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Sample records for undifferentiated peripheral inflammatory

  1. Algorithm for identification of undifferentiated peripheral inflammatory arthritis: a multinational collaboration through the 3e initiative

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    Hazlewood, Glen; Aletaha, Daniel; Carmona, Loreto; Landewé, Robert B. M.; van der Heijde, Désirée M.; Bijlsma, Johannes W. J.; Bykerk, Vivian P.; Canhão, Helena; Catrina, Anca I.; Durez, Patrick; Edwards, Christopher J.; Leeb, Burkhard F.; Mjaavatten, Maria D.; Martinez-Osuna, Pindaro; Montecucco, Carlomaurizio; Ostergaard, Mikkel; Serra-Bonett, Natali; Xavier, Ricardo M.; Zochling, Jane; Machado, Pedro; Thevissen, Kristof; Vercoutere, Ward; Bombardier, Claire

    2011-01-01

    To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA). An algorithm for identification of UPIA was developed by consensus during a roundtable meeting with an expert panel. It was informed by systematic reviews of the literature used to generate 10

  2. Diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis: a systematic review

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    Vercoutere, Ward; Thevissen, Kristof; Bombardier, Claire; Landewé, Robert B. M.

    2011-01-01

    To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology. A systematic

  3. Diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis: a systematic review.

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    Vercoutere, Ward; Thevissen, Kristof; Bombardier, Claire; Landewé, Robert B M

    2011-03-01

    To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology. A systematic literature search was carried out using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism, searching for prognostic and diagnostic markers of acute-phase reactants in adult UPIA. Articles that fulfilled predefined inclusion criteria were systematically reviewed, and the quality was appraised. Likelihood ratios (LR), sensitivity, and specificity for diagnostic and prognostic outcomes were calculated. A total of 18 publications out of 3699 identified references were included in the review. Only a small number of studies with significant heterogeneity, including different outcome measures and different cutoff values, were eligible for review, so pooling data was not possible. Overall, LR showed poor diagnostic and prognostic performance for most investigated acute-phase reactants. Available data showed some value for erythrocyte sedimentation rate in establishing a diagnosis in patients with undifferentiated arthritis; some prognostic and diagnostic value for C-reactive protein; some prognostic value for plasma viscosity in predicting persistence of arthritis; and some diagnostic value for sulfhydryl levels and matrix metalloproteinase-3 in establishing a diagnosis of rheumatoid arthritis. There is little published evidence concerning the diagnostic and predictive value of acute-phase reactants in patients with UPIA. Studies were heterogeneous, and "undifferentiated arthritis" was not well defined or was equivocally defined. The role of acute-phase reactants in diagnosing and predicting outcome in patients presenting with undifferentiated arthritis is

  4. Multinational evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis

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    Machado, P; Castrejon, I; Katchamart, W

    2011-01-01

    OBJECTIVE: To develop evidence-based recommendations on how to investigate and follow-up undifferentiated peripheral inflammatory arthritis (UPIA). METHODS: 697 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2008-9 consisting of three separate......, of which 250 were systematically reviewed. Ten multinational key recommendations about the investigation and follow-up of UPIA were formulated. One recommendation addressed differential diagnosis and investigations prior to establishing the operational diagnosis of UPIA, seven recommendations related......) and the final recommendation addressed monitoring of clinical disease activity in UPIA. CONCLUSIONS: Ten recommendations on how to investigate and follow-up UPIA in the clinical setting were developed. They are evidence-based and supported by a large panel of rheumatologists, thus enhancing their validity...

  5. [Evidence-based recommendations for the management of undifferentiated peripheral inflammatory arthritis (UPIA). The German perspective on the international 3e initiative].

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    Tarner, I H; Albrecht, K; Fleck, M; Gromnica-Ihle, E; Keyßer, G; Köhler, L; Kötter, I; Krüger, K; Kuipers, J; Nüßlein, H; Rubbert-Roth, A; Wollenhaupt, J; Schneider, M; Manger, B; Müller-Ladner, U

    2014-05-01

    Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations. Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice. A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references. The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.

  6. A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial

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    2014-01-01

    Background Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA. Methods A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of

  7. Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

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    Bouzouita Kamel

    2004-09-01

    Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

  8. Cortistatin attenuates inflammatory pain via spinal and peripheral actions.

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    Morell, María; Camprubí-Robles, María; Culler, Michael D; de Lecea, Luis; Delgado, Mario

    2014-03-01

    Clinical pain, as a consequence of inflammation or injury of peripheral organs (inflammatory pain) or nerve injury (neuropathic pain), represents a serious public health issue. Treatment of pain-related suffering requires knowledge of how pain signals are initially interpreted and subsequently transmitted and perpetuated. To limit duration and intensity of pain, inhibitory signals participate in pain perception. Cortistatin is a cyclic-neuropeptide that exerts potent inhibitory actions on cortical neurons and immune cells. Here, we found that cortistatin is a natural analgesic component of the peripheral nociceptive system produced by peptidergic nociceptive neurons of the dorsal root ganglia in response to inflammatory and noxious stimuli. Moreover, cortistatin is produced by GABAergic interneurons of deep layers of dorsal horn of spinal cord. By using cortistatin-deficient mice, we demonstrated that endogenous cortistatin critically tunes pain perception in physiological and pathological states. Furthermore, peripheral and spinal injection of cortistatin potently reduced nocifensive behavior, heat hyperalgesia and tactile allodynia in experimental models of clinical pain evoked by chronic inflammation, surgery and arthritis. The analgesic effects of cortistatin were independent of its anti-inflammatory activity and directly exerted on peripheral and central nociceptive terminals via Gαi-coupled somatostatin-receptors (mainly sstr2) and blocking intracellular signaling that drives neuronal plasticity including protein kinase A-, calcium- and Akt/ERK-mediated release of nociceptive peptides. Moreover, cortistatin could modulate, through its binding to ghrelin-receptor (GHSR1), pain-induced sensitization of secondary neurons in spinal cord. Therefore, cortistatin emerges as an anti-inflammatory factor with potent analgesic effects that offers a new approach to clinical pain therapy, especially in inflammatory states. Copyright © 2013 Elsevier Inc. All rights

  9. Peripheral Inflammatory Markers Contributing to Comorbidities in Autism

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    Martha Cecilia Inga Jácome

    2016-12-01

    Full Text Available This study evaluates the contribution of peripheral biomarkers to comorbidities and clinical findings in autism. Seventeen autistic children and age-matched typically developing (AMTD, between three to nine years old were evaluated. The diagnostic followed the Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DMS-IV and the Childhood Autism Rating Scale (CARS was applied to classify the severity. Cytokine profile was evaluated in plasma using a sandwich type ELISA. Paraclinical events included electroencephalography (EEG record. Statistical analysis was done to explore significant differences in cytokine profile between autism and AMTD groups and respect clinical and paraclinical parameters. Significant differences were found to IL-1β, IL-6, IL-17, IL-12p40, and IL-12p70 cytokines in individuals with autism compared with AMTD (p < 0.05. All autistic patients showed interictalepileptiform activity at EEG, however, only 37.5% suffered epilepsy. There was not a regional focalization of the abnormalities that were detectable with EEG in autistic patients with history of epilepsy. A higher IL-6 level was observed in patients without history of epilepsy with interictalepileptiform activity in the frontal brain region, p < 0.05. In conclusion, peripheral inflammatory markers might be useful as potential biomarkers to predict comorbidities in autism as well as reinforce and aid informed decision-making related to EEG findings in children with Autism spectrum disorders (ASD.

  10. Can magnetic resonance imaging differentiate undifferentiated arthritis?

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    Østergaard, Mikkel; Duer, Anne; Hørslev-Petersen, K

    2005-01-01

    A high sensitivity for the detection of inflammatory and destructive changes in inflammatory joint diseases makes magnetic resonance imaging potentially useful for assigning specific diagnoses, such as rheumatoid arthritis and psoriatic arthritis in arthritides, that remain undifferentiated after...... conventional clinical, biochemical and radiographic examinations. With recent data as the starting point, the present paper describes the current knowledge on magnetic resonance imaging in the differential diagnosis of undifferentiated arthritis....

  11. Central nervous system mast cells in peripheral inflammatory nociception

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    Ellmeier Wilfried

    2011-06-01

    Full Text Available Abstract Background Functional aspects of mast cell-neuronal interactions remain poorly understood. Mast cell activation and degranulation can result in the release of powerful pro-inflammatory mediators such as histamine and cytokines. Cerebral dural mast cells have been proposed to modulate meningeal nociceptor activity and be involved in migraine pathophysiology. Little is known about the functional role of spinal cord dural mast cells. In this study, we examine their potential involvement in nociception and synaptic plasticity in superficial spinal dorsal horn. Changes of lower spinal cord dura mast cells and their contribution to hyperalgesia are examined in animal models of peripheral neurogenic and non-neurogenic inflammation. Results Spinal application of supernatant from activated cultured mast cells induces significant mechanical hyperalgesia and long-term potentiation (LTP at spinal synapses of C-fibers. Lumbar, thoracic and thalamic preparations are then examined for mast cell number and degranulation status after intraplantar capsaicin and carrageenan. Intradermal capsaicin induces a significant percent increase of lumbar dural mast cells at 3 hours post-administration. Peripheral carrageenan in female rats significantly increases mast cell density in the lumbar dura, but not in thoracic dura or thalamus. Intrathecal administration of the mast cell stabilizer sodium cromoglycate or the spleen tyrosine kinase (Syk inhibitor BAY-613606 reduce the increased percent degranulation and degranulated cell density of lumbar dural mast cells after capsaicin and carrageenan respectively, without affecting hyperalgesia. Conclusion The results suggest that lumbar dural mast cells may be sufficient but are not necessary for capsaicin or carrageenan-induced hyperalgesia.

  12. Relationship of Inflammatory Biomarkers with Severity of Peripheral Arterial Disease

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    Kimihiro Igari

    2016-01-01

    Full Text Available Objective. The pentraxin family, including high-sensitivity C-reactive protein (hs-CRP, serum amyloid P (SAP, and pentraxin 3 (PTX3, has been identified as playing a key role in inflammatory reactions such as in atherosclerosis and cardiovascular disease. In this study, we examined the relationship between peripheral arterial disease (PAD and serum levels of pentraxins. Methods. This study was undertaken via a retrospective review of PAD patients with surgical intervention for lesions of the common femoral artery. We evaluated the preoperative patient conditions, hemodynamic status, such as ankle brachial index (ABI, and clinical ischemic conditions according to Rutherford classification. Preoperatively, we collected blood samples for determining the serum levels of hs-CRP, SAP, and PTX3. Results. Twelve PAD patients with common femoral arterial lesions were treated and examined. The hemodynamic severity of PAD was not negatively correlated with hs-CRP, SAP, or PTX3. The clinical severity evaluated by Rutherford classification was significantly positively correlated with the serum level of PTX3 (p=0.019. Conclusion. We demonstrated that PTX3 might be a better marker of PAD than hs-CRP and SAP. Furthermore, PTX3 might be a prognostic marker to evaluate the severity of PAD.

  13. Undifferentiated salivary gland carcinomas

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    Herbst, H.; Hamilton-Dutoit, S.; Jakel, K.T.

    2004-01-01

    Undifferentiated salivary gland carcinomas may be divided into small cell and large cell types. Among large cell undifferentiated carcinomas, lymphoepithelial carcinomas have to be distinguished, the latter of which are endemic in the Arctic regions and southern China where virtually all cases of...... at other primary sites, particularly when expressing the thyroid transcription factor-1 (TTF-1) Udgivelsesdato: 2004...

  14. Peripheral analgesic effects of ketamine in acute inflammatory pain

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    Pedersen, J L; Galle, T S; Kehlet, H

    1998-01-01

    BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain. METHODS: Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers.......02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn. CONCLUSIONS: Ketamine infiltration had brief local analgesic effects...

  15. Effect of peripheral morphine in a human model of acute inflammatory pain

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    Lillesø, J; Hammer, N A; Pedersen, J L

    2000-01-01

    Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

  16. Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD: a meta-analysis.

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    Linying Peng

    Full Text Available BACKGROUND: Postoperative cognitive dysfunction (POCD is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD. METHODS: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12.The standardized mean difference (SMD and the 95% confidence interval (95%CI were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis. RESULTS: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI] (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies, and interleukin(IL-6 (SMD[95%CI] (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies, but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies. CONCLUSIONS: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

  17. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit.

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    Klein, Silvan M; Vykoukal, Jody; Li, De-Pei; Pan, Hui-Lin; Zeitler, Katharina; Alt, Eckhard; Geis, Sebastian; Felthaus, Oliver; Prantl, Lukas

    2016-07-01

    Conduits preseeded with either Schwann cells or stem cells differentiated into Schwann cells demonstrated promising results for the outcome of nerve regeneration in nerve defects. The concept of this trial combines nerve repair by means of a commercially available nerve guidance conduit and preseeding with autologous, undifferentiated, adipose tissue-derived stem cells. Adipose tissue-derived stem cells were harvested from rats and subsequently seeded onto a U.S. Food and Drug Administration-approved type I collagen conduit. Sciatic nerve gaps 10 mm in length were created, and nerve repair was performed by the transplantation of either conduits preseeded with autologous adipose tissue-derived stem cells or acellular (control group) conduits. After 6 months, the motor and sensory nerve conduction velocity were assessed. Nerves were removed and examined by hematoxylin and eosin, van Gieson, and immunohistochemistry (S100 protein) staining for the quality of axonal regeneration. Nerve gaps treated with adipose tissue-derived stem cells showed superior nerve regeneration, reflected by higher motor and sensory nerve conduction velocity values. The motor and sensory nerve conduction velocity were significantly greater in nerves treated with conduits preseeded with adipose tissue-derived stem cells than in nerves treated with conduits alone (p adipose tissue-derived stem cell group. In this group, axon arrangement inside the conduits was more organized. Transplantation of adipose tissue-derived stem cells significantly improves motor and sensory nerve conduction velocity in peripheral nerve gaps. Preseeded conduits showed a more organized axon arrangement inside the conduit in comparison with nerve conduits alone. The approach used here could readily be translated into a clinical therapy. Therapeutic, V.

  18. Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis.

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    G Hodge

    Full Text Available Bronchiectasis (BE in children is common in some communities including Indigenous children in Australia. Relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: T-cells, natural killer (NK cells and NKT-like cells. We have shown that these cells produce increased cytotoxic (granzyme b and perforin and inflammatory (IFNγ and TNFα mediators in several adult chronic lung diseases and hypothesised that similar changes would be evident in children with BE.Intracellular cytotoxic mediators perforin and granzyme b and pro-inflammatory cytokines were measured in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from 12 children with BE and 10 aged-matched control children using flow cytometry.There was a significant increase in the percentage of CD8+ T cells and T and NKT-like subsets expressing perforin/granzyme and IFNγ and TNFα in blood in BE compared with controls. There was a further increase in the percentage of pro-inflammatory cytotoxic T cells in Indigenous compared with non-Indigenous children. There was no change in any of these mediators in BAL.Childhood bronchiectasis is associated with increased systemic pro-inflammatory/cytotoxic lymphocytes in the peripheral blood. Future studies need to examine the extent to which elevated levels of pro-inflammatory cytotoxic cells predict future co-morbidities.

  19. Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

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    Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

    2016-10-15

    Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

  20. Inflammatory Gene Expression in Whole Peripheral Blood at Early Stages of Sporadic Amyotrophic Lateral Sclerosis

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    Pol Andrés-Benito

    2017-10-01

    Full Text Available ObjectiveCharacterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS patients at early stage of disease to increase knowledge about peripheral inflammatory response in sALS.MethodsRNA expression levels of 45 genes were assessed by RT-qPCR in 22 sALS cases in parallel with 13 age-matched controls. Clinical and serum parameters were assessed at the same time.ResultsUpregulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL, and ICAM1 and extracellular matrix remodeling (MMP9 and TIMP2, as well as downregulation of certain chemokines (CCL5 and CXC5R, anti-inflammatory cytokines (IL10, TGFB2, and IL10RA, pro-inflammatory cytokines (IL-6, and T-cell regulators (CD2 and TRBC1 was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory, or bulbar, progression, peripheral leukocyte number, and integrity of RNA. MMP9 levels positively correlated with age, whereas CCR5, CCL5, and TRBC1 negatively correlated with age in sALS but not in controls. Relatively higher TNFA expression levels correlate with higher creatinine kinase protein levels in plasma.ConclusionPresent findings show early inflammatory responses characterized by upregulation of factors enabling extravasation of leukocytes and extracellular matrix remodeling in blood in sALS cases, in addition to increased TNFA levels paralleling skeletal muscle damage.

  1. Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria

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    Mutabingwa Theonest K

    2008-01-01

    Full Text Available Abstract Background Placental malaria (PM is an important cause of maternal and foetal mortality in tropical areas, and severe sequelae and mortality are related to inflammation in the placenta. Diagnosis is difficult because PM is often asymptomatic, peripheral blood smear examination detects parasitemia as few as half of PM cases, and no peripheral markers have been validated for placental inflammation. Methods In a cohort of Tanzanian parturients, PM was determined by placental blood smears and placental inflammation was assessed by histology and TNF mRNA levels. Maternal peripheral blood levels of several immune mediators previously implicated in PM pathogenesis, as well as ferritin and leptin were measured. The relationship between the levels of these soluble factors to PM and placental inflammation was examined. Results Peripheral levels of TNF, TNF-RI, TNF-RII, IL-1, IL-10, and ferritin were elevated during PM, whereas levels of IFN-γ, IL-4, IL-5 and IL-6 were unchanged and levels of leptin were decreased. In receiver operating characteristic curve analysis, IL-10 had the greatest area under the curve, and would provide a sensitivity of 60% with a false positive rate of 10%. At a cut off level of 15 pg/mL, IL-10 would detect PM with a sensitivity of 79.5% and a specificity of 84.3%. IL-10 levels correlated with placental inflammatory cells and placental TNF mRNA levels in first time mothers. Conclusion These data suggest that IL-10 may have utility as a biomarker for inflammatory PM in research studies, but that additional biomarkers may be required to improve clinical diagnosis and management of malaria during pregnancy.

  2. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

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    Popovich Phillip G

    2011-08-01

    Full Text Available Abstract In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI. In contrast with central nervous system (CNS axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as

  3. Peripheral inflammatory pain sensitisation is independent of mast cell activation in male mice.

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    Lopes, Douglas M; Denk, Franziska; Chisholm, Kim I; Suddason, Tesha; Durrieux, Camille; Thakur, Matthew; Gentry, Clive; McMahon, Stephen B

    2017-07-01

    The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. To clarify whether MC are involved in inflammatory pain states, we used a transgenic mouse line (Mctp5Cre-iDTR) in which MC could be depleted in an inducible manner by administration of diphtheria toxin. Our results show that ablation of MC in male mice did not result in any change in mechanical and thermal hypersensitivity in the CFA model of inflammatory pain. Similarly, edema and temperature triggered by CFA inflammation at the injection site remained identical in MC depleted mice compared with their littermate controls. In addition, we show that Mctp5Cre-iDTR mice display normal levels of mechanical hypersensitivity after local injection of nerve growth factor (NGF), a factor well characterised to produce peripheral sensitisation and for being upregulated upon injury and inflammation. We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.

  4. Peripheral Gamma Delta T cells secrete inflammatory cytokines in women with idiopathic recurrent pregnancy loss.

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    Talukdar, Ayantika; Rai, Reeta; Aparna Sharma, K; Rao, D N; Sharma, Alpana

    2018-02-01

    Gamma delta (γδ) T cells are known to link innate and adaptive immunity. Decidual γδ T cells are known to provide immunotolerance by producing IL-10 and TGF-β. In recurrent pregnancy loss (RPL) females, the role of peripheral γδ T cells remain unstudied. To investigate the different phenotypes of γδ T cells in the peripheral blood of women with idiopathic RPL and their possible involvement in RPL condition. A total of 120 women were recruited for the study. Peripheral blood lymphocytes were isolated and they were stained with appropriate antibodies to determine the phenotype of γδ T cells and major cytokines produced by them in the blood using flow cytometry. We observed a significant decrease in the proportion of CD3 + CD4 - CD8 - γδ T cells (p<0.001) and increase in the percentage of IFN-γ (p<0.05) and IL-17 (p<0.001) producing γδ T cells in RPL pregnant as compared to normal pregnant females. Increase in IFN-γ and IL-17-producing CD3 + CD4 - CD8 - γδ T cells is associated with creating inflammatory cytokine milieu, thereby, may contribute towards pregnancy loss in RPL females. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Electromagnetic Field Devices and Their Effects on Nociception and Peripheral Inflammatory Pain Mechanisms.

    Science.gov (United States)

    Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

    2016-03-01

    -dependent interaction between the mechanical interventions of EMF and cell signaling along the peripheral inflammatory pain pathway.

  6. Muscle pain induced by static contraction in rats is modulated by peripheral inflammatory mechanisms.

    Science.gov (United States)

    Santos, Diogo Francisco da Silva Dos; Melo Aquino, Bruna de; Jorge, Carolina Ocanha; Azambuja, Graciana de; Schiavuzzo, Jalile Garcia; Krimon, Suzy; Neves, Juliana Dos Santos; Parada, Carlos Amilcar; Oliveira-Fusaro, Maria Claudia Gonçalves

    2017-09-01

    Muscle pain is an important health issue and frequently related to static force exertion. The aim of this study is to evaluate whether peripheral inflammatory mechanisms are involved with static contraction-induced muscle pain in rats. To this end, we developed a model of muscle pain induced by static contraction performed by applying electrical pulses through electrodes inserted into muscle. We also evaluated the involvement of neutrophil migration, bradykinin, sympathetic amines and prostanoids. A single session of sustained static contraction of gastrocnemius muscle induced acute mechanical muscle hyperalgesia without affecting locomotor activity and with no evidence of structural damage in muscle tissue. Static contraction increased levels of creatine kinase but not lactate dehydrogenase, and induced neutrophil migration. Dexamethasone (glucocorticoid anti-inflammatory agent), DALBK (bradykinin B1 antagonist), Atenolol (β1 adrenoceptor antagonist), ICI 118,551 (β2 adrenoceptor antagonist), indomethacin (cyclooxygenase inhibitor), and fucoidan (non-specific selectin inhibitor) all reduced static contraction-induced muscle hyperalgesia; however, the bradykinin B2 antagonist, bradyzide, did not have an effect on static contraction-induced muscle hyperalgesia. Furthermore, an increased hyperalgesic response was observed when the selective bradykinin B1 agonist des-Arg 9 -bradykinin was injected into the previously stimulated muscle. Together, these findings demonstrate that static contraction induced mechanical muscle hyperalgesia in gastrocnemius muscle of rats is modulated through peripheral inflammatory mechanisms that are dependent on neutrophil migration, bradykinin, sympathetic amines and prostanoids. Considering the clinical relevance of muscle pain, we propose the present model of static contraction-induced mechanical muscle hyperalgesia as a useful tool for the study of mechanisms underlying static contraction-induced muscle pain. Copyright © 2017 IBRO

  7. 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.

  8. IGF1 potentiates the pro-inflammatory response in human peripheral blood mononuclear cells via MAPK.

    Science.gov (United States)

    Wolters, Thalijn Liliana Catharina; Netea, Mihai Gheorghe; Hermus, Adrianus Rudolfus Marinus Maria; Smit, Johannes Willem Adriaan; Netea-Maier, Romana Teodora

    2017-08-01

    Acromegaly is characterized by growth hormone (GH) and insulin-like growth factor 1 (IGF1) excess and is accompanied by an increased cardiovascular diseases (CVD) risk. As innate immune responses are crucial in CVD development, and IGF1 is linked to subclinical inflammation, we hypothesized that GH/IGF1 excess contributes to CVD development by potentiating systemic inflammation. We aimed to assess the effects of GH/IGF1 on inflammatory cytokine production. Whole blood from acromegaly patients and healthy volunteers and peripheral blood mononuclear cells (PBMCs) from healthy volunteers were stimulated with Toll-like receptor (TLR) ligands, with or without adding GH or IGF1 (in PBMC). Cytokine concentrations were measured by ELISA. The underlying signalling pathways were investigated by the inhibition of downstream targets of the IGF1 receptor. The following results were obtained. GH or IGF1 alone did not influence cytokine production in PBMCs. GH did not affect TLR-induced cytokine production, but co-stimulation with IGF1 dose dependently increased the TLR ligand-induced production of IL6 ( P  LPS-induced IL6 and TNF alpha production. In whole blood of acromegaly patients, ex vivo IL6 production was increased ( P  < 0.01). In conclusion, IGF1, but not GH, has pro-inflammatory effects, probably via the MAPK signalling pathway and might be involved in the pathogenesis of atherosclerosis in acromegaly. The increased IL10 production possibly counteracts the pro-inflammatory effects. © 2017 Society for Endocrinology.

  9. Peripheral antinociception and anti-inflammatory effects of sulphated polysaccharides from the alga Caulerpa mexicana.

    Science.gov (United States)

    Carneiro, José Gerardo; Rodrigues, José Ariévilo Gurgel; de Sousa Oliveira Vanderlei, Edfranck; Souza, Ricardo Basto; Quinderé, Ana Luíza Gomes; Coura, Chistiane Oliveira; de Araújo, Ianna Wivianne Fernandes; Chaves, Hellíada Vasconcelos; Bezerra, Mirna Marques; Benevides, Norma Maria Barros

    2014-10-01

    Sulphated polysaccharides from marine algae are widely used in biotechnological and pharmaceutical areas. In this study, we evaluated the effects of sulphated polysaccharides from the green marine alga Caulerpa mexicana (Cm-SPs) in nociceptive and inflammatory models in rodents. Cm-SPs (10 or 20 mg/kg), administered i.v. in Swiss mice, significantly reduced nociceptive responses, as measured by the number of writhes in response to acetic acid. Cm-SPs (10 or 20 mg/kg) also reduced second-phase responses in the formalin test, but did not exhibit a significant antinociceptive effect in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. Cm-SPs (5, 10 or 20 mg/kg), administered s.c. in wistar rats 1 hr before carrageenan, dextran, histamine or serotonin, were tested in paw oedema models. Cm-SPs (10 or 20 mg/kg) reduced carrageenan-induced paw oedema and myeloperoxidase activity in the paw. In addition, Cm-SPs (20 mg/kg) inhibited dextran- or histamine-induced paw oedema, but not serotonin-induced oedema, suggesting that histamine is the major target of Cm-SPs anti-oedematogenic activity. Finally, Cm-SPs (20 mg/kg) administered in mice did not show significant signs of toxicity. In conclusion, Cm-SPs appear to be promising natural modulatory agents for pain and inflammatory conditions. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  10. Association between perceived happiness levels and peripheral circulating pro-inflammatory cytokine levels in middle-aged adults in Japan.

    Science.gov (United States)

    Matsunaga, Masahiro; Isowa, Tokiko; Yamakawa, Kaori; Tsuboi, Hirohito; Kawanishi, Yoko; Kaneko, Hiroshi; Kasugai, Kunio; Yoneda, Masashi; Ohira, Hideki

    2011-01-01

    The idea that perceived happiness may be associated with health and well-being is a recent topic of focus. However, the neurobiological mechanisms underlying the positive effects of happiness on psychological and physiological wellness remain obscure. In this study, we attempted to clarify the association between systemic inflammation and happiness. We recruited 160 healthy volunteers for experiment 1 and compared peripheral inflammatory markers, namely the concentrations of pro-inflammatory cytokines in the serum, between perceived high-happiness and low-happiness groups. Subsequently, we recruited 7 romantic couples for experiment 2 and investigated changes in peripheral pro-inflammatory cytokine levels after the evocation of happiness, which was induced by warm physical contact with the partner. We found that circulating levels of interferon-γ (IFN-γ), which can affect brain functions and induce depressive symptoms, were lower in the high-happiness group than in the low-happiness group. A negative correlation between the levels of perceived happiness and IFN-γ concentrations was also observed. Furthermore, we also found that experimentally induced happiness could reduce peripheral IFN-γ levels. These results revealed an association between the perception of happiness and systemic inflammation. Increased happiness may suppress the peripheral circulation of pro-inflammatory cytokines.

  11. Role of Inflammatory Signaling in the Differential Effects of Saturated and Poly-unsaturated Fatty Acids on Peripheral Circadian Clocks.

    Science.gov (United States)

    Kim, Sam-Moon; Neuendorff, Nichole; Chapkin, Robert S; Earnest, David J

    2016-05-01

    Inflammatory signaling may play a role in high-fat diet (HFD)-related circadian clock disturbances that contribute to systemic metabolic dysregulation. Therefore, palmitate, the prevalent proinflammatory saturated fatty acid (SFA) in HFD and the anti-inflammatory, poly-unsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), were analyzed for effects on circadian timekeeping and inflammatory responses in peripheral clocks. Prolonged palmitate, but not DHA, exposure increased the period of fibroblast Bmal1-dLuc rhythms. Acute palmitate treatment produced phase shifts of the Bmal1-dLuc rhythm that were larger in amplitude as compared to DHA. These phase-shifting effects were time-dependent and contemporaneous with rhythmic changes in palmitate-induced inflammatory responses. Fibroblast and differentiated adipocyte clocks exhibited cell-specific differences in the time-dependent nature of palmitate-induced shifts and inflammation. DHA and other inhibitors of inflammatory signaling (AICAR, cardamonin) repressed palmitate-induced proinflammatory responses and phase shifts of the fibroblast clock, suggesting that SFA-mediated inflammatory signaling may feed back to modulate circadian timekeeping in peripheral clocks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Oral coinfection can stress peripheral lymphocyte to inflammatory activity in leprosy

    Directory of Open Access Journals (Sweden)

    Ana Carolina Fragoso Motta

    2013-01-01

    Full Text Available INTRODUCTION: This study evaluated the intracellular profile of interleukin-2 (IL-2, interleukin-4 (IL-4, interleukin-10 (IL-10 and interferon-γ (IFN-γ in peripheral blood mononuclear cells (PBMCs from leprosy patients based on oral infections presence to determine whether these coinfections could be associated with pro-inflammatory activity in leprosy. METHODS: Leprosy patients regardless of clinical form and specific leprosy treatment (n=38 were divided into two groups: Group I - leprosy patients with oral infections (n=19, and Group II - leprosy patients without oral infections (n=19. Non-leprosy patients presenting oral infections were assigned to the control Group (n=10. Intracellular IL-2, IL-4, IL-10 and IFN-γ production was evaluated by flow cytometry (FACS before and 7 days after controlling the oral infection in the Group I, before and 7 days after dental prophylaxis in the Group II, and during oral infection process in control Group. RESULTS: Low percentages of CD3+ lymphocytes bearing IL-2, IL-10 and IFN-γ were observed in the Group I and Group II at baseline and 7 days after therapy or prophylaxis compared to controls. Group I showed reduced percentages of IL-4 at baseline and 7 days after therapy compared to controls, or at baseline of Group II, and the Group II showed reduced percentages of CD3+ cells bearing IL-4 compared to control. An increase of the percentages of CD3+cells bearing IL-4 was observed in the Group I after the oral infections treatment. CONCLUSIONS: The occurrence of oral infections favors the intracellular cytokines expression and, probably, the inflammatory reaction operating as a stimulatory signal triggering the leprosy reactions.

  13. Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse to Porphyromonas gingivalis LPS

    Directory of Open Access Journals (Sweden)

    Yicong Liu

    2013-01-01

    Full Text Available We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response to Porphyromonas gingivalis (P.g. LPS. The expression of Toll-like receptor 2 (TLR2, TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. In in vitro studies, P.g. LPS induced the secretion of TNF-α and IL-1β from THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-α and IL-1β in leptomeningeal cells after treatment with the conditioned medium from P.g. LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment with P.g. LPS alone. Furthermore, the mean mRNA levels of TNF-α and IL-1β in microglia after treatment with the conditioned medium from P.g. LPS-stimulated leptomeningeal cells were significantly higher than those after P.g. LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced the P.g. LPS-induced TNF-α and IL-1 β production by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.

  14. Assessing Autophagy in Sciatic Nerves of a Rat Model that Develops Inflammatory Autoimmune Peripheral Neuropathies

    Directory of Open Access Journals (Sweden)

    Susana Brun

    2017-09-01

    Full Text Available The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199 peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves.

  15. Genome-wide peripheral blood leukocyte DNA methylation microarrays identified a single association with inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Harris, R Alan; Nagy-Szakal, Dorottya; Pedersen, Natalia

    2012-01-01

    Crohn's disease (CD) and ulcerative colitis (UC) are common forms of inflammatory bowel disease (IBD). Monozygotic (MZ) twin discordance rates and epidemiologic data implicate that environmental changes and epigenetic factors may play a pathogenic role in IBD. DNA methylation (the methylation of ...... of cytosines within CpG dinucleotides) is an epigenetic modification, which can respond to environmental influences. We investigated whether DNA methylation might be connected with IBD in peripheral blood leukocyte (PBL) DNA by utilizing genome-wide microarrays....

  16. Peripheral non-viral MIDGE vector-driven delivery of β-endorphin in inflammatory pain

    Directory of Open Access Journals (Sweden)

    Busch Melanie

    2009-12-01

    Full Text Available Abstract Background Leukocytes infiltrating inflamed tissue produce and release opioid peptides such as β-endorphin, which activate opioid receptors on peripheral terminals of sensory nerves resulting in analgesia. Gene therapy is an attractive strategy to enhance continuous production of endogenous opioids. However, classical viral and plasmid vectors for gene delivery are hampered by immunogenicity, recombination, oncogene activation, anti-bacterial antibody production or changes in physiological gene expression. Non-viral, non-plasmid minimalistic, immunologically defined gene expression (MIDGE vectors may overcome these problems as they carry only elements needed for gene transfer. Here, we investigated the effects of a nuclear localization sequence (NLS-coupled MIDGE encoding the β-endorphin precursor proopiomelanocortin (POMC on complete Freund's adjuvant-induced inflammatory pain in rats. Results POMC-MIDGE-NLS injected into inflamed paws appeared to be taken up by leukocytes resulting in higher concentrations of β-endorphin in these cells. POMC-MIDGE-NLS treatment reversed enhanced mechanical sensitivity compared with control MIDGE-NLS. However, both effects were moderate, not always statistically significant or directly correlated with each other. Also, the anti-hyperalgesic actions could not be increased by enhancing β-endorphin secretion or by modifying POMC-MIDGE-NLS to code for multiple copies of β-endorphin. Conclusion Although MIDGE vectors circumvent side-effects associated with classical viral and plasmid vectors, the current POMC-MIDGE-NLS did not result in reliable analgesic effectiveness in our pain model. This was possibly associated with insufficient and variable efficacy in transfection and/or β-endorphin production. Our data point at the importance of the reproducibility of gene therapy strategies for the control of chronic pain.

  17. INFLAMMATORY CELL NUMBER AND MEDIATORS IN BRONCHOALVEOLAR LAVAGE FLUID AND PERIPHERAL-BLOOD IN SUBJECTS WITH ASTHMA WITH INCREASED NOCTURNAL AIRWAYS NARROWING

    NARCIS (Netherlands)

    OOSTERHOFF, Y; KAUFFMAN, HF; RUTGERS, B; ZIJLSTRA, FJ; KOETER, GH; POSTMA, DS

    Background: Increased nocturnal airways narrowing (NAN) in asthma is thought to occur as the result of intensification of inflammatory processes in the airways. In this study we investigated the presence of inflammatory cells and mediators in bronchoalveolar lavage (BAL) fluid and peripheral blood

  18. Divergent effects of T cell costimulation and inflammatory cytokine production on autoimmune peripheral neuropathy provoked by Aire deficiency.

