesis patients carried a significant number (up to 13.87%) of CD8(+) lymphocytes specific for the HTLV-1 Tax11-19 peptide in their peripheral blood, which were not found in healthy controls. Simultaneous comparison of peripheral blood and cerebrospinal fluid from one patient revealed 2.5-fold more Tax11-19-specific T cells in the cerebrospinal fluid (23.7% vs. 9.4% in peripheral blood lymphocyte). Tax11-19-specific T cells were seen consistently over a 9-yr time course in one patient as far as 19 yrs after the onset of clinical symptoms. Further analysis of HTLV-1 Tax11-19-specific CD8(+) T lymphocytes in HAM/TSP patients showed different expression patterns of activation markers, intracellular TNF-alpha and gamma-interferon depending on the severity of the disease. Thus, visualization of antigen-specific T cells demonstrates that HTLV-1 Tax11-19-specific CD8(+) T cells are activated, persist during the chronic phase of the disease, and accumulate in cerebrospinal fluid, showing their pivotal role in the pathogenesis of this neurologic disease.

  8. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  9. The challenges and beauty of peripheral nerve regrowth.

    Science.gov (United States)

    Zochodne, Douglas W

    2012-03-01

    This review provides an overview of selected aspects of peripheral nerve regeneration and potential avenues to explore therapeutically. The overall coordinated and orchestrated pattern of recovery from peripheral nerve injury has a beauty of execution and progress that rivals all other forms of neurobiology. It involves changes at the level of the perikaryon, coordination with important peripheral glial partners, the Schwann cells, a controlled inflammatory response, and growth that overcomes surprising intrinsic roadblocks. Both regenerative axon growth and collateral sprouting encompass fascinating aspects of this story. Better understanding of peripheral nerve regeneration may also lead to enhanced central nervous system recovery. © 2012 Peripheral Nerve Society.

  10. Significant reduction of peripheral blood interleukin-35 and CD4+EBI3+ T cells, which are negatively correlated with an increase in the plasma IL-17 and cTnI level, in viral myocarditis patients

    Directory of Open Access Journals (Sweden)

    Han Ouyang

    2017-02-01

    Full Text Available Introduction: Viral myocarditis (VMC has become an increasingly common heart disease that endangers human health. In the present study, the plasma interleukin-35 (IL-35 level and the percentage of CD4 + EBI3 + T cells in VMC patients were detected to investigate the significance of changes in these parameters in the plasma of VMC patients and their association with the disease. Material and methods: ELISA was performed to detect the plasma IL-35 level and the percentage of peripheral blood CD4 + EBI3 + T cells in 40 VMC patients and in 20 healthy individuals. Moreover, the plasma IL-17 levels in the VMC patients and in the healthy individuals were detected using an ELISA, and the cardiac Troponin-I (cTnI levels were detected using a chemiluminescent microparticle immunoassay to compare the differences in the groups. Results : Plasma IL-35 level and the percentage of CD4 + EBI3 + T cells in acute phase VMC patients was lower than that in the healthy control group and the convalescent phase VMC patients. Additionally, the plasma IL-35 level in the VMC patients exhibited a negative correlation with the levels of cTnI and IL-17. The percentage of CD4 + EBI3 + T cells also showed a negative correlation with the levels of cTnI and IL-17. Conclusions : The plasma IL-35 level and the percentage of CD4 + EBI3 + T cells in VMC patients was reduced, and the amount of the decrease was associated with the severity of the disease. These results suggest that IL-35 and CD4 + EBI3 + T might play important roles in the progression of VMC and could be used as indictors of the disease.

  11. Vitamin D receptor in the paraventricular nucleus of the hypothalamus is necessary for beneficial effects of 1,25D[3] on peripheral glucose levels

    Science.gov (United States)

    While a wide range of data correlates low vitamin D levels with type 2 diabetes, few studies examine potential mechanisms by which vitamin D might impact key aspects of metabolism. The active form of 1alpha,25-dihydroxyvitamin D[3] (1,25D[3]; calcitriol) is hydroxylated in the liver and kidney from ...

  12. Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

    Science.gov (United States)

    Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

    2013-06-01

    The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. The impact of self-reported psychological stress levels on changes to peripheral blood immune biomarkers in recreational marathon runners during training and recovery.

    Science.gov (United States)

    Rehm, Kristina E; Elci, Okan U; Hahn, Kathryn; Marshall, Gailen D

    2013-01-01

    Marathon training is both physically and psychologically stressful, both of which can lead to altered immunity. The purpose of this study was to determine if the overall immunoregulatory changes associated with the physical stress of marathon training are affected by psychological stress. Nineteen recreational marathoners completed the Perceived Stress Scale (PSS), State-Trait Anxiety Inventory (STAI) and Penn State Worry Questionnaire (PSWQ), and had levels of T cell subpopulations and cytokine (IFNγ, IL4 and IL10) production determined 4 weeks before (baseline), 24-48 h before (prerace) and 1 week after (recovery) participation in a marathon. PSS scores decreased at the prerace visit compared to baseline and remained low at recovery. Compared to baseline, there were significant changes to numerous immune measures at the prerace visit, including decreases in Th1/Th2 ratio, Tc1/Tc2 ratio, Tr1 and Th3 cell populations as well as decreases in IFNγ/IL4 cytokine ratio and IL10 production. Most immune parameters had returned to near baseline values at the recovery visit. Higher levels of perceived stress, anxiety and worry exacerbated many of the alterations in immunity that were observed at the prerace visit. Higher levels of perceived stress and worry had significant effects on changes to Treg, IL4 production and the IFNγ/IL4 cytokine ratio. Stress had an additional impact on changes in IL10 production. High anxiety levels resulted in significant changes to Treg, Tr1 and Th3. These data suggest that recreational marathon runners with higher levels of psychological stress may be more at risk for the immune alterations that are common during periods of prolonged physical training. Copyright © 2013 S. Karger AG, Basel.

  14. Clinical Significance and Expression of PAF and TNF-alpha in Seminal Plasma of Leukocytospermic Patients

    Directory of Open Access Journals (Sweden)

    Chaodong Liu

    2012-01-01

    Full Text Available Objective. Discuss the changes and roles of PAF in the reproductive tract infection by observing the expression of platelet activating factor (PAF and tumor necrosis factor α (TNF-α in seminal plasma of patients with leukocytospermia. Methods. The seminal plasma was obtained from 22 cases of leukocytospermia and 15 cases of normal males; the peroxidase dyeing method was adopted for seminal plasma white blood count; the ELISA was adopted to test PAF and TNF-α concentration in seminal plasma. Result. PAF concentration ( ng/mL of leukocytospermia group was significantly lower than the normal group ( ng/mL, while TNF-α ( ng/mL was significantly higher than that of normal group ( ng/mL. There was negative correlation between PAF and TNF-α , (, ; the same situation existed in PAF and WBC (, ; but TNF-α was positively correlated to WBC (, . Conclusion. (1 Low expression of PAF and high expression of TNF-α in leukocytospermia affect the sperm motility, which is one of the reasons that leads to infertility. (2 Lower expression of PAF has its particularity during the reproductive tract infection.

  15. Molecular mechanisms underlying mancozeb-induced inhibition of TNF-alpha production

    International Nuclear Information System (INIS)

    Corsini, Emanuela; Viviani, Barbara; Birindelli, Sarah; Gilardi, Federica; Torri, Anna; Codeca, Ilaria; Lucchi, Laura; Bartesaghi, Stefano; Galli, Corrado L.; Marinovich, Marina; Colosio, Claudio

    2006-01-01

    Mancozeb, a polymeric complex of manganese ethylenebisdithiocarbamate with zinc salt, is widely used in agriculture as fungicide. Literature data indicate that ethylenebisdithiocarbamates (EBDTCs) may have immunomodulatory effects in humans. We have recently found in agricultural workers occupationally exposed to the fungicide mancozeb a statistically significant decrease in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF) production in leukocytes. TNF is an essential proinflammatory cytokine whose production is normally stimulated during an infection. The purpose of this work was to establish an in vitro model reflecting in vivo data and to characterize the molecular mechanism of action of mancozeb. The human promyelocytic cell line THP-1 was used as in vitro model to study the effects of mancozeb and its main metabolite ethylenthiourea (ETU) on LPS-induced TNF release. Mancozeb, but not ETU, at non-cytotoxic concentrations (1-100 μg/ml), induced a dose- and time-dependent inhibition of LPS-induced TNF release, reflecting in vivo data. The modulatory effect observed was not limited to mancozeb but also other EBDTCs, namely zineb and ziram, showed similar inhibitory effects. Mancozeb must be added before or simultaneously to LPS in order to observe the effect, indicating that it acts on early events triggered by LPS. It is known that nuclear factor-κB (NF-κB) tightly regulates TNF transcription. We could demonstrate that mancozeb, modulating LPS-induced reactive oxygen species generation, prevented IκB degradation and NF-κB nuclear translocation, which in turn resulted in decreased TNF production. To further understand the mechanism of the effect of mancozeb on TNF transcription, THP-1 cells were transfected with NF-κB promoter-luciferase construct, and the effect of mancozeb on luciferase activity was measured. Cells transfected with promoter constructs containing κB site showed decreased LPS-induced luciferase activity relative to control after mancozeb treatment, confirming NF-κB binding as an intracellular target of mancozeb. Overall, this study contributes to our understanding of the mechanism underlying mancozeb-induced immunotoxicity

  16. Biocatalyzed synthesis of difuranosides and their ability to trigger production of TNF-alpha

    Czech Academy of Sciences Publication Activity Database

    Chlubnová, Ilona; Králová, B.; Dvořáková, H.; Spiwok, V.; Filipp, Dominik; Nugier-Chauvin, C.; Daniellou, R.; Ferrieres, V.

    2016-01-01

    Roč. 26, č. 6 (2016), s. 1550-1553 ISSN 0960-894X R&D Projects: GA ČR(CZ) GP14-17194P Institutional support: RVO:68378050 Keywords : Carbohydrates * Furanosides * Immunostimulation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.454, year: 2016

  17. Manumycin A downregulates release of proinflammatory cytokines from TNF alpha stimulated human monocytes

    Czech Academy of Sciences Publication Activity Database

    Cecrdlová, E.; Petříčková, Kateřina; Kolesár, L.; Petříček, Miroslav; Sekerková, A.; Šváchová, V.; Stříž, I.

    2016-01-01

    Roč. 169, JAN 2016 (2016), s. 8-14 ISSN 0165-2478 R&D Projects: GA MŠk LH12191; GA MZd(CZ) NT13012 Institutional support: RVO:61388971 Keywords : Manumycin A * Cytokines * Immunomodulation Subject RIV: EC - Immunology Impact factor: 2.860, year: 2016

  18. Treatment of frozen shoulder with subcutaneous TNF-alpha blockade compared with local glucocorticoid injection

    DEFF Research Database (Denmark)

    Schydlowsky, Pierre; Szkudlarek, Marcin; Madsen, Ole Rintek

    2012-01-01

    We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid inject...

  19. Design, Synthesis, and Evaluation of Dihydrobenzo[cd]indole-6-sulfonamide as TNF-alpha Inhibitors

    Science.gov (United States)

    Deng, Xiaobing; Zhang, Xiaoling; Tang, Bo; Liu, Hongbo; Shen, Qi; Liu, Ying; Lai, Luhua

    2018-04-01

    Tumor necrosis factor-α (TNF-α) plays a pivotal role in inflammatory response. Dysregulation of TNF can lead to a variety of disastrous pathological effects, including auto-inflammatory diseases. Antibodies that directly targeting TNF-α have been proven effective in suppressing symptoms of these disorders. Compared to protein drugs, small molecule drugs are normally orally available and less expensive. Till now, peptide and small molecule TNF-α inhibitors are still in the early stage of development, and much more efforts should be made. In a previously study, we reported a TNF-α inhibitor, EJMC-1 with modest activity. Here, we optimized this compound by shape screen and rational design. In the first round, we screened commercial compound library for EJMC-1 analogs based on shape similarity. Out of the 68 compounds tested, 20 compounds showed better binding affinity than EJMC-1 in the SPR competitive binding assay. These 20 compounds were tested in cell assay and the most potent compound was 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide (S10) with an IC50 of 14 M, which was 2.2-fold stronger than EJMC-1. Based on the docking analysis of S10 and EJMC-1 binding with TNF-α, in the second round, we designed S10 analogues, purchased 7 of them and synthesized 7 new compounds. The best compound, 4e showed an IC50 value of 3 M in cell assay, which was 14-fold stronger than EJMC-1. 4e was among the most potent TNF-α organic compound inhibitors reported so far. Our study demonstrated that 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide analogues could be developed as potent TNF-α inhibitors. 4e can be further optimized for its activity and properties. Our study provides insights into designing small molecule inhibitors directly targeting TNF-α and for protein-protein interaction inhibitor design.