    Science.gov (United States)

    Zeng, Xiaopei L; Nagavalli, Anil; Smith, Colin-Jamal; Howard, James F; Su, Maureen A

    2013-04-15

    Chronic inflammatory demyelinating polyneuropathy results from autoimmune destruction of the peripheral nervous system and is a component of the multiorgan autoimmunity syndrome that results from Aire gene mutations in humans. In parallel, peripheral nervous system autoimmunity resembling chronic inflammatory demyelinating polyneuropathy develops spontaneously in NOD mice with a partial loss of Aire function (NOD.Aire(GW/+) mice) and is a T cell-mediated disease. In this study, we analyze how key aspects of T cell activation and function modulate disease development in Aire-deficient mice. We show that genetic ablation of the Th1 cytokine IFN-γ completely prevents clinical and electrophysiological evidence of neuropathy in NOD.Aire(GW/+) mice. IFN-γ deficiency is associated with absence of immune infiltration and decreased expression of the T cell chemoattractant IP-10 in sciatic nerves. Thus, IFN-γ is absolutely required for the development of autoimmune peripheral neuropathy in NOD.Aire(GW/+) mice. Because IFN-γ secretion is enhanced by B7-CD28 costimulation of T cells, we sought to determine the effects of these costimulatory molecules on neuropathy development. Surprisingly, B7-2 deficiency accelerated neuropathy development in NOD.Aire(GW/+) mice, and Ab blockade of both B7-1 and B7-2 resulted in fulminant, early-onset neuropathy. Thus, in contrast to IFN-γ, B7-2 alone and B7-1/B7-2 in combination function to ameliorate neuropathy development in NOD.Aire(GW/+) mice. Together, these findings reveal distinct and opposing effects of the T cell costimulatory pathway and IFN-γ production on the pathogenesis of autoimmune peripheral neuropathy.

  19. Pro-inflammatory cytokines involvement in the hesperidin antihyperalgesic effects at peripheral and central levels in a neuropathic pain model.

    Science.gov (United States)

    Carballo-Villalobos, A I; González-Trujano, M E; Alvarado-Vázquez, N; López-Muñoz, F J

    2017-04-01

    Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory and the increased incidence of neurodegenerative diseases. Flavonoids have long been used because of their anti-inflammatory potential activity and they are considered a promising alternative to alleviate neuropathic pain. The aim of this study was to investigate the antihyperalgesic effect of hesperidin and the presence of pro-inflammatory cytokines evaluated at peripheral and central levels in the chronic constriction injury as model of neuropathic pain in rats. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, as related to the presence of cytokines concentrations (TNF-α, IL-1β and IL-6) in sciatic nerve and segments of the spinal cord after 15 days chronic constriction injury model in rats receiving vehicle or hesperidin. Antihyperalgesic response of hesperidin (100 mg/kg) was associated to the presence of cytokines mainly at several sections of the spinal cord suggesting not only peripheral but also its involvement in central sensitization in the experimental neuropathic pain.

  20. PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

    International Nuclear Information System (INIS)

    Bernards, Nicholas

    2014-01-01

    The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [ 18 F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [ 18 F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [ 18 F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [ 18 F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [ 18 F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [ 18 F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author) [fr

  1. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity.

    Science.gov (United States)

    Amaya, Fumimasa; Wang, Haibin; Costigan, Michael; Allchorne, Andrew J; Hatcher, Jon P; Egerton, Julie; Stean, Tania; Morisset, Valerie; Grose, David; Gunthorpe, Martin J; Chessell, Iain P; Tate, Simon; Green, Paula J; Woolf, Clifford J

    2006-12-13

    We used a mouse with deletion of exons 4, 5, and 6 of the SCN11A (sodium channel, voltage-gated, type XI, alpha) gene that encodes the voltage-gated sodium channel Na(v)1.9 to assess its contribution to pain. Na(v)1.9 is present in nociceptor sensory neurons that express TRPV1, bradykinin B2, and purinergic P2X3 receptors. In Na(v)1.9-/- mice, the non-inactivating persistent tetrodotoxin-resistant sodium TTXr-Per current is absent, whereas TTXr-Slow is unchanged. TTXs currents are unaffected by the mutation of Na(v)1.9. Pain hypersensitivity elicited by intraplantar administration of prostaglandin E2, bradykinin, interleukin-1beta, capsaicin, and P2X3 and P2Y receptor agonists, but not NGF, is either reduced or absent in Na(v)1.9-/- mice, whereas basal thermal and mechanical pain sensitivity is unchanged. Thermal, but not mechanical, hypersensitivity produced by peripheral inflammation (intraplanatar complete Freund's adjuvant) is substantially diminished in the null allele mutant mice, whereas hypersensitivity in two neuropathic pain models is unchanged in the Na(v)1.9-/- mice. Na(v)1.9 is, we conclude, an effector of the hypersensitivity produced by multiple inflammatory mediators on nociceptor peripheral terminals and therefore plays a key role in mediating peripheral sensitization.

  2. Inflammatory cells in the peripheral nervous system in motor neuron disease

    NARCIS (Netherlands)

    Kerkhoff, H.; Troost, D.; Louwerse, E. S.; van Dijk, M.; Veldman, H.; Jennekens, F. G.

    1993-01-01

    We examined post-mortem material of the peripheral nervous system of 26 cases of motor neuron disease (MND) for the presence of lymphocyte subsets and macrophages. Findings were quantified and compared with those in control nerves. Lymphocytes in chronic and acute axonal degeneration were studied in

  3. Undifferentiated embryonal sarcoma of liver

    Directory of Open Access Journals (Sweden)

    Avyakta Kallam

    2015-12-01

    Full Text Available Undifferentiated embryonal sarcoma of the liver (UESL is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL.

  4. Undifferentiated Embryonal Sarcoma of Liver.

    Science.gov (United States)

    Kallam, Avyakta; Krishnamurthy, Jairam; Kozel, Jessica; Shonka, Nicole

    2015-12-29

    Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant hepatic tumor. A 47 year old male presented with symptoms of sour taste in his mouth, occasional nausea, indigestion and 15-pound weight loss over two months. He had an unremarkable upper gastrointestinal endoscopy. Imaging showed a large liver mass in the left hepatic lobe that was resected and then reported as UESL. He went on to develop lung metastases and was initially treated with doxorubicin and ifosfamide followed by switching of therapy to gemcitabine and docetaxel due to progression of disease. He had a good response after two cycles and went on to receive four more cycles, achieving stable disease. We can therefore conclude that the combination of gemcitabine and docetaxel is a potential therapeutic option for patients with UESL.

  5. Effects of exercise on brain and peripheral inflammatory biomarkers induced by total sleep deprivation in rats.

    Science.gov (United States)

    Chennaoui, M; Gomez-Merino, D; Drogou, C; Geoffroy, H; Dispersyn, G; Langrume, C; Ciret, S; Gallopin, T; Sauvet, F

    2015-01-01

    Physical exercise induces neuroprotection through anti-inflammatory effects and total sleep deprivation is reported an inflammatory process. We examined whether 7 weeks of exercise training attenuates markers of inflammation during total sleep deprivation (24-h wakefulness) in the rat brain and periphery. Four groups of 10 rats were investigated: Sedentary control, Sedentary sleep-deprived, Exercised control, and Exercised sleep-deprived. Sleep deprivation and exercise training were induced using slowly rotating wheels and a motorized treadmill. We examined mRNA expression of pro-inflammatory (IL-1β, TNF-α, and IL-6) cytokine-related genes using real-time PCR, and protein levels in the hippocampus and frontal cortex, as well as circulating concentrations. Compared to Sedentary control rats, hippocampal and cortical IL-1β mRNA expressions in Sedentary sleep-deprived rats were up-regulated (p sleep-deprived rats (p sleep-deprived rats compared to Sedentary control (p sleep deprivation-induced hippocampal IL-1β increases (mRNA expression and protein content) (p sleep deprivation-induced increase of IL-6 concentration (p sleep deprivation prevents pro-inflammatory responses in the rat hippocampus, particularly the IL-1β cytokine at the gene expression level and protein content.

  6. Peripheral Inflammatory Markers and Antioxidant Response during the post-acute and chronic phase after Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Federico Licastro

    2016-11-01

    Full Text Available Traumatic brain injury (TBI is a mechanical insult to the brain caused by external forces and associated with inflammation and oxidative stress. The patients may show different profiles of neurological recovery and a combination of oxidative damage and inflammatory processes can affect their courses. It is known that an over-expression of cytokines can be seen in peripheral blood in the early hours/days after the injury, but little is known about the weeks and months encompassing the post-acute and chronic phases. In addition, no information is available about the antioxidant responses mediated by the major enzymes that regulate ROS levels: superoxide dismutase (SOD, catalase (CAT, peroxidases, and GSH related enzymes. This study investigates the 6-month trends of inflammatory markers and antioxidant responses in 22 severe TBI patients with prolonged disorders of consciousness, consecutively recruited in a dedicated neuro-rehabilitation facility. Patients with a high degree of neurological impairment often show an uncertain outcome. In addition, the profiles of plasma activities were related to the neurological recovery after 12 months.Venous peripheral blood samples were taken blindly as soon as clinical signs and laboratory markers confirmed the absence of infections, 3 and 6 months later. The clinical and neuropsychological assessment continued up to 12 months. Nineteen patients completed the follow up. In the chronic phase, persistent high plasma levels of cytokines can interfere with cognitive functioning and higher post-acute levels of cytokines (IFN-g, TNF-a, IL1b, IL6 are associated with poorer cognitive recoveries 12 months later. Moreover, higher IFN- γ, higher TNF-α and lower glutathione peroxidase (GPx activity are associated with greater disability.The results add evidence of persistent inflammatory response, provide information about long-term imbalance of antioxidant activity and suggest that the over-production of cytokines and

  7. Peripheral Inflammatory Parameters in Late-Life Depression: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Mónica Martínez-Cengotitabengoa

    2016-12-01

    Full Text Available Depressive disorders appear relatively frequently in older patients, and therefore represent an important disease burden worldwide. Given the high levels of inflammatory parameters found in depressed elderly patients, the “inflammaging” hypothesis is gaining strength. In this systematic review, we summarize current evidence regarding the relationship between inflammatory parameters and late-life depression, with a unique focus on longitudinal studies to guarantee temporality. According to the data summarized in this review, the levels of some proinflammatory parameters—especially interleukin (IL-8, IL-6, and tumor necrosis factor (TNF-α—could serve as biomarkers for the future development of depressive symptoms in elderly patients. Proinflammatory cytokines seem to be associated with the future development of clinically significant depression, irrespective of baseline scores, thus indicating that inflammation temporally precedes and increases depression risk. As insufficient research has been conducted in this field, further prospective studies are clearly warranted.

  8. The relationship of endotoxaemia to peripheral and central nervous system inflammatory responses in Human African Trypanosomiasis.

    Science.gov (United States)

    Maclean, Lorna; Aboubaker, Eltayb A; Kennedy, Peter G E; Sternberg, Jeremy M

    2017-04-01

    Endotoxaemia has been described in cases of Human African trypanosomiasis (HAT), but it is unclear if this phenomenon influences inflammatory pathology either in the periphery or central nervous system (CNS). We studied endotoxin concentrations in the plasma and cerebrospinal fluid (CSF) of Trypanosoma brucei rhodesiense patients using the chromogenic Limulus Amoebocyte lysate assay. The relationship of endotoxin concentration to the presentation of gross signs of inflammation and the inflammatory/counter-inflammatory cytokine profile of the relevant compartments were analysed. We demonstrate that HAT patients exhibit parasitaemia-independent plasma endotoxaemia, and that this is associated with splenomegaly and lymphadenopathy. Endotoxin concentrations normalize rapidly after treatment. There was no evidence of endotoxin release in the CNS. A rapid normalization of endotoxin levels after treatment and lack of association with parasitaemia suggest that gut leakage is the main source of endotoxin in the circulation. Low CSF endotoxin concentrations and a lack of any association with neuroinflammatory markers or neurological sequelae suggest that endotoxin does not play a role in the pathogenesis of the disease in the CNS.

  9. Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis.

    Science.gov (United States)

    Carter, John D; Gérard, Hervé C; Espinoza, Luis R; Ricca, Louis R; Valeriano, Joanne; Snelgrove, Jessica; Oszust, Cynthia; Vasey, Frank B; Hudson, Alan P

    2009-05-01

    The majority of patients with Chlamydia-induced reactive arthritis do not present with the classic triad of arthritis, conjunctivitis/iritis, and urethritis. Moreover, acute chlamydial infections are often asymptomatic. The aim of the present study was to assess the prevalence of synovial Chlamydia trachomatis and Chlamydia pneumoniae infections in patients with chronic undifferentiated spondylarthritis (uSpA). Study patients met the European Spondylarthropathy Study Group criteria for SpA, without evidence of ankylosing spondylitis, psoriasis, inflammatory bowel disease, or preceding dysentery. Symptoms were present for >or=6 months. Each patient underwent a synovial biopsy; tissue and concomitantly obtained peripheral blood mononuclear cells (PBMCs) were analyzed by polymerase chain reaction (PCR) for C trachomatis and C pneumoniae DNA. Other data collected on the day of the biopsy included standard demographic information and medical history, including any known history of C trachomatis or C pneumoniae. Physical examination (including joint count, evaluation for dactylitis and/or enthesitis, and skin examination) and HLA-B27 typing were performed. Synovial tissue (ST) samples from 167 patients with osteoarthritis (OA) were used as controls. Twenty-six patients met the entry criteria and underwent synovial biopsy (25 knee, 1 wrist). Sixteen of them (62%) were positive for C trachomatis and/or C pneumoniae DNA (10 for C trachomatis, 4 for C pneumoniae, and 2 for both). PCR analysis of ST revealed the presence of Chlamydia significantly more frequently in patients with uSpA than in OA controls (P<0.0001). No specific clinical characteristics differentiated Chlamydia-positive from Chlamydia-negative patients. PBMCs from 4 of the 26 uSpA patients (15%) were positive for Chlamydia, and Chlamydia was found in ST from 2 of these 4 patients. No significant correlation between PCR positivity and HLA-B27 positivity was found. The frequency of Chlamydia-positive ST samples

  10. [Influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits].

    Science.gov (United States)

    Fan, Gui-cheng; Rong, Xin-zhou; Wang, Xue-min; Liu, Si-rong; Zhou, Yue-ping; Li, Qing-hui

    2012-12-01

    To explore the influence of exogenous putrescine and cadaverine on pro-inflammatory factors in the peripheral blood of rabbits. Forty ordinary adult New Zealand rabbits were divided into saline, necrotic tissue homogenate (NTH), putrescine, and cadaverine groups according to the random number table, with 10 rabbits in each group. Saline, NTH, 10 g/L putrescine, and 10 g/L cadaverine were respectively peritoneally injected into rabbits of corresponding group in the amount of 1 mL/kg. The blood sample in the volume of 2 mL was collected from the central artery of rabbit ears before injection and at 2, 6, 12, 24, 30, 36, 48, 60 hours post injection (PIH). Contents of TNF-α, IL-1, and IL-6 in the serum were determined with enzyme-linked immunosorbent assay. Data were processed with repeated measurement data analysis of variance and Spearman correlation analysis, and cubic model curve was applied in curve fitting for the contents of inflammatory factors. (1) The serum contents of TNF-α, IL-1, and IL-6 were increased in NTH, putrescine, and cadaverine groups in different degrees at most post injection time points. There was no significant change in the concentrations of the three pro-inflammatory factors in saline group, and they were significantly lower than those of the other three groups at most post injection time points (with F values from 3.49 to 13.58, P values all below 0.05). The serum contents of TNF-α, IL-1, and IL-6 in putrescine group began to increase at PIH 2, 6, and 6, which was similar to the trend of NTH group, but the changes were delayed compared with those of cadaverine group(all at PIH 2). The peak values of TNF-α, IL-1, and IL-6 in putrescine group were respectively (339 ± 36), (518 ± 44), and (265.9 ± 33.5) pg/mL, which were significantly lower than those of cadaverine group [ (476 ± 86), (539 ± 22), and (309.4 ± 27.1) pg/mL], with F values respectively 5.11, 1.90, and 5.56, P values all below 0.05. (2) The period of time in which

  11. Rate of Production of Inflammatory Cytokines TNF and IL- by Peripheral Blood Mononuclear Cells Stimulated with Mycolactone

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    P Mohajeri

    2010-08-01

    Full Text Available Introduction: Mycobacterium ulcerans is the etiological agent of Buruli ulcer (BU the third most common mycobacterial infection in humans after tuberculosis and leprosy. BU is now considered by the WHO to be an emerging infection of major concern. M. ulcerans produces mycolactone toxin, which is required for the organism’s virulence. Mycolactone destroys tissue and suppresses host immune responses. Methods: In this descriptive analytical study, peripheral blood mononuclear cells from three volunteers with no history of buruli ulcer were used. IL-6 and TNF produced by these cells at different preincubation times with LPS and mycolactone were measured by using ELISA kits. Results: This study showed hyper inhibition of IL-6 and TNF production by mycolactone. TNF levels in the control tubes (containing LPS in 4hours reached its maximum value and then decreased. While the production of IL-6 in the tube with fresh cells (zero time had the highest value, after 16hours, it reached its minimum. Conclusion: Since TNF and IL-6 are important immunity inflammatory cytokines, it can be well imagined that decrease of TNF production by this bacterium plays a role in weakening of inflammatory response. So Mycobacterium ulcerans destroys macrophages and at the same time prevents TNF production by important cells in innate immune mechanism.

  12. Computational Drug Repositioning for Peripheral Arterial Disease: Prediction of anti-inflammatory and pro-angiogenic therapeutics

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    Liang-Hui eChu

    2015-08-01

    Full Text Available Peripheral arterial disease (PAD results from atherosclerosis that leads to blocked arteries and reduced blood flow, most commonly in the arteries of the legs. PAD clinical trials to induce angiogenesis to improve blood flow conducted in the last decade have not succeeded. We have recently constructed PADPIN, protein-protein interaction network (PIN of PAD, and here we combine it with the drug-target relations to identify potential drug targets for PAD. Specifically, the proteins in the PADPIN were classified as belonging to the angiome, immunome, and arteriome, characterizing the processes of angiogenesis, immune response/inflammation, and arteriogenesis, respectively. Using the network-based approach we predict the candidate drugs for repositioning that have potential applications to PAD. By compiling the drug information in two drug databases DrugBank and PharmGKB, we predict FDA-approved drugs whose targets are the proteins annotated as anti-angiogenic and pro-inflammatory, respectively. Examples of pro-angiogenic drugs are carvedilol and urokinase. Examples of anti-inflammatory drugs are ACE inhibitors and maraviroc. This is the first computational drug repositioning study for PAD.

  13. Relation between systemic inflammatory markers, peripheral muscle mass, and strength in limb muscles in stable COPD patients

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    Ferrari R

    2015-08-01

    Full Text Available Renata Ferrari,1 Laura MO Caram,1 Marcia M Faganello,2 Fernanda F Sanchez,3 Suzana E Tanni,1 Irma Godoy1 1Botucatu Medical School, Department of Internal Medicine, Pneumology Area, Botucatu, São Paulo, 2Paulista State University, Department of Physiotherapy and Occupational Therapy, Marilia, São Paulo, 3Federal University of Amazonas, Department of Physiotherapy, Manaus, Amazonas, Brazil Abstract: The aim of this study was to investigate the association between systemic inflammatory mediators and peripheral muscle mass and strength in COPD patients. Fifty-five patients (69% male; age: 64±9 years with mild/very severe COPD (defined as forced expiratory volume in the first second [FEV1] =54%±23% were evaluated. We evaluated serum concentrations of IL-8, CRP, and TNF-α. Peripheral muscle mass was evaluated by computerized tomography (CT; midthigh cross-sectional muscle area (MTCSA and midarm cross-sectional muscle area (MACSA were obtained. Quadriceps, triceps, and biceps strength were assessed through the determination of the one-repetition maximum. The multiple regression results, adjusted for age, sex, and FEV1%, showed positive significant association between MTCSA and leg extension (0.35 [0.16, 0.55]; P=0.001, between MACSA and triceps pulley (0.45 [0.31, 0.58]; P=0.001, and between MACSA and biceps curl (0.34 [0.22, 0.47]; P=0.001. Plasma TNF-α was negatively associated with leg extension (-3.09 [-5.99, -0.18]; P=0.04 and triceps pulley (-1.31 [-2.35, -0.28]; P=0.01, while plasma CRP presented negative association with biceps curl (-0.06 [-0.11, -0.01]; P=0.02. Our results showed negative association between peripheral muscle mass (evaluated by CT and muscle strength and that systemic inflammation has a negative influence in the strength of specific groups of muscles in individuals with stable COPD. This is the first study showing association between systemic inflammatory markers and strength in upper limb muscles. Keywords

  14. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease

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    Jo Sangmee

    2011-05-01

    Full Text Available Abstract Background Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD. Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI and involved in their pathophysiology. Methods Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study. Plasma concentrations of four candidate biomarkers were measured in the normal control (NC, MCI, and AD group: interleukin-8 (IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1, and tumor necrosis factor-α (TNF-α. Body mass index (BMI, MMSE (Mini Mental State Examination, CDR(Clinical Dementia Rating score and homocystein level were recorded with social and demographic information. Results Total of 59 subjects were randomly selected for this analysis [NC (n = 21, MCI(n = 20 and AD(n = 18]. In demographic data, educational year was correlated with the diagnosis states (p p Conclusions Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

  15. Identification of peripheral inflammatory markers between normal control and Alzheimer's disease.

    Science.gov (United States)

    Kim, Sam-Moon; Song, Juhee; Kim, Seungwoo; Han, Changsu; Park, Moon Ho; Koh, Youngho; Jo, Sangmee Ahn; Kim, Young-Youl

    2011-05-12

    Multiple pathogenic factors may contribute to the pathophysiology of Alzheimer's disease (AD). Peripheral blood markers have been used to assess biochemical changes associated with AD and mild cognitive impairment (MCI) and involved in their pathophysiology. Plasma samples and clinical data were obtained from participants in the Ansan Geriatric Study (AGE study). Plasma concentrations of four candidate biomarkers were measured in the normal control (NC), MCI, and AD group: interleukin-8 (IL-8), IL-10, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α).Body mass index (BMI), MMSE (Mini Mental State Examination), CDR(Clinical Dementia Rating) score and homocystein level were recorded with social and demographic information. Total of 59 subjects were randomly selected for this analysis [NC (n = 21), MCI(n = 20) and AD(n = 18)]. In demographic data, educational year was correlated with the diagnosis states (p homocystein of the three groups, but no significant differences were found in each groups. The plasma IL-8 level was lower in MCI and AD patients compared with the normal control group (respectively, p < 0.0001). The MCI and AD patients had similar MCP-1, IL-10, and TNF-α level. Our study suggests the existence of an independent and negative relationship between plasma IL-8 levels and functional status in MCI and AD patients.

  16. Induction of RET dependent and independent pro-inflammatory programs in human peripheral blood mononuclear cells from Hirschsprung patients.

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    Marta Rusmini

    Full Text Available Hirschsprung disease (HSCR is a rare congenital anomaly characterized by the absence of enteric ganglia in the distal intestinal tract. While classified as a multigenic disorder, the altered function of the RET tyrosine kinase receptor is responsible for the majority of the pathogenesis of HSCR. Recent evidence demonstrate a strong association between RET and the homeostasis of immune system. Here, we utilize a unique cohort of fifty HSCR patients to fully characterize the expression of RET receptor on both innate (monocytes and Natural Killer lymphocytes and adaptive (B and T lymphocytes human peripheral blood mononuclear cells (PBMCs and to explore the role of RET signaling in the immune system. We show that the increased expression of RET receptor on immune cell subsets from HSCR individuals correlates with the presence of loss-of-function RET mutations. Moreover, we demonstrate that the engagement of RET on PBMCs induces the modulation of several inflammatory genes. In particular, RET stimulation with glial-cell line derived neurotrophic factor family (GDNF and glycosyl-phosphatidylinositol membrane anchored co-receptor α1 (GFRα1 trigger the up-modulation of genes encoding either for chemokines (CCL20, CCL2, CCL3, CCL4, CCL7, CXCL1 and cytokines (IL-1β, IL-6 and IL-8 and the down-regulation of chemokine/cytokine receptors (CCR2 and IL8-Rα. Although at different levels, the modulation of these "RET-dependent genes" occurs in both healthy donors and HSCR patients. We also describe another set of genes that, independently from RET stimulation, are differently regulated in healthy donors versus HSCR patients. Among these "RET-independent genes", there are CSF-1R, IL1-R1, IL1-R2 and TGFβ-1, whose levels of transcripts were lower in HSCR patients compared to healthy donors, thus suggesting aberrancies of inflammatory responses at mucosal level. Overall our results demonstrate that immune system actively participates in the physiopathology of

  17. Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile in Peripheral Blood Cells from CCP-positive Patients with RA.

    Science.gov (United States)

    Gertel, Smadar; Karmon, Gidi; Szarka, Eszter; Shovman, Ora; Houri-Levi, Esther; Mozes, Edna; Shoenfeld, Yehuda; Amital, Howard

    2018-03-01

    Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA. To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)-positive patients with RA and healthy controls were cocultured in vitro with ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested whether the stimulatory effects induced by ACPA could be inhibited by the addition of a new multiepitope citrullinated peptide (Cit-ME). We found that ACPA bind specifically to PBMC from CCP-positive patients with RA through the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4- to 13-fold increase) in PBMC derived from CCP-positive patients with RA. Moreover, ACPA upregulated IL-1β and IL-6 mRNA expression levels by 10- and 6-fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA, inhibited the ACPA-induced upregulation of IL-1β and IL-6 by 30%. ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA to decrease their pathogenic effects might provide a novel direction in developing therapeutic strategies for RA.

  18. Monoclonal antibody to a subset of human monocytes found only in the peripheral blood and inflammatory tissues

    Energy Technology Data Exchange (ETDEWEB)

    Zwadlo, G.; Schlegel, R.; Sorg, C.

    1986-07-15

    A monoclonal antibody is described that was generated by immunizing mice with cultured human blood monocytes. The antibody (27E10) belongs to the IgG1 subclass and detects a surface antigen at M/sub r/ 17,000 that is found on 20% of peripheral blood monocytes. The antigen is increasingly expressed upon culture of monocytes, reaching a maximum between days 2 and 3. Stimulation of monocytes with interferon-..gamma.. (IFN-..gamma..), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and lipopolysaccharide (LPS) Ylalanine (fMLP) increased the 27E10 antigen density. The amount of 27E10-positive cells is not or is only weakly affected. The antigen is absent from platelets, lymphotyces, and all tested human cell lines, yet it cross-reacts with 15% of freshly isolated granulocytes. By using the indirect immunoperoxidase technique, the antibody is found to be negative on cryostat sections of normal human tissue (skin, lung, and colon) and positive on only a few monocyte-like cells in liver and on part of the cells of the splenic red pulp. In inflammatory tissue, however, the antibody is positive on monocytes/macrophages and sometimes on endothelial cells and epidermal cells, depending on the stage and type of inflammation, e.g., BCG ranulomas are negative, whereas psoriasis vulgaris, atopic dermatitis, erythrodermia, pressure urticaria, and periodontitis contain positively staining cells. In contact eczemas at different times after elicitation (6 hr, 24 hr, and 72 hr), the 27E10 antigen is seen first after 24 hr on a few infiltrating monocytes/macrophages, which increase in numbers after 72 hr.

  19. Localization of macrophage inflammatory protein : Macrophage inflammatory PROTEIN-1 expression in rat brain after peripheral administration of lipopolysaccharide and focal cerebral ischemia

    NARCIS (Netherlands)

    Gourmala, NG; Limonta, S; Bochelen, D; Sauter, A; Boddeke, HWGM

    Macrophage inflammatory protein is a member of the C-C subfamily of chemokines, which exhibits, in addition to proinflammatory activities, a potent endogenous pyrogen activity. In this study, we analysed the time-course of expression and cellular source of macrophage inflammatory protein-1 alpha and

  20. Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

    Science.gov (United States)

    McMasters, James F.

    Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade

  1. Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated spondyloarthritis: a case report and review of the literature

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    Jea Andrew

    2011-07-01

    Full Text Available Abstract Introduction Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset, reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury. Case presentation We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation. Conclusions Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.

  2. Inflammatory Stress on Autophagy in Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease during 24 Months of Follow-Up.

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    Arnaud François

    Full Text Available Recent findings indicate that microglia in Alzheimer's disease (AD is senescent whereas peripheral blood mononuclear cells (PBMCs could infiltrate the brain to phagocyte amyloid deposits. However, the molecular mechanisms involved in the amyloid peptide clearance remain unknown. Autophagy is a physiological degradation of proteins and organelles and can be controlled by pro-inflammatory cytokines. The purpose of this study was to evaluate the impact of inflammation on autophagy in PBMCs from AD patients at baseline, 12 and 24 months of follow-up. Furthermore, PBMCs from healthy patients were also included and treated with 20 μM amyloid peptide 1-42 to mimic AD environment. For each patient, PBMCs were stimulated with the mitogenic factor, phytohaemagglutin (PHA, and treated with either 1 μM C16 as an anti-inflammatory drug or its vehicle. Autophagic markers (Beclin-1, p62/sequestosome 1 and microtubule-associated protein-light chain 3: LC3 were quantified by western blot and cytokines (Interleukin (IL-1β, Tumor necrosis Factor (TNF-α and IL-6 by Luminex X-MAP® technology. Beclin-1 and TNF-α levels were inversely correlated in AD PBMCs at 12 months post-inclusion. In addition, Beclin-1 and p62 increased in the low inflammatory environment induced by C16. Only LC3-I levels were inversely correlated with cognitive decline at baseline. For the first time, this study describes longitudinal changes in autophagic markers in PBMCs of AD patients under an inflammatory environment. Inflammation would induce autophagy in the PBMCs of AD patients while an anti-inflammatory environment could inhibit their autophagic response. However, this positive response could be altered in a highly aggressive environment.

  3. Acute sleep fragmentation does not alter pro-inflammatory cytokine gene expression in brain or peripheral tissues of leptin-deficient mice

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    Jennifer E. Dumaine

    2018-02-01

    Full Text Available Obesity and sleep fragmentation (SF are often co-occurring pro-inflammatory conditions in patients with obstructive sleep apnea. Leptin is a peptide hormone produced by adipocytes that has anorexigenic effects upon appetite while regulating immunity. The role of leptin in mediating inflammatory responses to SF is incompletely understood. Male C57BL/6j (lean and ob/ob mice (leptin-deficient mice exhibiting obese phenotype were subjected to SF or control conditions for 24 h using an automated SF chamber. Trunk blood and tissue samples from the periphery (liver, spleen, fat, and heart and brain (hypothalamus, prefrontal cortex, and hippocampus were collected. Quantitative PCR was used to determine relative cytokine gene expression of pro-inflammatory (IL-1β, TNF-α and anti-inflammatory (TGF-β1 cytokines. Enzyme-linked immunosorbent assay (ELISA was used to determine serum corticosterone concentration. Ob/ob mice exhibited elevated cytokine gene expression in liver (TNF-α, TGF-β1, heart (TGF-β1, fat (TNF-α, and brain (hippocampus, hypothalamus, prefrontal cortex: IL-1β, TNF-α compared with wild-type mice. Conversely, leptin deficiency decreased pro-inflammatory cytokine gene expression in heart (IL-1β, TNF-α. SF significantly increased IL-1β and TNF-α gene expression in fat and TGF-β1 expression in spleen relative to controls, but only in wild-type mice. SF increased basal serum corticosterone regardless of genotype. Taken together, these findings suggest that leptin deficiency affects cytokine gene expression differently in the brain compared to peripheral tissues with minimal interaction from acute SF.

  4. Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

    Science.gov (United States)

    Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

    2017-02-01

    Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

  5. Supplementation with orange and blackcurrant juice, but not vitamin E, improves inflammatory markers in patients with peripheral arterial disease

    DEFF Research Database (Denmark)

    Dalgård, Christine; Nielsen, Flemming Steen; Morrow, Jason D

    2009-01-01

    Inflammation and endothelial activation are associated with an increased risk of CVD and epidemiological evidence suggests an association between levels of markers of inflammation or endothelial activation and the intake of fruit. Also, vitamin E, a fat-soluble antioxidant, has anti-inflammatory ...

  6. Caspase-1 is involved in the genesis of inflammatory hypernociception by contributing to peripheral IL-1β maturation

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    Zamboni Dario S

    2010-10-01

    Full Text Available Abstract Background Caspase-1 is a cysteine protease responsible for the processing and secretion of IL-1β and IL-18, which are closely related to the induction of inflammation. However, limited evidence addresses the participation of caspase-1 in inflammatory pain. Here, we investigated the role of caspase-1 in inflammatory hypernociception (a decrease in the nociceptive threshold using caspase-1 deficient mice (casp1-/-. Results Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. The production of cytokines, PGE2 and neutrophil migration were evaluated by ELISA, radioimmunoassay and myeloperoxidase activity, respectively. The interleukin (IL-1β and cyclooxygenase (COX-2 protein expression were evaluated by western blotting. The mechanical hypernociception induced by intraplantar injection of carrageenin, tumour necrosis factor (TNFα and CXCL1/KC was reduced in casp1-/- mice compared with WT mice. However, the hypernociception induced by IL-1β and PGE2 did not differ in WT and casp1-/- mice. Carrageenin-induced TNF-α and CXCL1/KC production and neutrophil recruitment in the paws of WT mice were not different from casp1-/- mice, while the maturation of IL-1β was reduced in casp1-/- mice. Furthermore, carrageenin induced an increase in the expression of COX-2 and PGE2 production in the paw of WT mice, but was reduced in casp1-/- mice. Conclusion These results suggest that caspase-1 plays a critical role in the cascade of events involved in the genesis of inflammatory hypernociception by promoting IL-1β maturation. Because caspase-1 is involved in the induction of COX-2 expression and PGE2 production, our data support the assertion that caspase-1 is a key target to control inflammatory pain.

  7. The contribution of the endogenous TRPV1 ligands 9-HODE and 13-HODE to nociceptive processing and their role in peripheral inflammatory pain mechanisms.

    Science.gov (United States)

    Alsalem, Mohammad; Wong, Amy; Millns, Paul; Arya, Pallavi Huma; Chan, Michael Siang Liang; Bennett, Andrew; Barrett, David A; Chapman, Victoria; Kendall, David A

    2013-04-01

    The transient receptor potential vanilloid type 1 (TRPV1) plays a fundamental role in the detection of heat and inflammatory pain responses. Here we investigated the contribution of two potential endogenous ligands [9- and 13- hydroxyoctadecadienoic acid (HODE)] to TRPV1-mediated noxious responses and inflammatory pain responses. 9- and 13-HODE, and their precursor, linoleic acid, were measured in dorsal root ganglion (DRG) neurons and in the hindpaws of control and carrageenan-inflamed rats by liquid chromatography/tandem electrospray mass spectrometry. Calcium imaging studies of DRG neurons were employed to determine the role of TRPV1 in mediating linoleic acid, 9-HODE- and 13-HODE-evoked responses, and the contribution of 15-lipoxygenase to the generation of the HODEs. Behavioural studies investigated the contribution of 9- and 13-HODE and 15-lipoxygenase to inflammatory pain behaviour. 9-HODE (35 ± 7 pmol g(-1)) and 13-HODE (32 ± 6 pmol g(-1)) were detected in hindpaw tissue, but were below the limits of detection in DRGs. Following exposure to linoleic acid, 9- and 13-HODE were detected in DRGs and TRPV1 antagonist-sensitive calcium responses evoked, which were blocked by the 15-lipoxygenase inhibitor PD146176 and an anti-13-HODE antibody. Levels of linoleic acid were significantly increased in the carrageenan-inflamed hindpaw (P PD146176 significantly (P < 0.01) attenuated carrageenan-induced hyperalgesia. This study demonstrates that, although 9- and 13-HODE can activate TRPV1 in DRG cell bodies, the evidence for a role of these lipids as endogenous peripheral TRPV1 ligands in a model of inflammatory pain is at best equivocal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  8. Alteration in peripheral blood concentration of certain pro-inflammatory cytokines in cows developing retention of fetal membranes.