  20. A Rare Side Effect due to TNF-Alpha Blocking Agent: Acute Pleuropericarditis with Adalimumab

    Directory of Open Access Journals (Sweden)

    Hakan Ozkan

    2013-01-01

    Full Text Available Tumor necrosis factor-alpha antagonism is an important treatment strategy in patients with rheumatoid arthritis, psoriatic arthritis, vasculitis, and ankylosing spondylitis. Adalimumab is one of the well-known tumor necrosis factor-alpha blocking agents. There are several side effects reported in patients with adalimumab therapy. Cardiac side effects of adalimumab are rare. Only a few cardiac side effects were reported. A 61-year-old man treated with adalimumab for the last 6 months due to psoriatic arthritis presented with typically acute pleuropericarditis. Chest X-ray and echocardiography demonstrated marked pericardial effusion. Patient was successfully evaluated for the etiology of acute pleuro-pericarditis. Every etiology was excluded except the usage of adalimumab. Adalimumab was discontinued, and patient was treated with 1200 mg of ibuprofen daily. Control chest X-ray and echocardiography after three weeks demonstrated complete resolution of both pleural and pericardial effusions. This case clearly demonstrated the acute onset of pericarditis with adalimumab usage. Acute pericarditis and pericardial effusion should be kept in mind in patients with adalimumab treatment.

  1. Association study between functional polymorphisms in the TNF-alpha gene and obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Carolina Cappi

    2012-02-01

    Full Text Available Obsessive-compulsive disorder (OCD is a prevalent psychiatric disorder of unknown etiology. However, there is some evidence that the immune system may play an important role in its pathogenesis. In the present study, two polymorphisms (rs1800795 and rs361525 in the promoter region of the cytokine tumor necrosis factor-alpha (TNFA gene were genotyped in 183 OCD patients and in 249 healthy controls. The statistical tests were performed using the PLINK® software. We found that the A allele of the TNFA rs361525 polymorphism was significantly associated with OCD subjects, according to the allelic χ² association test (p=0.007. The presence of genetic markers, such as inflammatory cytokines genes linked to OCD, may represent additional evidence supporting the role of the immune system in its pathogenesis.

  2. Effects of Hyaluronic Acid Conjugation on Anti-TNF-alpha Inhibition of Inflammation in Burns

    Science.gov (United States)

    2014-05-01

    treating conditions characterized by intense inflammatory responses that worsen healing outcomes. Burn injuries represent a potential clinical ...induce keratinocytes , which are needed to repopulate the epidermis, to undergo apoptosis, further stalling the healing process.15 A number of studies ...provides a timeline for the burn study . Treatments were applied on days 0, 2 and 4, and the rats were euthanized and tissues around the burn were

  3. Cerebral tuberculoma in a patient receiving anti-TNF alpha (adalimumab) treatment.

    LENUS (Irish Health Repository)

    Lynch, Karen

    2010-10-01

    We report a case of a cerebral tuberculoma in a 60-year-old woman with rheumatoid arthritis while receiving the anti-tumor necrosis factor alpha monoclonal antibody, adalimumab (Humira), for active disease. MR brain imaging for dyspraxia revealed a left parietal ring-enhancing lesion, which on resection was shown to be a necrotizing granuloma. There were no associated pulmonary lesions, and the patient was systemically well. Sputum and urine cultures were negative for tuberculosis. The patient was treated with anti-tuberculous medications and made an excellent recovery. We consider this to be the first documented case of tuberculosis involving the central nervous system occurring in the setting of adalimumab treatment.

  4. Evaluation of new drugs in daily clinical practice: anti-TNF alpha in rheumatoid arthritis patients.

    NARCIS (Netherlands)

    Kievit, W.

    2008-01-01

    The objective of this thesis was to explore the value and the validity of data collected in daily clinical practice for drug evaluation and cost-effectiveness studies, using data collected on TNFa blocking agents in rheumatoid arthritis. First, the need for and value of information from daily

  5. Evaluation of new drugs in daily clinical practice: anti-TNF alpha in rheumatoid arthritis patients.

    OpenAIRE

    Kievit, W.

    2008-01-01

    The objective of this thesis was to explore the value and the validity of data collected in daily clinical practice for drug evaluation and cost-effectiveness studies, using data collected on TNFa blocking agents in rheumatoid arthritis. First, the need for and value of information from daily clinical practice was researched. Together, the results of Chapters 3, 4 and 5 illustrated that treatment of RA patients with anti-TNFa blocking agents in daily clinical practice was different from what ...

  6. Comparing the lifetime risks of TNF-alpha inhibitor use to common benchmarks of risk.

    Science.gov (United States)

    Kaminska, Edi; Patel, Isha; Dabade, Tushar S; Chang, Jongwha; Qureshi, Ayub A; O'Neill, Jenna L; Balkrishnan, Rajesh; Feldman, Steven R

    2013-04-01

    The study aims to illustrate the range of lifetime risks of lymphoma, tuberculosis (TB), and demyelinating diseases with TNF-α inhibitors in psoriasis patients. Previously published data and online resources were used to determine the risk of the TB, demyelinating disease, and lymphoma with and without TNF-α inhibitor treatment. Lifetime risks for heart disease and stroke were collected using a Medline search. All cancer, trauma, and environmental statistics were obtained from the data published by National Cancer Institute, National Safety Council, and the National Oceanic and Atmospheric Administration, respectively. The lifetime risks of TNF-α-inhibitor-linked conditions and comparators are as follows: TNF-α inhibitor-linked conditions: lymphoma with: without TNF-α inhibitors (0.5-4.8%:2.3%), TB with:without TNF-α inhibitors (0-17.1%:0.3%), and demyelinating disease with:without TNF-α inhibitors (0.1-1.7%:0.15%). Comparators: cancer (40.4%), heart disease (36.2%), stroke (18.4%), accidental death (3.0%), motor vehicle death (1.2%), and lightning strike (0.033%). Much of the data on lifetime risks of disease with TNF-α inhibitor were for patients with rheumatoid arthritis and not psoriasis. The risks of lymphoma, demyelinating diseases, and tuberculosis with TNF-α inhibitors are lower than risks patients face on a regular basis. Screening reduces the risk of tuberculosis in patients receiving TNF-α inhibitors.

  7. Correlation of Neopterin and TNF-alpha with Asymmetric Dimethylarginine in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Dedeh Yuniarty

    2011-12-01

    Full Text Available BACKGROUND: A large number of obesity in the community increases the incidence of Metabolic Syndrome (MetS that can increase the risks of heart disease, diabetes, and stroke. One of the possible causes of stroke is atherosclerosis. Atherosclerosis is initiated by the incidence of inflammation and endothelial dysfuction. Atherosclerosis is involved in an ongoing inflammatory response. At the beginning of atherosclerosis, when the endothel become inflamed, it expresses adhesion molecules  that attract monocytes. The monocytes then migrate into the intima due to endothelial dysfunction. Activation of macrophage occurs in the process of inflammation as the earliest type of lesion of atherosclerosis. In this study, monocyte/macrophage activation is marked by Neopterin. In other process of atherosclerosis, vascular nitric oxide (NO activity has a role as a potent endogenous vasodilator. In regulating the vascular tone, NO has a role to suppress vascular smooth muscle proliferation, inhibit platelet adhesion and aggregation, and interferes with the leukocyte-endothelial cell interaction. In MetS, hypercholesterolemia decreases NO activity. Asymmetric Dimethylarginine (ADMA has been characterized as an endogenous, competitive inhibitor of NO synthase. In this study, the incidence of endothelial dysfunction is marked by ADMA. The aim of this study was to discover the role of Neopterin in MetS patients by evaluating the correlation between Neopterin and ADMA in MetS through tumor necrosis factor (TNF-α or direct line. METHODS: The study was cross sectional on 64 males with MetS aged 30-65 years. The measurements of TNF-α concentrations was done, respectively. RESULTS: Neopterin concentration correlated with Log TNF-α concentration (r=0.311, p=0.012. There is no significant correlation between Neopterin and ADMA (r=0.012, p=0.930; ADMA and Log TNF-α (r=0.029, p=0.821. CONCLUSIONS: There is no significant correlation between Neopterin and ADMA through TNF-α or direct line. KEYWORDS: MetS, Neopterin, ADMA, NO, TNF-α.

  8. Relationship between iris constitution analysis and TNF-alpha gene polymorphism in hypertensives.

    Science.gov (United States)

    Yoo, Chun-Sang; Hwang, Woo-Jun; Hong, Seung-Heon; Lee, Hye-Jung; Jeong, Hyun-Ja; Kim, Su-Jin; Kim, Hyung-Min; Um, Jae-Young

    2007-01-01

    Iridology is a complementary and alternative medicine that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong hereditary component. Tumor necrosis factor-alpha (TNFalpha), a pleiotropic cytokine, has been implicated in many pathological processes including hypertension. In this paper, the relationship between iris constitution and TNFalpha gene polymorphism in those with hypertension is investigated. Eighty seven hypertensive individuals and 79 controls were classified according to iris constitution and the TNFalpha genotype of each individual determined. Compared to the controls, the frequency of the TNFalpha GA heterozygote was lower in the hypertensive group, although the statistical significance was marginal (p = 0.08). This result implies an association with resistance to the disease. In addition, the frequency of the cardio-renal connective tissue weakness type was significantly higher in the hypertensive group with the TNFalpha GG genotype, as compared to the controls (p = 0.001). An association is demonstrated among TNFalpha gene polymorphism, Koreans with hypertension, and iris constitution.

  9. Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

    2004-01-01

    Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

  10. Acute effects of propylthiouracil (PTU) on thyroidal iodide organification and peripheral iodothyronine deiodination: correlation with serum PTU levels measured by radioimmunoassay

    International Nuclear Information System (INIS)

    Cooper, D.S.; Saxe, V.C.; Meskell, M.; Maloof, F.; Ridgway, E.C.

    1981-01-01

    Propylthiouracil (PTU) levels in serum have been measured by RIA in five normal volunteers and four patients with untreated Graves's disease. Peak PTU levels after 50, 200, and 300 mg PTU were 0.91 +/- 0.13, 2.9 +/- 0.6, and 4.0 +/- 0.6 μg/ml in the normal subjects and 1.04 +/- 0.1, 4.5 +/- 0.7, and 7.1 +/- 0.4 μg/ml in the hyperthyroid patients, respectively. Peak PTU levels and PTU area under the curve were significantly greater at the 300-mg dose (P 123 I. Four hours after an oral dose of PTU, the hyperthyroid patients had a greater percentage of perchlorate-dischargeable 123 I than the euthyroid controls (+38 +/- 5% vs. 13 +/- 2%; P 3 and rT 3 were measured serially over 24 h after single oral doses of 50, 200, and 300 mg PTU. In normal volunteers, serum T 3 declined slightly but significantly after the 200- and 300-mg doses; an increase in rT 3 was also noted, but the changes did not attain statistical significance. In the hyperthyroid patients, serum T 3 fell from 501 +/- 29 to 379 +/- 27 ng/dl after 50 mg PTU (P 3 rose after each dose: from 119 +/- 12 to 131 +/- 11 ng/dl (P = NS) after 50 mg PTU, from 113 +/- 11 to 146 +/- 12 ng/dl (P < 0.02) after 200 mg PTU,

  11. Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

    Science.gov (United States)

    Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

    2013-08-01

    The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  12. Serum and gastric fluid levels of cytokines and nitrates in gastric diseases infected with Helicobacter pylori.

    Science.gov (United States)

    Mehmet, N; Refik, M; Harputluoglu, M; Ersoy, Y; Aydin, N Engin; Yildirim, B

    2004-04-01

    This case control study presents data on the concentrations of nitrite and nitrate and a variety of pro-inflammatory cytokines such as interleukin-1 beta (IL-1 beta), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor TNF-alpha in gastric fluid and serum. Patients with gastritis, gastric ulcer and gastric cancer are studied and grouped according to infection by Helicobacter pylori. The 208 patients who underwent upper gastrointestinal endoscopic examination were classified as follows; H. pylori-positive gastritis (n = 32), H. pylori-negative gastritis (n = 32), H. pylori-positive ulcers (n = 34), H. pylori-negative ulcers (n = 34), 43 patients with H. pylori-positive gastric cancer in addition to 33 H. pylori-negative healthy control individuals. Gastric fluids and blood samples were taken concomitantly. Cytokines and nitrite and nitrate determinations were attempted as soon as possible after collection of the samples. Nitrite and nitrate levels of serum and gastric fluids of H. pylori-positive gastritis and ulcers were higher than H. pylori-negative gastritis and ulcers. The concentrations of total nitrite and nitrate and cytokines (TNF-alpha, IL-2R, IL-6, and IL-8) in gastric fluids and sera of H. pylori-positive gastric cancer patients were higher than H. pylori-negative control groups. IL-1 beta level was significantly elevated in gastric fluid of infected cancer patients but not in serum. Taken together, the results suggest that an increase in cytokine-NO combination in gastric mucosa previously reported by many studies is not restricted to local infected gastric tissue but also detected in gastric fluid and sera of H. pylori-positive subjects and may have an important role in the pathogenesis and development of common gastric diseases.

  13. Trunk-to-Peripheral Fat Ratio Predicts Subsequent Blood Pressure Levels in Pubertal Children With Relatively Low Body Fat - Three-Year Follow-up Study.

    Science.gov (United States)

    Kouda, Katsuyasu; Ohara, Kumiko; Fujita, Yuki; Nakamura, Harunobu; Iki, Masayuki

    2016-07-25

    Only a few studies have examined the relationship between fat distribution measured by dual-energy X-ray absorptiometry (DXA) and blood pressure (BP), and no cohort study has targeted a pediatric population. The source population comprised all students registered as fifth graders in the 2 elementary schools in Hamamatsu, Japan. Of these, 258 children participated in both baseline (at age 11) and follow-up (at age 14) surveys. Body fat distribution was assessed using trunk-to-appendicular fat ratio (TAR) and trunk-to-leg fat ratio (TLR) measured by DXA. Relationships between BP levels and fat distribution (TAR or TLR) were examined after stratification by tertiles of whole-body fat.Systolic BP at follow-up was significantly (Pfat. Moreover, adjusted means of systolic and diastolic BPs in girls showed a significant increase from the lowest to highest tertile of TAR within the lowest tertile of whole-body fat. Body fat distribution in childhood could predict subsequent BP levels in adolescence. Children with a relatively low body fat that is more centrally distributed tended to show relatively high BP later on. (Circ J 2016; 80: 1838-1845).

  14. Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

    Science.gov (United States)

    Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

    1996-04-01

    1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice

  15. Increased levels of specific leukocyte- and platelet-derived substances during normal anti-tetanus antibody synthesis in patients with inactive Crohn disease

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Mortensen, T; Holten-Andersen, M

    2001-01-01

    , vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), plasminogen activator inhibitor type-1 (PAI-1) and myeloperoxidase (MPO) were determined in serum or plasma obtained on the same days. RESULTS: After inoculation anti-tetanus antibody levels were equally raised...... immunization in patients with Crohn disease and the subsequent release of various inflammatory mediators and growth factors in blood. METHODS: Ten patients with inactive disease and no concurrent medication and 12 age-and gender-matched healthy volunteers with anti-tetanus antibody levels less than 0.1 IU...... range and IL-6, TNF-alpha, MPO and histamine levels were unchanged in patients and volunteers during the study period. The levels of VEGF, TIMP-1 and PAI-1 were unchanged in the healthy volunteers during the study period, but were significantly (P

  16. IN VITRO STUDIES ON HEME OXYGENASE-1 AND P24 ANTIGEN HIV-1 LEVEL AFTERHYPERBARIC OXYGEN TREATMENTOFHIV-1 INFECTED ON PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS).

    Science.gov (United States)

    Budiarti, Retno; Kuntaman; Nasronudin; Suryokusumo; Khairunisa, Siti Qamariyah

    2018-01-01

    Heme oxygenase-1 (HO-1) is a protein secreted by immune cells as a part of immune response mechanism.HO-1 can be induced by variety agents that causingoxidative stress, such as exposure to 100% oxygenat2,4 ATA pressure.It plays a vital role in maintaining cellular homeostasis.This study was conducted to identify the effect of hyperbaric oxygen exposure in cultured ofPBMCthat infected by HIV-1. Primary culture of PBMCs were isolated from 16 healthy volunteers and HIV-1 infected MT4 cell line by co-culture. The PBMCs were aliquoted into two wells as control group and treatment group. The 16 samples of HIV-1 infected PBMCwere exposed to oxygen at 2,4 ATA in animal hyperbaric chamber forthree times in 30 minutes periods with 5 minutes spacing period, that called 1 session.The Treatment done on 5 sessions within 5 days. 16 samples of HIV-1 infected PMBCs that have no hyperbaric treatment became control group.The supernatant were measured the HO-1 production by ELISA andmRNA expression of HO-1 by real time PCR and the number ofantigen p24 HIV-1by ELISA. The result showed that there was no increasing of HO-1 at both mRNA level and protein level, there was a decreasing number of antigen p24 HIV-1 at the treatment group. In addition, hyperbaric exposure could not increase the expression of HO-1, more over the viral replication might be reduced by other mechanism. Hyperbaric oxygen could increases cellular adaptive response of PBMCs infected HIV-1 through increased expression of proteins that can inhibit HIV viralreplication.

  17. Brain-derived neurotrophic factor and autism: maternal and infant peripheral blood levels in the Early Markers for Autism (EMA) Study

    Science.gov (United States)

    Croen, Lisa A.; Goines, Paula; Braunschweig, Daniel; Yolken, Robert; Yoshida, Cathleen K.; Grether, Judith K.; Fireman, Bruce; Kharrazi, Martin; Hansen, Robin; Van de Water, Judy

    2008-01-01

    LAY ABSTRACT The diagnosis of autism is based solely on behavioral characteristics. There is currently no laboratory test that can be done to identify autism. In this study, we investigated a molecule called brain derived neurotrophic factor (BDNF) as a possible early biologic marker for autism. BDNF is a small protein found throughout the central nervous system and in circulating blood. We measured the level of BDNF in blood collected from women during pregnancy and from their babies at birth. We found that the concentration of BDNF in the maternal mid-pregnancy and newborn blood specimens was similar for children with autism, children with mental retardation, and children with typical development. The results of this study suggest that BDNF is unlikely to be a useful early biologic marker for autism. SCIENTIFIC ABSTRACT Objective To investigate levels of brain-derived neurotrophic factor (BDNF) in mid-pregnancy and neonatal blood specimens as early biologic markers for autism. Methods We conducted a population-based case-control study nested within the cohort of infants born from July 2000 – September 2001 to women who participated in the prenatal screening program in Orange County, California. Cases (n=84) were all children receiving services for autism at the Regional Center of Orange County. Two comparison groups from the same study population were included: children with mental retardation or developmental delay (n=49) receiving services at the same regional center, and children not receiving services for developmental disabilities, randomly sampled from the California birth certificate files (n=159), and frequency-matched to autism cases on sex, birth year, and birth month. BDNF concentrations were measured in archived mid-pregnancy and neonatal blood specimens drawn during routine prenatal and newborn screening using a highly sensitive bead-based assay (Luminex). Results The concentration of BDNF in maternal mid-pregnancy and neonatal specimens was

  18. Effects of Three Kinds of Curcuminoids on Anti-Oxidative System and Membrane Deformation of Human Peripheral Blood Erythrocytes in High Glucose Levels

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2015-01-01

    Full Text Available Background/Aims: Curcuminoids are the main bioactive constituents of the rhizome of turmeric. Erythrocytes lesions in diabetes are probably related to hyperglycemia and protein glycation. It has been reported that curcumin prevent lipid peroxidation. However, reports on the effects of demethoxycurcumin and bis-demethoxycurcumin on human erythrocytes at high glucose levels are scarce. Our aim is to investigate the effect of curcuminoids on oxidative stress and membrane of erythrocytes exposed to hyperglycemic condition. Methods: In this study, the different blood samples were treated with two doses of glucose (10 or 30 mM to mimic hyperglycemia in the presence or absence of three kinds of curcuminoids (5 or 10 μM in a medium at 37 °C for 24 h (Each experiment consists of 20 blood samples from 10 male and 10 female volunteers. The malondialdehyde was checked by HPLC, antioxidase (GSH and GSSG were measured by LC/MS, SOD was checked by WST-1 kit, morphology and phospholipid symmetry were detected by flow cytometry, confocal scanning microscope and scanning electron microscope. Results: The results illustrated that all three curcuminoids reduce oxidative stress damage on the membrane and maintain a better profile for erythrocytes. Furthermore, three curcuminoids had benefit effects on antioxidase. Conclusion: The three kinds of curcuminoids supplementation may prevent lipid peroxidation at different intensity and membrane dysfunction of human erythrocytes in hyperglycemia.

  19. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  20. Peripheral Artery Disease

    Science.gov (United States)

    ... pressure High blood cholesterol Coronary heart disease Stroke Metabolic syndrome Screening and Prevention Taking action to control your risk factors can help prevent or delay peripheral artery disease (P.A.D.) and its complications. Know your family history of health problems related to P.A. ...

  1. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The Role of Prophylactic Ibuprofen and N-Acetylcysteine on the Level of Cytokines in Periapical Exudates and the Post-Treatment Pain

    Directory of Open Access Journals (Sweden)

    Seyyed Mohsen Aghajanpour Mir

    2012-09-01

    Full Text Available Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive-microbial disturbances. Objective:To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- alpha, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- alpha, IL-6 and IL-17 levels were determined by ELISA and posttreatment pain was assessed using a visual analog scale (VAS. Results:There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion:The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain

  3. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Ostrowski, S R; Plomgaard, P; Fischer, C P

    2005-01-01

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in ...

  4. Peripheral orbit model

    CERN Document Server

    Hara, Yasuo

    1975-01-01

    Peripheral orbit model, in which an incoming hadron is assumed to revolve in a peripheral orbit around a target hadron, is discussed. The non-diffractive parts of two-body reaction amplitudes of hadrons are expressed in terms of the radius, width an absorptivity of the orbit. The radius of the orbit is about 1 fm and the width of the orbit is determined by the range of the interaction between the hadrons. The model reproduces all available experimental data on differential cross-sections and polarizations of $K^{-}p\\to K^{-}p$ and $\\bar K^{\\circ}n$ reactions for all angles successfully. This contribution is not included in the proceedings since it will appear in Progress of Theoretical Physics Vol. 51 (1974) No 2. Any person interested in the subject may apply for reprints to the author.

  5. Creating social presence through peripheral awareness

    NARCIS (Netherlands)

    Ruyter, de B.E.R.; Huijnen, C.A.G.J.; Markopoulos, P.; IJsselsteijn, W.A.; Stephanidis, C.; Jacko, J.