    Science.gov (United States)

    Boro, Prasanta; Kumaresan, A; Pathak, Rupal; Patbandha, T K; Kumari, Susavi; Yadav, Asha; Manimaran, A; Baithalu, R K; Attupuram, Nitin M; Mohanty, T K

    2015-06-01

    Retention of fetal membranes (RFM) adversely affects the production and reproduction potential of the affected cows leading to huge economic loss. Physiological separation of fetal membranes is reported to be an inflammatory process. The present study compared the concentrations of certain pro inflammatory cytokines [Interleukin 1β (IL-1), Interleukin 6 (IL-6), Interleukin 8 (IL-8) and Tumor necrosis factor α (TNF-α) between the cows that developed RFM (n=10) and the cows that expelled fetal membranes normally (n=10) to find out if they could serve as a predictive tool for RFM. Blood samples were collected from the cows from 30 days before expected parturition through day -21, day -14, day -7, day -5, day -3, day -1, on the day of parturition (day 0), day 1 postpartum and the pro-inflammatory cytokines were estimated in blood plasma by ELISA method. The IL-1β concentration was significantly lower (Pmembranes normally from 3 days before calving till the day of calving. The plasma concentrations of IL-6 and IL-8 were also lower (Pmembranes normally. It may be inferred that the concentrations of IL-1, IL-6, IL-8 and TNF-α around parturition were altered in cows developing RFM compared to those expelled fetal membranes normally. Copyright © 2015. Published by Elsevier B.V.

  9. Uncoupling of peripheral and master clock gene rhythms by reversed feeding leads to an exacerbated inflammatory response after polymicrobial sepsis in mice.

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    Oyama, Yoshimasa; Iwasaka, Hideo; Koga, Hironori; Shingu, Chihiro; Matsumoto, Shigekiyo; Noguchi, Takayuki

    2014-03-01

    Reversed feeding uncouples peripheral and master clock gene rhythms and leads to an increased risk of disease development. The aim of this study was to determine the effects of clock gene uncoupling on sepsis-induced inflammation using a mouse cecal ligation and puncture (CLP) model. C57BL/6N mice were entrained to a 12-h light-dark cycle (lights on at 7 AM). Mice were permitted ad libitum feeding either during the night (7 PM-7 AM) or the nonphysiological light phase (7 AM-7 PM) for a week before CLP. In daytime-fed mice, phase inversion of clock gene expression was observed in the liver, but not in the suprachiasmatic nucleus. Daytime-fed mice also had decreased body weight and food intake. Survival rate was significantly lower in daytime-fed mice (29%) compared with nighttime-fed mice (54%) 72 h after CLP (P = 0.03). Serum levels of interleukin 6 (IL-6), tumor necrosis factor α, high mobility group box 1, IL-1α, IL-9, eotaxin, and granulocyte colony-stimulating factor increased in daytime-fed mice compared with nighttime-fed mice after CLP. Baseline expression levels of sirtuin peroxisome 1 and proliferator-activated receptor γ coactivator 1α in the liver decreased in daytime-fed mice compared with nighttime-fed mice. Thus, daytime feeding induces clock gene uncoupling, which leads to decreased expression of longevity-related and energy metabolism proteins. Daytime feeding may also increase the levels of inflammatory cytokines, thereby increasing mortality in a mouse sepsis model. Our findings suggest that uncoupling of peripheral and master clock gene rhythms by reversed feeding exacerbates inflammatory responses.

  10. Comparison of burrowing and stimuli-evoked pain behaviors as end-points in rat models of inflammatory pain and peripheral neuropathic pain

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    Arjun eMuralidharan

    2016-05-01

    Full Text Available Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤450g of gravel on any two days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund’s complete adjuvant (FCA or saline, or underwent unilateral chronic constriction injury (CCI of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA- and CCI-rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability.

  11. Interleukin 35 (IL-35) and IL-37: Intestinal and peripheral expression by T and B regulatory cells in patients with Inflammatory Bowel Disease.

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    Fonseca-Camarillo, Gabriela; Furuzawa-Carballeda, Janette; Yamamoto-Furusho, Jesús K

    2015-10-01

    The aim of the study was to characterize and to quantify peripheral and tissue. IL-35- and IL-37-producing cells in Inflammatory Bowel Disease (IBD) patients. We studied a total of 38 active UC, 31 inactive UC, 17 active CD, and 13 inactive CD and 50 non-inflamed tissues as control group. Gene expression was measured by real time polymerase chain reaction (RT-PCR) and protein expression was evaluated in tissue by immunohistochemistry and in peripheral blood mononuclear cells by flow cytometry. Higher levels of IL-35 was produced by intestinal regulatory B cells and circulating regulatory CD4(+) and CD8(+) T cells in active vs. inactive disease or healthy donors (P<0.05). The IL-37 was conspicuously synthesized by circulating B cells, active natural killer cells and monocytes. These results suggest that down-regulation of inflammation in active IBD patients might be based on the increased expression of IL-35 and IL-37. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Secretome of Aggregated Embryonic Stem Cell-Derived Mesenchymal Stem Cell Modulates the Release of Inflammatory Factors in Lipopolysaccharide-Induced Peripheral Blood Mononuclear Cells

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    Mohammadi Ghahhari, Nastaran; Maghsood, Faezeh; Jahandideh, Saeed; Lotfinia, Majid; Lak, Shirin; Johari, Behrooz; Azarnezhad, Asaad; Kadivar, Mehdi

    2018-07-01

    Bone marrow mesenchymal stem cells (BM-MSCs) have emerged as a potential therapy for various inflammatory diseases. Because of some limitations, several recent studies have suggested the use of embryonic stem cell-derived MSCs (ESC-MSCs) as an alternative for BM-MSCs. Some of the therapeutic effects of the ESC-MSCs are related to the secretion of a broad array of cytokines and growth factors, known as secretome. Harnessing this secretome for therapeutic applications requires the optimization of production of secretary molecules. It has been shown that aggregation of MSCs into 3D spheroids, as a preconditioning strategy, can enhance immunomodulatory potential of such cells. In this study, we investigated the effect of secretome derived from human ESC-MSCs (hESC-MSCs) spheroids on secretion of IL-1β, IL-10, and tumor necrosis factor α (TNF-α) from lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMCs). In the present study, after immunophenotyping and considering mesodermal differentiation of hESC-MSCs, the cells were non-adherently grown to prepare 3D aggregates, and then conditioned medium or secretome was extracted from the cultures. Afterwards, the anti-inflammatory effects of the secretome were assessed in an in vitro model of inflammation. Results from this study showed that aggregate-prepared secretome from hESC-MSCs was able to significantly decrease the secretion of TNF-α (301.7 ± 5.906, p strategy to increase immunomodulatory characteristics of hESC-MSCs.

  13. Polysaccharide rich fractions from barks of Ximenia americana inhibit peripheral inflammatory nociception in mice Antinociceptive effect of Ximenia americana polysaccharide rich fractions

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    Kaira E.S. da Silva-Leite

    Full Text Available Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernociception, hot plate, or during 14 days for toxicity assay. The total polysaccharides fraction (TPL-Xa: 8.1% yield presented 43% carbohydrate (21% uronic acid and resulted in two main fractions after chromatography (FI: 12%, FII: 22% yield. FII showed better homogeneity/purity, content of 44% carbohydrate, including 39% uronic acid, arabinose and galactose as major monosaccharides, and infrared spectra with peaks in carbohydrate range for COO- groups of uronic acid. TPL-Xa (10 mg/kg and FII (0.1 and 1 mg/kg presented inhibitory effect in behavior tests that evaluate nociception induced by chemical and mechanical, but not thermal stimuli. TPL-Xa did not alter parameters of systemic toxicity. In conclusion, polysaccharides rich fractions of X. americana barks inhibit peripheral inflammatory nociception, being well tolerated by animals.

  14. Anti-allodynic effect of Buja in a rat model of oxaliplatin-induced peripheral neuropathy via spinal astrocytes and pro-inflammatory cytokines suppression.

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    Jung, Yongjae; Lee, Ji Hwan; Kim, Woojin; Yoon, Sang Hyub; Kim, Sun Kwang

    2017-01-14

    Oxaliplatin, a widely used anticancer drug against metastatic colorectal cancer, can induce acute peripheral neuropathy, which is characterized by cold and mechanical allodynia. Activation of glial cells (e.g. astrocytes and microglia) and increase of pro-inflammatory cytokines (e.g. IL-1β and TNF-α) in the spinal cord play a crucial role in the pathogenesis of neuropathic pain. Our previous study demonstrated that Gyejigachulbu-Tang (GBT), a herbal complex formula, alleviates oxaliplatin-induced neuropathic pain in rats by suppressing spinal glial activation. However, it remains to be elucidated whether and how Buja (Aconiti Tuber), a major ingredient of GBT, is involved in the efficacy of GBT. Cold and mechanical allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) in Sprauge-Dawley rats were evaluated by a tail immersion test in cold water (4 °C) and a von Frey hair test, respectively. Buja (300 mg/kg) was orally administrated for five consecutive days after the oxaliplatin injection. Glial activation in the spinal cord was quantified by immunohistochemical staining using GFAP (for astrocytes) and Iba-1 (for microglia) antibodies. The amount of spinal pro-inflammatory cytokines, IL-1β and TNF-α, were measured by ELISA. Significant behavioral signs of cold and mechanical allodynia were observed 3 days after an oxaliplatin injection. Oral administration of Buja significantly alleviated oxaliplatin-induced cold and mechanical allodynia by increasing the tail withdrawal latency to cold stimuli and mechanical threshold. Immunohistochemical analysis showed the activation of astrocytes and microglia and the increase of the IL-1β and TNF-α levels in the spinal cord after an oxaliplatin injection. Administration of Buja suppressed the activation of spinal astrocytes without affecting microglial activation and down-regulated both IL-1β and TNF-α levels in the spinal cord. Our results indicate that Buja has a potent anti-allodynic effect in a rat

  15. Temporal induction of pro-inflammatory and regulatory cytokines in human peripheral blood mononuclear cells by Campylobacter jejuni and Campylobacter coli.

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    Eman Hamza

    Full Text Available Campylobacter jejuni along with C. coli are major cause of human gastroenteritis worldwide. So far, the human immune response against Campylobacter is not entirely clear. We hypothesize that it is coordinated by an interaction between pro-inflammatory and regulatory cytokines which is influenced by bacterial and host-individual differences. Accordingly, we used peripheral blood mononuclear cells (PBMC from healthy donors to study the primary systemic immune response to C. jejuni and C. coli. PBMC were stimulated by different strains of C. jejuni and C. coli for three time points (5, 10, 24 hours. The production of the pro-inflammatory (IL-6, IL-8, IFN-γ and the regulatory (IL-10 cytokines were measured by ELISA. All strains induced higher levels of IL-8 and IL-6 than IFN-γ and IL-10. In contrast to IL-8 and IL-6, IL-10 showed a steeper increase over time. While IFN-γ did not show any further increase between 10 and 24 hours. Interestingly, there was a significant correlation between IL-8 and IL-10 which peaked at 24 hours. Despite the variability of the used bacterial strains, their effect on cytokine production was less pronounced than the inter-person differences. The strongest significant effect of the strain was on the level of IL-10. IL-10 and IL-6 were significantly influenced by strain-person interaction. In conclusion, the systemic immune response to C. coli and C. jejuni is characterized by an early pro-inflammatory reaction with later initiation of regulatory immune response which is influenced mainly by the host, explaining the individual variations in disease severity. Additional work is needed to determine the cellular sources of the produced cytokines as well as the campylobacter molecules that might contribute to this stimulation.

  16. Undifferentiated Febrile Illness in Kathmandu, Nepal

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    Thompson, Corinne N.; Blacksell, Stuart D.; Paris, Daniel H.; Arjyal, Amit; Karkey, Abhilasha; Dongol, Sabina; Giri, Abhishek; Dolecek, Christiane; Day, Nick; Baker, Stephen; Thwaites, Guy; Farrar, Jeremy; Basnyat, Buddha

    2015-01-01

    Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26–66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment. PMID:25667056

  17. Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood.

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    Ross, Kharah MacKenzie; Miller, Gregory; Culhane, Jennifer; Grobman, William; Simhan, Hyagriv N; Wadhwa, Pathik D; Williamson, Douglas; McDade, Thomas; Buss, Claudia; Entringer, Sonja; Adam, Emma; Qadir, Sameen; Keenan-Devlin, Lauren; Leigh, Adam K K; Borders, Ann

    2016-11-01

    Maternal inflammation undergoes adaptations during pregnancy, and excessive inflammation has been associated with adverse outcomes. One mechanism may be maternal inflammation transmission to the fetal compartment. Links between maternal pregnancy inflammation and fetal inflammation are poorly characterized. Principal components analysis was used to extract underlying inflammation components across cytokines (IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α) in two pregnancy cohorts (SPAH N=87, MOMS N=539) assessed during the second and third trimesters. Links between maternal inflammation over pregnancy and fetal (cord blood) inflammation were assessed. Substantial cytokine rank-order stability was observed in both cohorts, β's range .47-.96, P's blood inflammation, P's>.04. Maternal inflammation indices over pregnancy were associated with inflammation in cord blood at birth. Results have implications for understanding pregnancy inflammatory processes and how maternal inflammation may be transmitted to fetal circulation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Multiple Sites Ultrasonography of Peripheral Nerves in Differentiating Charcot–Marie–Tooth Type 1A from Chronic Inflammatory Demyelinating Polyradiculoneuropathy

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    Jingwen Niu

    2017-05-01

    Full Text Available IntroductionMultiple sites measurement of cross-sectional areas (CSA by ultrasound was performed to differentiate Charcot–Marie–Tooth type 1A (CMT1A and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP.MethodsNine patients with CMT1A, 28 patients with CIDP, and 14 healthy controls (HC were recruited prospectively. Consecutive ultrasonography scanning was performed from wrist to axilla on median and ulnar nerves. CSAs were measured at 10 predetermined sites of each nerve.ResultsCMT1A had significantly larger CSAs at all sites of median and ulnar nerves (p < 0.01. In CMT1A, CSAs increased gradually and homogeneously from distal to proximal along the nerve, except potential entrapment sites. CIDP displayed three different morphological patterns, including mild enlargement in 15 patients, prominent segmental enlargement in 12, and slight enlargement in 1, among which different treatment responses were observed. All patients with mild nerve enlargement treated with intravenous immunoglobulin were responsive (7/7, while less than half of those with prominent segmental enlargement (3/7 were responsive (p < 0.01.DiscussionConsecutive scan along the nerve and multiple sites measurement by ultrasound could supply more detailed morphological feature of the nerve and help to differentiate CMT1A from CIDP.

  19. Undifferentiated connective tissue dysplasia in adolescents

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    G. Yu. Kalayeva

    2014-01-01

    Full Text Available Objective: to study the spectrum and frequency of dysplasia-dependent and connective tissue dysplasia-associated disorders in adolescents. One hundred and ten 10-to-14-year-old pupils of one of the Leninsk-Kuznetsky schools were examined. The presence and degree of undifferentiated connective tissue dysplasia (UCTD were established according to the phenotypic characters; joint mobility was rated using the standard Beighton methods. The adolescents showed a high prevalence of the signs of UCTD whose degree corresponded to that of joint hypermobility. The latter was accompanied by joint pain in 89 (33,3% adolescents in the study group or concurrent with scoliosis in 77,8% and platypodia in 22,2%. In a control group (я=29, scoliosis and platypodia were 2 and 3,3 times rarer, respectively; complaints of arthralgia were absent. After 3 years, the number of adolescents with platypodia increased up to 33,3% in the study group and up to 10,3% in the control group; that of teenagers with scoliosis did up to 81,5and 41,4%, respectively. A larger number of adolescents with CTD were noted to have vegetovascular disorders, more commonly with parasympathotonia with insufficient autonomic performance support. A great difference was retained in the frequency of myopia and biliary dyskinesia and in the incidence of respiratory infections. Thus, the high prevalence of dysplasia-dependent disorders in adolescents suggests that there is a need for the early detection of the signs of CTD in children to timely implement a package of prevention and health-improvement measures.

  20. Changes in some pro-and anti-inflammatory cytokines produced by bovine peripheral blood mononuclear cells following foot and mouth disease vaccination

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    N. Delirezh

    2016-09-01

    Full Text Available Interleukin (IL-17 is exclusively produced by CD4 helper T-cells upon activation. It most often acts as a pro-inflammatory cytokine, which stimulates the release of pro-inflammatory cytokines IL-6, IL-8, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF. In this study, we studied the in-vitro IL-17 response to specific antigens and a variety of mitogens and compared the IL-17 response to IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-γ responses. We used a foot and mouth disease (FMD vaccine as specific antigens and mitogens (phytohemagglutinin [PHA], pokeweed mitogen [PWM], and concanavalin A [Con A] to stimulate peripheral blood mononuclear cells (PBMCs of vaccinated calves. Cell culture supernatant was harvested and analyzed for cytokines, using commercially available bovine ELISA kits. The mitogens induced a significant increase in IL-17 production. IL-17 was produced at high levels in response to the T cell-stimulated mitogens, PHA, and Con A, and at low levels in response to PWM mitogens. In contrast, level of the produced IL-17 cytokines in response to the FMDV antigens was lower as compared to those produced by mitogens. The FMDV antigens and mitogens significantly increased IL-17 production. There was not a correlation between IL-17 production and type-1 cytokine, IFN-γ, and IL-2, while there was a correlation between type-2 cytokine, IL-4, and IL-5 at either cytokine level produced by PBMCs stimulated by FMDV antigens. Moreover, there was an interaction between IL-17 and IL-6, that is, as IL-6 cytokine level elevated or diminished, IL-17 cytokine level increased or decreased, as well.

  1. Effect of Infla-Kine supplementation on the gene expression of inflammatory markers in peripheral mononuclear cells and on C-reactive protein in blood

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    Nina A. Mikirova

    2017-10-01

    Full Text Available Abstract Background Chronic inflammation is a predisposing factor to numerous degenerative diseases including cancer, heart failure and Alzheimer’s disease. Infla-Kine is a natural supplement comprised of a proprietary blend of Lactobacillus fermentum extract, burdock seed (arctigenin, zinc, alpha lipoic acid, papaya enzyme and an enhanced absorption bio-curcumin complex (BCM-95®. Methods Infla-Kine was administered twice daily to 24 health volunteers for 4 weeks. Quantitative RT-PCR was used to assess mRNA transcripts of IL-1b, IL8, IL-6, NF-κB, and TNF-α from peripheral blood mononuclear cells (PBMC. C reactive protein (CRP was measured from serum. Additionally, quality of life questionnaires were employed to assess general feeling of well-being. Assessments were made before treatment and at conclusion of treatment (4 weeks. Results As compared to pre-treatment, after 4 weeks, a statistically significant reduction of IL8, IL-6, NF-κB, and TNF-α transcripts was observed in PBMC. Furthermore, reduction of IL-1b transcript and serum CRP was observed but did not reach statistical significance. Quality of life improvements were most prevalent in muscle and joint pains. Conclusions Overall, our data demonstrate that twice daily administration of Infla-Kine for 4 weeks reduces inflammatory markers and quality of life in healthy volunteers.

  2. Centella asiatica modulates cancer cachexia associated inflammatory cytokines and cell death in leukaemic THP-1 cells and peripheral blood mononuclear cells (PBMC's).

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    Naidoo, Dhaneshree Bestinee; Chuturgoon, Anil Amichund; Phulukdaree, Alisa; Guruprasad, Kanive Parashiva; Satyamoorthy, Kapaettu; Sewram, Vikash

    2017-08-01

    Cancer cachexia is associated with increased pro-inflammatory cytokine levels. Centella asiatica (C. asiatica) possesses antioxidant, anti-inflammatory and anti-tumour potential. We investigated the modulation of antioxidants, cytokines and cell death by C. asiatica ethanolic leaf extract (C LE ) in leukaemic THP-1 cells and normal peripheral blood mononuclear cells (PBMC's). Cytotoxcity of C LE was determined at 24 and 72 h (h). Oxidant scavenging activity of C LE was evaluated using the 2, 2-diphenyl-1 picrylhydrazyl (DPPH) assay. Glutathione (GSH) levels, caspase (-8, -9, -3/7) activities and adenosine triphosphate (ATP) levels (Luminometry) were then assayed. The levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and IL-10 were also assessed using enzyme-linked immunosorbant assay. C LE decreased PBMC viability between 33.25-74.55% (24 h: 0.2-0.8 mg/ml C LE and 72 h: 0.4-0.8 mg/ml C LE ) and THP-1 viability by 28.404% (72 h: 0.8 mg/ml C LE ) (p < 0.0001). Oxidant scavenging activity was increased by C LE (0.05-0.8 mg/ml) (p < 0.0001). PBMC TNF-α and IL-10 levels were decreased by C LE (0.05-0.8 mg/ml) (p < 0.0001). However, PBMC IL-6 and IL-1β concentrations were increased at 0.05-0.2 mg/ml C LE but decreased at 0.4 mg/ml C LE (p < 0.0001). In THP-1 cells, C LE (0.2-0.8 mg/ml) decreased IL-1β and IL-6 whereas increased IL-10 levels (p < 0.0001). In both cell lines, C LE (0.05-0.2 mg/ml, 24 and 72 h) increased GSH concentrations (p < 0.0001). At 24 h, caspase (-9, -3/7) activities was increased by C LE (0.05-0.8 mg/ml) in PBMC's whereas decreased by C LE (0.2-0.4 mg/ml) in THP-1 cells (p < 0.0001). At 72 h, C LE (0.05-0.8 mg/ml) decreased caspase (-9, -3/7) activities and ATP levels in both cell lines (p < 0.0001). In PBMC's and THP-1 cells, C LE proved to effectively modulate antioxidant activity, inflammatory cytokines and cell death. In THP-1 cells, C LE decreased pro-inflammatory cytokine levels

  3. Anti-inflammatory effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in neuronal cultures of dorsal root ganglia and myelinating cells of the peripheral nervous system.

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    Ramesh, Geeta; Meisner, Olivia C; Philipp, Mario T

    2015-12-23

    Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), could result in cognitive impairment, motor dysfunction, and radiculoneuritis. We hypothesized that inflammation is a key factor in LNB pathogenesis and recently evaluated the effects of dexamethasone, a steroidal anti-inflammatory drug, and meloxicam a non-steroidal anti-inflammatory drug (NSAID), in a rhesus monkey model of acute LNB. Dexamethasone treatment significantly reduced the levels of immune mediators, and prevented inflammatory and/or neurodegenerative lesions in the central and peripheral nervous systems, and apoptosis in the dorsal root ganglia (DRG). However, infected animals treated with meloxicam showed levels of inflammatory mediators, inflammatory lesions, and DRG cell apoptosis that were similar to that of the infected animals that were left untreated. To address the differential anti-inflammatory effects of dexamethasone and meloxicam on neuronal and myelinating cells of the peripheral nervous system (PNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in rhesus DRG cell cultures and primary human Schwann cells (HSC), using multiplex enzyme-linked immunosorbent assays (ELISA). We also ascertained the ability of these drugs to modulate cell death as induced by live Bb in HSC using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay and the potential of dexamethasone to modulate Bb-induced apoptosis in HSC by the TUNEL assay. Earlier, we reported that dexamethasone significantly reduced Bb-induced immune mediators and apoptosis in rhesus DRG cell cultures. Here, we report that dexamethasone but not meloxicam significantly reduces the levels of several cytokines and chemokines as induced by live Bb, in HSC and DRG cell cultures. Further, meloxicam does not significantly alter Bb-induced cell death in HSC, while dexamethasone protects HSC against Bb-induced cell death. These data

  4. Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease

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    Shahmanesh, M.; Brunst, M.; Sukthankar, A.; Pearce, J. H.; Gaston, J. S.

    1999-01-01

    OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could

  5. Involvement of the peripheral sensory and sympathetic nervous system in the vascular endothelial expression of ICAM-1 and the recruitment of opioid-containing immune cells to inhibit inflammatory pain.

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    Mousa, Shaaban A; Shaqura, Mohammed; Brendl, Ute; Al-Khrasani, Mahmoud; Fürst, Susanna; Schäfer, Michael

    2010-11-01

    Endogenous opioids are known to be released within certain brain areas following stressful stimuli. Recently, it was shown that also leukocytes are a potential source of endogenously released opioid peptides following stress. They activate sensory neuron opioid receptors and result in the inhibition of local inflammatory pain. An important prerequisite for the recruitment of such leukocytes is the expression of intracellular adhesion molecule-1 (ICAM-1) in blood vessels of inflamed tissue. Here, we investigated the contribution of peripheral sensory and/or sympathetic nerves to the enhanced expression of ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes to promote the inhibition of inflammatory pain. Selective degeneration of either peripheral sensory or sympathetic nerve fibers by their respective neurotoxins, capsaicin or 6-hydroxydopamime, significantly reduced the subcutaneous immigration of β-endorphin- (END-) and met-enkephalin- (ENK-)-containing polymorphonuclear leukocytes (PMN) (in the early phase) and mononuclear cells (in the late phase) during painful Freund's complete adjuvant (FCA) rat hind paw inflammation. In contrast, this treatment did not alter the percentage of opioid peptide-containing leukocytes in the circulation. Calcitonin gene-related peptide- (CGRP-) and tyrosine hydroxylase- (TH-) immunoreactive (IR) nerve fibers were in close contact to ICAM-1 IR blood vessels within inflamed subcutaneous tissue. The selective degeneration of sensory or sympathetic nerve fibers attenuated the enhanced expression of vascular endothelial ICAM-1 after intraplantar (i.pl.) FCA and abolished endogenous opioid peptide-mediated peripheral analgesia. Our results suggest that, during localized inflammatory pain, peripheral sensory and sympathetic nerve fibers augment the expression of vascular endothelial ICAM-1 simultaneously with the increased recruitment of opioid peptide-containing leukocytes which consequently

  6. Association of peripheral arterial disease with periodontal disease: analysis of inflammatory cytokines and an acute phase protein in gingival crevicular fluid and serum.

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    Çalapkorur, M Unlu; Alkan, B A; Tasdemir, Z; Akcali, Y; Saatçi, E

    2017-06-01

    Inflammation is a common feature of both peripheral arterial disease (PAD) and periodontal disease. The aim of this study was to evaluate the relationship between PAD and periodontal disease by examining the levels of inflammatory cytokines (pentraxin 3 and interleukin 1β) and high sensitive C-reactive protein from gingival crevicular fluid and serum. A total of 60 patients were included in this cross-sectional study. Patients were divided into two groups based on ankle-brachial index values: with PAD (test group) and non-PAD (control group). Demographic evaluations, clinical periodontal examinations and biochemical analysis for pentraxin 3, interleukin 1β and high sensitive C-reactive protein were performed to compare the two groups. There were no significant differences with respect to gender, age, body mass index, or smoking history (duration, amount) between the two groups (p > 0.05). There were no significant differences between the two groups in terms of clinical periodontal parameters (p > 0.05). Neither gingival crevicular fluid nor serum levels of the cytokines showed differences between the two groups. Logistic regression analysis revealed that, after adjusting for confounding factors (age, gender, diabetes, hypertension and body mass index), periodontitis raised the odds ratio for having PAD to 5.842 (95% confidence interval: 1.558-21.909). Although there were no significant differences with respect to clinical periodontal parameters and biochemical analyses between the study group and control, periodontitis did raise the odds ratio for having PAD. To clarify this possible relationship, future prospective studies are needed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Comparison of whole blood and peripheral blood mononuclear cell gene expression for evaluation of the perioperative inflammatory response in patients with advanced heart failure.

    Directory of Open Access Journals (Sweden)

    Galyna Bondar

    Full Text Available Heart failure (HF prevalence is increasing in the United States. Mechanical Circulatory Support (MCS therapy is an option for Advanced HF (AdHF patients. Perioperatively, multiorgan dysfunction (MOD is linked to the effects of device implantation, augmented by preexisting HF. Early recognition of MOD allows for better diagnosis, treatment, and risk prediction. Gene expression profiling (GEP was used to evaluate clinical phenotypes of peripheral blood mononuclear cells (PBMC transcriptomes obtained from patients' blood samples. Whole blood (WB samples are clinically more feasible, but their performance in comparison to PBMC samples has not been determined.We collected blood samples from 31 HF patients (57±15 years old undergoing cardiothoracic surgery and 7 healthy age-matched controls, between 2010 and 2011, at a single institution. WB and PBMC samples were collected at a single timepoint postoperatively (median day 8 postoperatively (25-75% IQR 7-14 days and subjected to Illumina single color Human BeadChip HT12 v4 whole genome expression array analysis. The Sequential Organ Failure Assessment (SOFA score was used to characterize the severity of MOD into low (≤ 4 points, intermediate (5-11, and high (≥ 12 risk categories correlating with GEP.Results indicate that the direction of change in GEP of individuals with MOD as compared to controls is similar when determined from PBMC versus WB. The main enriched terms by Gene Ontology (GO analysis included those involved in the inflammatory response, apoptosis, and other stress response related pathways. The data revealed 35 significant GO categories and 26 pathways overlapping between PBMC and WB. Additionally, class prediction using machine learning tools demonstrated that the subset of significant genes shared by PBMC and WB are sufficient to train as a predictor separating the SOFA groups.GEP analysis of WB has the potential to become a clinical tool for immune-monitoring in patients with MOD.

  8. Diffusion tensor imaging can be used to detect lesions in peripheral nerves in patients with chronic inflammatory demyelinating polyneuropathy treated with subcutaneous immunoglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Markvardsen, Lars H.; Andersen, Henning [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Vaeggemose, Michael [Aarhus University Hospital, Department of Neurology, Aarhus C (Denmark); Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark); Ringgaard, Steffen [Aarhus University Hospital, Department of Diagnostic Imaging: MR Research Centre, Aarhus (Denmark)

    2016-08-15

    Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) has shown that fractional anisotropy (FA) is lower in peripheral nerves in chronic inflammatory demyelinating polyneuropathy (CIDP). We examined whether DTI correlates to muscle strength or impairment. MRI of sciatic and tibial nerves was performed on 3-T MR scanner by obtaining T2- and DTI-weighted sequences with fat saturation. On each slice of T2-weighted (T2w) and DTI, the tibial and sciatic nerves were segmented and served for calculation of signal intensity. On DTI images, pixel-by-pixel calculation of FA and apparent diffusion coefficient (ADC) was done. Muscle strength at knee and ankle was determined by isokinetic dynamometry and severity of CIDP by neuropathy impairment score (NIS). Fourteen CIDP patients treated with subcutaneous immunoglobulin were compared to gender- and age-matched controls. T2w values expressed as a nerve/muscle ratio (nT2w) were unchanged in CIDP versus controls 0.93 ± 0.21 versus 1.02 ± 0.21 (P = 0.10). FA values were lower in CIDP compared to controls 0.38 ± 0.07 versus 0.45 ± 0.05 (P < 0.0001), and ADC values were higher in CIDP versus controls 1735 ± 232 versus 1593 ± 116 x 10{sup -6} mm{sup 2}/s (P = 0.005). In CIDP, FA values correlated to clinical impairment (NIS) (r = -0.57, P = 0.03), but not to muscle strength. FA value in the sciatic nerve distinguishes CIDP from controls with a sensitivity and a specificity of 92.9 %. CIDP patients have unchanged nT2w values, lower FA values, and higher ADC values of sciatic and tibial nerves compared to controls. FA values correlated to NIS but were unrelated to muscle strength. DTI of sciatic nerves seems promising to differentiate CIDP from controls. (orig.)

  9. Intensive combined modality therapy of small round cell and undifferentiated sarcomas in children and young adults

    International Nuclear Information System (INIS)

    Bader, J.L.; Dewan, R.; Watkins, E.; Kinsella, T.J.; Glatstein, E.; STeinberg, S.M.

    1989-01-01

    Seventy-five patients (ages 4-35 years) with the following small round cell tumors and undifferentiated sarcoma were treated at the National Cancer Institute: Ewing's sarcome (n=32), peripheral neuroepithelioma (n=14), rhabdomyosarcoma (n=24), undifferentiated sarcoma (n=5). Most patients had poor prognostic features including 36 (48%) with metastatic disease, and 42 (56%) with central (truncal) tumors (22 in the pelvis). Treatment included 5 cycles of intensive induction chemotherapy with vincristine, cyclophosphamide and adriamycin, plus aggressive local radiation therapy using simulation and computerized treatment planning for all patients. Thereafter, complete clinical responses were consolidated with intensive chemotherapy, total body irradiation and autologous bone marrow transplantation. There were three local only failures, 10 local plus distant failures, 36 distant only failures, 3 treatment-related deaths, and one intercurrent death. Overall actuarial survival and event-free survival at 4 years are 49 and 29%, respectively. Actuarial freedom from local progression was seen in 74% of patients at 4 years, quite remarkable considering the bulk and location of most of these tumors. Without aggressive surgery, many of these high risk patients had satisfactory outcomes, but better systemic treatments are still needed.(author). 44 refs.; 8 figs.; 6 tabs

  10. PDGFRa amplification in multiple skin lesions of undifferentiated pleomorphic sarcoma: A clue for intimal sarcoma metastases.

    Science.gov (United States)

    Osio, Amélie; Vignon-Pennamen, Marie-Dominique; Pedeutour, Florence; Le Maignan, Christine; Koskas, Fabien; Lebbé, Célèste; Janin, Anne; Battistella, Maxime

    2017-05-01

    A 62-year-old human immunodeficiency virus-positive man was admitted for multiple cutaneous and subcutaneous nodules on his lower limbs, corresponding to an undifferentiated proliferation of spindle and pleomorphic cells, with irregular nuclei and numerous mitoses. The tumor cells were negative for a large panel of immunohistochemical markers, except CD10. MDM2 immunohistochemical staining was also negative, leading to the diagnosis of Fédération Nationale des Centres de Lutte contre le Cancer grade III undifferentiated pleomorphic sarcoma (UPS). Array-comparative genomic hybridization showed a highly complex karyotype, with amplification of the 4q12 region, an area that contains only the platelet-derived growth factor receptor α (PDGFRa) gene. This amplification of PDFGRa, molecular hallmark of intimal sarcoma (IS), led to the diagnosis of skin IS metastasis. A positron emission tomography showed a hypermetabolic mass protruding in the preaortic area, consistent with the diagnosis of aortic IS. Our study shows that a rare differential diagnosis in peripheral UPS can be IS skin metastasis, and underlines the importance of molecular analyses in UPS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Noun-Verb Ambiguity in Chronic Undifferentiated Schizophrenia

    Science.gov (United States)

    Goldfarb, Robert; Bekker, Natalie

    2009-01-01

    This study investigated noun-verb retrieval patterns of 30 adults with chronic undifferentiated schizophrenia and 67 typical adults, to determine if schizophrenia affected nouns (associated with temporal lobe function) differently from verbs (associated with frontal lobe function). Stimuli were homophonic homographic homonyms, balanced according…

  12. Management of undifferentiated embryonal sarcoma of the liver in ...

    African Journals Online (AJOL)

    Background. Undifferentiated embryonal sarcoma of the liver (UESL) is a rare neoplasm, and the third-most common paediatric hepatic malignancy. However, no treatment guidelines exist. No randomised, controlled trials support specific combinations of therapy. Objective. To compare presentation and management of ...