    2003-01-01

    This paper describes an experimental assessment of affective user benefits that may result from peripheral awareness of a remote friend or group of friends during a shared viewing of a televised event. The experiment suggests that awareness supported through a visual display enhances the level of

  6. Consequences of peripheral frequency selectivity for nonsimultaneous masking

    NARCIS (Netherlands)

    Duifhuis, H.

    1973-01-01

    The frequency selectivity of the peripheral ear (e.g., at the VIIIth nerve level) is so acute that onset and offset transients in responses to short signals produce a nonnegligible extension of the signal duration. Thus, peripheral excitation patterns produced by signals which were separated in time

  7. Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial.

    Directory of Open Access Journals (Sweden)

    Weidong Xiong

    2010-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK. This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs, in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-alpha and IFN-gamma. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials.

  8. Supplementation by thylakoids to a high carbohydrate meal decreases feelings of hunger, elevates CCK levels and prevents postprandial hypoglycaemia in overweight women

    DEFF Research Database (Denmark)

    Stenblom, Eva-Lena; Montelius, Caroline; Östbring, Karolina

    2013-01-01

    Thylakoids are chlorophyll-containing membranes in chloroplasts that have been isolated from green leaves. It has been previously shown that thylakoids supplemented with a high-fat meal can affect cholecystokinin (CCK), ghrelin, insulin and blood lipids in humans, and can act to suppress food...... intake and prevent body weight gain in rodents. This study investigates the addition of thylakoids to a high carbohydrate meal and its effects upon hunger motivation and fullness, and the levels of glucose, insulin, CCK, ghrelin and tumour necrosis factor (TNF)-alpha in overweight women. Twenty...... moderately overweight female subjects received test meals on three different occasions; two thylakoid enriched and one control, separated by 1 week. The test meals consisted of a high carbohydrate Swedish breakfast, with or without addition of thylakoids. Blood samples and VAS-questionnaires were evaluated...

  9. Daspsone Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    P A Sarojini

    1988-01-01

    Full Text Available A 24 year old lady being treated with 300 mg of dapsone daily for dermatitits herpetiformis, developed weakness and wasting of muscles of feet with claw hand deformity and t drop, 2 months tater. Neurological examination and nerve conduction studies conformed the presence of a peripheral motor neuropathy. Dapsone was discontinued and the patient was treated with cotrimatoxazole, gluten-free diet and supportive therapy. This satisfactorily controlled the dermatological lesion without adversely affecting the resolution of her neuropthy. Symptomatic improvement reported by the patient was confirmed by EMG and nerve conduction studies.

  10. Peripheral ossifying fibroma

    Directory of Open Access Journals (Sweden)

    Ameet Mani

    2010-01-01

    Full Text Available The peripheral ossifying fibroma (POF is an exophytic gingival mass of fibrous connective tissue covered with a surface epithelium associated with the formation of randomly dispersed foci of a mineralized product consisting of bone, cementum-like tissue, or dystrophic calcifications having a recurrent rate of nearly 20%. It is one of the most common reactive gingival lesions, which have often been called by the generic term "epulis." This case report describes the clinical and histopathological findings of POF, its differential diagnosis, and treatment.

  11. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Reinhard, Henrik; Wiinberg, Niels; Hansen, Peter R

    2011-01-01

    for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS...... AND RESULTS: P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score=400, carotid intima...

  12. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  13. Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

    DEFF Research Database (Denmark)

    Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

    1994-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

  14. Peripheral degenerative joint diseases

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2008-03-01

    Full Text Available Osteoarthritis, a degenerative joint disease, is the most commonrheumatic disorder mainly in a geriatric population. Manifestationsare pain, stiffness and functional loss in the affected joint.According to etiology it is classifi ed as primary (or idiopathicand secondary. Some risk factors for disease development aregenetics, race, age, sex, obesity, occupational activities andarticular biomechanics. Pathogenesis is the same for any cause orlocalization, being catabolic alterations, with synthesis, inhibitionand reparing intent of the cartilage matrix. Metalloproteinases andcytokines (IL-1,IL-6,TNF-α actions promote infl ammatory reactionand cartilage degradation. Pain, the most important symptom,does not correlate with radiologic fi ndings. Peripheral osteoarthritisoccurs predominantly in the knee, hip and hand. Diagnosis is basedon clinical features, laboratorial tests and radiological changes.Rheumatological associations’ guidelines for treatment includenon-pharmacologic (education, physiotherapy, assistive devices,and pharmacologic (analgesics, anti-infl ammatory drugs therapyand surgery. Arthroplasty seems to work better than medicines, butshould be used if other treatments have failed.

  15. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  16. Quality assessment of online patient education resources for peripheral neuropathy.

    Science.gov (United States)

    Hansberry, David R; Suresh, Ragha; Agarwal, Nitin; Heary, Robert F; Goldstein, Ira M

    2013-03-01

    Given its practicality, the internet is a primary resource for patients afflicted with diseases like peripheral neuropathy. Therefore, it is important that the readily available online resources on peripheral neuropathy are tailored to the general public, particularly concerning readability. Patient education resources were downloaded from the US National Library of Medicine, Mayo Clinic, National Institute of Neurological Disorders and Stroke, Neuropathy.org, GBS/CIDP Foundation International, Hereditary Neuropathy Foundation, Charcot-Marie-Tooth Association, Foundation for Peripheral Neuropathy, and Neuropathy Action Foundation websites. All patient education material related to peripheral neuropathy was evaluated for its level of readability using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level. The FRE scores averaged 43.4 with only the US National Library of Medicine scoring above 60 (76.5). The Flesch-Kincaid Grade Level scores averaged 11.0. All scores were above a seventh-grade level except the US National Library of Medicine, which had a score of a fifth-grade reading level. Most Americans may not fully benefit from patient education resources concerning peripheral neuropathy education on many of the websites. Only the US National Library of Medicine, which is written at a fifth-grade level, is likely to benefit the average American. © 2013 Peripheral Nerve Society.

  17. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  18. 25-Hydroxyvitamin D and Peripheral Immune Mediators

    DEFF Research Database (Denmark)

    Thorsen, Steffen; Pipper, Christian; Skogstrand, Kristin

    2017-01-01

    Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470...... patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981–1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997–2005. A variety of peripheral immune mediators were measured and compared...... to total 25(OH)D levels (25(OH)D2 + 25(OH)D3). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH...

  19. Ionic mechanisms in peripheral pain.

    Science.gov (United States)

    Fransén, Erik

    2014-01-01

    Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs. © 2014 Elsevier Inc. All rights reserved.

  20. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  1. Computed tomographic findings of intrahepatic peripheral cholangiocarcinoma

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Suh, Soo Jhi; Kim, Ho Joon; Chun, Byung Hee

    1986-01-01

    Cholangiocarcinoma is synonymous with bile duct carcinoma, and can originate in a small intrahepatic bile duct (peripheral type), a major intrahepatic duct including the hepatic hills, an extrahepatic duct, or near the papilla of Vater (central type). In a sense bile duct carcinoma of the peripheral type is cholangiocarcinoma of the liver; it has the same gross configuration as hepatocellular carcinoma, resulting in difficulty to differentiate on the CT. The authors studied CT findings of 14 cases of pathologically proven peripheral type cholangiocarcinoma of the liver during the last 4 years. The results were as follows: 1. Of 14 cases, 8 were female and 6 were male, and the age ranged from 5th to 7th decades. 2. Preoperative clinical diagnosis were as follows: hepatoma 8 cases, abscess 5 cases and metastasis 1 case in order of frequency. 3. Diagnosis were confirmed by hepatic lobectomy in 7 cases, wedge resection in 5 cases and needle biopsy in 2 case. 4. Laboratory findings were not specific, but there were only 2 cases with elevated alpha-fetoprotein level. 5. Associated diseases were gallstones in 1 case, intrahepatic duct stones in 1 case, extrahepatic duct stones in 2 cases, acute or chronic cholecystitis in 5 cases and CS in 3 cases. 6. Angiographic and scintigraphic findings were helpful in differential diagnosis from hepatoma but ultrasonography was non-specific. 7. The number of tumor were solitary in 12 cases and multiple in 2 cases. Among solitary cases, the site of involvement of the liver were right lobe in 8 cases and left lobe in 4 cases. 8. Common CT features of the intrahepatic peripheral cholangiocinoma of the liver were irregular, inhomogeneous, occasionally peripherally enhancing, low density liver mass, frequently accompanied by diffuse or segmental dilatation of the intrahepatic bile duct. If there were normal alpha fetoprotein level, positive skin and/or stool examination for CS and diffuse or segmental dilatation of the intrahepatic duct

  2. Central and peripheral control of food intake.

    Science.gov (United States)

    Abdalla, M M I

    2017-01-01

    The maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. The obesity has an evil effect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity.

  3. Central and peripheral control of food intake

    Directory of Open Access Journals (Sweden)

    Abdalla M. M. I.

    2017-01-01

    Full Text Available The maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. The obesity has an evil effect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity.

  4. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  5. Network node for peripheral sharing

    International Nuclear Information System (INIS)

    Bobbitt, J.; Johnson, M.

    1977-01-01

    A module which enables several independent computer systems to share the peripherals (graphics display and line printer) of a PDP-11 computer is described. The module requires no software support in the PDP-11

  6. Auditory attention activates peripheral visual cortex.

    Directory of Open Access Journals (Sweden)

    Anthony D Cate

    Full Text Available BACKGROUND: Recent neuroimaging studies have revealed that putatively unimodal regions of visual cortex can be activated during auditory tasks in sighted as well as in blind subjects. However, the task determinants and functional significance of auditory occipital activations (AOAs remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We examined AOAs in an intermodal selective attention task to distinguish whether they were stimulus-bound or recruited by higher-level cognitive operations associated with auditory attention. Cortical surface mapping showed that auditory occipital activations were localized to retinotopic visual cortex subserving the far peripheral visual field. AOAs depended strictly on the sustained engagement of auditory attention and were enhanced in more difficult listening conditions. In contrast, unattended sounds produced no AOAs regardless of their intensity, spatial location, or frequency. CONCLUSIONS/SIGNIFICANCE: Auditory attention, but not passive exposure to sounds, routinely activated peripheral regions of visual cortex when subjects attended to sound sources outside the visual field. Functional connections between auditory cortex and visual cortex subserving the peripheral visual field appear to underlie the generation of AOAs, which may reflect the priming of visual regions to process soon-to-appear objects associated with unseen sound sources.

  7. Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-07-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD, which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin, which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

  8. Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

    Science.gov (United States)

    Central memory T cells (Tcm’s) and polyfunctional CD4 T responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB); however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by ...

  9. Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

    Directory of Open Access Journals (Sweden)

    Mayara Fernanda Maggioli

    2016-10-01

    Full Text Available Central memory T cells (Tcm and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB; however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated. BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection, non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

  10. Genomic profiling of tumor necrosis factor alpha (TNF-alpha) receptor and interleukin-1 receptor knockout mice reveals a link between TNF-alpha signaling and increased severity of 1918 pandemic influenza virus infection

    Science.gov (United States)

    The influenza pandemic of 1918-1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated pro-inflammatory cytokine response. In the present study, we...

  11. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  12. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy

    Science.gov (United States)

    Kramer, Rita; Bielawski, Jacek; Kistner-Griffin, Emily; Othman, Alaa; Alecu, Irina; Ernst, Daniela; Kornhauser, Drew; Hornemann, Thorsten; Spassieva, Stefka

    2015-01-01

    Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and cisplatin chemotherapy. In the current study, we tested the involvement of a novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1-Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses l-alanine instead of l-serine as its amino acid substrate. We tested whether treatment of cells with paclitaxel (250 nM, 1 µM) and cisplatin (250 nM, 1 µM) would result in elevated cellular levels of 1-deoxysphingolipids. Our results revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent elevation of 1-deoxysphingolipids levels and an increase in the message and activity of serine palmitoyltransferase (P peripheral neuropathy symptoms [evaluated by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1-deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients with breast cancer who were treated with paclitaxel chemotherapy. Our results showed that there was an association between the incidence and severity of neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P neuropathy (P peripheral neuropathy.—Kramer, R., Bielawski, J., Kistner-Griffin, E., Othman, A., Alecu, I., Ernst, D., Kornhauser, D., Hornemann, T., Spassieva, S. Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy. PMID:26198449

  13. Evaluating relationship in cytokines level, Fibromyalgia Impact Questionnaire and Body Mass Index in women with Fibromyalgia syndrome.

    Science.gov (United States)

    Ghizal, Fatima; Das, Siddharth Kumar; Verma, Narsingh; Mahdi, Abbas Ali

    2016-01-01

    Cytokines (TNF-α and IL-6) levels are reported to be perturbed in Fibromyalgia syndrome (FMS) patients. Moreover, Body Mass Index (BMI) may also be related to disturbed cytokines level. Therefore, the present study was planned to evaluate the levels of cytokines and to correlate them with BMI and Fibromyalgia Impact Questionnaire Revised (FIQR) in female FMS patients (n= 60) and control group (n= 60). 4 ml of blood samples were taken from both the group of patients and controls to measure the levels of IL-6 and TNF-α . Symptoms of FMS were assessed by FIQR. BMI was calculated by a standard formula of weight in kilograms divided by height in meter square. There were significant differences in BMI levels in FMS patients than in control group. However, no significant association was found between BMI and TNF-α levels, and BMI and IL-6 levels in patient and control groups. However, a significant association was found between FIQR and BMI in patients group. On the basis of the results we conclude that the levels of IL-6 and TNF-alpha are not associated with BMI in FMS patients. Furthermore, patients with higher BMI may fall at the risk of FMS. Therefore, weight management may be an important aspect for treatment of FMS patients.

  14. Peripheral Atherectomy: Applications and Techniques.

    Science.gov (United States)

    Mittleider, Derek; Russell, Erich

    2016-06-01

    Peripheral atherectomy is a class of procedures that is rapidly increasing in volume. Multiple classes of devices exist, and newer variants are added to the market annually. The devices see wide application for de novo lesions, in-stent restenosis, and adjunctive therapy for drug-coated balloons. The body of evidence supporting atherectomy is less robust than for many other peripheral therapies. The frequency and severity of complications from atherectomy can be significant compared with angioplasty and stenting, and familiarity with preventative and bailout techniques is essential for the interventionalist. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [Atherectomy for peripheral arterial disease].

    Science.gov (United States)

    Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

    2015-04-13

    Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

  16. Imaging of the peripheral retina

    Directory of Open Access Journals (Sweden)

    Marcus Kernt

    2013-01-01

    Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

  17. Blood glucose and insulin levels in patients with peripheral vestibular disease Avaliação da curva glicoinsulinêmica nos pacientes com vestibulopatia periférica

    Directory of Open Access Journals (Sweden)

    Ana Paula Serra

    2009-10-01

    Full Text Available Metabolic disorders can cause dizziness. AIM: to study the prevalence of glucose and glucose-insulin alterations in patients with peripheral vestibular disorders by studying the four-hour glucose-insulin curve; to check at what time there was the highest prevalence of altered cases and whether the glucose and insulin curves together are better than the isolate glucose curve and fasting glucose curve. MATERIALS AND METHODS: retrospective study, analyzing 81 four-hour glucose-insulin curves in patients with peripheral vestibular dizziness. RESULTS: Four-hour glucose-insulin curve alterations happened in 87.7% of the patients. Hypoglycemia was seen in 61.7% of the cases, hyperinsulinemia in 55.5%, hyperglycemia in 27.2%, glucose intolerance in 12.3% and hypoinsulinemia in 1.2%. Normal tests were seen in 12.3 % of the cases and altered fasting glucose in 23.5%. CONCLUSIONS: The four-hour glucose-insulin curve analysis showed that 87.7% of the patients with dizziness and suspicion of peripheral vestibular disorder had glucose or insulin metabolism disorders. The highest number of alterations was seen up to the third and fourth hour of the glucose-insulin curve. The glucose and insulin curves together overcame the glucose curve alone and fasting glucose curve in regards of the prevalence of altered cases.Alterações metabólicas podem causar tontura. OBJETIVOS: Identificar a prevalência das alterações glicêmicas e glicoinsulinêmicas em pacientes com vestibulopatia periférica por meio da curva glicoinsulinêmica de 4 horas; verificar em que momento do exame foi encontrada a maior prevalência de casos alterados e se as curvas glicêmica e insulinêmica em conjunto superam a curva glicêmica isolada e glicemia de jejum. MATERIAL E MÉTODO: Estudo retrospectivo, com análise de 81 curvas glicoinsulinêmicas de quatro horas em pacientes com queixa de tontura de origem vestibular periférica. RESULTADOS: Alterações na curva glicoinsulinêmica de 4

  18. Peripheral changes in endometriosis-associated pain

    Science.gov (United States)

    Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

    2014-01-01

    elevated neurotrophin levels and pain severity seems to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neuotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated. PMID:24859987

  19. Imaging of a glioma using peripheral benzodiazepine receptor ligands

    Energy Technology Data Exchange (ETDEWEB)

    Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

    1987-02-01

    Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

  20. Total white blood cell counts and LPS-induced TNF alpha production by monocytes of pregnant, pseudopregnant and cyclic rats

    NARCIS (Netherlands)

    Faas, MM; Moes, H; van der Schaaf, G; de Leij, LFMH; Heineman, MJ

    Pregnancy in the rat may be associated with an activated innate immune system. Therefore, we investigated monocyte function as well as total white blood cell (WBC) counts during the follicular phase of the ovarian cycle, pregnancy and pseudopregnancy in the rat. Rats were equipped with a permanent

  1. Total white blood cell counts and LPS-induced TNF alpha production by monocytes of pregnant, pseudopregnant and cyclic rats

    NARCIS (Netherlands)

    Faas, M. M.; Moes, H.; van der Schaaf, G.; de Leij, L. F. M. H.; Heineman, M. J.

    2003-01-01

    Pregnancy in the rat may be associated with an activated innate immune system. Therefore, we investigated monocyte function as well as total white blood cell (WBC) counts during the follicular phase of the ovarian cycle, pregnancy and pseudopregnancy in the rat. Rats were equipped with a permanent

  2. TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

    International Nuclear Information System (INIS)

    Pregi, Nicolas; Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

    2009-01-01

    The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-α. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-α or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-α. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-κB nuclear translocation, TNF-α induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-κB, through mechanisms involving Jak/STAT and PI3K signalling pathways

  3. Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

    Science.gov (United States)

    Arjona, M Montes de Oca; Pérez-Cano, R; Garcia-Juárez, R; Martín-Aspas, A; del Alamo, C Fernández Gutiérrez; Girón-González, J A

    2006-04-01

    The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

  4. Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy.

    Science.gov (United States)

    Shenoi, Mithun M; Iltis, Isabelle; Choi, Jeunghwan; Koonce, Nathan A; Metzger, Gregory J; Griffin, Robert J; Bischof, John C

    2013-05-06

    Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1-2 h followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted manner. We anticipate our work to direct investigations into more potent tumor vasculature specific combinations of VDAs and nanoparticles with the goal of transitioning optimal regimens into clinical trials.

  5. Suppressive effect of glucocorticoids on TNF-alpha production is associated with their clinical effect in multiple sclerosis

    NARCIS (Netherlands)

    van Winsen, L.M.L.; Polman, C.H.; Dijkstra, C.D.; Tilders, F.J.H.; Uitdehaag, B.M.J.

    2010-01-01

    A reduced sensitivity to glucocorticoids can affect the clinical effect of treatment with high-dose intravenous methylprednisolone in multiple sclerosis. We prospectively studied 27 multiple sclerosis patients who were treated with intravenous methylprednisolone. Before and after treatment in vitro

  6. Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists

    Directory of Open Access Journals (Sweden)

    Urbano PCM

    2014-07-01

    Full Text Available Paulo César Martins Urbano,1 Vanete Thomaz Soccol,1 Valderilio Feijó Azevedo2 1Biotechnology and Bioprocess Engineering Program, Federal University of Parana, Curitiba, Parana, Brazil; 2Hospital de Clínicas, Federal University of Parana, Curitiba, Parana, Brazil Abstract: Various criteria are necessary to assess the efficacy and safety of biological medications in order to grant companies the right to register these medications with the appropriate bodies that regulate their sale. The imminent expiration of the patents on reference biological products which block the cytokine TNF-α (tumor necrosis factor-α raises the possibility of bringing so-called biosimilars to the market (similar to the biologicals of reference products. This occurrence is inevitable, but criteria to adequately evaluate these medications are now needed. Even among controversy, there is a demand from publications correlating the pro-apoptotic mechanism of the original TNF-α antagonists (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol in the treatment of rheumatoid arthritis and other diseases. In this article, the authors discuss the possibility of utilizing the pro-apoptotic effect correlated with the regulation of the anti-apoptotic proteins FLIP and NF-κB as new criteria for analyzing the pharmacodynamics of possible biosimilar TNF-α antagonists which should be submitted to regulatory agencies for evaluation. Keywords: anti-TNF drugs, rheumatoid arthritis, apoptosis, NF-κB, FLIP

  7. Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate

    DEFF Research Database (Denmark)

    Hengstman, G.J.; Bleecker, J.L. De; Feist, E.

    2008-01-01

    and the occurrence of an infusion reaction. The few patients who did reach the primary endpoint showed improvement in all aspects studied. CONCLUSION: Infliximab combined with weekly methotrexate might be safe and well tolerated in a small subgroup of patients with drug-naive recent-onset myositis. At present, we do...

  8. Comparative Efficacy and Acceptability of Anti-TNF-Alpha Therapy in Ankylosing Spondylitis: A Mixed-Treatments Comparison

    Directory of Open Access Journals (Sweden)

    Yehua Wang

    2016-09-01

    Full Text Available Background: Tumor necrosis factor α (TNFα antagonists, namely, golimumab, adalimumab, infliximab, etanercept and certolizumab have been prescribed to alleviate and treat ankylosing spondylitis (AS. However, the lack of comparative evidence does not enable us to make constructive recommendations particularly for AS patient populations. Methods: Eligible controlled trials regarding the above 5 anti-TNFα therapies were searched electronically through PubMed, Embase and Cochrane until April 1, 2015. Odds ratios (ORs were estimated and compared for efficacy (ASAS20, ASAS40, ASAS5/6 responses and ASAS partial remission and acceptability (serious adverse effects (SAE among the anti-TNFα reagents. Results: Totally, 25 trials with 2989 participants were incorporated in this mixed treatment comparison. All the 5 TNFα blockers achieved better ASAS20, ASAS40, ASAS5/6 and ASAS-PR responses than the placebo. Furthermore, there was no significant distinction existed among inter-drug comparisons, except that unfavorable effects induced by certolizumab seemed to be less severe than those by etanercept (OR = 0.22, 95% CI: 0.05-0.93. Apart from that, etanercept was estimated to arrive at the most favorable ASAS20 response (90.6% and SAE (83.6%, while infliximab seemed to accomplish the best ASAS40 (83.6% and ASAS-PR responses (77.3%. In addition, adalimumab was estimated to rank the highest ASAS5/6 response (75.0%. Conclusions: Etanercept, infliximab and adalimumab might be prioritized among the commonly recognized 5 anti-TNFα therapies specific for AS patients, though existing evidence did not suffice to confirm significant superiority among the above 5 anti-TNFα reagent.