  13. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society

    NARCIS (Netherlands)

    Hughes, R. A. C.; Bouche, P.; Cornblath, D. R.; Evers, E.; Hadden, R. D. M.; Hahn, A.; Illa, I.; Koski, C. L.; Léger, J. M.; Nobile-Orazio, E.; Pollard, J.; Sommer, C.; van den Bergh, P.; van Doorn, P. A.; van Schaik, I. N.

    2006-01-01

    Numerous sets of diagnostic criteria have sought to define chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and randomized trials and systematic reviews of treatment have been published. The objective is to prepare consensus guidelines on the definition, investigation and treatment

  14. 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.

  15. Undifferentiated pleomorphic sarcoma of the neck – A case report

    Directory of Open Access Journals (Sweden)

    Jane Peiwen Lim

    Full Text Available Undifferentiated pleomorphic sarcoma very rarely affect the neck. We report a case of a 62 year old man who presented with a right sided skin lump which he noticed after sustaining a neck contusion in a road traffic accident about one year ago. The initial CT and ultrasound scans of the lump were suggestive of a thrombosed varix. Clinical examination showed a hard skin nodule with signs of tethering. He underwent a wide excision of the skin nodule and the histology showed undifferentiated pleomorphic sarcoma with margins involved. He subsequently underwent another re-excision of margins and pectoralis major flap reconstruction. Following surgery, he was also prescribed adjuvant radiotherapy and he remains well about 12 months after follow up. The surgical management of undifferentiated pleomorphic sarcoma in the neck is challenging due to the proximity of critical neck structures and the need to obtain clear margins. Thus, adjuvant radiotherapy is often used to improve disease control. Keywords: Case report, Sarcoma, Margins, Surgery, Adjuvant radiotherapy

  16. Promoter DNA hypermethylation and gene repression in undifferentiated Arabidopsis cells.

    Directory of Open Access Journals (Sweden)

    María Berdasco

    Full Text Available Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this undifferentiated state. Here we report the use of genetic and pharmacological experimental approaches to show that Arabidopsis cell suspensions and calluses specifically repress some genes as a result of promoter DNA hypermethylation. We found that promoters of the MAPK12, GSTU10 and BXL1 genes become hypermethylated in callus cells and that hypermethylation also affects the TTG1, GSTF5, SUVH8, fimbrin and CCD7 genes in cell suspensions. Promoter hypermethylation in undifferentiated cells was associated with histone hypoacetylation and primarily occurred at CpG sites. Accordingly, we found that the process specifically depends on MET1 and DRM2 methyltransferases, as demonstrated with DNA methyltransferase mutants. Our results suggest that promoter DNA methylation may be another important epigenetic mechanism for the establishment and/or maintenance of the undifferentiated state in plant cells.

  17. Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

    Science.gov (United States)

    Meng, Huicui; Ba, Zhaoyong; Lee, Yujin; Peng, Jiayu; Lin, Junli; Fleming, Jennifer A; Furumoto, Emily J; Roberts, Robert F; Kris-Etherton, Penny M; Rogers, Connie J

    2017-03-01

    Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14 + HLA-DR + cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14 + HLA-DR + cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

  18. [Peripheral ulcerative keratitis].

    Science.gov (United States)

    Stamate, Alina-cristina; Avram, Corina Ioana; Malciolu, R; Oprea, S; Zemba, M

    2014-01-01

    Ulcerative keratitis is frequently associated with collagen vascular diseases and presents a predilection for peripheral corneal localization, due to the distinct morphologic and immunologic features of the limbal conjunctiva, which provides access for the circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates an immune-mediated vasculitis process, with inflammatory cells and mediators involvement by alteration of the vascular permeability. Peripheral ulcerative keratitis generally correlates with exacerbations of the background autoimmune systemic disease. Associated sceritis, specially the necrotizing form, is usually observed in severe cases, which may evolve in corneal perforation and loss of vision. Although the first-line of treatment in acute phases is represented by systemic administration of corticosteroids, immunosuppressive and cytotoxic agents are necessary for the treatment of peripheral ulcerative keratitis associated with systemic diseases.

  19. Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated Carcinoma.

    Science.gov (United States)

    Kuo, Phoebe; Manes, R Peter; Schwam, Zachary G; Judson, Benjamin L

    2017-01-01

    Objective Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies examining outcomes of combined modality treatment versus other treatment modalities have not been performed. The objective of our study was to present outcomes for multimodality therapy through use of the National Cancer Database. Study Design Retrospective cohort study. Setting National Cancer Database. Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were identified. Kaplan-Meier analyses were performed to find 5-year cumulative survival rates. Multivariate Cox regression evaluated overall survival based on treatment when adjusting for other prognostic factors (age, primary site, sex, race, comorbidity, insurance, and TNM stage). Within the surgery + chemoradiotherapy group, survival analysis was also performed to compare outcomes for induction and adjuvant chemotherapy. Results The cumulative 5-year survival rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In multivariate analysis, surgery + chemoradiotherapy was associated with significantly improved overall survival versus surgery + radiotherapy and radiotherapy but not significantly different from chemoradiotherapy. Within the surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did not have associated differences in survival. Conclusion Combined modality therapy (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved survival outcomes versus other treatment modalities in patients with sinonasal undifferentiated carcinoma.

  20. Primary renal undifferentiated sarcoma as an infiltrative mass in a 12 year old boy

    International Nuclear Information System (INIS)

    Kim, Yong Hee; Kim, Myung Joon; Lee, Mi Jung; Kim, Se Hwa

    2015-01-01

    Undifferentiated sarcomas are rare tumors not classified into any sarcoma subtype. Due to their rarity, imaging findings of undifferentiated sarcomas are poorly characterized. The purpose of this report was to present imaging findings of a pathologically confirmed undifferentiated sarcoma originated from the left kidney of a 12-year-old boy. The mass was infiltrative involving the renal pelvis. It mimicked massive hilar lymphadenopathy with a preserved renal contour visible by both ultrasonography and CT. Renal vein thrombosis was also observed. Although undifferentiated sarcomas are rare, they should be considered in differential diagnosis of infiltrative renal masses with renal pelvis invasion in children

  1. The expression profile of miR-23b is not altered in peripheral blood mononuclear cells of patients with idiopathic inflammatory myopathies [v1; ref status: indexed, http://f1000r.es/20z

    Directory of Open Access Journals (Sweden)

    Martina Remakova

    2013-10-01

    Full Text Available Idiopathic inflammatory myopathies (IIM belong to a group of autoimmune disorders, primarily characterized by chronic inflammation of human skeletal muscle tissue. The etiology of these diseases is unknown, however, genetic predisposition plays a significant role in disease onset. Beside the known genetic risk located in the MHC complex, the epigenetic modifications including changes in miRNAs expression profiles have been recently implicated recently in many autoimmune diseases. Micro RNA molecules are involved in many physiological processes, including the regulation of the immune response. In our study we have focused on the miR-23b, as it represents a novel promising autoimmunity regulator molecule. Downregulation of miR-23b was recently described in patients with rheumatoid arthritis and systemic lupus erythematosus. We have measured the expression miR-23b peripheral blood mononuclear cells of patients with dermatomyositis and polymyositis. No meaningful difference was found in comparison with healthy controls.

  2. Uncoupling of peripheral and master clock gene rhythms by reversed feeding leads to an exacerbated inflammatory response after polymicrobial sepsis in mice

    OpenAIRE

    小山, 淑正

    2014-01-01

    Reversed feeding uncouples peripheral and master clock gene rhythms and leads to an increased risk of disease development. The aim of this study was to determine the effects of clock gene uncoupling on sepsis-induced inflammation using a mouse cecal ligation and puncture (CLP) model. C57BL/6N mice were entrained to a 12-h light-dark cycle (lights on at 0700). Mice were permitted ad libitum feeding either during the night (1900-0700) or the non-physiological light phase (0700-1900) for a week ...

  3. Polysaccharide rich fractions from barks of Ximenia americana inhibit peripheral inflammatory nociception in mice Antinociceptive effect of Ximenia americana polysaccharide rich fractions

    OpenAIRE

    Silva-Leite, Kaira E.S. da; Assreuy, Ana M.S.; Mendonça, Laryssa F.; Damasceno, Luis E.A.; Queiroz, Maria G.R. de; Mourão, Paulo A.S.; Pires, Alana F.; Pereira, Maria G.

    2017-01-01

    Abstract Ximenia americana L., Olacaceae, barks are utilized in folk medicine as analgesic and anti-inflammatory. The objective was to evaluate the toxicity and antinociceptive effect of polysaccharides rich fractions from X. americana barks. The fractions were obtained by extraction with NaOH, followed by precipitation with ethanol and fractionation by ion exchange chromatography. They were administered i.v. or p.o. before nociception tests (writhing, formalin, carragenan-induced hypernocice...

  4. Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype?

    OpenAIRE

    Jyonouchi, Harumi; Geng, Lee; Davidow, Amy L

    2014-01-01

    Background Some children with autism spectrum disorders (ASD) are characterized by fluctuating behavioral symptoms following immune insults, persistent gastrointestinal (GI) symptoms, and a lack of response to the first-line intervention measures. These children have been categorized as the ASD-inflammatory subtype (ASD-IS) for this study. We reported a high prevalence of non-IgE mediated food allergy (NFA) in young ASD children before, but not all ASD/NFA children reveal such clinical featur...

  5. Grape Consumption Increases Anti-Inflammatory Markers and Upregulates Peripheral Nitric Oxide Synthase in the Absence of Dyslipidemias in Men with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Jiyoung Lee

    2012-12-01

    Full Text Available We evaluated the effects of grape consumption on inflammation and oxidation in the presence or absence of dyslipidemias in metabolic syndrome (MetS. Men with MetS (n = 24, 11 with high triglycerides and low HDL and 13 with no dyslipidemia were recruited and randomly allocated to consume daily either 46 g of lyophilized grape powder (GRAPE, equivalent to 252 g fresh grapes, or placebo with an identical macronutrient composition and caloric value as GRAPE for four weeks. After a three-week washout, participants followed the alternate treatment. We measured changes between placebo and GRAPE periods in inflammatory and oxidative stress markers both in circulation and in gene expression. Changes in plasma adiponectin (p < 0.05, interleukin (IL-10 (p < 0.005 and in mRNA expression of the inducible isoform of nitric oxide synthase (iNOS (p < 0.25 were increased in the GRAPE compared to the placebo period only in those individuals without dyslipidemia. Additionally, plasma IL-10 was negatively correlated with NOX2 expression, a marker of oxidative stress (r = −0.55, p < 0.01, while iNOS expression was positively correlated with the expression of superoxide dismutase 2 (r = 0.642, p < 0.01, a key anti-oxidative enzyme. Grape consumption displayed anti-oxidative and increased anti-inflammatory markers in the absence of the inflammatory milieu associated with dyslipidemias.

  6. On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death.

    Science.gov (United States)

    Kell, Douglas B; Pretorius, Etheresia

    2015-11-01

    We have recently highlighted (and added to) the considerable evidence that blood can contain dormant bacteria. By definition, such bacteria may be resuscitated (and thus proliferate). This may occur under conditions that lead to or exacerbate chronic, inflammatory diseases that are normally considered to lack a microbial component. Bacterial cell wall components, such as the endotoxin lipopolysaccharide (LPS) of Gram-negative strains, are well known as potent inflammatory agents, but should normally be cleared. Thus, their continuing production and replenishment from dormant bacterial reservoirs provides an easy explanation for the continuing, low-grade inflammation (and inflammatory cytokine production) that is characteristic of many such diseases. Although experimental conditions and determinants have varied considerably between investigators, we summarise the evidence that in a great many circumstances LPS can play a central role in all of these processes, including in particular cell death processes that permit translocation between the gut, blood and other tissues. Such localised cell death processes might also contribute strongly to the specific diseases of interest. The bacterial requirement for free iron explains the strong co-existence in these diseases of iron dysregulation, LPS production, and inflammation. Overall this analysis provides an integrative picture, with significant predictive power, that is able to link these processes via the centrality of a dormant blood microbiome that can resuscitate and shed cell wall components.

  7. Clinical and Endoscopic Features of Undifferentiated Gastric Cancer in Patients with Severe Atrophic Gastritis.

    Science.gov (United States)

    Kishino, Maiko; Nakamura, Shinichi; Shiratori, Keiko

    2016-01-01

    Differentiated gastric cancer generally develops in the atrophic gastric mucosa, although undifferentiated cancer is sometimes encountered in patients with severe atrophic gastritis. We characterized the endoscopic features of undifferentiated gastric cancer in patients with severe atrophic gastritis. Stage IA early gastric cancer was diagnosed in 501 patients who were admitted to our hospital between April 2003 and March 2012. The endoscopic and pathological findings were compared among 29 patients with undifferentiated cancer and severe atrophic gastritis, 104 patients with undifferentiated cancer and mild/moderate atrophic gastritis and 223 patients with well-differentiated cancer and severe atrophic gastritis. Endoscopic atrophic gastritis was classified according to the Kimura-Takemoto classification as no gastritis, C-1 and C-2 (mild), C-3 and O-1 (moderate) or O-2 and O-3 (severe). The tumors were larger and showed deeper mural invasion in the patients with undifferentiated cancer and severe atrophic gastritis than in those with well-differentiated cancer and severe gastritis or undifferentiated cancer and mild/moderate gastritis. On endoscopy, undifferentiated cancer associated with severe gastritis was often red in color. It is often difficult to diagnose early undifferentiated gastric cancer, especially in patients with severe atrophic gastritis. The present study characterized the important endoscopic features of such tumors.

  8. Bem Sex Role Inventory Undifferentiated Score: A Comparison of Sexual Dysfunction Patients with Sexual Offenders.

    Science.gov (United States)

    Dwyer, Margretta; And Others

    1988-01-01

    Examined Bem Sex Role undifferentiated scores on 93 male sex offenders as compared with 50 male sexually dysfunctional patients. Chi-square analyses revealed significant difference: offenders obtained undifferentiated scores more often than did sexual dysfunctional population. Concluded that Bem Sex Role Inventory is useful in identifying sexual…

  9. Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis. A prospective, randomized 9-month comparison.

    Science.gov (United States)

    Carter, John D; Valeriano, Joanne; Vasey, Frank B

    2004-10-01

    Chlamydia is a known trigger of reactive arthritis (ReA). It may also be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent, metabolically active, Chlamydiae have been observed in the synovial tissue of these patients years after their initial exposure. Trials with lymecycline and rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro data suggest that persistent Chlamydia become resistant to chronic monotherapy of tetracyclines or rifampin, whereas no such resistance is noted when rifampin is added to antimicrobials that are active against Chlamydia. Rifampin and doxycycline also show synergistic effect against Chlamydia. In addition, rifampin inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key role in the chronic persistent state of Chlamydia. We conducted a prospective, randomized 9-month trial to evaluate the efficacy of doxycycline versus a combination of doxycycline and rifampin in the treatment of uSpA. The study enrolled 30 patients with chronic inflammatory arthritis (average disease duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group criteria, with no evidence of inflammatory bowel disease, psoriasis, ankylosing spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po twice daily or a combination of doxycycline 100 mg po twice daily and rifampin 600 mg po daily. They received a 4-question self-questionnaire and a blinded joint examination at each visit. The questions include a visual analog scale (VAS) for their current amount of back pain, duration of morning stiffness, back pain at night, and peripheral joint pain. The blinded joint examination consisted of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined as those who improved > or = 20% in at least 4 of the 6 variables at 9 months of therapy. Comparing the doxycycline + rifampin

  10. Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development.

    Science.gov (United States)

    Keskin, Ilknur; Kaplan, Suleyman; Kalkan, Serpil; Sutcu, Mustafa; Ulkay, M Basak; Esener, O Burak

    2015-04-01

    The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS+MLT10), DS with high-dose melatonin administered (DS+MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (pmelatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (pmelatonin prophylaxis can prevent these effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. BCNT studies for application to the undifferentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Dagrosa, Maria A.; Viaggi, Mabel E.; Cabrini, Romulo L.; Juvenal, Guillermo J.; Pisarev, Mario A.; Garavaglia, Ricardo N.; Farias, Silvia S.; Belli, Carolina; Larripa, Irene; Gangitano, David

    2000-01-01

    Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10 B-boronated compounds by some tumours, followed by irradiation with an appropriate neutron beam. The radioactive boron originated ( 11 B) decays releasing 7 Li, gamma rays and alpha particles, and these latter will destroy the tumour. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. Animal Model: To develop an animal model of undifferentiated thyroid carcinoma (UTC), which may be useful to study of BNCT. The UTC human cell line ARO was implanted into the back of the nude mice. We performed successive passages in mouse after tumor culturing in order to obtain an animal model similar to the human tumor. We studied the kinetics and the tumoral histology, the capability to induce metastasis, the biokinetics of in vitro growth, as well as cytogenetic and molecular aspects. Histological specimens of tumor showed extensive viability with high mitotic activity. At 117 days, the tumors reached a size of 1700 mm 3 and showed a central necrotic portion with a thin layer of viable cells presence of micro metastasis could be observed in the lung. The kinetics of growth both in vivo and in vitro showed that when the number of passages in mouse increases the growth rate decreases. The cytogenetic and molecular studies did not show differences between the original line and the sublines that could explain this phenotypic change. Moreover, the cytogenetic studies proved that the ARO cell line and its sublines showed a complex clonal karyotype including structural alterations with deletions and translocations involving chromosomes 5, 7, 8, 9p, 11p, 17q 19p, and 20q that were consistent with earlier reported data in UTC. In vivo BNCT studies: ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg bw) was injected via i.p. The

  12. Analgesic properties of a peripherally acting and GalR2 receptor-preferring galanin analog in inflammatory, neuropathic, and acute pain models.

    Science.gov (United States)

    Metcalf, Cameron S; Klein, Brian D; McDougle, Daniel R; Zhang, Liuyin; Smith, Misty D; Bulaj, Grzegorz; White, H Steve

    2015-01-01

    There are ongoing efforts to develop pain therapeutics with novel mechanisms of action that avoid common side effects associated with other analgesics. The anticonvulsant neuropeptide galanin is a potent regulator of neuronal excitability and has a well established role in pain modulation, making it a potential target for novel therapies. Our previous efforts focused on improving blood-brain-barrier penetration and enhancing the metabolic stability of galanin analogs to protect against seizures. More recently, we designed peripherally acting galanin analogs that reduce pain-related behaviors by acting in the periphery and exhibit preferential binding toward galanin receptor (GalR)2 over GalR1. In this study, we report preclinical studies of a monodisperse oligoethylene glycol-containing galanin analog, NAX 409-9 (previously reported as GalR2-dPEG24), in rodent analgesic and safety models. Results obtained with NAX 409-9 in these tests were compared with the representative analgesics gabapentin, ibuprofen, acetylsalicylic acid, acetaminophen, and morphine. In mice that received intraplantar carrageenan, NAX 409-9 increased paw withdrawal latency with an ED50 of 6.6 mg/kg i.p. NAX 409-9 also increased the paw withdrawal threshold to mechanical stimulation following partial sciatic nerve ligation in rats (2 mg/kg). Conversely, NAX 409-9 had no effect in the tail flick or hot plate assays (up to 24 mg/kg). Importantly, NAX 409-9 did not negatively affect gastrointestinal motility (4-20 mg/kg), respiratory rate (40-80 mg/kg), or bleed time (20 mg/kg). These studies illustrate that this nonbrain-penetrating galanin analog reduces pain behaviors in several models and does not produce some of the dose-limiting toxicities associated with other analgesics. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  13. Optimization of the application of BNCT to undifferentiated thyroid cancer

    International Nuclear Information System (INIS)

    Dagrosa, M.A.; Thomasz, L.; Longhino, J.

    2006-01-01

    The possible increase in BNCT efficacy for undifferentiated thyroid carcinoma (UTC) using BPA plus BOPP and nicotinamide (NA) as a radiosensitizer on the BNCT reaction was analyzed. In these studies nude mice were transplanted with the ARO cells and after 14 days they were treated as follows: 1) Control; 2) NCT (neutrons alone); 3) NCT plus NA (100 mg/kg bw/day for 3 days); 4) BPA (350 mg/kg bw) + neutrons; 5) BPA+ NA+ neutrons; 6) BPA+BOPP (60 mg/kg bw) + neutrons. The flux of hyperthermal neutrons was 2.8 10 8 during 85 min. Neutrons alone or with NA caused some tumor growth delay, while in the BPA, BPA+NA and BPA+BOPP groups a 100% halt of tumor growth was observed. When the initial tumor volume was 50 mm 3 or less a complete cure was found in BPA+NA (2/2); BPA (1/4); BPA+BOPP (7/7). After 90 days of complete regression, recurrence of tumor was observed in 2/2 BPA/NA (2/2) and BPA+BOPP (1/7). Caspase 3 activity was increased in BPA+NA (p<0.05 vs controls). BPA plus NA increased tumor apoptosis but only the combination of BPA+BOPP increased significantly BNCT efficiency. (author)

  14. Targeted therapeutics in inflammatory atherosclerosis

    NARCIS (Netherlands)

    Alaarg, Amr Muhmed Sabry Abdelhakeem

    2017-01-01

    Atherosclerosis, a chronic inflammatory vascular disease, which has been recently identified in 5000-year mummies, remains undefeated. It is the most common underlying cause of deadly cardiovascular diseases (CVD), including heart attacks, strokes, and peripheral vascular diseases. This tremendous

  15. Paeoniflorin down-regulates ATP-induced inflammatory cytokine production and P2X7R expression on peripheral blood mononuclear cells from patients with primary Sjögren's syndrome.

    Science.gov (United States)

    Yu, Jingya; Chen, Yong; Li, Mingcai; Gao, Qiaoyan; Peng, Yong; Gong, Qiongyao; Zhang, Zhen; Wu, Xiudi

    2015-09-01

    This study determined the effects of paeoniflorin (PF) on the expression of purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) expressed on peripheral blood mononuclear cells (PBMCs) and production of ATP-induced pro-inflammatory cytokines released by PBMCs in patients with primary Sjögren's syndrome (pSS). The pharmacological functions and cytotoxic effects of PF were dose dependent in PBMCs from 20 newly diagnosed pSS patients and 20 normal individuals. The optimum dose of PF was 100μM. PF significantly down-regulated the production of interleukin (IL)-1β and IL-6 from pSS PBMCs, and significantly inhibited ATP-induced expression of P2X7R, that might contribute to reduced IL-1β and IL-6. mRNA and protein levels of P2X7R on pSS PBMCs were significantly higher than in normal individuals (p=0.03, pP2X7R mRNA and protein levels were decreased significantly (pP2X7R on pSS PBMCs, indicating that PF might be useful for the management of pSS via down-regulating P2X7R expression. Thus, PF may provide a new therapeutic approach to regulate P2X7R-mediated pathologic responses of pSS. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Progression rate of ankylosing spondylitis in patients with undifferentiated spondyloarthritis

    Science.gov (United States)

    Xia, Qing; Fan, Dazhi; Yang, Xiao; Li, Xiaona; Zhang, Xu; Wang, Mengmeng; Xu, Shengqian; Pan, Faming

    2017-01-01

    Abstract Background: The idea that undifferentiated spondyloarthritis (uSpA) represents the early undifferentiated stage of ankylosing spondylitis (AS) and other well-defined SpA subtypes is well known. The gist of this study is to assess the rate estimate of patients with uSpA evolved to AS during long-term follow-up. Methods: A systematic search was implemented to identify pertinent articles. The primary outcome was the rate estimate that patients with uSpA fulfilling the diagnosis of AS according to the modified New York criteria during follow-up. The rate estimate and corresponding 95% confidence interval (95%CI) were pooled by the random-effects model in STATA 11.0 software. Meta-regression analyses were adopted to explore the sources of heterogeneity. The quality assessment was conducted by the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and the Begg test and the Egger test were applied to assess publication bias. Results: Sixteen papers were finally included in this study after screening 1299 citations. The pooled rate of patients with uSpA progression to AS synthesized from the 16 papers was 0.323 (95%CI 0.257–0.389). Subgroup analysis based on the length of follow-up showed that the rate at the time-point of 5, 8, and 10 years follow-up was 0.220 (95%CI 0.110–0.330), 0.291 (95%CI 0.257–0.325), and 0.399 (95%CI 0.190–0.608), respectively; while the rate in Asia, Europe, and Latin America was 0.367 (95%CI 0.282–0.452), 0.228 (95%CI 0.066–0.390), and 0.269 (95%CI 0.209–0.329), respectively. Meta-regression analysis indicated that the length of follow-up alone accounts for 45.23% of the total heterogeneity. Nearly half of the papers scored fair quality and none publication bias was identified based on the Begg test and the Egger test. Further, line chart describes an obviously increased trend for the patients with uSpA fulfilling the diagnosis of AS over time. Conclusion: The

  17. Peripheral Neuropathy

    Science.gov (United States)

    ... arsenic can cause peripheral neuropathy. In addition, certain insecticides and solvents have also been known to cause ... ranges from clinical studies of the genetics and natural history of hereditary neuropathies to basic science investigations ...

  18. Spindle and Giant Cell Type Undifferentiated Carcinoma of the Proximal Bile Duct

    OpenAIRE

    Ide, Takao; Miyoshi, Atsushi; Kitahara, Kenji; Kai, Keita; Noshiro, Hirokazu

    2012-01-01

    Undifferentiated spindle and giant cell carcinoma is an extremely rare malignant neoplasm arising in the extrahepatic bile duct. We herein present the case of a 67-year-old male who developed an undifferentiated spindle and giant cell carcinoma of the proximal bile duct. A nodular infiltrating tumor was located at the proximal bile duct, resulting in obstructive jaundice. Histologically, the tumor was composed of mainly spindle-shaped and giant cells and showed positive immunoreactivity for b...

  19. Effectiveness of physical exam signs for early detection of critical illness in pediatric systemic inflammatory response syndrome.

    Science.gov (United States)

    Scott, Halden F; Donoghue, Aaron J; Gaieski, David F; Marchese, Ronald F; Mistry, Rakesh D

    2014-11-19

    Early detection of compensated pediatric septic shock requires diagnostic tests that are sensitive and specific. Four physical exam signs are recommended for detecting pediatric septic shock prior to hypotension (cold extremities, mental status, capillary refill, peripheral pulse quality); this study tested their ability to detect patients who develop organ dysfunction among a cohort of undifferentiated pediatric systemic inflammatory response syndrome patients. A prospective cohort of 239 pediatric emergency department patients physical exams on a standardized form. Abstraction of the medical record determined outcomes including organ dysfunction, intensive care unit stay, serious bacterial infection, and therapies. Organ dysfunction occurred in 13/239 (5.4%) patients. Presence of at least one sign was significantly associated with organ dysfunction (Relative Risk: 2.71, 95% CI: 1.05-6.99), and presence of at least two signs had a Relative Risk = 4.98 (95% CI: 1.82-13.58). The sensitivity of exam findings ranged from 8-54%, specificity from 84-98%. Signs were associated with increased risk of intensive care and fluid bolus, but not with serious bacterial infection, intravenous antibiotics or admission. Altered mental status and peripheral pulse quality were significantly associated with organ dysfunction, while abnormal capillary refill time and presence of cold, mottled extremities were not. Certain recommended physical exam signs were associated with increased risk of organ dysfunction, a rare outcome in this undifferentiated pediatric population with fever and tachycardia. Sensitivity was low, while specificity was high. Additional research into optimally sensitive and specific diagnostic strategies is needed.

  20. Enhanced expression of extracellular calcium sensing receptor in monocyte-differentiated versus undifferentiated HL-60 cells: potential role in regulation of a nonselective cation channel.

    Science.gov (United States)

    Yamaguchi, T; Ye, C; Chattopadhyay, N; Sanders, J L; Vassilev, P M; Brown, E M

    2000-05-01

    Human promyelocytic leukemia cells (HL-60) have been used widely as a model for studying the differentiation of hematopoietic progenitor cells in vitro. After treatment with phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], HL-60 cells differentiate into cells with the phenotype of monocytes/macrophages. We previously showed that peripheral blood monocytes and the murine J774 monocytic cell line express the CaR, and myeloid progenitors in the bone marrow and myeloid cells in peripheral blood other than monocytes express lower levels of the CaR. Therefore, we investigated whether undifferentiated HL-60 cells express a functional G protein-coupled, extracellular calcium (Ca(2+)(o))-sensing receptor (CaR) and if the expression of the CaR increases as these cells differentiate along the monocytic lineage. The use of reverse transcription-polymerase chain reaction (RT-PCR) with CaR-specific primers, followed by sequencing of the amplified products, identified an authentic CaR transcript in undifferentiated HL-60 cells. Both immunocytochemistry and Western blot analysis using a CaR-specific antiserum detected low levels of CaR protein expression in undifferentiated HL-60 cells. The levels of CaR protein increased considerably following treatment of the cells with PMA (50 nM) or 1,25(OH)(2)D(3) (100 nM) for 5 days. Northern analysis using a CaR-specific riboprobe identified CaR transcripts in undifferentiated HL-60 cells, but CaR mRNA levels did not change appreciably after treatment with either agent, suggesting that upregulation of CaR protein occurs at a translational level. PMA-treated HL-60 cells expressed a nonselective cation channel (NCC), and the calcimimetic CaR activator, NPS R-467, but not its less active stereoisomer, NPS S-467, as well as the polycationic CaR agonist, neomycin, activated this NCC, demonstrating that the CaR expressed in these cells is functionally active. Therefore, HL-60 cells exhibit an increase in Ca

  1. A comparative study of renal dysfunction in patients with inflammatory arthropathies: strong association with cardiovascular diseases and not with anti-rheumatic therapies, inflammatory markers or duration of arthritis.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2012-02-01

    AIMS: The aim of this study was to investigate the prevalence of chronic kidney disease (CKD) among comparable patients with rheumatoid arthritis (RA) and seronegative inflammatory arthritis, and to explore any predictive factors for renal impairment. METHODS: Consecutive patients with peripheral joint disease (oligo and polyarthritis) were recruited from our inflammatory arthritis clinics. We divided patients in two groups: RA group and seronegative inflammatory arthritis group. The cohort consisted of 183 patients (RA = 107, seronegative arthritis = 76 [psoriatic arthritis = 69, undifferentiated oligoarthritis = 7]). Estimated glomerular filtration rate (eGFR) was calculated using the established Modification of Diet in Renal Disease equation. Demographic details, disease-specific characteristics, anti-rheumatic drugs and the presence of cardiovascular diseases were recorded. RESULTS: In total, 17.48% (n = 32) of the cohort had CKD. There was no statistically significant variation between the two groups as regards baseline demographics, disease characteristics, use of anti-rheumatic drugs and the presence of individual cardiovascular diseases. We found that eGFR and the presence of CKD were similar among these groups. Among patients with CKD, 72% had undiagnosed CKD. No association of statistical significance was noted between CKD and the use of corticosteroids, disease-modifying antirheumatic drugs and anti-tumor necrosis factor agents. The association of cardiovascular diseases with CKD remained significant after adjusting for confounders (age, gender, duration of arthritis, high C-reactive protein, use of anti-rheumatic drugs). CONCLUSIONS: Patients with inflammatory arthritis are more prone to have CKD. This could have serious implications, as the majority of rheumatology patients use non-steroidal anti-inflammatory drugs and different immunosuppressives, such as methotrexate. No association of kidney dysfunction was noted with inflammatory disease

  2. The effects of selected drugs, including chlorpromazine and non-steroidal anti-inflammatory agents, on polyclonal IgG synthesis and interleukin 1 production by human peripheral blood mononuclear cells in vitro.

    Science.gov (United States)

    Martinez, F; Coleman, J W

    1989-01-01

    We tested a range of drugs for their effects on in vitro polyclonal IgG synthesis by human peripheral blood mononuclear cells (PBMC) stimulated with the lectin pokeweed mitogen (PWM). The test drugs were selected on the basis of reported disruptive effects on immune function in vivo. IgG production between day 4 and days 7 or 8 of culture was measured by biotin-streptavidin sandwich ELISA. The anti-psychotic agent chlorpromazine (0.55-1.7 microM) enhanced IgG synthesis to approximately double control levels. In contrast, the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin, piroxicam, ibuprofen and aspirin inhibited IgG synthesis by up to 50%, with a rank order of potency that reflects their activity as inhibitors of cyclo-oxygenase. Phenytoin, procainamide, propylthiouracil, methimazole, D-penicillamine and D-penicillamine-L-cysteine all failed to modulate IgG synthesis at non-toxic concentrations. The potentiation and inhibition of IgG synthesis by chlorpromazine and indomethacin, respectively, was observed only when the drug was present during the first 24 h of culture. Neither chlorpromazine nor indomethacin, at non-toxic concentrations, affected PHA- and PWM-stimulated proliferation of PBMC. In addition, chlorpromazine, indomethacin and piroxicam, at concentrations which produced maximal modulation of IgG synthesis, and D-penicillamine and D-penicillamine-L-cysteine at 10 microM failed to influence production of interleukin-1-like activity. We conclude that chlorpromazine and NSAIDs, although they exert opposite effects on IgG synthesis, act at an early stage of B cell differentiation that appears to be independent of interleukin 1 synthesis and early proliferative events. PMID:2788047

  3. [Paraneoplastic dermatomyositis revealing an undifferentiated nasopharyngeal carcinoma: about a case].

    Science.gov (United States)

    Ziani, Fatima Zahra; Brahmi, Sami Aziz; Najib, Rajae; Kanab, Rajae; Arifi, Samia; Mernissi, Fatima Zahra; Mellas, Nawfal

    2016-01-01

    Dermatomyositis (DM) is an inflammatory disease of unknown origin that manifests as a myopathy associated with typical skin lesions. Association between DM and cancer is frequent (from 18% to 32% according to case series). It was described for the first time by Stertz in 1916 in association with gastric cancer. All histological types and sites of cancer in the general population may be associated with DM. Its association with nasopharyngeal carcinoma (NPC) is rarely described and the incidence proportion is 1 case of nasopharyngeal carcinoma per 1.000 persons.