  9. Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by Mononuclear Cells in Healthy Adults

    NARCIS (Netherlands)

    Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost

    2016-01-01

    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however,

  10. Interleukin-1beta and TNF-alpha: reliable targets for protective therapies in Parkinson´s Disease?

    Directory of Open Access Journals (Sweden)

    María Celeste Leal

    2013-04-01

    Full Text Available Neuroinflammation has received increased attention as a target for putative neuroprotective therapies in Parkinson´s Disease (PD. Two prototypic pro-inflammatory cytokines Interleukin-1beta (IL-1 and Tumor necrosis factor-alpha (TNF have been implicated as main effectors of the functional consequences of neuroinflammation on neurodegeneration in PD models. In this review, we describe that the functional interaction between these cytokines in the brain differs from the periphery (e.g. their expression is not induced by each other and present data showing predominantly a toxic effect of these cytokines when expressed at high doses and for a sustained period of time in the substantia nigra pars compacta (SN. In addition, we highlight opposite evidence showing protective effects of these two main cytokines when conditions of duration, amount of expression or state of activation of the target or neighboring cells are changed. Furthermore, we discuss these results in the frame of previous disappointing results from anti-TNF clinical trials against Multiple Sclerosis, another neurodegenerative disease with a clear neuroinflammatory component. In conclusion, we hypothesize that the available evidence suggests that the duration and dose of IL-1 or TNF expression is crucial to predict their functional effect on the SN. Since these parameters are not amenable for measurement in the SN of PD patients, we call for an in-depth analysis to identify downstream mediators that could be common to the toxic (and not the protective effects of these cytokines in the SN. This strategy could spare the possible neuroprotective effect of these cytokines operative in the patient at the time of treatment, increasing the probability of efficacy in a clinical setting. Alternatively, receptor-specific agonists or antagonists could also provide a way to circumvent undesired effects of general anti-inflammatory or specific anti IL-1 or TNF therapies against PD.

  11. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha

    DEFF Research Database (Denmark)

    Czermak, B J; Sarma, V; Bless, N M

    1999-01-01

    production in vitro and in vivo. Two rat CXC chemokines (macrophage inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant (CINC)) as well as three rat CC chemokines (MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein (MCP)-1) were investigated. Chemokine generation in vitro...

  12. The Role and Regulation of TNF-Alpha in Normal Rat Mammary Gland During Development and in Breast Cancer.

    Science.gov (United States)

    1996-07-01

    autocrine synthesis of TNFcx by the MEC as well. Normally, there is strict control of the expression of this cytokine; however, it is possible that any...1,2-benz-anthracene (DMBA) (Sigma, St. Louis, MO) (in corn oil) p.o. using standard protocols (30) or via i.p. injection of 1-methyl-l- nitrosourea ...Beutler, B. Dexamethasone and pentoxifylline inhibit endotoxin- induced cachectin/tumor necrosis factor synthesis at separate points in the signalling

  13. The Role of MEKK3 Signaling Pathway in the Resistance of Breast Cancer Cells to TNF- (alpha) -Mediated Apoptosis

    National Research Council Canada - National Science Library

    Huang, Qiaojia

    2003-01-01

    ...-alpha treatment, and MEKK3 is an essential component of this process. I constructed expression vectors that express dominant negative forms of MEKK3 that will be used to block the MEKK3-down stream cascades...

  14. The Role and Regulation of TNF-Alpha in Normal Rat Mammary Gland During Development and in Breast Cancer

    National Research Council Canada - National Science Library

    Varela, Linda

    1998-01-01

    The pleiotropic cytokine tumor necrosis factor-alpha (TNF) has previously been shown to regulate both the proliferation and differentiation of normal rat mammary epithelial cells (MEC) in primary culture...

  15. Inhibition by TNF-alpha and IL-4 of cationic lipid mediated gene transfer in cystic fibrosis tracheal gland cells.

    Science.gov (United States)

    Bastonero, Sonia; Gargouri, Myriem; Ortiou, Sandrine; Guéant, Jean-Louis; Merten, Marc D

    2005-11-01

    In vivo, tracheal gland serous cells highly express the cystic fibrosis transmembrane conductance regulator (cftr) gene. This gene is mutated in the lethal monogenic disease cystic fibrosis (CF). Clinical trials in which the human CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in weak and transient gene expression. As CF is characterized by mucus inspissation, airway infection, and severe inflammation, we tested the hypothesis that inflammation and especially two cytokines involved in the Th1/Th2 inflammatory response, interleukin 4 (IL-4) and TNFalpha, could inhibit gene transfer efficiency using a model of human CF tracheal gland cells (CF-KM4) and Lipofectamine reagent as a transfection reagent. The specific secretory defects of CF-KM4 cells were corrected by Lipofectamine-mediated human CFTR gene transfer. However, this was altered when cells were pre-treated with IL-4 and TNFalpha. Inhibition of luciferase reporter gene expression by IL-4 and TNFalpha pre-treated CF-KM4 cells was measured by activity and real-time RT-PCR. Both cytokines induced similar and synergistic inhibition of transgene expression and activity. This cytokine-mediated inhibition could be prevented by anti-inflammatory agents such as glucocorticoids but not by non-steroidal (NSAI) agents. This data suggests that an inflammatory context generated by IL-4 and TNFalpha can inhibit human CFTR gene transfer in CF tracheal gland cells and that glucocorticoids may have a protecting action. Copyright (c) 2005 John Wiley & Sons, Ltd.

  16. Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system

    DEFF Research Database (Denmark)

    Taupin, V; Renno, T; Bourbonnière, L

    1997-01-01

    are a target of immune attack. TNF-alpha also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-alpha at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal...

  17. Association of tumor necrosis factor alpha gene polymorphism G-308A with pseudoexfoliative glaucoma in the Pakistani population.

    NARCIS (Netherlands)

    Khan, M.I.; Micheal, S.; Rana, N.; Akhtar, F.; Hollander, A.I. den; Ahmed, A.; Qamar, R.

    2009-01-01

    PURPOSE: The purpose of the present study was to determine the role of the tumor necrosis factor alpha (TNF-alpha) gene polymorphism G-308A and total serum immunoglobulin E (TsIgE) levels in the onset of pseudoexfoliation glaucoma (PEXG) in Pakistani patients. METHODS: The TNF-alpha polymorphism

  18. Peripheral facial weakness (Bell's palsy).

    Science.gov (United States)

    Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

    2013-06-01

    Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

  19. MEGACARYOCYTES IN THE PERIPHERAL CIRCULATION

    Science.gov (United States)

    Minot, George R.

    1922-01-01

    A megacaryocyte is seen commonly as an occasional cell in the peripheral blood of patients with myelogenous leucemia. Less commonly they appear in relatively large numbers. These giant cells also may occur in the blood under other conditions. Their presence is indicative of a bone marrow under intense strain. PMID:19868650

  20. [Ultrasound-guided peripheral catheterization].

    Science.gov (United States)

    Salleras-Duran, Laia; Fuentes-Pumarola, Concepció

    2016-01-01

    Peripheral catheterization is a technique that can be difficult in some patients. Some studies have recently described the use of ultrasound to guide the venous catheterization. To describe the success rate, time required, complications of ultrasound-guided peripheral venous catheterization. and patients and professionals satisfaction The search was performed in databases (Medline-PubMed, Cochrane Library, CINAHL and Cuiden Plus) for studies published about ultrasound-guided peripheral venous catheterization performed on patients that provided results on the success of the technique, complications, time used, patient satisfaction and the type of professional who performed the technique. A total of 21 studies were included. Most of them get a higher success rate 80% in the catheterization ecoguide and time it is not higher than the traditional technique. The Technical complications analyzed were arterial puncture rates and lower nerve 10%. In all studies measuring and comparing patient satisfaction in the art ecoguide is greater. Various professional groups perform the technique. The use of ultrasound for peripheral pipes has a high success rate, complications are rare and the time used is similar to that of the traditional technique. The technique of inserting catheters through ultrasound may be learned by any professional group performing venipuncture. Finally, it gets underscores the high patient satisfaction with the use of this technique. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  2. What Is Peripheral Artery Disease?

    Science.gov (United States)

    ... or bluish color to the skin A lower temperature in one leg compared to the other leg Poor nail growth on the toes and decreased hair growth on the legs Erectile dysfunction, especially among men who have diabetes Diagnosis Peripheral artery disease (P.A.D.) is diagnosed based ...

  3. Peripheral neuropathy in thalassemia

    International Nuclear Information System (INIS)

    Sawaya, Raja A.; Tahir, A.; Zahad, L.

    2006-01-01

    Patients with thalassemia may complain of numbness and weakness of lower extremities. The aim of the study was to determine whether these patients suffer from a polyneuropathy and to determine any contributing factors for the development of neuropathy. We examined 30 patients with thalasemia major and intermedia, clinically and electrophysiologically. We correlated these findings with demographics, blood status and treatment and compared electrophysiologic data with 30 age and sex matched normal subjects or historical controls. We found that 78% of thalassemia patients suffer from a mild sensory polyneuropathy. The neuropathy seemed to be worse in the intermedia type. Thalassemia patients who received blood transfusions and deferoaximine had better nerve faction than those who did not, irrespective of the dose of the deferoxamine. The neuropathy was worse for the older patients, irrespective of the sex. The hemoglobin level, and the fact that some patients underwent spleenctomy, did not affect the status of the patient's nerves. Patients with thalassemia may suffer from a sensor polyneuropathy especially as they grow older and they are not optimally treated. (author)

  4. Peripheral blood signatures of lead exposure.

    Directory of Open Access Journals (Sweden)

    Heather G LaBreche

    Full Text Available BACKGROUND: Current evidence indicates that even low-level lead (Pb exposure can have detrimental effects, especially in children. We tested the hypothesis that Pb exposure alters gene expression patterns in peripheral blood cells and that these changes reflect dose-specific alterations in the activity of particular pathways. METHODOLOGY/PRINCIPAL FINDING: Using Affymetrix Mouse Genome 430 2.0 arrays, we examined gene expression changes in the peripheral blood of female Balb/c mice following exposure to per os lead acetate trihydrate or plain drinking water for two weeks and after a two-week recovery period. Data sets were RMA-normalized and dose-specific signatures were generated using established methods of supervised classification and binary regression. Pathway activity was analyzed using the ScoreSignatures module from GenePattern. CONCLUSIONS/SIGNIFICANCE: The low-level Pb signature was 93% sensitive and 100% specific in classifying samples a leave-one-out crossvalidation. The high-level Pb signature demonstrated 100% sensitivity and specificity in the leave-one-out crossvalidation. These two signatures exhibited dose-specificity in their ability to predict Pb exposure and had little overlap in terms of constituent genes. The signatures also seemed to reflect current levels of Pb exposure rather than past exposure. Finally, the two doses showed differential activation of cellular pathways. Low-level Pb exposure increased activity of the interferon-gamma pathway, whereas high-level Pb exposure increased activity of the E2F1 pathway.

  5. Angioplasty and stent placement - peripheral arteries - discharge

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000234.htm Angioplasty and stent placement - peripheral arteries - discharge To use the sharing ... peripheral artery). You may have also had a stent placed. To perform the procedure: Your doctor inserted ...

  6. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    Science.gov (United States)

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  7. Peripheral surgical wounding and age-dependent neuroinflammation in mice.

    Directory of Open Access Journals (Sweden)

    Zhipeng Xu

    Full Text Available Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, Iba1 positive cells (the marker of microglia activation, CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

  8. Tenascin-C in peripheral nerve morphogenesis.

    Science.gov (United States)

    Chiquet, M; Wehrle-Haller, B

    1994-01-01

    The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in developing peripheral nerves of the chick embryo; synthesis of its mRNA peaks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor and sensory neurons. The ability to grow neurites on TN-C is developmentally regulated: sensory neurons from 4-day chick embryos (the stage at which peripheral nerves start to develop) grow immediately and rapidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-terminal (distal) portion of TN-C subunits. Integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is completely blocked by antibodies to beta 1 integrins. In striking contrast to neuronal processes, nerve satellite cells can attach to a TN-C substrate but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibronectin or laminin act as selective barriers that allow neurites to pass while holding up satellite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is shared by other molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Coaching Peripheral Vision Training for Soccer Athletes

    Science.gov (United States)

    Marques, Nelson Kautzner, Jr.

    2010-01-01

    Brazilian Soccer began developing its current emphasis on peripheral vision in the late 1950s, by initiative of coach of the Canto do Rio Football Club, in Niteroi, Rio de Janeiro, a pioneer in the development of peripheral vision training in soccer players. Peripheral vision training gained world relevance when a young talent from Canto do Rio,…

  10. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    Science.gov (United States)

    Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

    2013-01-01

    This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

  11. Monitoring sweep in peripheral waterflood

    International Nuclear Information System (INIS)

    Rouser, B.J.; Al-Askar, Y.A.; Hassoun, T.H.

    1991-01-01

    This paper examines the techniques used and the results obtained in monitoring the water advance in a peripheral waterflood of a carbonate reservoir. The peripheral pattern used in the subject reservoir gives a water advanced similar to that obtained in a water drive reservoir. However, monitoring this particular reservoir is complicated by the use of a low salinity brine for flooding and the areal shape of the reservoir. The use of pulsed neutron capture logging in conjunction with production logging has been effective in differentiating between oil and water in porous zones in existing producers. The use of the two logs has been successful despite the problems normally encountered when logging open hole completions in a reservoir being flooded with a low salinity brine. Results have been confirmed and enhanced by open hole logs of new wells being drilled in the water invaded areas

  12. Peripheral nerve conduits: technology update

    Directory of Open Access Journals (Sweden)

    Arslantunali D

    2014-12-01

    Full Text Available D Arslantunali,1–3,* T Dursun,1,2,* D Yucel,1,4,5 N Hasirci,1,2,6 V Hasirci,1,2,7 1BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU, Ankara, Turkey; 2Department of Biotechnology, METU, Ankara, Turkey; 3Department of Bioengineering, Gumushane University, Gumushane, Turkey; 4Faculty of Engineering, Department of Medical Engineering, Acibadem University, Istanbul, Turkey; 5School of Medicine, Department of Histology and Embryology, Acibadem University, Istanbul, Turkey; 6Department of Chemistry, Faculty of Arts and Sciences, METU, Ankara, Turkey; 7Department of Biological Sciences, Faculty of Arts and Sciences, METU, Ankara, Turkey *These authors have contributed equally to this work Abstract: Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers and designs (tubular, fibrous, and matrix type are being presented. Keywords: peripheral nerve injury, natural biomaterials, synthetic biomaterials

  13. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...SUPPLEMENTARY NOTES 14. ABSTRACT In current war trauma, 20-30% of all extremity injuries and >80% of penetrating injuries being associated with peripheral nerve...through both axonal advance and in revascularization of the graft following placement. We are confident that this technology may allow us to

  14. Communication, Consumption and Peripheral Politics

    Directory of Open Access Journals (Sweden)

    NÍZIA VILLAÇA

    2009-02-01

    Full Text Available This essay analyses central/peripheral dynamics and its new semantics in the big scenario of globalization. The processes of hybridization between the local and the global spaces are discussed focusing the strategies of inclusion and exclusion through some examples from media and cultural industry. The methodology helps to reflect about the theme using elements of epistemology communication, consumer society and cultural studies.

  15. Peripheral facial palsy in children.

    Science.gov (United States)

    Yılmaz, Unsal; Cubukçu, Duygu; Yılmaz, Tuba Sevim; Akıncı, Gülçin; Ozcan, Muazzez; Güzel, Orkide

    2014-11-01

    The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential. © The Author(s) 2013.

  16. Gene expression of desaturase (FADS1 and FADS2) and Elongase (ELOVL5) enzymes in peripheral blood: association with polyunsaturated fatty acid levels and atopic eczema in 4-year-old children.

    Science.gov (United States)

    Chisaguano, Aida Maribel; Montes, Rosa; Pérez-Berezo, Teresa; Castellote, Ana Isabel; Guerendiain, Marcela; Bustamante, Mariona; Morales, Eva; García-Esteban, Raquel; Sunyer, Jordi; Franch, Angels; López-Sabater, M Carmen

    2013-01-01

    It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson's rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.

  17. Gene Expression of Desaturase (FADS1 and FADS2) and Elongase (ELOVL5) Enzymes in Peripheral Blood: Association with Polyunsaturated Fatty Acid Levels and Atopic Eczema in 4-Year-Old Children

    Science.gov (United States)

    Chisaguano, Aida Maribel; Montes, Rosa; Pérez-Berezo, Teresa; Castellote, Ana Isabel; Guerendiain, Marcela; Bustamante, Mariona; Morales, Eva; García-Esteban, Raquel; Sunyer, Jordi; Franch, Àngels; López-Sabater, M. Carmen

    2013-01-01

    Abstract Background It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children. Methods AE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson’s rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE. Results Children with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1. Conclusions and Significance Changes in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children. PMID:24167612

  18. Circadian clocks are resounding in peripheral tissues.

    Directory of Open Access Journals (Sweden)

    Andrey A Ptitsyn

    2006-03-01

    Full Text Available Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.

  19. Cutaneous manifestations of diabetic peripheral neuropathy.

    Science.gov (United States)

    Dogiparthi, S N; Muralidhar, K; Seshadri, K G; Rangarajan, S

    2017-01-01

    There is a rise in number of people diagnosed with Diabetes Mellitus. The incidence is rising in modern Indian society because of Industrial development and drastically changing lifestyles. Diabetic neuropathies are microvascular disorders that are usually associated with the duration of Diabetes. Among the various forms, the most common is Diabetic Peripheral Neuropathy. The disease if neglected leads to chronic ulcer formation leading to amputations frequently. Hence the aim of this study is to document the early cutaneous changes and create an early awareness in the importance of controlling Diabetes. The study consisted of 205 patients with Type 2 DM. Participant's neuropathy status was determined based on Neuropathy Disability Score and Diabetic Neuropathy Symptom Score. Among the Skin changes documented, the common changes seen were: Peripheral hair loss in 185 (90.2%), Xerosis in 168 (82%), Anhydrosis in 162 (79%), Plantar Fissures in 136 (66.3%), Plantar Ulcer in 80 (39%), common nail changes documented were Onychomycosis in 165 (80.5%) and Onychauxis in 53 (25.8%) patients in relation to the occupation and duration of Diabetes mellitus. In conclusion, it is important to control glycemic levels in the all stages of Diabetes and institute foot care measures to prevent the complications of neuropathy.

  20. Quantification of BCR-ABL transcripts in peripheral blood cells and ...

    African Journals Online (AJOL)

    Purpose: To investigate the feasibility of using peripheral blood plasma samples as surrogates for blood cell sampling for quantification of breakpoint cluster region-Abelson oncogene (BCR-ABL) transcript levels to monitor treatment responses in chronic myeloid leukemia (CML) patients. Methods: Peripheral blood samples ...

  1. Peripheral doses from pediatric IMRT

    International Nuclear Information System (INIS)

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-01-01

    Peripheral dose (PD) data exist for conventional fields (≥10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10 -10 scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from

  2. Peripheral arterial disease and revascularization of the diabetic foot.

    Science.gov (United States)

    Forsythe, R O; Brownrigg, J; Hinchliffe, R J

    2015-05-01

    Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi-level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised--treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non-revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell-based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches. © 2014 John Wiley & Sons Ltd.

  3. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  4. Peripheral arterial angiography and interventional treatment in diabetic foot ulcers

    International Nuclear Information System (INIS)

    Guo Xiaohua; Cheng Yongde; Hu Suying; He Jianrong; Lin Kaiqin; Jin Honglai; Shi Shijie

    2003-01-01

    Objective: To assess the changes of peripheral arteries and choice of interventional treatment in diabetic foot ulcers. Methods: Thirty-six diabetic patients with foot ulcers were examined by lower extremity DSA with simultaneous ultrasonic Doppler examination for correlative study and interventional treatment carried out in 17 segmental stenotic cases. Among them, 12 patients were treated by PTA and 5 patients by intravascular stenting. Results: Irregular stenoses and obstruction were observed in all patients with peripheral foot ulcers. DSA examination was more reliable comparing with Doppler examination for demonstration of the arterial injury above the level of popliteal artery. PTA and primary stenting were effective in all of these subjects outcoming with promotion of the lower extremity arterial blood perfusion and foreseen curing efficacy. Conclusions: Peripheral arterial stenoses were common in diabetic patients with foot ulcers. In clinical practice, DSA examination and interventional treatment could give a fertile prognosis and reduce disabling

  5. Hepatic abscess versus peripheral cholangiocarcinoma: Sonographic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Chung, Kyoo Byung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Chang Hee [Kunkuk University College of Medicine, Chung-Ju Hospital, Chung-Ju (Korea, Republic of)

    2000-12-15

    To find out the sonographic findings that are useful to differentiate hepatic abscess from peripheral cholangiocarcinoma. Twenty-two hepatic abscesses and 22 peripheral cholangiocarcinomas which had been confirmed histologically were included in this study. Objective points were echo characteristics of the lesion, internal septation, presence of peripheral low echoic rim, demarcation from normal liver(well or poorly defined), posterior enhancement, multiplicity, dilatation of bile duct(obstructive or non-obstructive), intrahepatic duct stone, pleural effusion, and intra-abdominal fluid collection. Echo characteristics of the lesion were classified in-to four types. Type I; Predominantly echogenic with hypoechoic portion, type II; Echogenic without hypoechoic portion, type III; Predominantly hypoechoic with echogenic portion, type IV; Hypoechoic without echogenic portion. 1)Nine abscesses and 2 peripheral cholangiocarcinomas were type I(p=0.037), 2)One abscess and 18 peripheral cholangiocarcinomas were type II(p=0.001), 3)Seven abscesses and none of peripheral cholangiocarcinomas were type III(p=0.001), 4)Five abscesses and 2 peripheral cholangiocarcinomas were type IV(p=0.410). Only 7 abscesses showed internal septations(p=0.013). One abscess and 9 peripheral cholangiocarcinomas showed peripheral hypoechoic halos(p=0.012). Only 9 peripheral cholangiocarcinomas showed obstructive bile duct dilatation (p=0.001). There were no statistically significant differences between abscess and peripheral cholangiocarcinoma on other objective points. Predominantly echogenic with hypoechoic portion, predominantly hypoechoic with echogenic portion, and internal septation are the features suggestive of hepatic abscess, and echogenic without hypoechoic portion, peripheral hypoechoic halo, obstructive bile duct dilatation are suggestive of peripheral cholangiocarcinoma. Therefore these sonographic findings are helpful to differentiate hepatic abscess from peripheral

  6. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (Interleukin Beta, Interleukin 6, tumor necrosis factor alpha) levels after high- and low-dose total-body irradiation in humans

    International Nuclear Information System (INIS)

    Girinsky, T.A.; Pallardy, M.; Comoy, E.; Benassi, T.; Roger, R.; Ganem, G.; Socie, G.; Cossett, J.M.; Magdelenat, H.

    1994-01-01

    Total-body irradiation (TBI) induces an increase in levels of granulocytes and cortisol in blood. To explore the underlying mechanisms, we studied 26 patients who had TBI prior to bone marrow transplantation. Our findings suggest that only a high dose of TBI (10 Gy) was capable of activating the hypothalamopituitary area since corticotropin-releasing factor and blood adrenocorticotropic hormone levels increased at the end of the TBI. There was a concomitant increase in the levels of interleukin 6 and tumor necrosis factor in blood, suggesting that these cytokines might activate the hypothalamo-pituitary adrenal axis. Interleukin 1 was not detected. Since vascular injury is a common after radiation treatment, it is possible that interleukin 6 was secreted by endothelial cells. The exact mechanisms of the production of cyctokines induced by ionizing radiation remain to be determined. 25 refs., 1 fig

  7. Peripheral blood mononuclear cells of patients with latent autoimmune diabetes secrete higher levels of pro- & anti-inflammatory cytokines compared to those with type-1 diabetes mellitus following in vitro stimulation with β-cell autoantigens

    Directory of Open Access Journals (Sweden)

    Darshan Badal

    2017-01-01

    Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.