  4. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

    Maekawa, Naoya; Konnai, Satoru; Takagi, Satoshi; Kagawa, Yumiko; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Deguchi, Tatsuya; Nakajima, Chie; Kato, Yukinari; Yamamoto, Keiichi; Uemura, Hidetoshi; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  5. Gynecologic Cancer InterGroup (GCIG) consensus review for high-grade undifferentiated sarcomas of the uterus

    NARCIS (Netherlands)

    Pautier, Patricia; Nam, Eun Ji; Provencher, Diane M.; Hamilton, Anne L.; Mangili, Giorgia; Siddiqui, Nadeem Ahmad; Westermann, Anneke M.; Reed, Nicholas Simon; Harter, Philipp; Ray-Coquard, Isabelle

    2014-01-01

    High-grade undifferentiated sarcomas (HGUSs) are rare uterine malignancies arising from the endometrial stroma. They are poorly differentiated sarcomas composed of cells that do not resemble proliferative-phase endometrial stroma. High-grade undifferentiated sarcomas are characterized by aggressive

  6. FEATURES OF CLINICAL COURSE OF GASTROESOPHAGEAL REFLUX DISEASE IN NEWLY RECRUITED WITH CONNECTIVE TISSUE UNDIFFERENTIATED DYSPLASIA SYNDROME

    Directory of Open Access Journals (Sweden)

    E.I. Kashkina

    2008-12-01

    Full Text Available The presence of connective tissue undifferentiated dysplasia syndrome against a background of psychological stress at newly recruited can promote the risk of gastroesophageal reflux disease occurrence. To the utmost, correlation between the gastroesophageal reflux disease and such manifestations of connective tissue undifferentiated dysplasia syndrome as asthenic constitution, chest deformation, Gothic palate and hypermobility of joints was found

  7. Bone edema on magnetic resonance imaging is an independent predictor of rheumatoid arthritis development in patients with early undifferentiated arthritis

    DEFF Research Database (Denmark)

    Duer-Jensen, Anne; Hørslev-Petersen, Kim; Hetland, Merete Lund

    2011-01-01

    To study magnetic resonance imaging (MRI) as a tool for early diagnosis of rheumatoid arthritis (RA) in patients with early undifferentiated arthritis (UA).......To study magnetic resonance imaging (MRI) as a tool for early diagnosis of rheumatoid arthritis (RA) in patients with early undifferentiated arthritis (UA)....

  8. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

    International Nuclear Information System (INIS)

    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele; Merli, Laura; Adamsbaum, Catherine

    2016-01-01

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  9. Undifferentiated Embryonic Cell Transcription Factor 1 Regulates ESC Chromatin Organization and Gene Expression

    NARCIS (Netherlands)

    Kooistra, Susanne M.; van den Boom, Vincent; Thummer, Rajkumar P.; Johannes, Frank; Wardenaar, Rene; Tesson, Bruno M.; Veenhoff, Liesbeth M.; Fusetti, Fabrizia; O'Neill, Laura P.; Turner, Bryan M.; de Haan, Gerald; Eggen, Bart J. L.; O’Neill, Laura P.

    2010-01-01

    Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES

  10. Azathioprine-induced shock in a patient suffering from undifferentiated erosive oligoarthritis

    NARCIS (Netherlands)

    Demirtaş-Ertan, G.; Rowshani, A. T.; ten Berge, I. J. M.

    2006-01-01

    Shock due to a hypersensitivity response to azathioprine is unpredictable, occurs seldom and bears a potentially fatal outcome. Azathioprine is widely used in the treatment of autoimmune diseases and in solid organ transplantation. Here, we present a patient who suffered from undifferentiated

  11. Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children

    Energy Technology Data Exchange (ETDEWEB)

    Gabor, Flaviu; Franchi-Abella, Stephanie; Pariente, Daniele [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Merli, Laura [Bambino Gesu Children' s Hospital, Unit of Hepato-Biliary and Transplant Surgery, Department of Surgery and Transplantation Centre, Rome (Italy); Adamsbaum, Catherine [Bicetre Hospital, Department of Pediatric Radiology, Le Kremlin-Bicetre (France); Paris Sud University, Faculty of Medicine, Le Kremlin-Bicetre (France); Universite Paris-Saclay, LTCI, CNRS, Telecom Paris Tech, Paris (France)

    2016-11-15

    Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI. (orig.)

  12. Pleomorphic undifferentiated sarcoma of urinary bladder with calcified pulmonary metastasis: A rare entity

    Directory of Open Access Journals (Sweden)

    Prasad Mylarappa

    2013-01-01

    Full Text Available We report the case of a 29-year-old male who presented to us with hematuria, dysuria and bilateral flank pain. On evaluation, the patient was found to have primary pleomorphic undifferentiated sarcoma of bladder with calcified pulmonary metastasis, confirmed with computerized tomography scan and immunohistochemistry.

  13. Acute undifferentiated fever in Binh Thuan province, Vietnam: imprecise clinical diagnosis and irrational pharmaco-therapy

    NARCIS (Netherlands)

    Phuong, Hoang L.; de Vries, Peter J.; Nagelkerke, Nico; Giao, Phan T.; Hung, Le Q.; Binh, Tran Q.; Nga, Tran T. Thanh; Nam, Nguyen V.; Kager, Piet A.

    2006-01-01

    OBJECTIVES: To describe the characteristics of patients consulting commune primary healthcare posts for acute undifferentiated fever not being malaria (AUF), and to explore the diagnostic and therapeutic responses of the healthcare workers. METHODS: All patients presenting with AUF at 12 commune

  14. Long-term culture of undifferentiated spermatogonia isolated from immature and adult bovine testes.

    Science.gov (United States)

    Suyatno; Kitamura, Yuka; Ikeda, Shuntaro; Minami, Naojiro; Yamada, Masayasu; Imai, Hiroshi

    2018-03-01

    Undifferentiated spermatogonia eventually differentiate in the testis to produce haploid sperm. Within this cell population, there is a small number of spermatogonial stem cells (SSCs). SSCs are rare cells in the testis, and their cellular characteristics are poorly understood. Establishment of undifferentiated cell line would provide an indispensable tool for studying their biological nature and spermiogenesis/spermatogenesis in vitro. However, there have been few reports on the long-term culture of undifferentiated spermatogonia in species other than rodents. Here, we report the derivation and long-term in vitro culture of undifferentiated spermatogonia cell lines from immature and adult bovine testes. Cell lines from immature testes were maintained in serum-free culture conditions in the presence of glial-cell-line-derived neurotropic factor (GDNF) and bovine leukemia inhibitory factor (bLIF). These cell lines have embryonic stem (ES)-like cell morphology, express pluripotent-stem-cell-specific and germ-cell-specific markers at the protein and mRNA levels, and contributed to the inner cell mass (ICM) of embryos in the blastocyst stage. Meanwhile, cell lines established from adult testes were maintained in low-serum media in the presence of 6-bromoindirubin-3'-oxime (BIO). These cell lines have characteristics resembling those of previously reported male mouse germ cell lines as confirmed by their botryoidally aggregated morphology, as well as the expression of germ-cell-specific markers and pluripotent stem cell markers. These findings could be useful for the development of long-term culture of undifferentiated spermatogonia, which could aid in conservation of species and improvement of livestock production through genome editing technology. © 2018 Wiley Periodicals, Inc.

  15. Possibility of Undifferentiated Human Thigh Adipose Stem Cells Differentiating into Functional Hepatocytes

    Directory of Open Access Journals (Sweden)

    Jong Hoon Lee

    2012-11-01

    Full Text Available BackgroundThis study aimed to investigate the possibility of isolating mesenchymal stem cells (MSCs from human thigh adipose tissue and the ability of human thigh adipose stem cells (HTASCs to differentiate into hepatocytes.MethodsThe adipose-derived stem cells (ADSCs were isolated from thigh adipose tissue. Growth factors, cytokines, and hormones were added to the collagen coated dishes to induce the undifferentiated HTASCs to differentiate into hepatocyte-like cells. To confirm the experimental results, the expression of hepatocyte-specific markers on undifferentiated and differentiated HTASCs was analyzed using reverse transcription polymerase chain reaction and immunocytochemical staining. Differentiation efficiency was evaluated using functional tests such as periodic acid schiff (PAS staining and detection of the albumin secretion level using enzyme-linked immunosorbent assay (ELISA.ResultsThe majority of the undifferentiated HTASCs were changed into a more polygonal shape showing tight interactions between the cells. The differentiated HTASCs up-regulated mRNA of hepatocyte markers. Immunocytochemical analysis showed that they were intensely stained with anti-albumin antibody compared with undifferentiated HTASCs. PAS staining showed that HTASCs submitted to the hepatocyte differentiation protocol were able to more specifically store glycogen than undifferentiated HTASCs, displaying a purple color in the cytoplasm of the differentiated HTASCs. ELISA analyses showed that differentiated HTASCs could secrete albumin, which is one of the hepatocyte markers.ConclusionsMSCs were islolated from human thigh adipose tissue differentiate to heapatocytes. The source of ADSCs is not only abundant abdominal adipose tissue, but also thigh adipose tissue for cell therapy in liver regeneration and tissue regeneration.

  16. Peripheral circulation.

    Science.gov (United States)

    Laughlin, M Harold; Davis, Michael J; Secher, Niels H; van Lieshout, Johannes J; Arce-Esquivel, Arturo A; Simmons, Grant H; Bender, Shawn B; Padilla, Jaume; Bache, Robert J; Merkus, Daphne; Duncker, Dirk J

    2012-01-01

    Blood flow (BF) increases with increasing exercise intensity in skeletal, respiratory, and cardiac muscle. In humans during maximal exercise intensities, 85% to 90% of total cardiac output is distributed to skeletal and cardiac muscle. During exercise BF increases modestly and heterogeneously to brain and decreases in gastrointestinal, reproductive, and renal tissues and shows little to no change in skin. If the duration of exercise is sufficient to increase body/core temperature, skin BF is also increased in humans. Because blood pressure changes little during exercise, changes in distribution of BF with incremental exercise result from changes in vascular conductance. These changes in distribution of BF throughout the body contribute to decreases in mixed venous oxygen content, serve to supply adequate oxygen to the active skeletal muscles, and support metabolism of other tissues while maintaining homeostasis. This review discusses the response of the peripheral circulation of humans to acute and chronic dynamic exercise and mechanisms responsible for these responses. This is accomplished in the context of leading the reader on a tour through the peripheral circulation during dynamic exercise. During this tour, we consider what is known about how each vascular bed controls BF during exercise and how these control mechanisms are modified by chronic physical activity/exercise training. The tour ends by comparing responses of the systemic circulation to those of the pulmonary circulation relative to the effects of exercise on the regional distribution of BF and mechanisms responsible for control of resistance/conductance in the systemic and pulmonary circulations. © 2012 American Physiological Society

  17. Update on peripheral ulcerative keratitis

    Directory of Open Access Journals (Sweden)

    Yagci A

    2012-05-01

    Full Text Available Ayse YagciEge University, School of Medicine, Department of Ophthalmology, Izmir, TurkeyAbstract: Ulcerative inflammation of the cornea occurs in the perilimbal cornea, and is associated with autoimmune collagen vascular and arthritic diseases. Rheumatoid arthritis is the most frequent underlying disease. The tendency for peripheral location is due to the distinct morphologic and immunologic characteristics of the limbal conjunctiva, which provides access for circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates immune-mediated vasculitis, and causes inflammatory cell and protein leakage due to vessel wall damage. Development of peripheral ulcerative keratitis associated with systemic disease may represent worsening of a potentially life-threatening disease. Accompanying scleritis, particularly the necrotizing form, is usually observed in severe cases, which may result in corneal perforation and loss of vision. Although first-line treatment with systemic corticosteroids is indicated for acute phases, immunosuppressive and cytotoxic agents are required for treatment of peripheral ulcerative keratitis associated with multisystem disorders. Recently, infliximab, a chimeric antibody against proinflammatory cytokine tumor necrosis factor-alpha, was reported to be effective in cases refractory to conventional immunomodulatory therapy. The potential side effects of these therapies require close follow-up and regular laboratory surveillance.Keywords: autoimmune disease, peripheral ulcerative keratitis, treatment, tumor necrosis factor-alpha

  18. Primary Pleomorphic Undifferentiated Sarcoma—a Rare Renal Localization: A Case Report

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    Soufiane Mellas

    2012-01-01

    Full Text Available Undifferentiated pleomorphic sarcoma is known as a soft tissue sarcoma. Very few cases of this tumor originating from the renal parenchyma or renal capsule have been reported. We report a case of a 70-year-old patient admitted for enormous ureterohydronephrosis and pyelonephritis due to a pelvic ureter lithiasis. After draining by ureteral double J catheter, a nephroureterectomy was performed for nonfunctional kidney confirmed by scintigraphy. The histopathological study shows a pleomorphic undifferentiated sarcoma. The patient was sent to oncologists. Chemotherapy was proposed but the family decided to stop the treatment. The patient passed away 10 months later. Clinicians and pathologists should be aware of the very low occurrence of this renal tumor, which is extremely rare. Currently there is no consensus about its management. Our case extends the literature concerning this tumor.

  19. Primary CNS anaplastic diffuse large B-cell lymphoma mimicking undifferentiated metastatic tumors: a case report.

    Science.gov (United States)

    Yang, Tianyu; Belverud, Shawn; Yeh, Albert Y; Bandovic, Jela; Farmer, Peter; Woldenberg, Rona F; Demopoulos, Alexis; Schulder, Michael; Li, Jian Yi

    2010-02-01

    Primary central nervous system lymphoma (PCNSL) is a rare intracranial tumor, with an annual incidence of six per million population. Anaplastic variant of primary CNS diffuse large B-cell lymphoma is less common; to our knowledge, there is only one other case report in the world literature. We describe a 71 year old immunocompetent female without significant past medical history who presented with confusion and a homogeneously enhancing midline mass. The patient underwent craniotomy for tumor biopsy, followed by high-dose methotrexate-based chemotherapy despite a remarkably low performance status. Histologically, this tumor was composed of undifferentiated polymorphic tumor cells, multi-nucleated giant cells, extensive necrosis, and conspicuous mitotic activity, mimicking undifferentiated metastatic tumors. Immunohistochemical stains demonstrated immunopositivity of tumor cells for CD20, MUM-1, and BCL-6, and negative staining for CD3, CD10, and CD30. The clinical course, diagnostic workup, pathologic correlates, and treatment outcomes are described.

  20. Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register

    DEFF Research Database (Denmark)

    Lindström, U; Exarchou, S; Sigurdardottir, V

    2015-01-01

    (AS) and undifferentiated SpA (uSpA) in the NPR against the established classification criteria [modified New York (mNY), Assessment of SpondyloArthritis international Society (ASAS), Amor, and European Spondyloarthropathy Study Group (ESSG) criteria]. METHOD: All patients with an ICD-8/9/10 code...... for AS or uSpA had high PPVs, suggesting that our case identification in the Swedish NPR can be used for nationwide, population-based, epidemiological studies of these diseases....

  1. 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.

  2. Undifferentiated-type gastric adenocarcinoma: prognostic impact of three histological types

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    Lee Han

    2012-11-01

    Full Text Available Abstract Background The prognostic value of the three constituents of undifferentiated-type gastric adenocarcinoma remains unclear. The present study assessed the clinicopathological characteristics and prognosis of undifferentiated-type mucinous adenocarcinoma (uMAC and signet ring cell carcinoma (SRC compared with those of poorly differentiated adenocarcinoma (PDAC. Methods In total, 1,376 patients with undifferentiated-type gastric adenocarcinoma were included, consisting of 1,002 patients diagnosed with PDAC, 54 with uMAC and 320 with SRC. Clinicopathological factors and survival rates were compared among the three histological types. Results Significant differences in the distribution of pathological stages were observed among the groups. Patients with SRC had a significantly better survival rate than those with PDAC or uMAC, in both the all patients including non-curative resected patients and curative-resected groups. In addition, there was significant difference in survival between the PDAC and uMAC groups. Multivariate analysis suggested that age, gender, tumor depth, lymph node metastasis and curability significantly affected survival. Histological type was not an independent prognostic factor. There was no significant difference in the pattern of recurrence among the three groups. Conclusions The uMAC and SRC had worse and favorable prognosis compared with PDCA, respectively. However, there were no differences in survival by pathological stage, thus histological type was not an independent predictor of prognosis.

  3. Expression of Neural Markers by Undifferentiated Mesenchymal-Like Stem Cells from Different Sources

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    Dana Foudah

    2014-01-01

    Full Text Available The spontaneous expression of neural markers, already demonstrated in bone marrow (BM mesenchymal stem cells (MSCs, has been considered as evidence of the MSCs’ predisposition to differentiate toward neural lineages, supporting their use in stem cell-based therapy for neural repair. In this study we have evaluated, by immunocytochemistry, immunoblotting, and flow cytometry experiments, the expression of neural markers in undifferentiated MSCs from different sources: human adipose stem cells (hASCs, human skin-derived mesenchymal stem cells (hS-MSCs, human periodontal ligament stem cells (hPDLSCs, and human dental pulp stem cells (hDPSCs. Our results demonstrate that the neuronal markers βIII-tubulin and NeuN, unlike other evaluated markers, are spontaneously expressed by a very high percentage of undifferentiated hASCs, hS-MSCs, hPDLSCs, and hDPSCs. Conversely, the neural progenitor marker nestin is expressed only by a high percentage of undifferentiated hPDLSCs and hDPSCs. Our results suggest that the expression of βIII-tubulin and NeuN could be a common feature of stem cells and not exclusive to neuronal cells. This could result in a reassessment of the use of βIII-tubulin and NeuN as the only evidence proving neuronal differentiation. Further studies will be necessary to elucidate the relevance of the spontaneous expression of these markers in stem cells.

  4. Chronic peripheral inflammation, hippocampal neurogenesis, and behavior.

    Science.gov (United States)

    Chesnokova, Vera; Pechnick, Robert N; Wawrowsky, Kolja

    2016-11-01

    Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effect of cyclosporin A on inflammatory cytokine production by U937 monocyte-like cells

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    Juan E. Losa Garcia

    2000-01-01

    Full Text Available Cyclosporin A (CsA is an immunosuppresor drug that has been used in the treatment of several types of inflammatory diseases. In some of them the inhibition of T-lymphocyte activation does not suitably account for the observed beneficial effect, suggesting that CsA could act on other types of cells. The present study was undertaken to determine the effect of CsA on inflammatory cytokine secretion by U937 monocyte cells. Undifferentiated and dimethylsulfoxide (DMSO differentiated U937 cells were incubated with different concentrations of CsA (200, 20 and 2 ng/mL in the presence or absence of phorbol-myristateacetate (PMA. Interleukin-1g (IL-1β, tumor necrosis factor-α (TNF-α, IL-6 and IL-8 levels were measured in supernatants using specific enzyme-linked immunosorbent assays. At the highest concentration used (200 ng/mL CsA decreased the basal and stimulated secretion of all the inflammatory cytokines studied in both undifferentiated and differentiated cells, with the only exception of PMA-stim ulated IL-1 secretion by undifferentiated cells. However, only basal secretion of interleukin-8 in both undifferentiated and DMSO-differentiated U937 cells was significantly reduced by CsA at the highest concentration (200 ng/ mL. At therapeutic concentrations in vivo, CsA exerts a predominant effect on IL-8 secretion by human mononuclear phagocytes.

  6. Case of Six-Year Disease-Free Survival with Undifferentiated Carcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Hiroyuki Saito

    2016-08-01

    Full Text Available Undifferentiated carcinoma of the pancreas (UDC is rare and has a dismal prognosis. Here, we report a case of 6-year disease-free survival with a mixed type of UDC and UDC with osteoclast-like giant cells, with a high mitotic index as well as perineural, lymphatic, vessel, and diaphragmatic invasion. The patient underwent radical distal pancreatectomy and was subsequently treated with adjuvant chemotherapy using gemcitabine plus S-1 followed by maintenance chemotherapy with oral tegafur-uracil. The patient has been doing well with no evidence of recurrence for more than 6 years after surgery.

  7. Undifferentiated pleomorphic sarcoma: indolent, tail-like recurrence of a high-grade tumor

    Energy Technology Data Exchange (ETDEWEB)

    Alpert, Justin S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Boland, Patrick [Memorial Sloan Kettering Cancer Center, Division of Orthopaedic Surgery, Department of Surgery, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Hameed, Meera [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Panicek, David M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States)

    2018-01-15

    Recurrence of a soft tissue sarcoma typically manifests as a round or oval mass at imaging, and recurrent high-grade soft tissue sarcomas generally enlarge relatively rapidly. We present a case of high-grade undifferentiated pleomorphic sarcoma in the calf of a 48-year-old male that recurred as a thin, curvilinear ''tail'' of enhancing tissue at magnetic resonance imaging (MRI), with extremely indolent growth over a 7-year period. The unusual imaging finding of a slowly enlarging ''tail'' should not be dismissed as postoperative changes, even for a high-grade soft tissue sarcoma. (orig.)

  8. Is Depression an Inflammatory Disorder?

    Science.gov (United States)

    Miller, Andrew H.

    2012-01-01

    Studies consistently report that groups of individuals with major depressive disorder (MDD) demonstrate increased levels of a variety of peripheral inflammatory biomarkers when compared with groups of nondepressed individuals. These findings are often interpreted as meaning that MDD, even in medically healthy individuals, may be an inflammatory condition. In this article, we examine evidence for and against this idea by looking more closely into what the actual patterns of inflammatory findings indicate in terms of the relationship between MDD and the immune system. Data are presented in support of the idea that inflammation only contributes to depression in a subset of patients versus the possibility that the depressogenic effect of inflammatory activation is more widespread and varies depending on the degree of vulnerability any given individual evinces in interconnected physiologic systems known to be implicated in the etiology of MDD. Finally, the treatment implications of these various possibilities are discussed. PMID:21927805

  9. A monoclonal antibody recognizes undifferentiation-specific carbohydrate moieties expressed on cell surface of the human dental pulp cells.

    Science.gov (United States)

    Kang, Kyung-Jung; Ko, Seon-Yle; Ryu, Chun-Jeih; Jang, Young-Joo

    2017-05-01

    Human dental pulp cells are obtained from dental pulp tissue, and have the ability to form dentin and a pulp-like complex. Although adult stem cells have been identified from the primary culture by using specific cell surface markers, the identity of surface markers for the purification of stem cells within the dental pulp population are still unclear. Previously, we had constructed monoclonal antibodies against the undifferentiated cell-specific surface markers of human dental pulp cells (hDPCs) by performing decoy immunization. Among them, a monoclonal antibody against the cell surface antigen of the undifferentiated hDPCs (named UPSA-1) was purified and its heavy and light chain consensus regions were analyzed. The cell surface binding affinity of UPSA-1 mAb on the undifferentiated hDPCs was stronger than that on the differentiated cells. When tunicamycin was applied to hDPSCs during culture, the cell surface binding affinity of the antibody was dramatically decreased, and dentinogenic differentiation was reduced. The purified UPSA-1 antigen band resulting from immunoprecipitation disappeared or shifted down on the SDS-PAGE by deglycosylation. These data suggested that glycosylation on the cell surface might be a marker of an undifferentiated state, and that UPSA-1 mAb might be useful for identifying the carbohydrate moiety on the cell surface of undifferentiated pulp cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Prevalence of undifferentiated fever in adults of Rawalpindi having primary dengue fever.

    Science.gov (United States)

    Zafar, Humaira; Hayyat, Abbas; Akhtar, Naeem; Rizwan, Syeda Fatima

    2013-06-01

    The objectives of the study were to highlight early subclinical presentation of dengue viral infection (DVI) as an undifferentiated febrile illness. The descriptive cross-sectional study was carried out at Microbiology Department, Rawalpindi Medical College from March to September 2009. Stratified random sampling was used to select subjects from various urban and rural areas of Rawalpindi, and Serum IgG anti-dengue antibodies were detected by using 3rd generation enzyme-linked immunosorbent assay (ELISA). Out of the total 240 subjects, 69 (28.75%) were found to be positive for anti-dengue IgG antibodies. Of the positive cases, 41 (59.4%) - comprising 31 (44.9%) urban residents - and 10 (14.4%) rural residents presented with a previous history of undifferentiated fever (p<0.05). It was concluded that primary DVI can present as subclinical form in healthy population residing in rural and urban areas of Rawalpindi, which is an alarming situation indicating the spread of disease in the study area.

  11. Prevalence of undifferentiated fever in adults of Rawalpindi having primary dengue fever

    International Nuclear Information System (INIS)

    Zafar, H.; Hayyat, A.; Akhtar, N.

    2013-01-01

    The objectives of the study were to highlight early subclinical presentation of dengue viral infection (DVI) as an undifferentiated febrile illness. The descriptive cross-sectional study was carried out at Microbiology Department, Rawalpindi Medical College from March to September 2009. Stratified random sampling was used to select subjects from various urban and rural areas of Rawalpindi, and Serum IgG anti-dengue antibodies were detected by using 3rd generation enzyme-linked immunosorbent assay (ELISA). Out of the total 240 subjects, 69 (28.75%) were found to be positive for anti-dengue IgG antibodies. Of the positive cases, 41 (59.4%) - comprising 31 (44.9%) urban residents - and 10 (14.4%) rural residents presented with a previous history of undifferentiated fever (p<0.05). It was concluded that primary DVI can present as subclinical form in healthy population residing in rural and urban areas of Rawalpindi, which is an alarming situation indicating the spread of disease in the study area. (author)

  12. Peripheral Vascular Disease

    Science.gov (United States)

    ... Topics FAQs Peripheral Vascular Disease Peripheral vascular disease (PVD) involves damage to or blockage in the blood ... the organs in and below your stomach area. PVD may also affect the arteries leading to your ...

  13. 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.

  14. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant α1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker

    International Nuclear Information System (INIS)

    Lockhart, Andrew; Davis, Bill; Matthews, Julian C.; Rahmoune, Hassan; Hong, Guizhu; Gee, Antony; Earnshaw, David; Brown, John

    2003-01-01

    The peripheral benzodiazepine receptor ligand PK11195 has been used as an in vivo marker of neuroinflammation in positron emission tomography studies in man. One of the methodological issues surrounding the use of the ligand in these studies is the highly variable kinetic behavior of [ 11 C]PK11195 in plasma. We therefore undertook a study to measure the binding of [ 3 H]PK11195 to whole human blood and found a low level of binding to blood cells but extensive binding to plasma proteins. Binding assays using [ 3 H]PK11195 and purified human plasma proteins demonstrated a strong binding to α1-acid glycoprotein (AGP) and a much weaker interaction with albumin. Immunodepletion of AGP from plasma resulted in the loss of plasma [ 3 H]PK11195 binding demonstrating: (i) the specificity of the interaction and (ii) that AGP is the major plasma protein to which PK11195 binds with high affinity. PK11195 was able to displace fluorescein-dexamethasone from AGP with IC 50 of 11 C]PK11195 to the brain parenchyma in diseases with blood brain barrier breakdown. Finally, local synthesis of AGP at the site of brain injury may contribute the pattern of [ 11 C]PK11195 binding observed in neuroinflammatory diseases

  15. Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding.

    Directory of Open Access Journals (Sweden)

    Steven Lotz

    Full Text Available An essential aspect of stem cell culture is the successful maintenance of the undifferentiated state. Many types of stem cells are FGF2 dependent, and pluripotent stem cells are maintained by replacing FGF2-containing media daily, while tissue-specific stem cells are typically fed every 3rd day. Frequent feeding, however, results in significant variation in growth factor levels due to FGF2 instability, which limits effective maintenance due to spontaneous differentiation. We report that stabilization of FGF2 levels using controlled release PLGA microspheres improves expression of stem cell markers, increases stem cell numbers and decreases spontaneous differentiation. The controlled release FGF2 additive reduces the frequency of media changes needed to maintain stem cell cultures, so that human embryonic stem cells and induced pluripotent stem cells can be maintained successfully with biweekly feedings.

  16. Can Villin be Used to Identify Malignant and Undifferentiated Normal Digestive Epithelial Cells?

    Science.gov (United States)

    Robine, S.; Huet, C.; Moll, R.; Sahuquillo-Merino, C.; Coudrier, E.; Zweibaum, A.; Louvard, D.

    1985-12-01

    We have investigated the presence of villin (a Ca2+-regulated actin binding protein) in various tissues (normal or malignant) and in established cell lines by using sensitive immunochemical techniques on cell extracts and immunofluorescence analysis on frozen sections. Our results show that villin is a marker that can be used to distinguish normal differentiated epithelial cells from the simple epithelia lining the gastrointestinal tract and renal tubules. Villin is found in the absorptive cells of the small and large intestines, in the duct cells of pancreas and biliary system, and in the cells of kidney proximal tubules. Furthermore, undifferentiated normal and tumoral cells of intestinal origin in vivo and in cell culture express villin. Therefore, expression of villin is seen in cells that do not necessarily display the morphological features characteristic of their terminally differentiated state, such as the microvilli-lined brush border. We suggest the possible clinical implications of using villin as a marker in the diagnosis of metastatic adenocarcinomas.

  17. Recurrent ovarian undifferentiated carcinoma resembling hepatoid morphology treated with pegylated liposomal doxorubicin and bevacizumab.

    Science.gov (United States)

    Ishiguro, Tatsuya; Kashima, Kastunori; Yachida, Nozomi; Motoyama, Teiichi; Enomoto, Takayuki

    2017-05-01

    Hepatoid carcinomas are undifferentiated epithelial carcinomas that are pathologically similar to hepatocellular carcinoma, but occur in a variety of organs. Hepatoid carcinomas, as strictly defined, typically produce α-fetoprotein. In addition, a standard effective chemotherapy regimen for hepatoid carcinoma has yet to be established. We present a case of advanced primary ovarian cancer that was pathologically similar to hepatoid carcinoma without staining for α-fetoprotein or hepatocyte paraffin 1. The primary ovarian, metastatic, and recurrent tumors shared similar pathological characteristics. Fourth-line chemotherapy with pegylated liposomal doxorubicin and bevacizumab was effective in treating the recurrent tumor, even though this disease had recurred three times. © 2017 Japan Society of Obstetrics and Gynecology.

  18. Undifferentiated embryonic cell transcription factor 1 regulates ESC chromatin organization and gene expression

    DEFF Research Database (Denmark)

    Kooistra, Susanne M; van den Boom, Vincent; Thummer, Rajkumar P

    2010-01-01

    Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES...... cell chromatin structure. Using chromatin immunoprecipitation-on-chip analysis, we identified >1,700 UTF1 target genes that significantly overlap with previously identified Nanog, Oct4, Klf-4, c-Myc, and Rex1 targets. Gene expression profiling showed that UTF1 knock down results in increased expression...... of a large set of genes, including a significant number of UTF1 targets. UTF1 knock down (KD) ES cells are, irrespective of the increased expression of several self-renewal genes, Leukemia inhibitory factor (LIF) dependent. However, UTF1 KD ES cells are perturbed in their differentiation in response...

  19. New strategies for the treatment of undifferentiated thyroid cancer and poorly differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Juvenal, Guillermo J.

    2006-01-01

    Undifferentiated thyroid cancer, which accounts for about 5-10% of thyroid cancer cases, is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Oncogenes and tumor suppressor genes are involved in the genetic changes that underlie thyroid cancer, as all kinds of tumors. The characterization of these proteins is being exploited to delineate new therapeutic strategies for the treatment of this cancer. This work is focused on those compounds or therapeutic approaches that are being used in clinical essays or in animal models. (author) [es

  20. Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide.

    Directory of Open Access Journals (Sweden)

    Marta Pera

    Full Text Available Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2 plays a central role in the stress. Huprines, a group of potent acetylcholinesterase inhibitors (AChEIs, have shown a broad cholinergic pharmacological profile. Recently, it has been observed that huprine X (HX improves cognition in non transgenic middle aged mice and shows a neuroprotective activity (increased synaptophysin expression in 3xTg-AD mice. Consequently, in the present experiments the potential neuroprotective effect of huprines (HX, HY, HZ has been analyzed in two different in vitro conditions: undifferentiated and NGF-differentiated PC12 cells. Cells were subjected to oxidative insult (H2O2, 200 µM and the protective effects of HX, HY and HZ (0.01 µM-1 µM were analyzed after a pre-incubation period of 24 and 48 hours. All huprines showed protective effects in both undifferentiated and NGF-differentiated cells, however only in differentiated cells the effect was dependent on cholinergic receptors as atropine (muscarinic antagonist, 0.1 µM and mecamylamine (nicotinic antagonist, 100 µM reverted the neuroprotection action of huprines. The decrease in SOD activity observed after oxidative insult was overcome in the presence of huprines and this effect was not mediated by muscarinic or nicotinic receptors. In conclusion, huprines displayed neuroprotective properties as previously observed in in vivo studies. In addition, these effects were mediated by cholinergic receptors only in differentiated cells. However, a non-cholinergic mechanism, probably through an increase in SOD activity, seems to be also involved in the neuroprotective effects of huprines.

  1. Undifferentiated and Differentiated PC12 Cells Protected by Huprines Against Injury Induced by Hydrogen Peroxide

    Science.gov (United States)

    Pera, Marta; Camps, Pelayo; Muñoz-Torrero, Diego; Perez, Belen; Badia, Albert; Clos Guillen, M Victoria

    2013-01-01

    Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and hydrogen peroxide (H2O2) plays a central role in the stress. Huprines, a group of potent acetylcholinesterase inhibitors (AChEIs), have shown a broad cholinergic pharmacological profile. Recently, it has been observed that huprine X (HX) improves cognition in non transgenic middle aged mice and shows a neuroprotective activity (increased synaptophysin expression) in 3xTg-AD mice. Consequently, in the present experiments the potential neuroprotective effect of huprines (HX, HY, HZ) has been analyzed in two different in vitro conditions: undifferentiated and NGF-differentiated PC12 cells. Cells were subjected to oxidative insult (H2O2, 200 µM) and the protective effects of HX, HY and HZ (0.01 µM–1 µM) were analyzed after a pre-incubation period of 24 and 48 hours. All huprines showed protective effects in both undifferentiated and NGF-differentiated cells, however only in differentiated cells the effect was dependent on cholinergic receptors as atropine (muscarinic antagonist, 0.1 µM) and mecamylamine (nicotinic antagonist, 100 µM) reverted the neuroprotection action of huprines. The decrease in SOD activity observed after oxidative insult was overcome in the presence of huprines and this effect was not mediated by muscarinic or nicotinic receptors. In conclusion, huprines displayed neuroprotective properties as previously observed in in vivo studies. In addition, these effects were mediated by cholinergic receptors only in differentiated cells. However, a non-cholinergic mechanism, probably through an increase in SOD activity, seems to be also involved in the neuroprotective effects of huprines. PMID:24086337

  2. Epidemiology of Peripheral Neuropathy: An Indian Perspective.

    Science.gov (United States)

    Trivedi, Sweety; Pandit, Alak; Ganguly, Goutam; Das, Shyamal Kumar

    2017-01-01

    Peripheral neuropathy (PN) is a common disorder and presents as diagnostic and therapeutic challenge to physicians and neurologists. In epidemiological studies from India from various regions the overall prevalence of PN varied from 5 to 2400 per 10,000 population in various community studies. India is composed of a multiethnic, multicultural population who are exposed to different adverse environmental factors such as arsenic and lead. Use of different chemotherapeutic agents with propensity to affect peripheral nerves, increasing methods of diagnosis of connective tissue disorders and use of immunomodulating drugs, growing aging population is expected to change the spectrum and burden of peripheral neuropathy in the community. The other important aspect of peripheral neuropathies is in terms of the geographical and occupational distribution especially of toxic neuropathies like arsenic which is common in eastern belt; lead, mercury and organo-phosphorous compounds where occupational exposures are major sources. Inflammatory neuropathies either due to vasculitis or G B Syndrome, chronic inflammatory polyradiculopathies are another major group of neuropathies which is increasing due to increase longevity of Indian subjects and immunological impairment, also adds to morbidity of the patients and are potentially treatable. Leprous neuropathy is common in India and although its frequency is significantly decreasing because of national control program yet pure neuritic form still remains a cause of concern and similar is the case with another infective cause like diptheric neurpathy. Thus this article is an attempt to cover major categories and also highlight the areas where further studies are needed.

  3. A Comparison of Androgynous, Feminine, Masculine, and Undifferentiated Women on Self-Esteem, Body Satisfaction, and Sexual Satisfaction.

    Science.gov (United States)

    Kimlicka, Thomas; And Others

    1983-01-01

    Compared sex-role orientations of female undergraduates (N=204) who completed the Bem Sex Role Inventory. Androgyny and masculinity were associated with self-esteem, body satisfaction, and sexual satisfaction. Androgynous and masculine subjects were generally similar and well adjusted; feminine and undifferentiated subjects were similar and less…

  4. Inhibition by pectic oligosaccharides of the invasion of undifferentiated and differentiated Caco-2 cells by Campylobacter jejuni

    Science.gov (United States)

    The ability of pectic oligosaccharides (POS) to inhibit adherence to and invasion of undifferentiated (UC) and differentiated (DC) Caco-2 cells by Campylobacter jejuni (C. jejuni) was investigated. It was observed that both adherence and invasion were significantly higher in UC than in DC. POS (2.5 ...

  5. Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?

    DEFF Research Database (Denmark)

    Carneiro, Ana; Francis, Princy; Bendahl, Pär-Ola

    2009-01-01

    Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS...

  6. Etiologies of acute undifferentiated fever and clinical prediction of scrub typhus in a non-tropical endemic area.

    Science.gov (United States)

    Jung, Ho-Chul; Chon, Sung-Bin; Oh, Won Sup; Lee, Dong-Hyun; Lee, Ho-Jin

    2015-02-01

    Scrub typhus usually presents as acute undifferentiated fever. This cross-sectional study included adult patients presenting with acute undifferentiated fever defined as any febrile illness for ≤ 14 days without evidence of localized infection. Scrub typhus cases were defined by an antibody titer of a ≥ fourfold increase in paired sera, a ≥ 1:160 in a single serum using indirect immunofluorescence assay, or a positive result of the immunochromatographic test. Multiple regression analysis identified predictors associated with scrub typhus to develop a prediction rule. Of 250 cases with known etiology of acute undifferentiated fever, influenza (28.0%), hepatitis A (25.2%), and scrub typhus (16.4%) were major causes. A prediction rule for identifying suspected cases of scrub typhus consisted of age ≥ 65 years (two points), recent fieldwork/outdoor activities (one point), onset of illness during an outbreak period (two points), myalgia (one point), and eschar (two points). The c statistic was 0.977 (95% confidence interval = 0.960-0.994). At a cutoff value ≥ 4, the sensitivity and specificity were 92.7% (79.0-98.1%) and 90.9% (86.0-94.3%), respectively. Scrub typhus, the third leading cause of acute undifferentiated fever in our region, can be identified early using the prediction rule. © The American Society of Tropical Medicine and Hygiene.

  7. Peripheral artery disease - legs

    Science.gov (United States)

    Peripheral vascular disease; PVD; PAD; Arteriosclerosis obliterans; Blockage of leg arteries; Claudication; Intermittent claudication; Vaso-occlusive disease of the legs; Arterial insufficiency of ...

  8. Acute undifferentiated fever in India: a multicentre study of aetiology and diagnostic accuracy.

    Science.gov (United States)

    Mørch, Kristine; Manoharan, Anand; Chandy, Sara; Chacko, Novin; Alvarez-Uria, Gerardo; Patil, Suvarna; Henry, Anil; Nesaraj, Joel; Kuriakose, Cijoy; Singh, Ashita; Kurian, Siby; Gill Haanshuus, Christel; Langeland, Nina; Blomberg, Bjørn; Vasanthan Antony, George; Mathai, Dilip

    2017-10-04

    The objectives of this study were to determine the proportion of malaria, bacteraemia, scrub typhus, leptospirosis, chikungunya and dengue among hospitalized patients with acute undifferentiated fever in India, and to describe the performance of standard diagnostic methods. During April 2011-November 2012, 1564 patients aged ≥5 years with febrile illness for 2-14 days were consecutively included in an observational study at seven community hospitals in six states in India. Malaria microscopy, blood culture, Dengue rapid NS1 antigen and IgM Combo test, Leptospira IgM ELISA, Scrub typhus IgM ELISA and Chikungunya IgM ELISA were routinely performed at the hospitals. Second line testing, Dengue IgM capture ELISA (MAC-ELISA), Scrub typhus immunofluorescence (IFA), Leptospira Microscopic Agglutination Test (MAT), malaria PCR and malaria immunochromatographic rapid diagnostic test (RDT) Parahit Total™ were performed at the coordinating centre. Convalescence samples were not available. Case definitions were as follows: Leptospirosis: Positive ELISA and positive MAT. Scrub typhus: Positive ELISA and positive IFA. Dengue: Positive RDT and/or positive MAC-ELISA. Chikungunya: Positive ELISA. Bacteraemia: Growth in blood culture excluding those defined as contaminants. Malaria: Positive genus-specific PCR. Malaria was diagnosed in 17% (268/1564) and among these 54% had P. falciparum. Dengue was diagnosed in 16% (244/1564). Bacteraemia was found in 8% (124/1564), and among these Salmonella typhi or S. paratyphi constituted 35%. Scrub typhus was diagnosed in 10%, leptospirosis in 7% and chikungunya in 6%. Fulfilling more than one case definition was common, most frequent in chikungunya where 26% (25/98) also had positive dengue test. Malaria and dengue were the most common causes of fever in this study. A high overlap between case definitions probably reflects high prevalence of prior infections, cross reactivity and subclinical infections, rather than high prevalence of

  9. Longitudinal analysis of quality of life in patients with undifferentiated connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Iudici M

    2017-02-01

    Full Text Available Michele Iudici, Rosaria Irace, Antonella Riccardi, Giovanna Cuomo, Serena Vettori, Gabriele Valentini Rheumatology Section, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Introduction/objectives: To prospectively assess the quality of life (QoL of patients affected by undifferentiated connective tissue diseases (UCTDs and to identify factors associated with changes over time.Patients and methods: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36 questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia.Results: At presentation, scores lower than the average of the general population were detected in 34 (74% and 41 (89% patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud’s phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p = 0.0009. No patient feature was found to be associated with the basal mental component summary score. During 24 months of follow-up, a significant improvement (ie, a change ≥5 from baseline in physical component summary and mental component summary scores was observed in 14 (33.3% and 20 (43.4% patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p < 0.001, while those who improved in the mental component more frequently had a history of either glucocorticoids (p = 0.043 or immunosuppressors (p = 0.037 intake during follow-up.Conclusion: UCTD patients perceive a worse QoL, regardless of Raynaud’s phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing

  10. Anti-inflammatory, anti-nociceptive and antipyretic potential of ...

    African Journals Online (AJOL)

    Materials and Methods: Extracts of Terminalia citrina fruits were evaluated at doses of 200mg/kg, 400mg/kg and 600mg/kg in albino mice for preventive effect in inflammatory edema, peripheral pain sensation and pyrexia. Carrageenan induced paw edema method was utilized to evaluate anti-inflammatory activity.

  11. Promoted neuronal differentiation after activation of alpha4/beta2 nicotinic acetylcholine receptors in undifferentiated neural progenitors.

    Directory of Open Access Journals (Sweden)

    Takeshi Takarada

    Full Text Available BACKGROUND: Neural progenitor is a generic term used for undifferentiated cell populations of neural stem, neuronal progenitor and glial progenitor cells with abilities for proliferation and differentiation. We have shown functional expression of ionotropic N-methyl-D-aspartate (NMDA and gamma-aminobutyrate type-A receptors endowed to positively and negatively regulate subsequent neuronal differentiation in undifferentiated neural progenitors, respectively. In this study, we attempted to evaluate the possible functional expression of nicotinic acetylcholine receptor (nAChR by undifferentiated neural progenitors prepared from neocortex of embryonic rodent brains. METHODOLOGY/PRINCIPAL FINDINGS: Reverse transcription polymerase chain reaction analysis revealed mRNA expression of particular nAChR subunits in undifferentiated rat and mouse progenitors prepared before and after the culture with epidermal growth factor under floating conditions. Sustained exposure to nicotine significantly inhibited the formation of neurospheres composed of clustered proliferating cells and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction activity at a concentration range of 1 µM to 1 mM without affecting cell survival. In these rodent progenitors previously exposed to nicotine, marked promotion was invariably seen for subsequent differentiation into cells immunoreactive for a neuronal marker protein following the culture of dispersed cells under adherent conditions. Both effects of nicotine were significantly prevented by the heteromeric α4β2 nAChR subtype antagonists dihydro-β-erythroidine and 4-(5-ethoxy-3-pyridinyl-N-methyl-(3E-3-buten-1-amine, but not by the homomeric α7 nAChR subtype antagonist methyllycaconitine, in murine progenitors. Sustained exposure to nicotine preferentially increased the expression of Math1 among different basic helix-loop-helix proneural genes examined. In undifferentiated progenitors from embryonic mice

  12. Pelvic Inflammatory Disease (PID)

    Science.gov (United States)

    ... FAQs Pelvic Inflammatory Disease (PID) Page Navigation ▼ ACOG Pregnancy Book Pelvic Inflammatory Disease (PID) Patient Education FAQs Pelvic Inflammatory Disease (PID) Patient Education Pamphlets - ...

  13. Evaluation of florfenicol for the treatment of undifferentiated fever in feedlot calves in western Canada.

    Science.gov (United States)

    Booker, C W; Jim, G K; Guichon, P T; Schunicht, O C; Thorlakson, B E; Lockwood, P W

    1997-01-01

    A study was conducted in western Canada to evaluate the efficacy of florfenicol for the treatment of undifferentiated fever (UF) in feedlot calves. One hundred and twenty-five recently weaned, auction market derived, crossbred, beef steer calves suffering from UF were allocated to 1 of 2 experimental groups as follows: florfenicol, which was intramuscular florfenicol administered at the rate of 20 mg/kg body weight at the time of allocation (day 0) and again 48 h later; or control, which was intramuscular saline administered at the same volume as florfenicol at the time of allocation and again 48 h later. Eighty-four calves were allocated to the florfenicol group and 41 calves were allocated to the control group. Outcome measures describing animal health, body weight, and rectal temperature parameters were used to determine the efficacy of florfenicol for the treatment of UF. The 1st relapse of UF, 2nd relapse of UF, overall mortality, bovine respiratory disease mortality, and haemophilosis mortality rates were significantly (P florfenicol group than in the control group. Animals in the florfenicol group were significantly (P florfenicol group was significantly (P florfenicol is an efficacious antimicrobial for the treatment of UF. PMID:9285135

  14. Histologic and Genetic Advances in Refining the Diagnosis of “Undifferentiated Pleomorphic Sarcoma”

    Directory of Open Access Journals (Sweden)

    Antonella Viterbo

    2013-02-01

    Full Text Available Undifferentiated pleomorphic sarcoma (UPS is an inclusive term used for sarcomas that defy formal sub-classification. The frequency with which this diagnosis is assigned has decreased in the last twenty years. This is because when implemented, careful histologic assessment, immunohistochemistry, and ultra-structural evaluation can often determine lineage of differentiation. Further attrition in the diagnostic frequency of UPS may arise by using array-comparative genomic hybridization. Gene expression arrays are also of potential use as they permit hierarchical gene clustering. Appraisal of the literature is difficult due to a historical perspective in which specific molecular diagnostic methods were previously unavailable. The American Joint Committee on Cancer (AJCC classification has changed with different inclusion criteria. Taxonomy challenges also exist with the older term “malignant fibrous histiocytoma” being replaced by “UPS”. In 2010 an analysis of multiple sarcoma expression databases using a 170-gene predictor, re-classified most MFH and “not-otherwise-specified” (NOS tumors as liposarcomas, leiomyosarcomas or fibrosarcomas. Interestingly, some of the classifier genes are potential molecular therapeutic targets including Insulin-like growth factor 1 (IGF-1, Peroxisome proliferator-activated receptor γ (PPARγ, Nerve growth factor β (NGF β and Fibroblast growth factor receptor (FGFR.

  15. MR imaging of myxofibrosarcoma and undifferentiated sarcoma with emphasis on tail sign; diagnostic and prognostic value

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Hye Jin; Hong, Sung Hwan; Kang, Yusuhn; Choi, Ja-Young; Yi, Minkyong [Seoul National University College of Medicine, Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Moon, Kyung Chul [Seoul National University College of Medicine, Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Han-Soo; Han, Ilkyu [Seoul National University College of Medicine, Seoul National University Hospital, Department of Orthopedic Surgery, Seoul (Korea, Republic of); Kang, Heung Sik [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-City, Gyeongi-Do (Korea, Republic of)

    2014-08-15

    To assess the prevalence of the tail sign in soft tissue sarcomas and determine whether the local recurrence rate differed based on the presence of the tail sign. In our retrospective study, myxofibrosarcoma (MFS, n = 25) and undifferentiated sarcoma (US, n = 38) comprised group 1, and the remaining tumours (n = 115) were assigned to group 2. Location, size, and imaging features of the tumours were assessed on MRI. The radiological-pathological correlation of the tail sign was analysed. The tail sign, thick fascial enhancement extending from the tumour margin, was more common and significantly thicker in group 1. In the subgroup analysis between MFS and US, there was no significant difference in the presence of a tail sign. Histological examination revealed extensive tumour cell infiltrations along the deep fascia from the main mass. Patients with a tail sign had a worse local recurrence-free survival than patients without it, not only in all tumours (p < 0.01), but also in group 1 (p = 0.019) The tail sign was a common MRI feature of both MFS and US, and was also associated with worse local recurrence-free survival. Radiologists should be aware of these MRI findings and inform the surgeon preoperatively in order to obtain a sufficient surgical margin to minimise the risk of local tumour recurrence. (orig.)

  16. Undifferentiated connective tissue disease presenting with prevalent interstitial lung disease: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Sfriso Paolo

    2011-06-01

    Full Text Available Abstract Undifferentiated connective tissue diseases (UCTDs are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported. We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.

  17. Risk factors for the occurrence of undifferentiated carcinoma of nasopharyngeal type: A case-control study

    Directory of Open Access Journals (Sweden)

    Nešić Vladimir

    2010-01-01

    Full Text Available Introduction. The incidence rate of nasopharyngeal carcinoma in Serbia is less than one per 100,000 citizens, which classifies it as a region with low incidence for this disease. Objective. The aim of this study was to test some hypotheses of the risk factors for undifferentiated carcinoma of nasopharyngeal type (UCNT in the low incidence population. Methods. A case-control study was used for the research. The study included 45 cases with histopathological diagnosis of UCNT and 90 controls. Cases and the controls were individually matched by sex, age (±3 years, and place of residence (city-village. Data were gathered about sociodemographic characteristics, occupational exposure to harmful agents, habits, diet, personal history, and family history. In the analysis of the data, conditional univariate and multivariate logistic regression analyses were applied. Results. According to the results of multivariate logistic regression analysis UCNT was significantly positively associated with 'passive smoking' of tobacco in the family during childhood, frequent consumption of industrially manufactured food additives for enhancing flavour and frequent consumption of white bread. UCNT was significantly negatively associated with frequent consumption of margarine, olive oil and cornbread. Conclusion. In our low incidence population, an independent risk factor for the occurrence of UCNT was 'passive smoking' of tobacco in the family during childhood, use of industrially manufactured food with additives for enhancing flavour and consumption of white bread. Multicentric study enrolling a greater number of cases would be desirable.

  18. Predict rheumatoid arthritis conversion from undifferentiated arthritis with dynamic contrast-enhanced MRI and laboratory indexes.

    Science.gov (United States)

    Lei, Xinwei; Li, Huixia; Zhan, Ying; Qu, Jin

    2018-01-15

    To investigate the clinical value of dynamic contrast-enhanced MRI (DCE-MRI) and laboratory indexes in predicting conversion from undifferentiated arthritis (UA) to rheumatoid arthritis (RA). A total 81 DMARD-naive UA patients were studied. 37 cases were ultimately diagnosed as RA, 32 cases were diagnosed as other types of arthritis, and the remaining cases were still UA during the 1-year follow-up. The DCE-MRI and laboratory measures were fed into a logistic regression analysis. Wash-in rate and anti-cyclic citrullinated peptide (anti-CCP) antibody served as the final variables into the regression equation (pCCP antibody positive achieved a sensitivity of 37.8% and specificity of 90.9%. The combination of wash-in rate and anti-CCP antibody positive improved specificity (100%) but not sensitivity (27.3%). The conversion from UA to RA is highly predictable. The wash-in rate of DCE-MRI can be used as an important biomarker to predict UA progression.

  19. Undifferentiated tropical febrile illness in Cordoba, Colombia: Not everything is dengue.

    Science.gov (United States)

    Mattar, Salim; Tique, Vaneza; Miranda, Jorge; Montes, Eney; Garzon, Denisses

    In Colombia, undifferentiated tropical febrile illness (UTFI) are frequent and of considerable concern. They also share many clinical features. Between 2012 and 2013 in an endemic tropical area of Cordoba, Colombia, we conducted a prospective study to establish an etiological diagnosis of UTFI. Using diagnostic tests for dengue, leptospirosis, hantavirus, malaria, rickettsia, brucellosis, hepatitis A and B on 100 patients recruited for the study. We identified 69 patients with presumed UTFI: leptospirosis (n=27), dengue (n=26), hantavirus infection (n=4), malaria (n=4), rickettsial infection (n=2), hepatitis A (n=1), and brucellosis (n=1); no hepatitis B cases were detected. Co-infections with malaria and leptospirosis (n=1), hepatitis A and dengue (n=1), hantavirus and dengue (n=1), hantavirus, dengue, and leptospirosis (n=1) were also identified. No etiologic agent was identified for 31 patients. We conclude that other etiologic agents besides dengue virus deserve greater attention by physicians and public health authorities in tropical area of Colombia. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  20. Squamous cell carcinoma and undifferentiated carcinoma of the inner nose and the paranasal sinuses

    International Nuclear Information System (INIS)

    Wustrow, J.; Rudert, H.; Diercks, M.; Beigel, A.

    1989-01-01

    272 patients with tumours of the nasal cavity and paranasal sinuses were followed up from 1949 until 1982. 53% of the tumours were classified as squamous cell or undifferentiated carcinomata. The most common site of squamous cell carcinoma is the maxillary sinus (50%). Distant metastases and regional lymph node metastases are rarely seen at presentation regardless of the size of the primary tumour. Metastases usually indicate a tumour dependent death in the near future. The main prognostic indicators are the size of the tumour (significantly worse prognosis for T4 in comparison to T2 or T3 tumours) and the localisation (significantly better prognosis for tumours of the floor of the nasal cavity or the nasal septum compared to tumours of the paranasal sinuses). The age of the patient or the degree of differentiation of the tumour did not influence on the survival rate. Tumour dependent deaths rarely occur after more than five years. Patients were assigned to two treatment groups and matched according to the tumour stage. One group received surgery only, whereas the second group received a combined treatment of surgery with subsequent radiotherapy. There was a significant difference between the two groups in favour of the surgical treatment. According to these data we recommend surgical excision without postoperative irradiation in cases where complete removal of the tumor has been histologically proven. (orig./MG) [de

  1. Aging results in molecular changes in an enriched population of undifferentiated rat spermatogonia.

    Science.gov (United States)

    Paul, Catriona; Nagano, Makoto; Robaire, Bernard

    2013-12-01

    A strong correlation exists between increasing paternal age and a decline in reproductive function. Testis aging is associated with testicular atrophy, increased DNA damage, and de novo mutations. It is unclear whether these problems arise from the spermatogonial stem cells (SSCs), a buildup of anomalies as older germ cells progress through spermatogenesis, or both. We hypothesize that with the continual divisions of SSCs that maintain the germ cell population, an alteration of these cells occurs over time. To test this, we utilized young (4-mo-old) and aged (18- and 21-mo-old) transgenic rats that express GFP in germ cells only. We first examined the number and activity of SSCs from the different age groups by transplantation. Aged rats had numerically fewer SSCs than young rats (age, we isolated an SSC-enriched population of CD9-positive (CD9(+)) cells using fluorescence-activated cell sorting (confirmed by transplantation studies) and extracted RNA for microarray analysis. In the aged CD9(+) cells, 60 transcripts were upregulated and more than 500 downregulated compared to the young cells. An altered expression was found for transcripts involved in mitosis and in DNA damage response. These results suggest molecular alterations in the SSC-enriched population of aged CD9(+) cells, implying that reproductive aging originates in the undifferentiated cells of spermatogenesis.

  2. Biodistribution of p-borophenylalanine (BPA) in dogs with spontaneous undifferentiated thyroid carcinoma (UTC)

    International Nuclear Information System (INIS)

    Dagrosa, M.A.; Viaggi, M.; Rebagliati, R. Jimenez; Castillo, V.A.; Batistoni, D.; Cabrini, R.L.; Castiglia, S.; Juvenal, G.J.; Pisarev, M.A.

    2004-01-01

    Human undifferentiated thyroid carcinoma (UTC) is a very aggressive tumor which lacks an adequate treatment. The UTC human cell line ARO has a selective uptake of BPA in vitro and after transplanting into nude mice. Applications of boron neutron capture therapy (BNCT) to mice showed a 100% control of growth and a 50% histological cure of tumors with an initial volume of 50 mm 3 or less. As a further step towards the potential application in humans we have performed the present studies. Four dogs with diagnosis of spontaneous UTC were studied. A BPA-fructose solution was infused during 60 min and dogs were submitted to thyroidectomy. Samples of blood and from different areas of the tumors (and in one dog from normal thyroid) were obtained and the boron was determined by ICP-OES. Selective BPA uptake by the tumor was found in all animals, the tumor/blood ratios ranged between 2.02 and 3.76, while the tumor/normal thyroid ratio was 6.78. Individual samples had tumor/blood ratios between 8.36 and 0.33. These ratios were related to the two histological patterns observed: homogeneous and heterogeneous tumors. We confirm the selective uptake of BPA by spontaneous UTC in dogs and plan to apply BNCT in the future

  3. Application of a prediction model for the progression of rheumatoid arthritis in patients with undifferentiated arthritis.

    Science.gov (United States)

    Arana-Guajardo, Ana; Pérez-Barbosa, Lorena; Vega-Morales, David; Riega-Torres, Janett; Esquivel-Valerio, Jorge; Garza-Elizondo, Mario

    2014-01-01

    Different prediction rules have been applied to patients with undifferentiated arthritis (UA) to identify those that progress to rheumatoid arthritis (RA). The Leiden Prediction Rule (LPR) has proven useful in different UA cohorts. To apply the LPR to a cohort of patients with UA of northeastern Mexico. We included 47 patients with UA, LPR was applied at baseline. They were evaluated and then classified after one year of follow-up into two groups: those who progressed to RA (according to ACR 1987) and those who did not. 43% of the AI patients developed RA. In the RA group, 56% of patients obtained a score ≤ 6 and only 15% ≥ 8. 70% who did not progress to RA had a score between 6 and ≤ 8. There was no difference in median score of LPR between groups, p=0.940. Most patients who progressed to RA scored less than 6 points in the LPR. Unlike what was observed in other cohorts, the model in our population did not allow us to predict the progression of the disease. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  4. Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

    Directory of Open Access Journals (Sweden)

    Ana Alonso-Larruga

    2017-01-01

    Full Text Available The term undifferentiated connective tissue disease (UCTD is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis. It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.

  5. Proteomic analysis of plasma membranes isolated from undifferentiated and differentiated HepaRG cells

    Directory of Open Access Journals (Sweden)

    Sokolowska Izabela

    2012-08-01

    Full Text Available Abstract Liver infection with hepatitis B virus (HBV, a DNA virus of the Hepadnaviridae family, leads to severe disease, such as fibrosis, cirrhosis and hepatocellular carcinoma. The early steps of the viral life cycle are largely obscure and the host cell plasma membrane receptors are not known. HepaRG is the only proliferating cell line supporting HBV infection in vitro, following specific differentiation, allowing for investigation of new host host-cell factors involved in viral entry, within a more robust and reproducible environment. Viral infection generally begins with receptor recognition at the host cell surface, following highly specific cell-virus interactions. Most of these interactions are expected to take place at the plasma membrane of the HepaRG cells. In the present study, we used this cell line to explore changes between the plasma membrane of undifferentiated (− and differentiated (+ cells and to identify differentially-regulated proteins or signaling networks that might potentially be involved in HBV entry. Our initial study identified a series of proteins that are differentially expressed in the plasma membrane of (− and (+ cells and are good candidates for potential cell-virus interactions. To our knowledge, this is the first study using functional proteomics to study plasma membrane proteins from HepaRG cells, providing a platform for future experiments that will allow us to understand the cell-virus interaction and mechanism of HBV viral infection.

  6. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected ...

  7. Peripheral Arterial Disease

    Science.gov (United States)

    Peripheral arterial disease (PAD) happens when there is a narrowing of the blood vessels outside of your heart. The cause of ... smoking. Other risk factors include older age and diseases like diabetes, high blood cholesterol, high blood pressure, ...

  8. Occlusive Peripheral Arterial Disease

    Science.gov (United States)

    ... Lower Your Stroke Risk? Ecstasy May Help Some PTSD Sufferers, but Safety Issues Remain First Death Reported ... of these factors contributes not only to the development of occlusive peripheral arterial disease but also to ...

  9. A Predictive Model to Classify Undifferentiated Fever Cases Based on Twenty-Four-Hour Continuous Tympanic Temperature Recording

    Directory of Open Access Journals (Sweden)

    Pradeepa H. Dakappa

    2017-01-01

    Full Text Available Diagnosis of undifferentiated fever is a major challenging task to the physician which often remains undiagnosed and delays the treatment. The aim of the study was to record and analyze a 24-hour continuous tympanic temperature and evaluate its utility in the diagnosis of undifferentiated fevers. This was an observational study conducted in the Kasturba Medical College and Hospitals, Mangaluru, India. A total of ninety-six (n=96 patients were presented with undifferentiated fever. Their tympanic temperature was recorded continuously for 24 hours. Temperature data were preprocessed and various signal characteristic features were extracted and trained in classification machine learning algorithms using MATLAB software. The quadratic support vector machine algorithm yielded an overall accuracy of 71.9% in differentiating the fevers into four major categories, namely, tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases. The area under ROC curve for tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases was found to be 0.961, 0.801, 0.815, and 0.818, respectively. Good agreement was observed [kappa = 0.618 (p<0.001, 95% CI (0.498–0.737] between the actual diagnosis of cases and the quadratic support vector machine learning algorithm. The 24-hour continuous tympanic temperature recording with supervised machine learning algorithm appears to be a promising noninvasive and reliable diagnostic tool.

  10. A Predictive Model to Classify Undifferentiated Fever Cases Based on Twenty-Four-Hour Continuous Tympanic Temperature Recording.

    Science.gov (United States)

    Dakappa, Pradeepa H; Prasad, Keerthana; Rao, Sathish B; Bolumbu, Ganaraja; Bhat, Gopalkrishna K; Mahabala, Chakrapani

    2017-01-01

    Diagnosis of undifferentiated fever is a major challenging task to the physician which often remains undiagnosed and delays the treatment. The aim of the study was to record and analyze a 24-hour continuous tympanic temperature and evaluate its utility in the diagnosis of undifferentiated fevers. This was an observational study conducted in the Kasturba Medical College and Hospitals, Mangaluru, India. A total of ninety-six ( n = 96) patients were presented with undifferentiated fever. Their tympanic temperature was recorded continuously for 24 hours. Temperature data were preprocessed and various signal characteristic features were extracted and trained in classification machine learning algorithms using MATLAB software. The quadratic support vector machine algorithm yielded an overall accuracy of 71.9% in differentiating the fevers into four major categories, namely, tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases. The area under ROC curve for tuberculosis, intracellular bacterial infections, dengue fever, and noninfectious diseases was found to be 0.961, 0.801, 0.815, and 0.818, respectively. Good agreement was observed [kappa = 0.618 ( p machine learning algorithm. The 24-hour continuous tympanic temperature recording with supervised machine learning algorithm appears to be a promising noninvasive and reliable diagnostic tool.

  11. Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies

    Directory of Open Access Journals (Sweden)

    Rao Mahendra S

    2005-10-01

    Full Text Available Abstract Background The identification of molecular pathways of differentiation of embryonic stem cells (hESC is critical for the development of stem cell based medical therapies. In order to identify biomarkers and potential regulators of the process of differentiation, a high quality microarray containing 16,659 seventy base pair oligonucleotides was used to compare gene expression profiles of undifferentiated hESC lines and differentiating embryoid bodies. Results Previously identified "stemness" genes in undifferentiated hESC lines showed down modulation in differentiated cells while expression of several genes was induced as cells differentiated. In addition, a subset of 194 genes showed overexpression of greater than ≥ 3 folds in human embryoid bodies (hEB. These included 37 novel and 157 known genes. Gene expression was validated by a variety of techniques including another large scale array, reverse transcription polymerase chain reaction, focused cDNA microarrays, massively parallel signature sequencing (MPSS analysis and immunocytochemisty. Several novel hEB specific expressed sequence tags (ESTs were mapped to the human genome database and their expression profile characterized. A hierarchical clustering analysis clearly depicted a distinct difference in gene expression profile among undifferentiated and differentiated hESC and confirmed that microarray analysis could readily distinguish them. Conclusion These results present a detailed characterization of a unique set of genes, which can be used to assess the hESC differentiation.

  12. Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies.

    Science.gov (United States)

    Bhattacharya, Bhaskar; Cai, Jingli; Luo, Youngquan; Miura, Takumi; Mejido, Josef; Brimble, Sandii N; Zeng, Xianmin; Schulz, Thomas C; Rao, Mahendra S; Puri, Raj K

    2005-10-05

    The identification of molecular pathways of differentiation of embryonic stem cells (hESC) is critical for the development of stem cell based medical therapies. In order to identify biomarkers and potential regulators of the process of differentiation, a high quality microarray containing 16,659 seventy base pair oligonucleotides was used to compare gene expression profiles of undifferentiated hESC lines and differentiating embryoid bodies. Previously identified "stemness" genes in undifferentiated hESC lines showed down modulation in differentiated cells while expression of several genes was induced as cells differentiated. In addition, a subset of 194 genes showed overexpression of greater than > or = 3 folds in human embryoid bodies (hEB). These included 37 novel and 157 known genes. Gene expression was validated by a variety of techniques including another large scale array, reverse transcription polymerase chain reaction, focused cDNA microarrays, massively parallel signature sequencing (MPSS) analysis and immunocytochemisty. Several novel hEB specific expressed sequence tags (ESTs) were mapped to the human genome database and their expression profile characterized. A hierarchical clustering analysis clearly depicted a distinct difference in gene expression profile among undifferentiated and differentiated hESC and confirmed that microarray analysis could readily distinguish them. These results present a detailed characterization of a unique set of genes, which can be used to assess the hESC differentiation.

  13. Conditionally replicating adenovirus prevents pluripotent stem cell–derived teratoma by specifically eliminating undifferentiated cells

    Directory of Open Access Journals (Sweden)

    Kaoru Mitsui

    Full Text Available Incomplete abolition of tumorigenicity creates potential safety concerns in clinical trials of regenerative medicine based on human pluripotent stem cells (hPSCs. Here, we demonstrate that conditionally replicating adenoviruses that specifically target cancers using multiple factors (m-CRAs, originally developed as anticancer drugs, may also be useful as novel antitumorigenic agents in hPSC-based therapy. The survivin promoter was more active in undifferentiated hPSCs than the telomerase reverse transcriptase (TERT promoter, whereas both promoters were minimally active in differentiated normal cells. Accordingly, survivin-responsive m-CRA (Surv.m-CRA killed undifferentiated hPSCs more efficiently than TERT-responsive m-CRAs (Tert.m-CRA; both m-CRAs exhibited efficient viral replication and cytotoxicity in undifferentiated hPSCs, but not in cocultured differentiated normal cells. Pre-infection of hPSCs with Surv.m-CRA or Tert.m-CRA abolished in vivo teratoma formation in a dose-dependent manner following hPSC implantation into mice. Thus, m-CRAs, and in particular Surv.m-CRAs, represent novel antitumorigenic agents that could facilitate safe clinical applications of hPSC-based regenerative medicine.

  14. Transcription profiling by array of the response of Arabidopsis cultivar Columbia etiolated seedlings and undifferentiated tissue culture cells to the spaceflight environment

    Data.gov (United States)

    National Aeronautics and Space Administration — We address a key baseline question of whether gene expression changes are induced by the orbital environment and then we ask whether undifferentiated cells cells...

  15. Protective Role of Hypothermia Against Heat Stress in Differentiated and Undifferentiated Human Neural Precursor Cells: A Differential Approach for the Treatment of Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Sandeep Kumar Vishwakarma

    2017-11-01

    Conclusion: Mild-hypothermia treatment induces attenuated heat shock response against heat stress resulting in induced HSP-70 expression that significantly improves structure and function of both undifferentiated human NPCs and differentiated neurons.

  16. Clinical, epidemiological and virological features of dengue virus infections in vietnamese patients presenting to primary care facilities with acute undifferentiated fever

    NARCIS (Netherlands)

    Thai, Khoa T. D.; Phuong, Hoang Lan; Thanh Nga, Tran Thi; Giao, Phan Trong; Hung, Le Quoc; van Nam, Nguyen; Binh, Tran Quang; Simmons, Cameron; Farrar, Jeremy; Hien, Tran Thinh; Rogier van Doorn, H.; de Jong, Menno D.; de Vries, Peter J.

    2010-01-01

    Objectives: To explore clinical and virological characteristics and describe the epidemiology of dengue in patients who presented with acute undifferentiated fever (AUF) at primary health centers (PHC) in Binh Thuan Province, Vietnam. Methods: A prospective observational study was conducted from

  17. Vegetative status characteristics in children with neurological pathology on the background of undifferentiated connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Tyazka O.V.

    2016-03-01

    Full Text Available Background. Disorders of the autonomic nervous system are the most common pathological conditions detected in 20% - 85% of children and adolescents according to different authors' data. Assessment of the vegetative status in the period of intensive growth and differentiation of organs and tissues that is characteristic of childhood is of great practical importance. Identification of vegetative dysregulation is an important diagnostic measure in children's health status evaluation especially in patients with undifferentiated connective tissue dysplasia (UNDCT taking into account its genetic determinism and debut in childhood. Genetically determined biochemical disorders in the connective tissue followed by formation of characteristic pathological substrates cause dysregulation of sympathoadrenal system and correlate with UNDCT severity degree. Material and methods. There were 100 children aged from 5 to 16 years engaged in the investigation. All of them were treated in the neurological department of the City clinical hospital №4. All patients were divided into two groups: basic group, which included 50 children with neurological disorders and UNDC, and control one, which consisted of 50 children with neurological disorders without UNDCT. The survey included obstetric history analysis, anthropometry to determine the ratio of longitudinal and transverse dimensions (the index of Vervica; clinical and neurological examination (study of reflex&motor areas, sensory function, coordination; laboratory methods (clinical blood count and biochemical blood tests to determine the level of potassium and calcium ions, instrumental methods (electroencephalography, rheoencephalography, magnetic resonance imaging of the brain. Osokina's table was used for baseline autonomic tone assessment. The evaluation was conducted by counting the number of signs. Subsequently was performed the summation of the scores with the determination of the percentage of predominant

  18. ARG1 Functions in the Physiological Adaptation of Undifferentiated Plant Cells to Spaceflight

    Science.gov (United States)

    Zupanska, Agata K.; Schultz, Eric R.; Yao, JiQiang; Sng, Natasha J.; Zhou, Mingqi; Callaham, Jordan B.; Ferl, Robert J.; Paul, Anna-Lisa

    2017-11-01

    Scientific access to spaceflight and especially the International Space Station has revealed that physiological adaptation to spaceflight is accompanied or enabled by changes in gene expression that significantly alter the transcriptome of cells in spaceflight. A wide range of experiments have shown that plant physiological adaptation to spaceflight involves gene expression changes that alter cell wall and other metabolisms. However, while transcriptome profiling aptly illuminates changes in gene expression that accompany spaceflight adaptation, mutation analysis is required to illuminate key elements required for that adaptation. Here we report how transcriptome profiling was used to gain insight into the spaceflight adaptation role of Altered response to gravity 1 (Arg1), a gene known to affect gravity responses in plants on Earth. The study compared expression profiles of cultured lines of Arabidopsis thaliana derived from wild-type (WT) cultivar Col-0 to profiles from a knock-out line deficient in the gene encoding ARG1 (ARG1 KO), both on the ground and in space. The cell lines were launched on SpaceX CRS-2 as part of the Cellular Expression Logic (CEL) experiment of the BRIC-17 spaceflight mission. The cultured cell lines were grown within 60 mm Petri plates in Petri Dish Fixation Units (PDFUs) that were housed within the Biological Research In Canisters (BRIC) hardware. Spaceflight samples were fixed on orbit. Differentially expressed genes were identified between the two environments (spaceflight and comparable ground controls) and the two genotypes (WT and ARG1 KO). Each genotype engaged unique genes during physiological adaptation to the spaceflight environment, with little overlap. Most of the genes altered in expression in spaceflight in WT cells were found to be Arg1-dependent, suggesting a major role for that gene in the physiological adaptation of undifferentiated cells to spaceflight.