  8. Peripheral Mechanisms of Ischemic Myalgia

    Directory of Open Access Journals (Sweden)

    Luis F. Queme

    2017-12-01

    Full Text Available Musculoskeletal pain due to ischemia is present in a variety of clinical conditions including peripheral vascular disease (PVD, sickle cell disease (SCD, complex regional pain syndrome (CRPS, and even fibromyalgia (FM. The clinical features associated with deep tissue ischemia are unique because although the subjective description of pain is common to other forms of myalgia, patients with ischemic muscle pain often respond poorly to conventional analgesic therapies. Moreover, these patients also display increased cardiovascular responses to muscle contraction, which often leads to exercise intolerance or exacerbation of underlying cardiovascular conditions. This suggests that the mechanisms of myalgia development and the role of altered cardiovascular function under conditions of ischemia may be distinct compared to other injuries/diseases of the muscles. It is widely accepted that group III and IV muscle afferents play an important role in the development of pain due to ischemia. These same muscle afferents also form the sensory component of the exercise pressor reflex (EPR, which is the increase in heart rate and blood pressure (BP experienced after muscle contraction. Studies suggest that afferent sensitization after ischemia depends on interactions between purinergic (P2X and P2Y receptors, transient receptor potential (TRP channels, and acid sensing ion channels (ASICs in individual populations of peripheral sensory neurons. Specific alterations in primary afferent function through these receptor mechanisms correlate with increased pain related behaviors and altered EPRs. Recent evidence suggests that factors within the muscles during ischemic conditions including upregulation of growth factors and cytokines, and microvascular changes may be linked to the overexpression of these different receptor molecules in the dorsal root ganglia (DRG that in turn modulate pain and sympathetic reflexes. In this review article, we will discuss the

  9. Isotopic diagnosis of peripheral thrombosis

    International Nuclear Information System (INIS)

    Cornu, Pierre; Scalet, Michel

    1975-01-01

    Radio-isotope diagnosis of peripheral venous thrombosis, using tracer doses of iodine-labelled fibrinogen, provides an important contribution to the solution of the worrying problem of pulmonary embolism due to latent phlebitis. This elegant and precise technique permits early diagnosis of venous thrombosis of the lower limbs at a subclinical stage. It has permitted determination of the frequency, both after surgery and after myocardial infarction, and above all, it provides an objective criterion for assessment of the efficacy of prophylactic measures proposed [fr

  10. Radioimmunological progesteron determination in peripheral bovine blood

    International Nuclear Information System (INIS)

    Ender, M.

    1974-01-01

    A radioimmunological method of determination of the progesterone level in peripheral bovine blood is described which enables a monitoring of the corpus luteum function under varying conditions. There is no dependence of the corpus luteum function on the pituitary gland after endogenous prolactin inhibition with a synthetic prolactin inhibitor in the oestrus cycle and in the end-phase of gravidity. In hysterectomized animals, however, the inhibition of endogenous LH leads to luteolysis. The release of endogenous LH, induced by the administration of an LH release hormone, causes a short increase in progesterone production in the middle phase of the cycle only. The administration of exogenous glucocorticoids during the oestrus cycle did not influence the corpus luteum function. The method described is used in a field test to determine the right time for artificial insemination. There is a significant difference between the progesterone values of impregnated and non-pregnant animals at 16-18 days after insemination. (BSC/AK) [de

  11. Human keratinocytes are a source for tumor necrosis factor alpha: Evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light

    International Nuclear Information System (INIS)

    Koeck, A.S.; Schwarz, T.; Kirnbauer, R.; Urbanski, A.; Perry, P.; Ansel, J.C.; Luger, T.A.

    1990-01-01

    Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation

  12. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Directory of Open Access Journals (Sweden)

    Tim D Williams

    2011-08-01

    Full Text Available The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  13. Towards a system level understanding of non-model organisms sampled from the environment: a network biology approach.

    Science.gov (United States)

    Williams, Tim D; Turan, Nil; Diab, Amer M; Wu, Huifeng; Mackenzie, Carolynn; Bartie, Katie L; Hrydziuszko, Olga; Lyons, Brett P; Stentiford, Grant D; Herbert, John M; Abraham, Joseph K; Katsiadaki, Ioanna; Leaver, Michael J; Taggart, John B; George, Stephen G; Viant, Mark R; Chipman, Kevin J; Falciani, Francesco

    2011-08-01

    The acquisition and analysis of datasets including multi-level omics and physiology from non-model species, sampled from field populations, is a formidable challenge, which so far has prevented the application of systems biology approaches. If successful, these could contribute enormously to improving our understanding of how populations of living organisms adapt to environmental stressors relating to, for example, pollution and climate. Here we describe the first application of a network inference approach integrating transcriptional, metabolic and phenotypic information representative of wild populations of the European flounder fish, sampled at seven estuarine locations in northern Europe with different degrees and profiles of chemical contaminants. We identified network modules, whose activity was predictive of environmental exposure and represented a link between molecular and morphometric indices. These sub-networks represented both known and candidate novel adverse outcome pathways representative of several aspects of human liver pathophysiology such as liver hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More generally, this pioneering study has important implications as it can be applied to model molecular mechanisms of compensatory adaptation to a wide range of scenarios in wild populations.

  14. Transdermal optogenetic peripheral nerve stimulation

    Science.gov (United States)

    Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

    2017-06-01

    Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

  15. Diagnostic approach to peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Misra Usha

    2008-01-01

    Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

  16. Statin use and peripheral sensory perception: a pilot study.

    Science.gov (United States)

    West, Brenton; Williams, Cylie M; Jilbert, Elise; James, Alicia M; Haines, Terry P

    2014-06-01

    Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183). This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.

  17. Mobile phone generated vibrations used to detect diabetic peripheral neuropathy.

    Science.gov (United States)

    May, Jonathan David; Morris, Matthew William John

    2017-12-01

    In the current United Kingdom population the incidence of diabetic peripheral neuropathy is increasing. The presence of diabetic neuropathy affects decision making and treatment options. This study seeks to evaluate if the vibrations generated from a mobile phone can be used to screen patients for diabetic peripheral neuropathy. This study comprised of 61 patients; a control group of 21 patients; a lower limb injury group of 19 patients; a diabetic peripheral neuropathy group of 21 patients. The control and injury group were recruited randomly from fracture clinics. The diabetic peripheral neuropathy group were randomly recruited from the diabetic foot clinic. The 61 patients were examined using a 10g Semmes-Weinstein monofilament, a 128Hz tuning fork and a vibrating mobile phone. The points tested were, index finger, patella, lateral malleoli, medial malleoli, heel, first and fifth metatarsal heads. The most accurate location of all the clinical tests was the head of the 1st metatarsal at 0.86. The overall accuracy of the tuning fork was 0.77, the ten gram monofilament 0.79 and the mobile phone accuracy was 0.88. The control group felt 420 of 441 tests (95%). The injury group felt 349 of 399 tests (87%). The neuropathic group felt 216 of 441 tests (48%). There is a significant difference in the number of tests felt between the control and both the injury and neuropathic groups. pperipheral neuropathy. The most accurate location to test for diabetic peripheral neuropathy is the head of the 1st metatarsal. Screening for diabetic peripheral neuropathy in the index finger and patella were inaccurate. An injury to the lower limb affects the patient's vibration sensation, we would therefore recommend screening the contralateral limb to the injury. This study represents level II evidence of a new diagnostic investigation. Copyright © 2016 European Foot and Ankle Society. All rights reserved.

  18. Baseline frequency of chromosomal aberrations and sister chromatid exchanges in peripheral blood lymphocytes of healthy individuals living in Turin (North-Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms on the levels of genomic damage.

    Science.gov (United States)

    Santovito, Alfredo; Cervella, Piero; Delpero, Massimiliano

    2016-05-01

    The increased exposure to environmental pollutants has led to the awareness of the necessity for constant monitoring of human populations, especially those living in urban areas. This study evaluated the background levels of genomic damage in a sample of healthy subjects living in the urban area of Turin (Italy). The association between DNA damage with age, sex and GSTs polymorphisms was assessed. One hundred and one individuals were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were performed. Mean values of SCEs and CAs were 5.137 ± 0.166 and 0.018 ± 0.002, respectively. Results showed age and gender associated with higher frequencies of these two cytogenetic markers. The eldest subjects (51-65 years) showed significantly higher levels of genomic damage than younger individuals. GSTs polymorphisms did not appear to significantly influence the frequencies of either markers. The CAs background frequency observed in this study is one of the highest reported among European populations. Turin is one of the most polluted cities in Europe in terms of air fine PM10 and ozone and the clastogenic potential of these pollutants may explain the high frequencies of chromosomal rearrangements reported here.

  19. Peripheral chemokine levels in women with recurrent major depression with suicidal ideation Níveis periféricos de quimiocina em mulheres com depressão maior com ideação suicida

    Directory of Open Access Journals (Sweden)

    Rodrigo Grassi-Oliveira

    2012-03-01

    Full Text Available OBJECTIVE: To compare serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 between female patients with recurrent major depressive disorder (MDD and healthy controls, verifying if there is a difference in the levels of these mediators between those with or without current suicidal ideation. METHODS: Thirty female outpatients with recurrent MDD were divided in two groups accordingly the presence or absence of suicidal ideation. These groups were compared with 16 healthy controls. Serum levels of MCP-1/CCL2, RANTES/CCL5, and Eotaxin/CCL11 were determined. Depression severity was evaluated by Beck Depression Inventory (BDI. Suicidal ideation was assessed by SCID-I and BDI. RESULTS: Patients with recurrent MDD and healthy controls did not differ in age, socioeconomic status, and education. All patients reported high scores of BDI (mean, SD, n; 29.75, 10.55, 28. Multivariable analysis of covariance adjusted for age and BMI showed that MDD patients with suicidal ideation presented lower levels of MCP-1/ CCL2 and RANTES/CCL5 (p OBJETIVO: Comparar os níveis séricos de MCP-1/CCL2, RANTES/CCL5 e Eotaxin/CCL11 entre pacientes do sexo feminino com transtorno depressivo maior (TDM recorrente e controles saudáveis, verificando se há diferença nos níveis desses mediadores entre os indivíduos com ou sem ideação suicida. MÉTODOS: Trinta pacientes do sexo feminino com TDM recorrente foram divididas em dois grupos de acordo com a presença ou ausência de ideação suicida. Esses grupos foram comparados com 16 controles saudáveis. Os níveis séricos de MCP-1/CCL2, RANTES/CCL5 e Eotaxin/CCL11 foram determinados. A gravidade da depressão foi avaliada usando o Beck Depression Inventory (BDI e a ideação suicida foi avaliada usando o SCID-I e o BDI. RESULTADOS: As pacientes com TDM recorrente e os controles saudáveis não diferiram em idade, status socioeconômico e educação. Todas as pacientes relataram altas pontuações no BDI (média, SD, n

  20. Intraoperative Ultrasound for Peripheral Nerve Applications.

    Science.gov (United States)

    Willsey, Matthew; Wilson, Thomas J; Henning, Phillip Troy; Yang, Lynda J-S

    2017-10-01

    Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Peripheral Vestibular System Disease in Vestibular Schwannomas

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

    2015-01-01

    density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas...... are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which...

  2. Peripheral refractive correction and automated perimetric profiles.

    Science.gov (United States)

    Wild, J M; Wood, J M; Crews, S J

    1988-06-01

    The effect of peripheral refractive error correction on the automated perimetric sensitivity profile was investigated on a sample of 10 clinically normal, experienced observers. Peripheral refractive error was determined at eccentricities of 0 degree, 20 degrees and 40 degrees along the temporal meridian of the right eye using the Canon Autoref R-1, an infra-red automated refractor, under the parametric conditions of the Octopus automated perimeter. Perimetric sensitivity was then undertaken at these eccentricities (stimulus sizes 0 and III) with and without the appropriate peripheral refractive correction using the Octopus 201 automated perimeter. Within the measurement limits of the experimental procedures employed, perimetric sensitivity was not influenced by peripheral refractive correction.

  3. Peripheral visual performance enhancement by neurofeedback training.