  19. Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

    Science.gov (United States)

    Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

    To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  20. Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer

    Science.gov (United States)

    Asakawa, Yukiko; Ohtaka, Masahiko; Maekawa, Shinya; Fukasawa, Mitsuharu; Nakayama, Yasuhiro; Yamaguchi, Tatsuya; Inoue, Taisuke; Uetake, Tomoyoshi; Sakamoto, Minoru; Sato, Tadashi; Kawaguchi, Yoshihiko; Fujii, Hideki; Mochizuki, Kunio; Hada, Masao; Oyama, Toshio; Yasumura, Tomotaka; Omata, Kosaku; Nishiyama, Atsushi; Naito, Keiichi; Hata, Hideo; Haba, Yoshiaki; Miyata, Kazuyuki; Saitoh, Haruhisa; Yamadera, Yoichi; Miura, Kazuo; Kawaoi, Akira; Abe, Tohru; Tsunoda, Hajime; Honda, Yuji; Kurosaki, Masayuki; Enomoto, Nobuyuki

    2015-01-01

    AIM: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor. PMID:25759537

  1. Radiation-induced apoptosis in undifferentiated cells of the developing brain as a biological defense mechanism

    International Nuclear Information System (INIS)

    Inouye, Minioru; Tamaru, Masao.

    1994-01-01

    Undifferentiated neural (UN) cells of the developing mammalian brain are highly sensitive to the lethal effects of ionizing radiation. Nuclear and cytoplasmic condensation, transglutaminase activation, and internucleosomal DNA cleavage reveal radiation-induced cell death in the ventricular zone of the cerebral mantle and external granular layer of the cerebellum to be due to apoptosis. A statistically significant increase of cell mortality can be induced by 0.03 Gy X-irradiation, and the mortality increases linearly with increasing doses. It is not changed by split doses, probably because of the very slow repair of cellular damage and a lack of adaptive response. Although extensive apoptosis in the UN cell population results in microcephaly and mental retardation, it possesses the ability to recover from a considerable cell loss and to form the normal structure of the central nervous system. The number of cell deaths needed to induce tissue adnormalities in the adult murine brain rises in the range of 15-25% of the germinal cell population; with the threshold doses at about 0.3 Gy for cerebral anomalies and 1 Gy for cerebellar abnormalities. Threshold level is similarly suggested in prenatally exposed A-bomb survivors. High radiosensitivity of UN cells is assumed to be a manifestation of the ability of the cell to commit suicide when injured. Repeated replication of DNA and extensive gene expression are required in future proliferation and differentiation. Once an abnormality in DNA was induced and fixed in the UN cell, it would be greatly amplified and prove a danger in producing malformations and tumors. These cells would thus commit suicide for the benefit of the individual to eliminate their acquired genetic abnormalities rather than make DNA repair. UN cells in the developing brain are highly radiosensitive and readily involved in apoptosis. Paradoxically, however, this may be to protect individuals against teratogenesis and tumorigenesis. (J.P.N.)

  2. CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ke, Chien-Chih [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Liu, Ren-Shyan [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, National PET/Cyclotron Center, Taipei (China); National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei (China); Yang, An-Hang [Taipei Veterans General Hospital, Department of Pathology and Laboratory Medicine, Taipei (China); National Yang-Ming University, Department of Pathology, School of Medicine, Taipei (China); Liu, Ching-Sheng [National Yang-Ming University Medical School, Department of Nuclear Medicine, School of Medicine, Taipei (China); Chi, Chin-Wen [National Yang-Ming University, Institute of Pharmacology, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China); Tseng, Ling-Ming [National Yang Ming University, Institute of Clinical Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Tsai, Yi-Fan [Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Ho, Jennifer H. [Taipei Medical University, Graduate Institute of Clinical Medicine, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Department of Ophthalmology, Taipei (China); Taipei Medical University-Wan Fang Medical Center, Center for Stem Cell Research, Taipei (China); Lee, Chen-Hsen [NRPGM, Molecular and Genetic Imaging Core, Taipei (China); National Yang-Ming University, School of Medicine, Taipei (China); Taipei Veterans General Hospital, Department of Surgery, Taipei (China); Lee, Oscar K. [Taipei Veterans General Hospital, Department of Orthopedics, Taipei (China); National Yang-Ming University, Stem Cell Research Center, Taipei (China); Taipei Veterans General Hospital, Department of Medical Research and Education, Taipei (China)

    2013-01-15

    {sup 131}I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133{sup +} cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133{sup +} cells and higher radioresistance. After {gamma}-irradiation of the cells, the CD133{sup +} population was enriched due to the higher apoptotic rate of CD133{sup -} cells. In vivo {sup 131}I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133{sup +} cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133{sup +} cells. (orig.)

  3. Glycoconjugates as target antigens in peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Ljubica Suturkova

    2014-12-01

    Full Text Available Identification and characterization of antigens present at the human peripheral nerve is a great challenge in the field of neuroimmunology. The latest investigations are focused on the understanding of the biology of glycoconjugates present at the peripheral nerve, and their immunological reactivity. Increased titers of antibodies that recognize carbohydrate determinants of glycoconjugates (glycolipids and glycoproteins are associated with distinct neuropathic syndromes. There is considerable cross-reactivity among anti-ganglioside antibodies, resulting from shared oligosaccharide epitopes, possibly explaining the overlap in syndromes observed in many affected patients. Sera from patients with neuropathies (GBS, chronic inflammatory demielynating polyneuropathy - CIDP, multifocal motor neuropathy - MMN, cross-react with glycoproteins isolated from human peripheral nerve and from Campylobacter jejuni O:19. The frequency of occurrence of antibodies against these glycoproteins is different, depending of the type of neuropathy. Identification of the cross-reactive glycoproteins and possible additional auto antigens could be useful in laboratory evaluation of peripheral neuropathies and help to develop a more effective therapeutic approach.

  4. Sigma-1 receptor and inflammatory pain.

    Science.gov (United States)

    Gris, Georgia; Cobos, Enrique José; Zamanillo, Daniel; Portillo-Salido, Enrique

    2015-06-01

    The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion channels to modulate their activity. Sig-1R is located in areas of the central and peripheral nervous system that are key to pain control. Previous preclinical studies have suggested a potential therapeutic use of Sig-1R antagonists for the management of neuropathic pain. Recent studies using pharmacological and genetic tools have explored the role of Sig-1R in inflammatory pain conditions. Mice lacking the Sig-1R have shown different patterns of phenotypic responses to inflammatory injury. Systemic or peripheral administration of several Sig-1R antagonists, including the selective Sig-1R antagonist S1RA, inhibited both mechanical and thermal hypersensitivity in several preclinical models of inflammatory pain. These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain.

  5. [Physical activity and peripheral arterial obstructive disease].

    Science.gov (United States)

    Calanca, Luca; Pellegrin, Maxime; Mazzolai, Lucia

    2010-02-10

    Intermittent claudication (IC) is the most common clinical manifestation of atherosclerotic peripheral arterial disease. Exercise training plays a major role in treating patients with IC. Regular exercise increases functional walking capacity, reduces cardiovascular mortality and improves quality of life. This seems to be achieved by: favorable effect on cardiovascular risk factors, anti-inflammatory effect, increased collateral blood flux, improved rheology profile, endothelial function, fibrinolysis, and muscular metabolism. However, exact mechanisms underlying beneficial effect of exercise remain largely unknown. Exercise modalities will be discussed in this article.

  6. Inflammatory pathways in spondyloarthritis.

    Science.gov (United States)

    Hreggvidsdottir, Hulda S; Noordenbos, Troy; Baeten, Dominique L

    2014-01-01

    Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional evidence from human and animal studies support a role of these pathways in the disease. TNF has a key role in SpA as blockade significantly reduces inflammation and destruction, however the treatment does not halt new bone formation. New insights into the TNF pathway were recently obtained from an animal model specifically overexpressing the transmembrane form of TNF. This model leads to axial and peripheral new bone formation which is not seen in soluble TNF overexpression models, indicating different pathogenic roles of soluble and transmembrane TNF in arthritis development. Besides TNF, the IL-23/IL-17 axis is emerging as an important inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17 blockade has been shown to be efficacious for AS patients in a phase II trial. In this review, we focus on the cytokine pathways that have recently been genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review the current genetic, experimental and human in vivo data available and discuss how these different pathways are involved in the pathophysiology of SpA. Additionally, we discuss how these pathways relate to the pathogenic new bone formation in SpA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Study of acute undifferentiated fever cases and their etiologies in rural Konkan area of Maharashtra state

    Directory of Open Access Journals (Sweden)

    Patil S. N

    2016-08-01

    Full Text Available Background: Acute undifferentiated fever (AUF is a common cause for which the patients seek health care in India. It is region specific and has similar clinical presentation, with varied etiologies. Due to this it posses challenge to the diagnosis, treatment and public health. Majority of patients present with nondescript symptoms. Scrub typhus, Malaria, Enteric Fever, Dengue, Leptospirosis, Chikungunya, Spotted fever, Rickettsiosis, Hantavirus, Q fever, Brucellosis, Influenza and other bacterial infections are some of the common etiologies of AUF. The prevalence of local AUF etiologies helps to prioritize differential diagnosis and guide the treatment. The study aimed to find out the predominant AUF etiologies in the rural Konkan area of Maharashtra state in India. Materials and Methods: This prospective observational study was conducted at a tertiary care hospital on the samples received from District hospitals and Primary health centers from Sindhudurg District of Maharashtra state for the duration of October 2012 to January 2014. Patients with age 5years and with classical symptoms of febrile illness were included in the study. About 500 blood samples received were investigated for Malaria, Bacterial culture sensitivity, Leptospira culture, ELISA for scrub typhus, Brucella, Dengue and Leptospira and further evaluated for commonest region specific AUF etiology. Results: The study included 500 blood samples obtained from patients presenting with classical symptoms of AUF. Samples received from males showed highest number of positive cases amounting for 82.47% with majority of cases (83% cases in middle age group. The sero-positivity of samples accounted for 42.8%. Brucella was the most common cause of AUF (28.50% followed by Leptospira (27.10% and Scrub typhus (21.49%. Interestingly there were no positive cases of malaria and only 11.21% samples positive for Dengue which are considered as most common AUF etiologies and treated accordingly

  8. The educational needs of patients with undifferentiated spondyloarthritis: Validation of the ENAT questionnaire and needs assessment.

    Science.gov (United States)

    Bremander, A; Haglund, E; Bergman, S; Ndosi, M

    2018-02-07

    The aim of the present study was to validate the Swedish version of the educational needs assessment tool (SwENAT) in undifferentiated spondyloarthritis (USpA) and use it to study the educational needs of patients with USpA. This was a cross-sectional study, recruiting a random sample of patients with USpA from a hospital register in Sweden. Educational needs data were collected, together with disease activity and function indices (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Bath Ankylosing Spondylitis Functional Index [BASFI]). Rasch analysis was utilized to evaluate the construct validity, internal consistency and unidimensionality of the SwENAT before studying differences in educational needs between patient subgroups (gender, age and disease severity). Complete responses were obtained from 77 patients (48 women), with a mean age (standard deviation [SD]) of 50 (12) years, a disease duration of 16 (11) years, a BASDAI score of 4.9 (1.9) and a BASFI score of 3.1 (2.3). The SwENAT satisfied the requirements of the Rasch model (χ 2 = 11.488; p = 0.119), including strict unidimensionality. Overall, the mean (SD) SwENAT score was 86 (32). Women reported higher needs than men in the domains of pain (mean [SD] 13.1 [6.8] versus 10.1 [6.0]; p = 0.05); movement (mean [SD] 13.0 [5.5] versus 9.9 [5.7]; p = 0.02) and self-help (mean [SD] 17.0 [5.8] versus 14.1 [5.0]; p = 0.03). Higher disease activity (BASDAI >4) was associated with higher educational needs (mean [SD] 92.6 [31.9] versus 73.7 [29.4]; p = 0.02). These data suggest that the SwENAT is valid in USpA. Women and patients with higher disease activity are more likely to have high levels of educational needs, so special attention and strategies to target patient education are warranted. Copyright © 2018 John Wiley & Sons, Ltd.

  9. Expression of the chitinase family glycoprotein YKL-40 in undifferentiated, differentiated and trans-differentiated mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Daniel J Hoover

    Full Text Available The glycoprotein YKL-40 (CHI3L1 is a secreted chitinase family protein that induces angiogenesis, cell survival, and cell proliferation, and plays roles in tissue remodeling and immune regulation. It is expressed primarily in cells of mesenchymal origin, is overexpressed in numerous aggressive carcinomas and sarcomas, but is rarely expressed in normal ectodermal tissues. Bone marrow-derived mesenchymal stem cells (MSCs can be induced to differentiate into various mesenchymal tissues and trans-differentiate into some non-mesenchymal cell types. Since YKL-40 has been used as a mesenchymal marker, we followed YKL-40 expression as undifferentiated MSCs were induced to differentiate into bone, cartilage, and neural phenotypes. Undifferentiated MSCs contain significant levels of YKL-40 mRNA but do not synthesize detectable levels of YKL-40 protein. MSCs induced to differentiate into chondrocytes and osteocytes soon began to express and secrete YKL-40 protein, as do ex vivo cultured chondrocytes and primary osteocytes. In contrast, MSCs induced to trans-differentiate into neurons did not synthesize YKL-40 protein, consistent with the general absence of YKL-40 protein in normal CNS parenchyma. However, these trans-differentiated neurons retained significant levels of YKL-40 mRNA, suggesting the mechanisms which prevented YKL-40 translation in undifferentiated MSCs remained in place, and that these trans-differentiated neurons differ in at least this way from neurons derived from neuronal stem cells. Utilization of a differentiation protocol containing β-mercaptoethanol resulted in cells that expressed significant amounts of intracellular YKL-40 protein that was not secreted, which is not seen in normal cells. Thus the synthesis of YKL-40 protein is a marker for MSC differentiation into mature mesenchymal phenotypes, and the presence of untranslated YKL-40 mRNA in non-mesenchymal cells derived from MSCs reflects differences between differentiated and

  10. Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam

    Directory of Open Access Journals (Sweden)

    Binh Tran Q

    2010-09-01

    Full Text Available Abstract Background Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics. This study investigate if educating primary health center (PHC staff or introducing rapid diagnostic tests (RDTs improve diagnostic resolution and accuracy for acute undifferentiated fever (AUF and reduce prescription of antibiotics and costs for patients. Methods In a PHC randomized intervention study in southern Vietnam, the presumptive diagnoses for AUF patients were recorded and confirmed by serology on paired (acute and convalescence sera. After one year, PHCs were randomized to four intervention arms: training on infectious diseases (A, the provision of RDTs (B, the combination (AB and control (C. The intervention lasted from 2002 until 2006. Results The frequency of the non-etiologic diagnosis "undifferentiated fever" decreased in group AB, and - with some delay- also in group B. The diagnosis "dengue" increased in group AB, but only temporarily, although dengue was the most common cause of fever. A correct diagnosis for dengue initially increased in groups AB and B but only for AB this was sustained. Antibiotics prescriptions increased in group C. During intervention it initially declined in AB with a tendency to increase afterwards; in B it gradually declined. There was a substantial increase of patients' costs in B. Conclusions The introduction of RDTs for infectious diseases such as dengue, through free market principles, does improve the quality of the diagnosis and decreases the prescription of antibiotics at the PHC level. However, the effect is more sustainable in combination with

  11. Randomised primary health center based interventions to improve the diagnosis and treatment of undifferentiated fever and dengue in Vietnam.

    Science.gov (United States)

    Phuong, Hoang L; Nga, Tran T T; Giao, Phan T; Hung, Le Q; Binh, Tran Q; Nam, Nguyen V; Nagelkerke, Nico; de Vries, Peter J

    2010-09-21

    Fever is a common reason for attending primary health facilities in Vietnam. Response of health care providers to patients with fever commonly consists of making a presumptive diagnosis and proposing corresponding treatment. In Vietnam, where malaria was brought under control, viral infections, notably dengue, are the main causes of undifferentiated fever but they are often misdiagnosed and inappropriately treated with antibiotics.This study investigate if educating primary health center (PHC) staff or introducing rapid diagnostic tests (RDTs) improve diagnostic resolution and accuracy for acute undifferentiated fever (AUF) and reduce prescription of antibiotics and costs for patients. In a PHC randomized intervention study in southern Vietnam, the presumptive diagnoses for AUF patients were recorded and confirmed by serology on paired (acute and convalescence) sera. After one year, PHCs were randomized to four intervention arms: training on infectious diseases (A), the provision of RDTs (B), the combination (AB) and control (C). The intervention lasted from 2002 until 2006. The frequency of the non-etiologic diagnosis "undifferentiated fever" decreased in group AB, and - with some delay- also in group B. The diagnosis "dengue" increased in group AB, but only temporarily, although dengue was the most common cause of fever. A correct diagnosis for dengue initially increased in groups AB and B but only for AB this was sustained. Antibiotics prescriptions increased in group C. During intervention it initially declined in AB with a tendency to increase afterwards; in B it gradually declined. There was a substantial increase of patients' costs in B. The introduction of RDTs for infectious diseases such as dengue, through free market principles, does improve the quality of the diagnosis and decreases the prescription of antibiotics at the PHC level. However, the effect is more sustainable in combination with training; without it RDTs lead to an excess of costs.

  12. [Clinical overview of auto-inflammatory diseases].

    Science.gov (United States)

    Georgin-Lavialle, S; Rodrigues, F; Hentgen, V; Fayand, A; Quartier, P; Bader-Meunier, B; Bachmeyer, C; Savey, L; Louvrier, C; Sarrabay, G; Melki, I; Belot, A; Koné-Paut, I; Grateau, G

    2018-04-01

    Monogenic auto-inflammatory diseases are characterized by genetic abnormalities coding for proteins involved in innate immunity. They were initially described in mirror with auto-immune diseases because of the absence of circulating autoantibodies. Their main feature is the presence of peripheral blood inflammation in crisis without infection. The best-known auto-inflammatory diseases are mediated by interleukines that consisted in the 4 following diseases familial Mediterranean fever, cryopyrinopathies, TNFRSF1A-related intermittent fever, and mevalonate kinase deficiency. Since 10 years, many other diseases have been discovered, especially thanks to the progress in genetics. In this review, we propose the actual panorama of the main known auto-inflammatory diseases. Some of them are recurrent fevers with crisis and remission; some others evaluate more chronically; some are associated with immunodeficiency. From a physiopathological point of view, we can separate diseases mediated by interleukine-1 and diseases mediated by interferon. Then some polygenic inflammatory diseases will be shortly described: Still disease, Schnitzler syndrome, aseptic abscesses syndrome. The diagnosis of auto-inflammatory disease is largely based on anamnesis, the presence of peripheral inflammation during attacks and genetic analysis, which are more and more performant. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  13. Crosstalk between the heart and peripheral organs in heart failure.

    Science.gov (United States)

    Jahng, James Won Suk; Song, Erfei; Sweeney, Gary

    2016-03-11

    Mediators from peripheral tissues can influence the development and progression of heart failure (HF). For example, in obesity, an altered profile of adipokines secreted from adipose tissue increases the incidence of myocardial infarction (MI). Less appreciated is that heart remodeling releases cardiokines, which can strongly impact various peripheral tissues. Inflammation, and, in particular, activation of the nucleotide-binding oligomerization domain-like receptors with pyrin domain (NLRP3) inflammasome are likely to have a central role in cardiac remodeling and mediating crosstalk with other organs. Activation of the NLRP3 inflammasome in response to cardiac injury induces the production and secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition to having local effects in the myocardium, these pro-inflammatory cytokines are released into circulation and cause remodeling in the spleen, kidney, skeletal muscle and adipose tissue. The collective effects of various cardiokines on peripheral organs depend on the degree and duration of myocardial injury, with systematic inflammation and peripheral tissue damage observed as HF progresses. In this article, we review mechanisms regulating myocardial inflammation in HF and the role of factors secreted by the heart in communication with peripheral tissues.

  14. Acupuncture for peripheral joint osteoarthritis.

    NARCIS (Netherlands)

    Manheimer, Eric; Cheng, K.; Linde, Klaus; Lao, Lixing; Yoo, Junghee; Wieland, Susan; van der Windt, Daniëlle Awm; Berman, Brian M.; Bouter, Lex M.

    2010-01-01

    BACKGROUND: Peripheral joint osteoarthritis is a major cause of pain and functional limitation. Few treatments are safe and effective. OBJECTIVES: To assess the effects of acupuncture for treating peripheral joint osteoarthritis. SEARCH STRATEGY: We searched the Cochrane Central Register of

  15. Undifferentiated bronchial fibroblasts derived from asthmatic patients display higher elastic modulus than their non-asthmatic counterparts.

    Science.gov (United States)

    Sarna, Michal; Wojcik, Katarzyna A; Hermanowicz, Pawel; Wnuk, Dawid; Burda, Kvetoslava; Sanak, Marek; Czyż, Jarosław; Michalik, Marta

    2015-01-01

    During asthma development, differentiation of epithelial cells and fibroblasts towards the contractile phenotype is associated with bronchial wall remodeling and airway constriction. Pathological fibroblast-to-myofibroblast transition (FMT) can be triggered by local inflammation of bronchial walls. Recently, we have demonstrated that human bronchial fibroblasts (HBFs) derived from asthmatic patients display some inherent features which facilitate their FMT in vitro. In spite of intensive research efforts, these properties remain unknown. Importantly, the role of undifferentiated HBFs in the asthmatic process was systematically omitted. Specifically, biomechanical properties of undifferentiated HBFs have not been considered in either FMT or airway remodeling in vivo. Here, we combine atomic force spectroscopy with fluorescence microscopy to compare mechanical properties and actin cytoskeleton architecture of HBFs derived from asthmatic patients and non-asthmatic donors. Our results demonstrate that asthmatic HBFs form thick and aligned 'ventral' stress fibers accompanied by enlarged focal adhesions. The differences in cytoskeleton architecture between asthmatic and non-asthmatic cells correlate with higher elastic modulus of asthmatic HBFs and their increased predilection to TGF-β-induced FMT. Due to the obvious links between cytoskeleton architecture and mechanical equilibrium, our observations indicate that HBFs derived from asthmatic bronchi can develop considerably higher static tension than non-asthmatic HBFs. This previously unexplored property of asthmatic HBFs may be potentially important for their myofibroblastic differentiation and bronchial wall remodeling during asthma development.

  16. A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

    Science.gov (United States)

    Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

    2017-08-07

    Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

  17. 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 ...

  18. 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.

  19. Peripheral vascular injuries

    Directory of Open Access Journals (Sweden)

    Celal Yavuz

    2009-01-01

    Full Text Available Aim: To determine etiology and management in patients with peripheral vascular trauma.Materials and Methods: From 2005 to 2006 with a diagnosis of peripheral artery injury, 69 cases admitted to Diyarbakır State Hospital Department of Cardiovascular surgery.Results: These cases have been respectively reviewed. The causes of injuries were; penetrating injuries in 60 cases (87%, blunt trauma in seven cases (10% and gunshot injuries in two cases (3%. In 53 cases (74% upper extremity, in 15 cases (21% lower extremity was involved. As a surgical procedure, in 34 cases (47% end-to-end anastomosis, in 28 cases (39% lateral suture, in five cases (7% venous graft interposition, in five cases (7% ligation was performed.Conclusion: Early intervention, transfusion of fluid and blood, systemic anticoagulation, preoperative and postoperative detailed debridement decreased the morbidity and mortality rates.

  20. Peripheral Opioid Analgesia

    Science.gov (United States)

    1999-07-16

    well. Morphine was isolated in 1806 and as early as 1850 it was used medicinally in conjunction with anesthesia , and it continues to be used for pain...and morphine stimulate POMC expression which is probably mediated through CRH. In the periphery of humans, rats and cows the POMC mRNA is 200-300 base...use of any copyrighted material in the dissenation entitled: "Peripheral Opioid Analgesia" beyond brief excerpts is with the pennission of the

  1. Painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    SUN Bo

    2013-09-01

    Full Text Available Painful peripheral neuropathy (PPN is characterized by neuropathic pain (NP, which is accompanied by dysfunction of motor, sensory and autonomic nervous system. It always involves small nerve fibers, including A δ and C fibers. PPN can be classified into two types according to etiology: hereditary and acquired. Pain of PPN can manifest as spontaneous pain and stimulus-evoked pain (allodynia, hyperalgesia and hyperpathia. The manifestation of typical cases is length-dependent, which firstly involves the feet, and then progresses proximally and to the hands, presenting a glove-stock pattern. PPN can be either an isolated disease entity or part of other diseases. The former indicates idiopathic small fiber neuropathy (SFN, while the latter contains various diseases involving peripheral nerve fibers, including systemic diseases such as diabetes mellitus and peripheral neuropathy with other causes. The accessory examinations of PPN include quantitative sensory testing (QST, intraepidermal nerve fiber density (IENFD, sympathetic skin response (SSR, etc. Among them, IENFD is the "golden standard" for SFN. The major therapeutic methods are to control primary diseases and relieve pain. Medications alleviating neuropathic pain consist of carbamazepine, pregabalin, gabapentin and amitriptyline, etc.

  2. Analgesic and anti-inflammatory activity of root bark of Grewia asiatica Linn. in rodents

    Directory of Open Access Journals (Sweden)

    Udaybhan Singh Paviaya

    2013-01-01

    Conclusions: The present study indicates that root bark of G. asiatica exhibits peripheral and central analgesic effect and anti-inflammatory activity, which may be attributed to the various phytochemicals present in root bark of G. asiatica.

  3. The Immunological Basis of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Francesca A. R. Silva

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are chronic ailments, Crohn’s disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

  4. Undifferentiated Pleomorphic Sarcoma and the Importance of Considering the Oncogenic and Immune-Suppressant Role of the Human T-Cell Lymphotropic Virus Type 1: A Case Report

    Directory of Open Access Journals (Sweden)

    Sergio Lupo

    2017-05-01

    Full Text Available IntroductionSoft-tissue sarcomas account for 0.7% of all malignant tumors, with an incidence rate of 3 per 100,000 persons/year. The undifferentiated pleomorphic sarcoma (UPS with giant cells, a high grade tumor of soft tissue, is very unusual, especially in young adults before the age of 40. Human T-cell lymphotropic virus type 1 (HTLV-1 is a human retrovirus, classified as group 1 human carcinogens by The International Agency for Research on Cancer, that causes an aggressive malignancy known as adult T-cell lymphoma/leukemia and a progressive chronic inflammatory neurological disease named HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. HTLV-1 causes accumulation of genetic mutations in the host genome that could contribute to cellular transformation, one of the oncogenic features of HTLV-1.Case reportWe describe a case of a young woman with UPS who suffered from HAM/TSP with 3 years of evolution. In 2013, the patient started with neurological symptoms: weakness in the legs and bladder dysfunction. One year later, the patient developed a mild paraparesis in both extremities, anti-HTLV-1 antibodies were detected in plasma and in cerebrospinal fluid, and HAM/TSP was confirmed. In November 2015, a benign ganglion cyst was first suspected without intervention and by March 2016 a sarcoma was diagnosed. Three weeks after surgical resection, the tumor aroused in deep tissue and behaved aggressively, implicating a curative wide resection of the fibula, joint reconstruction, and soft-tissue graft. Histopathological examination confirmed UPS with giant cells.Concluding remarksThe unapparent subclinical immunodeficiency state due to HTLV-1 infection deserves to be considered in order to carefully monitor the possibility of developing any type of cancer. Besides, reaching an accurate and timely diagnosis of UPS can be challenging due to the difficulty in diagnosis/classification and delayed consultation. In this particular case

  5. Peripheral odontogenic myxoma

    Directory of Open Access Journals (Sweden)

    Sanober Tasnime

    2016-01-01

    Full Text Available Odontogenic myxomas are a rare benign odontogenic mesenchymal tumor found exclusively in the tooth-bearing area of the jaw and are usually located centrally in the mandible. Soft tissue localization is rarely seen and is classified as peripheral odontogenic myxoma (POM. POM is slow growing and less aggressive as compared to central myxoma. It has a low recurrence rate, comprises 3-6% of all odontogenic tumors. Only a few cases of POM on maxillary gingiva are reported in the literature. Here, we present an unusual case of primary POM occurring in the gingiva of anterior maxilla in a 14-year-old female patient.

  6. Peripheral odontogenic myxoma.

    Science.gov (United States)

    Tasnime, Sanober; Saxena, Chitrapriya; Bansal, Vishal; Wadhwan, Vijay

    2016-01-01

    Odontogenic myxomas are a rare benign odontogenic mesenchymal tumor found exclusively in the tooth-bearing area of the jaw and are usually located centrally in the mandible. Soft tissue localization is rarely seen and is classified as peripheral odontogenic myxoma (POM). POM is slow growing and less aggressive as compared to central myxoma. It has a low recurrence rate, comprises 3-6% of all odontogenic tumors. Only a few cases of POM on maxillary gingiva are reported in the literature. Here, we present an unusual case of primary POM occurring in the gingiva of anterior maxilla in a 14-year-old female patient.

  7. 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.

  8. In Vivo and In Vitro Dynamics of Undifferentiated Embryonic Cell Transcription Factor 1

    Directory of Open Access Journals (Sweden)

    Christina Galonska

    2014-03-01

    Full Text Available Pluripotent stem cells retain the ability to differentiate into the three germ layers and germline. As a result, there is a major interest in characterizing regulators that establish and maintain pluripotency. The network of transcription factors continues to expand in complexity, and one factor, undifferentiated embryonic cell transcription factor 1 (UTF1, has recently moved more into the limelight. To facilitate the study of UTF1, we report the generation and characterization of two reporter lines that enable efficient tracking, mapping, and purification of endogenous UTF1. In particular, we include a built-in biotinylation system in our targeted locus that allows efficient and reliable pulldown. We also use this reporter to show the dynamic regulation of Utf1 in distinct stem cell conditions and demonstrate its utility for reprogramming studies. The multipurpose design of the reporter lines enables many directions of future study and should lead to a better understanding of UTF1’s diverse roles.

  9. COMPARATIVE ANALYSIS OF LONG-TERM RESULTS OF SURGICAL AND COMBINATION THERAPY FOR DIFFERENTIATED ADENOCARCINOMA AND UNDIFFERENTIATED GASTRIC CANCER

    Directory of Open Access Journals (Sweden)

    A. G. Davtyan

    2013-01-01

    Full Text Available The comparative analysis of long-term results of surgical and combined modality treatment for differentiated adenocarcinoma and undifferentiated gastric carcinoma (UGC has been presented. Treatment outcomes of patients with differentiated adenocarcinoma were shownto be significantly superior to those of patients with UGC (р=0,001. Intensive preoperative radiation therapy at a total dose of 20–27 Gy resulted in a significant improvement of treatment outcomes in patients with UGC, showing no any improvement of treatment outcomes in patients with differentiated adenocarcinoma. The benefits of combination treatment for patients with UGC were observed in cases with tumors not spreading through the serosa (рТ1–3 and with no evidence of regional lymph nodes involvement (N0.

  10. Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status

    Directory of Open Access Journals (Sweden)

    de Carvalho Marcelo

    2011-03-01

    Full Text Available Abstract Background In the bone marrow, hematopietic and mesenchymal stem cells form a unique niche in which the oxygen tension is low. Hypoxia may have a role in maintaining stem cell fate, self renewal and multipotency. However, whereas most studies addressed the effect of transient in vitro exposure of MSC to hypoxia, permanent culture under hypoxia should reflect the better physiological conditions. Results Morphologic studies, differentiation and transcriptional profiling experiments were performed on MSC cultured in normoxia (21% O2 versus hypoxia (5% O2 for up to passage 2. Cells at passage 0 and at passage 2 were compared, and those at passage 0 in hypoxia generated fewer and smaller colonies than in normoxia. In parallel, MSC displayed (>4 fold inhibition of genes involved in DNA metabolism, cell cycle progression and chromosome cohesion whereas transcripts involved in adhesion and metabolism (CD93, ESAM, VWF, PLVAP, ANGPT2, LEP, TCF1 were stimulated. Compared to normoxic cells, hypoxic cells were morphologically undifferentiated and contained less mitochondrias. After this lag phase, cells at passage 2 in hypoxia outgrew the cells cultured in normoxia and displayed an enhanced expression of genes (4-60 fold involved in extracellular matrix assembly (SMOC2, neural and muscle development (NOG, GPR56, SNTG2, LAMA and epithelial development (DMKN. This group described herein for the first time was assigned by the Gene Ontology program to "plasticity". Conclusion The duration of hypoxemia is a critical parameter in the differentiation capacity of MSC. Even in growth promoting conditions, hypoxia enhanced a genetic program that maintained the cells undifferentiated and multipotent. This condition may better reflect the in vivo gene signature of MSC, with potential implications in regenerative medicine.

  11. [Autonomic peripheral neuropathy].

    Science.gov (United States)

    Adams, David; Cauquil, Cecile; Lozeron, Pierre

    2012-11-01

    The mechanisms of dysautonomic disturbances are varied and mostly acquired. They can result from lesions of sympathetic or parasympathetic vegetative fibers located in the peripheral contingent, or in the somatic contingent by demyelination or axonal loss; or more rarely by cellular bodies in the sympathetic or parasympathetic ganglia. Several chronic peripheral neuropathies can be associated with dysautonomia. Only some causes need to be known because they can be clinically significant. Dysautonomia may be seen during chronic acquired neuropathies but also acute or subacute ones. The most frequent cause in the world is the dysautonomia of the diabetes; it affects all the systems; the cardiovascular dysfunction has an impact on the prognosis for survival when it is severe. Hereditary autonomic neuropathies are rare; they can declare themselves very early during the Riley-Day syndrome or very late during amyloid polyneuropathies due to transthyretin gene mutation. The diagnosis can be confirmed by molecular biology. The dysautonomia is frequent and often severe. These neuropathies justify symptomatic treatment to improve quality of life. For some of them, a specific treatment can be proposed to treat the causal affection to try to stop the progression of the disease. Copyright © 2012. Published by Elsevier Masson SAS.

  12. 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.

  13. Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study

    Science.gov (United States)

    Mueller, Tara C.; Siv, Sovannaroth; Khim, Nimol; Kim, Saorin; Fleischmann, Erna; Ariey, Frédéric; Buchy, Philippe; Guillard, Bertrand; González, Iveth J.; Christophel, Eva-Maria; Abdur, Rashid; von Sonnenburg, Frank; Bell, David; Menard, Didier

    2014-01-01

    In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue- and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects. PMID:24755844

  14. IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with radiographic progression in undifferentiated arthritis

    NARCIS (Netherlands)

    Ursum, J.; van der Weijden, M.A.C.; van Schaardenburg, D.; Prins, A.P.; Dijkmans, B.A.C.; Twisk, J.W.R.; Crusius, J.B.A.; van der Horst-Bruinsma, I.E.

    2010-01-01

    Objective. In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and

  15. Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.

    Science.gov (United States)

    Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Singh, Arun S; Eckardt, Mark A; Nelson, Scott D; Russell, Tara A; Dry, Sarah M; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Singh, Shree Ram; Eilber, Fritz C; Hoffman, Robert M

    2018-03-18

    Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. Published by Elsevier Inc.

  16. Tenocytes, pro-inflammatory cytokines and leukocytes: a relationship?

    OpenAIRE

    Al-Sadi, Onays; Schulze-Tanzil, Gundula; Kohl, Benjamin; Lohan, Anke; Lemke, Marion; Ertel, Wolfgang; John, Thilo

    2012-01-01

    Leukocyte derived pro-inflammatory mediators could be involved in tendon healing and scar formation. Hence, the effect of autologous leukocytes (PBMCs, peripheral blood mononuclear cells and neutrophils) on primary rabbit Achilles tenocytes gene expression was tested in insert assisted co-cultures.

  17. Antinociceptive and Anti-Inflammatory Effects of Solvent Extracts of ...

    African Journals Online (AJOL)

    Erah

    Solvent Extracts of Tagetes erectus Linn (Asteraceae). NV Shinde*, KG Kanase, ... Soxhlet extractor and refluxed continuously for 6 h. The solvent ... of the plant extract. Most of the so-called peripheral analgesics possess anti-inflammatory properties and, in some cases, also antipyretic activity besides analgesia. For many ...

  18. 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.

  19. [Peripheral arterial thromboembolism in Crohn's disease].

    Science.gov (United States)

    Ferrer, Isabel; Benavent, Guillem; Bastida, Guillermo; Arnau, Miguel Ángel; Iborra, Marisa; Beltrán, Belén; Aguas, Mariam; Hinojosa, Joaquín; Nos, Pilar

    2013-01-01

    Inflammatory Bowel Disease (IBD) usually affects the gastrointestinal tract, although some patients can also develop extraintestinal manifestations, such as vascular symptoms both venous and arterial ones. The former being more frequent than the latter. We report the case of a 62-year-old male, diagnosed of Crohńs disease (CD) (A3,L1+L4,B3), admitted to hospital for treatment of a retroperitoneal abscess. He presented a peripheral arterial thromboembolism during his stay, which required urgent embolectomy. After anticoagulation with low-molecular-weight heparin (LMWH), vascular magnetic resonance imaging revealed a large thrombus involving the descent aorta, which was solved with surgery and long-term anticoagulation. Peripheral arterial thrombosis is a rare extraintestinal manifestation of IBD. Nevertheless it is always important to consider it in patients with IBD. Prophylactic treatment should be made with low-molecular-weight heparin (LMWH) and definitive treatment with a combination of LMWH and surgery. Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

  20. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... the body—in both hands or in both feet. Some types of peripheral neuropathy develop suddenly, while others progress more slowly over many years. The symptoms of peripheral neuropathy often include: ... sleeping because of feet and leg pain Loss of balance and coordination ...

  1. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    rodents as a function of time after surgery. As predicted, those animals in the negative control group (no repair following nerve deficit injury ...80% of penetrating injuries being associated with peripheral nerve damage, typically involve large segmental nerve deficits. Standard repair uses...technology for repair of peripheral nerve injuries involving significant neural deficit with improved functional outcomes for the wounded warrior. The

  2. Neurological Manifestations In Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    youssef HNACH

    2015-06-01

    Full Text Available IntroductionThe purpose of this retrospective study was to report neurological manifestations noted in patients who were monitored for inflammatory bowel disease, in order to document the pathophysiological, clinical, progressive, and therapeutic characteristics of this entity.Material and methodsWe conducted a retrospective study on patients monitored -in the gastroenterology service in Ibn Sina Hospital in Rabat, Morocco- for inflammatory bowel disease from 1992 till 2013 and who developed neurological manifestations during its course. Patients with iatrogenic complications were excluded, as well as patients with cerebrovascular risk factors.ResultsThere were 6 patients, 4 of whom have developed peripheral manifestations. Electromyography enabled the diagnosis to be made and the outcome was favorable with disappearance of clinical manifestations and normalization of the electromyography.The other 2 patients, monitored for Crohn’s disease, developed ischemic stroke. Cerebral computed tomography angiography provided positive and topographic diagnosis. Two patients were admitted to specialized facilities.ConclusionNeurological manifestations in inflammatory bowel disease are rarely reported.  Peripheral neuropathies and stroke remain the most common manifestations. The mechanisms of these manifestations are not clearly defined yet. Currently, we hypothesize the interaction of immune mediators.

  3. 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.

  4. Inflammatory myofibroblastic tumor

    Directory of Open Access Journals (Sweden)

    Sangeeta Palaskar

    2011-01-01

    Full Text Available Inflammatory myofibroblastic tumor is an uncommon lesion of unknown cause. It encompasses a spectrum of myofibroblastic proliferation along with varying amount of inflammatory infiltrate. A number of terms have been applied to the lesion, namely, inflammatory pseudotumor, fibrous xanthoma, plasma cell granuloma, pseudosarcoma, lymphoid hamartoma, myxoid hamartoma, inflammatory myofibrohistiocytic proliferation, benign myofibroblatoma, and most recently, inflammatory myofibroblastic tumor. The diverse nomenclature is mostly descriptive and reflects the uncertainty regarding true biologic nature of these lesions. Recently, the concept of this lesion being reactive has been challenged based on the clinical demonstration of recurrences and metastasis and cytogenetic evidence of acquired clonal chromosomal abnormalities. We hereby report a case of inflammatory pseudotumor and review its inflammatory versus neoplastic behavior.

  5. Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics

    Directory of Open Access Journals (Sweden)

    Maria Carolina O. Rodrigues

    2012-01-01

    Full Text Available Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

  6. Clinicopathological study of vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Rong-fang DONG

    2014-06-01

    Full Text Available Objective To summarize the clinical features and neuropathological characteristics in patients with vasculitic peripheral neuropathy (VPN. Methods Clinical manifestations, laboratory examination and neuromuscular biopsy characteristics of 11 patients with VPN were retrospectively analyzed. The lesion of nerve, muscle and skin was observed under optical and electron microscope. Immunohistochemical analyses were carried out to detect neurofilament (NF, myelin basic protein (MBP, peripheral myelin protein 22 (PMP22 and S-100 protein (S-100 and further observing the neuropathy of neuraxon, myelin sheath and Schwann cells, and to detect human leukocyte antigen DR (HLA-DR, CD68, CD3 and CD20 to observe inflammatory cell infiltration. Immunofluorescent staining was used to detect the deposition of IgA, IgM, IgG and addiment C3 on vascular wall. The staining of periodic acid-Schiff (PAS, NADH-tetrazolium reductase (NADH-TR and modified Gomori trichrome (MGT were used to judge the myopathy. Results 1 Angiopathies were mainly manifested by small vessels of epineurium and perineurium, and infiltrated inflammatory cells were mainly CD3 + T cells. Three patients had active vasculitis, and 8 patients had non-active vasculitis. Among these 8 patients, 4 patients mainly presented fibrous obliteration of blood vessel, with slight inflammatroy cell infiltration, and the other 4 patients mainly showed perivascular inflammation. 2 Neuropathy: 6 patients had axon degeneration, and 5 patients had axon degeneration associated with demyelination. All of them demonstrated a reduction in myelinated fibers, mainly large diameter myelinated fibers, even on end-stage. 3 Muscle biopsy showed neurogenic atrophy. 4 Clinicopathologic diagnosis: among these 11 patients, 8 patients were diagnosed as systemic vasculitic peripheral neuropathy (SVPN, among whom 5 patients were diagnosed as primary systemic vasculitis [including 1 patient as Churg-Strauss syndrome (CSS, 2 patients as

  7. 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...

  8. Current peripheral bypass surgery: various clinical studies

    NARCIS (Netherlands)

    Slaa, Alexander te

    2011-01-01

    Substantial post-operative edema occurs in the majority of patients who undergo peripheral bypass surgery due to severe peripheral arterial disease (PAD). The pathophysiological mechanisms that underlay edema formation following peripheral bypass surgery include hyperemia, an increased capillary

  9. Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student.

    Science.gov (United States)

    Magid, Margret S; Shah, Darshana T; Cambor, Carolyn L; Conran, Richard M; Lin, Amy Y; Peerschke, Ellinor I B; Pessin, Melissa S; Harris, Ilene B

    2015-01-01

    The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula.

  10. CD10 positive recurrent undifferentiated mammary sarcoma in a young female: a rare case report with brief review of literature

    Directory of Open Access Journals (Sweden)

    Kachnar Varma

    2015-06-01

    Full Text Available Undifferentiated mammary sarcoma is extremely rare and the diagnosis is made only after exclusion of metaplastic carcinomas and malignant phyllodes tumor. Mammary sarcomas mostly display specified entities like liposarcomas or angiosarcomas. A 18-year-old female presented in 2010 with a right breast lump for which lumpectomy was done and on histopathological examination benign phyllodes tumor was diagnosed. In 2011, there was a recurrence at site of excised margin and on fine needle aspiration (FNA the diagnosis of benign breast disease was made; a small biopsy was received for which diagnosis of myoepithelial lesion was given. Then, the whole mass was excised, but histopathological examination report could not be followed up. In 2013, she again presented with a mass arising from the previously excised margin; on FNA, it was diagnosed as malignant sarcomatous lesion. Microscopy showed spindle shaped cells in diffuse and fascicular pattern with plump ovoid nuclei; coarse chromatin and eosinophilic cytoplasm were seen. Few round to ovoid cells with eccentric nuclei and showing bi- or multi-nucleation were present. Large area of necrosis and hemorrhage was present, too. No breast glands were found. Later on, diagnosis was confirmed on immunohistochemical examination. The case was considered worth due to the young age of the patient and lack of differentiation of the lesion in any specific type of sarcoma and CD10 positivity.

  11. Retroperitoneal undifferentiated pleomorphic sarcoma having microsatellite instability associated with Muir-Torre syndrome: case report and review of literature.

    Science.gov (United States)

    Lee, Nathan; Luthra, Rajyalakshmi; Lopez-Terrada, Dolores; Wang, Wei-Lien; Lazar, Alexander J

    2013-08-01

    Muir-Torre syndrome represents a rare autosomal dominant familial cancer predisposition disorder defined by the occurrence of cutaneous sebaceous tumors and an internal malignancy, most commonly gastrointestinal carcinoma. Most examples of hereditary non-polyposis cancer syndrome (Lynch syndrome), including the Muir-Torre syndrome, are associated with microsatellite instability (MSI) and germline mutations in mismatch repair genes-most commonly MLH1 or MSH2. We present a 58-year-old man with Muir-Torre syndrome and a large retroperitoneal mass (14.3 cm in greatest dimension) encompassing the left adrenal gland. Sections showed a cellular malignant tumor composed of spindle cells with a high mitotic index and lacking morphologic evidence of adipocytic differentiation. It was weakly reactive for smooth muscle actin (SMA) and negative for desmin, CD117, CD31, CD34, S100 protein and pan-cytokeratin. Further immunohistochemical analysis revealed intact expression of MLH1 but loss of MSH2 in tumor nuclei. Compared to non-neoplastic tissue, the tumor showed MSI in five of seven dinucleotide markers. Fluorescence in situ hybridization (FISH) failed to reveal 12q15 amplification, effectively excluding dedifferentiated liposarcoma as a diagnostic consideration. This is a rare case of a patient with Muir-Torre syndrome who developed a related high-grade undifferentiated pleomorphic sarcoma as the associated internal malignancy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Application of the boron neutron capture therapy to undifferentiated thyroid cancer using two boron compounds (BPA and BOPP)

    International Nuclear Information System (INIS)

    Viaggi, Mabel; Dagrosa, Maria A.; Juvenal, Guillermo J.; Pisarev, Mario A.; Longhino, Juan M.; Blaumann, Hernan R.; Calzetta Larrieu, Osvaldo A.; Kahl, Stephen B.

    2004-01-01

    We have shown the selective uptake of boronophenylalanine (BPA) by undifferentiated thyroid cancer (UTC) human cell line ARO, both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(ba-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 days before BPA, and the animals were sacrificed 60 min after the ip injection of BPA, a significant increase in boron uptake by the tumor was found (38-45ppm with both compounds Vs. 20 ppm with BPA alone). Five days post the ip BOPP injection and 1 hr after BPA, the ratios were: tumor/blood 3,75; tumor /distal skin 2. Other important ratios were tumor/thyroid 6,65 and tumor/lung 3,8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy). (author)

  13. Immunohistochemical expression of estrogens and progesterone receptors in carcinoma ex pleomorphic adenoma-undifferentiated and adenocarcinoma types.

    Science.gov (United States)

    Tarakji, Bassel; Nassani, Mohammad Z; Sloan, Philip

    2010-05-01

    Cancer of the salivary gland is one of the common cancers in the head and the neck regions. This type of cancer develops in the minor and the major salivary glands, and it sometimes metastasizes to other organs, particularly the lung. Morphologic mimicry and similarity in the expression of steroid hormone receptors between salivary gland tumours and breast tumours are well-known phenomena and are occasionally debated in the field of surgical pathology. The expression of sex hormone receptors in some tumours suggests a role for these receptors in tumor pathogenesis and therapy. Previous studies of the expression of estrogens and progesterone receptors in salivary gland tumours have reported conflicting results. Our study aimed to characterize alteration in the immunohistochemical expression of oestrogens receptor and progesterone receptor in the tumour cells of carcinoma arising in pleomorphic adenoma. 27 cases of carcinoma arising in pleomorphic adenoma (undifferentiated and adenocarcinoma types) were examined. The results showed that 27 (100 %) of 27 cases had negative nuclear staining for either oestrogens or progesterone receptors. Our data suggest that carcinomas arising in pleomorphic adenoma were not dependent on endocrine function.

  14. Hemorrhagic fever with renal syndrome and Crimean-Congo hemorrhagic fever as causes of acute undifferentiated febrile illness in Bulgaria.

    Science.gov (United States)

    Christova, Iva; Younan, Rasha; Taseva, Evgenia; Gladnishka, Teodora; Trifonova, Iva; Ivanova, Vladislava; Spik, Kristin; Schmaljohn, Connie; Mohareb, Emad

    2013-03-01

    Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are the 2 widespread viral hemorrhagic fevers occurring in Europe. HFRS is distributed throughout Europe, and CCHF has been reported mainly on the Balkan Peninsula and Russia. Both hemorrhagic fevers are endemic in Bulgaria. We investigated to what extent acute undifferentiated febrile illness in Bulgaria could be due to hantaviruses or to CCHF virus. Using enzyme-linked immunosorbent assays (ELISAs), we tested serum samples from 527 patients with acute febrile illness for antibodies against hantaviruses and CCHF virus. Immunoglobulin M (IgM) antibodies against hantaviruses were detected in 15 (2.8%) of the patients. Of the 15 hantavirus-positive patients, 8 (1.5%) were positive for Dobrava virus (DOBV), 5 (0.9%) were positive for Puumala virus (PUUV), and the remaining 2 were positive for both hantaviruses. A plaque reduction neutralization test (PRNT) confirmed 4 of the 10 DOBV-positive samples. PRNT was negative for all PUUV-positive samples. Serologic evidence of recent CCHF virus infection was found in 13 (2.5%) of the patients. Interestingly, HFRS and CCHF were not only detected in well-known endemic areas of Bulgaria but also in nonendemic regions. Our results suggested that in endemic countries, CCHF and/or HFRS might appear as a nonspecific febrile illness in a certain proportion of patients. Physicians must be aware of possible viral hemorrhagic fever cases, even if hemorrhages or renal impairment are not manifested.

  15. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.

    Science.gov (United States)

    Magnusson, Mattias; Sierra, Maria I; Sasidharan, Rajkumar; Prashad, Sacha L; Romero, Melissa; Saarikoski, Pamela; Van Handel, Ben; Huang, Andy; Li, Xinmin; Mikkola, Hanna K A

    2013-01-01

    Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

  16. Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.

    Directory of Open Access Journals (Sweden)

    Mattias Magnusson

    Full Text Available Lack of HLA-matched hematopoietic stem cells (HSC limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC stroma that protects human hematopoietic stem/progenitor cells (HSPC from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+ characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.

  17. Peripheral Artery Disease and Diabetes

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Peripheral Artery Disease & Diabetes Updated:Jan 26,2016 People with diabetes are ... life. This content was last reviewed January 2016. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  18. 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

  19. Comparative efficacy of tulathromycin versus a combination of florfenicol-oxytetracycline in the treatment of undifferentiated respiratory disease in large numbers of sheep

    OpenAIRE

    Mohsen Champour; Alinaghi Taghipour

    2015-01-01

    The objective of this study was to compare the efficacy of tulathromycin (TUL) with a combination of florfenicol (FFC) and long-acting oxytetracycline (LAOTC) in the treatment of naturally occurring undifferentiated respiratory diseases in large numbers of sheep. In this study, seven natural outbreaks of sheep pneumonia in Garmsar, Iran were considered. From these outbreaks, 400 sheep exhibiting the signs of respiratory diseases were selected, and the sheep were randomly divided into two equa...

  20. Highly sensitive in vitro methods for detection of residual undifferentiated cells in retinal pigment epithelial cells derived from human iPS cells.

    Directory of Open Access Journals (Sweden)

    Takuya Kuroda

    Full Text Available Human induced pluripotent stem cells (hiPSCs possess the capabilities of self-renewal and differentiation into multiple cell types, and they are free of the ethical problems associated with human embryonic stem cells (hESCs. These characteristics make hiPSCs a promising choice for future regenerative medicine research. There are significant obstacles, however, preventing the clinical use of hiPSCs. One of the most obvious safety issues is the presence of residual undifferentiated cells that have tumorigenic potential. To locate residual undifferentiated cells, in vivo teratoma formation assays have been performed with immunodeficient animals, which is both costly and time-consuming. Here, we examined three in vitro assay methods to detect undifferentiated cells (designated an in vitro tumorigenicity assay: soft agar colony formation assay, flow cytometry assay and quantitative real-time polymerase chain reaction assay (qRT-PCR. Although the soft agar colony formation assay was unable to detect hiPSCs even in the presence of a ROCK inhibitor that permits survival of dissociated hiPSCs/hESCs, the flow cytometry assay using anti-TRA-1-60 antibody detected 0.1% undifferentiated hiPSCs that were spiked in primary retinal pigment epithelial (RPE cells. Moreover, qRT-PCR with a specific probe and primers was found to detect a trace amount of Lin28 mRNA, which is equivalent to that present in a mixture of a single hiPSC and 5.0×10⁴ RPE cells. Our findings provide highly sensitive and quantitative in vitro assays essential for facilitating safety profiling of hiPSC-derived products for future regenerative medicine research.

  1. The CIPRUS study, a nurse-led psychological treatment for patients with undifferentiated somatoform disorder in primary care: study protocol for a randomised controlled trial

    OpenAIRE

    Sitnikova, Kate; Leone, Stephanie S.; Zonneveld, Lyonne N. L.; van Marwijk, Harm W. J.; Bosmans, Judith E.; van der Wouden, Johannes C.; van der Horst, Henri?tte E.

    2017-01-01

    Background Up to a third of patients presenting medically unexplained physical symptoms in primary care may have a somatoform disorder, of which undifferentiated somatoform disorder (USD) is the most common type. Psychological interventions can reduce symptoms associated with USD and improve functioning. Previous research has either been conducted in secondary care or interventions have been provided by general practitioners (GPs) or psychologists in primary care. As efficiency and cost-effec...

  2. Effect of inflammatory mediators on cardiovascular function.

    Science.gov (United States)

    Müller-Werdan, Ursula; Prondzinsky, Roland; Werdan, Karl

    2016-10-01

    Inflammatory mediators can interfere with cardiovascular system. This article describes some recent findings in this field. In septic cardiomyopathy, direct and indirect interactions of endotoxin with the pacemaker current contribute to cardiac autonomic dysfunction and inadequately high heart rate, worsening prognosis. In myocardial infarction, inflammatory blood cells correlate with impaired coronary microvascular reperfusion. In cardiogenic shock, systemic inflammation and development of multiorgan dysfunction syndrome have a major impact on mortality. Shock patients have low levels of activated protein C and high levels of the endogenous danger signal molecule peroxiredoxin 1; both conditions might represent further therapeutic targets. As major cause of cytopathic hypoxia, mitochondrial dysfunction has also been identified in mitochondria from peripheral blood mononuclear cells in paediatric septic shock. Transcatheter aortic valve endocarditis, a new endocarditis entity after transcatheter aortic valve implantation in old and very old patients, needs our special attention, because immunosenescence may modify the clinical course in a negative sense. Systemic spreading of endocarditis to septic shock adds to the local valve infection the problem of septic shock. Not only in septic shock, but also in classic heart diseases like cardiogenic shock and endocarditis, the detrimental role of inflammatory mediators becomes more and more evident, whereas effective anti-inflammatory treatment concepts are still missing.

  3. Hyaline globule-like structures in undifferentiated sarcoma cells of malignant müllerian mixed tumor of the fallopian tube.

    Science.gov (United States)

    Kuroda, Naoto; Inui, Yasunobu; Ohara, Masahiko; Hirouchi, Takashi; Mizuno, Keiko; Kubo, Ayumi; Hayashi, Yoshihiro; Enzan, Hideaki; Lee, Gang-Hong

    2007-03-01

    Malignant müllerian mixed tumors (MMMTs) of the fallopian tube are very rare neoplasms, and we present such a case with unusual findings here. A 57-year-old Japanese woman, after she received a medical checkup, underwent salpingo-oophorectomy on the suspicion of ovarian cancer. At the time of operation, the main tumor was present predominantly in the fallopian tube. Microscopically, the tumor consisted of carcinoma and sarcoma components. The carcinoma showed moderately to poorly differentiated adenocarcinoma. The sarcoma consisted of predominantly undifferentiated sarcoma and focally rhabdomyosarcomatous cells with abundant eosinophilic cytoplasm. Immunohistochemically, the differentiation toward rhabdomyosarcoma was confirmed. Interestingly, the cytoplasm of undifferentiated sarcoma cells contained hyaline globule-like structures. These structures showed a positive reaction for PAS, and these structures were not digested by the diastase pretreatment. Ultrastructurally, hyaline globule-like structures corresponded to lysosomes. Finally, pathologists should keep in mind that undifferentiated sarcoma cells in MMMT of the fallopian tube may contain hyaline globule-like structures in the cytoplasm.

  4. Comparative efficacy of tulathromycin versus a combination of florfenicol-oxytetracycline in the treatment of undifferentiated respiratory disease in large numbers of sheep

    Directory of Open Access Journals (Sweden)

    Mohsen Champour

    2015-09-01

    Full Text Available The objective of this study was to compare the efficacy of tulathromycin (TUL with a combination of florfenicol (FFC and long-acting oxytetracycline (LAOTC in the treatment of naturally occurring undifferentiated respiratory diseases in large numbers of sheep. In this study, seven natural outbreaks of sheep pneumonia in Garmsar, Iran were considered. From these outbreaks, 400 sheep exhibiting the signs of respiratory diseases were selected, and the sheep were randomly divided into two equal groups. The first group was treated with a single injection of TUL (dosed at 2.5 mg/kg body weight, and the second group was treated with concurrent injections of FFC (dosed at 40 mg/kg bwt and LAOTC (dosed at 20 mg/kg bwt. In the first group, 186 (93% sheep were found to be cured 5 days after the injection, and 14 (7% sheep needed further treatment, of which 6 (3% were cured, and 8 (4% died. In the second group, 172 (86% sheep were cured after the injections, but 28 (14% sheep needed further treatment, of which 10 (5% were cured, and 18 (9% died. This study revealed that TUL was more efficacious as compared to the combined treatment using FFC and LAOTC. As the first report, this field trial describes the successful treatment of undifferentiated respiratory diseases in large numbers of sheep. Thus, TUL can be used for the treatment of undifferentiated respiratory diseases in sheep. [J Adv Vet Anim Res 2015; 2(3.000: 279-284

  5. Absence of a Classically Activated Macrophage Cytokine Signature in Peripheral Spondylarthritis, Including Psoriatic Arthritis

    NARCIS (Netherlands)

    Vandooren, Bernard; Noordenbos, Troy; Ambarus, Carmen; Krausz, Sarah; Cantaert, Tineke; Yeremenko, Nataliya; Boumans, Maartje; Lutter, Rene; Tak, Paul P.; Baeten, Dominique

    2009-01-01

    Objective. Peripheral spondylarthritis (SpA) is characterized by macrophages that express CD163, a marker of alternative activation (M2). The purpose of this study was to assess whether this differential infiltration with macrophage subsets was associated with a different local inflammatory milieu

  6. Osteoprotegerin is higher in peripheral arterial disease regardless of glycaemic status.

    LENUS (Irish Health Repository)

    O'Sullivan, Eoin P

    2010-12-01

    Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)\\/RANKL\\/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.

  7. Heterogeneity of Bovine Peripheral Blood Monocytes

    Directory of Open Access Journals (Sweden)

    Jamal Hussen

    2017-12-01

    Full Text Available Peripheral blood monocytes of several species can be divided into different subpopulations with distinct phenotypic and functional properties. Herein, we aim at reviewing published work regarding the heterogeneity of the recently characterized bovine monocyte subsets. As the heterogeneity of human blood monocytes was widely studied and reviewed, this work focuses on comparing bovine monocyte subsets with their human counterparts regarding their phenotype, adhesion and migration properties, inflammatory and antimicrobial functions, and their ability to interact with neutrophilic granulocytes. In addition, the differentiation of monocyte subsets into functionally polarized macrophages is discussed. Regarding phenotype and distribution in blood, bovine monocyte subsets share similarities with their human counterparts. However, many functional differences exist between monocyte subsets from the two species. In contrast to their pro-inflammatory functions in human, bovine non-classical monocytes show the lowest phagocytosis and reactive oxygen species generation capacity, an absent ability to produce the pro-inflammatory cytokine IL-1β after inflammasome activation, and do not have a role in the early recruitment of neutrophils into inflamed tissues. Classical and intermediate monocytes of both species also differ in their response toward major monocyte-attracting chemokines (CCL2 and CCL5 and neutrophil degranulation products (DGP in vitro. Such differences between homologous monocyte subsets also extend to the development of monocyte-derived macrophages under the influence of chemokines like CCL5 and neutrophil DGP. Whereas the latter induce the differentiation of M1-polarized macrophages in human, bovine monocyte-derived macrophages develop a mixed M1/M2 macrophage phenotype. Although only a few bovine clinical trials analyzed the correlation between changes in monocyte composition and disease, they suggest that functional differences between

  8. ‘I’m fishing really’ — inflammatory marker testing in primary care: a qualitative study

    Science.gov (United States)

    Watson, Jessica; de Salis, Isabel; Hamilton, Willie; Salisbury, Chris

    2016-01-01

    Background Inflammatory markers can be helpful as part of the diagnostic workup for specific diseases or for monitoring disease activity. A third use is as a screening and/or triage tool to differentiate between the presence or absence of disease. Most research into inflammatory markers looks at diagnosis of specific diseases and comes from secondary care. Qualitative studies to explore when and why clinicians use these tests in primary care are lacking. Aim To identify clinicians’ approaches to inflammatory marker testing in primary care. Design and setting Qualitative study with 26 GPs and nurse practitioners. Method Interviews were conducted using a semi-structured topic guide. Clinicians reviewed recent cases of inflammatory marker testing in their pathology inbox. Interviews were audiorecorded and transcribed. Qualitative analysis was conducted by two of the authors. Results Clinicians are uncertain about the appropriate use of inflammatory markers and differ in their approach to testing patients with undifferentiated symptoms. Normal or significantly elevated inflammatory markers are seen as helpful, but mildly raised inflammatory markers in the context of non-specific symptoms are difficult to interpret. Clinicians describe a tension between not wanting to ‘miss anything’ and, on the other hand, being wary of picking up borderline abnormalities that can lead to cascades of further tests. Diagnostic uncertainty is a common reason for inflammatory marker testing, with the aim to reassure; however, paradoxically, inconclusive results can generate a cycle of uncertainty and anxiety. Conclusion Further research is needed to define when inflammatory marker testing is useful in primary care and how to interpret results. PMID:26852797

  9. Unique circumferential peripheral keratitis in relapsing polychondritis: A case report.

    Science.gov (United States)

    Motozawa, Naohiro; Nakamura, Takahiro; Takagi, Seiji; Fujihara, Masashi; Hirami, Yasuhiko; Ishida, Kazuhiro; Sotozono, Chie; Kurimoto, Yasuo

    2017-10-01

    Relapsing polychondritis (RP) is a rare collagen disease characterized by inflammation and destruction of cartilage throughout the body. The paper details the clinical course of a case of RP with unique circumferential peripheral keratitis. A 54-year-old Japanese woman was referred to the hospital presenting with auricular and ocular pain. Based on the auricle biopsy results and the three presenting symptoms (bilateral auricular chondritis, inflammatory arthritis and ocular inflammation), her condition was diagnosed as RP. The three presenting symptoms gradually improved with prednisolone (PSL), methylprednisolone and cyclophosphamide combination therapy, followed by PSL, methotrexate and infliximab combination therapy. However, one month after the initial visit, despite ongoing treatment, a unique circumferential peripheral keratitis suddenly occurred, in which the corneal infiltration gradually clumped together and shrank at the peripheral area. The eye and ear pain showed exacerbations and remissions on reducing the dosage of steroid drugs. The general condition was improved on altering systemic therapy to PSL, methotrexate and tocilizumab. Keratitis gradually disappeared within 10 months of the initial visit. This is the first report of a case of RP causing unique circumferential peripheral keratitis. This keratitis occurred despite use of focal and systemic steroids and showed improvement with general recovery. This may indicate that stabilization of general condition is important for recovery from keratitis in RP.

  10. Idiopathic inflammatory myopathies

    NARCIS (Netherlands)

    van der Kooi, A. J.; de Visser, M.

    2014-01-01

    Idiopathic inflammatory myopathies (IIMs), except for sporadic inclusion body myositis (sIBM), present with subacute symmetrical weakness of the limb girdle muscles, an elevated serum creatine kinase activity, and inflammatory cells in the muscle biopsy (necrotizing autoimmune myopathy being an

  11. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  12. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Science.gov (United States)

    Cao, Yan; Zhang, Wensong; Wu, Jie; Zhang, Hong

    2017-01-01

    Peripheral ulcerative keratitis (PUK) is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener granulomatosis (WG), relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis. PMID:28785483

  13. Efficient recovery of undifferentiated human embryonic stem cell cryopreserved with hydroxyethyl starch, dimethyl sulphoxide and serum replacement.

    Science.gov (United States)

    Orellana, Maristela Delgado; De Santis, Gil Cunha; Abraham, Kuruvilla Joseph; Fontes, Aparecida Maria; Magalhães, Danielle Aparecida Rosa; Oliveira, Viviane de Cássia; Costa, Everton de Brito Oliveira; Palma, Patrícia Vianna Bonini; Covas, Dimas Tadeu

    2015-08-01

    The therapeutic use of human embryonic stem cells (hESCs) is dependent on an efficient cryopreservation protocol for long-term storage. The aim of this study was to determine whether the combination of three cryoprotecting reagents using two freezing systems might improve hESC recovery rates with maintenance of hESC pluripotency properties for potential cell therapy application. Recovery rates of hESC colonies which were frozen in three cryoprotective solutions: Me2SO/HES/SR medium, Defined-medium® and Me2SO/SFB in medium solution were evaluated in ultra-slow programmable freezing system (USPF) and a slow-rate freezing system (SRF). The hESC pluripotency properties after freezing-thawing were evaluated. We estimated the distribution frequency of survival colonies and observed that independent of the freezing system used (USPF or SRF) the best results were obtained with Me2SO/HES/SR as cryopreservation medium. We showed a significant hESC recovery colonies rate after thawing in Me2SO/HES/SR medium were 3.88 and 2.9 in USPF and SRF, respectively. The recovery colonies rate with Defined-medium® were 1.05 and 1.07 however in classical Me2SO medium were 0.5 and 0.86 in USPF and SRF, respectively. We showed significant difference between Me2SO/HES/SR medium×Defined-medium® and between Me2SO/HES/SR medium×Me2SO medium, for two cryopreservation systems (Psystem which resulted in hESC colonies that remain undifferentiated, maintain their in vitro and in vivo pluripotency properties and genetic stability. This approach may be suitable for cell therapy studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Tissue engineering approaches to develop decellularized tendon matrices functionalized with progenitor cells cultured under undifferentiated and tenogenic conditions

    Directory of Open Access Journals (Sweden)

    Daniele D’Arrigo

    2017-11-01

    Full Text Available Tendon ruptures and retractions with an extensive tissue loss represent a major clinical problem and a great challenge in surgical reconstruction. Traditional approaches consist in autologous or allogeneic grafts, which still have some drawbacks. Hence, tissue engineering strategies aimed at developing functionalized tendon grafts. In this context, the use of xenogeneic tissues represents a promising perspective to obtain decellularized tendon grafts. This study is focused on the identification of suitable culture conditions for the generation of reseeded and functional decellularized constructs to be used as tendon grafts. Equine superficial digital flexor tendons were decellularized, reseeded with mesenchymal stem cells (MSCs from bone marrow and statically cultured in two different culture media to maintain undifferentiated cells (U-MSCs or to induce a terminal tenogenic differentiation (T-MSCs for 24 hours, 7 and 14 days. Cell viability, proliferation, morphology as well as matrix deposition and type I and III collagen production were assessed by means of histological, immunohistochemical and semi-quantitative analyses. Results showed that cell viability was not affected by any culture conditions and active proliferation was maintained 14 days after reseeding. However, seeded MSCs were not able to penetrate within the dense matrix of the decellularized tendons. Nevertheless, U-MSCs synthesized a greater amount of extracellular matrix rich in type I collagen compared to T-MSCs. In spite of the inability to deeply colonize the decellularized matrix in vitro, reseeding tendon matrices with U-MSCs could represent a suitable method for the functionalization of biological constructs, considering also any potential chemoattractant capability of the newly deposed extracellular matrix to recruit resident cells. This bioengineering approach can be exploited to produce functionalized tendon constructs for the substitution of large tendon defects.

  15. Sarcoma indiferenciado primário no sistema nervoso central Primary undifferentiated sarcoma of the central nervous system

    Directory of Open Access Journals (Sweden)

    Milton Marcio Machota Junior

    2012-04-01

    Full Text Available INTRODUÇÃO: O sarcoma de sistema nervoso central (SNC é uma neoplasia rara, com incidência de 0,1% a 4,3% dos tumores intracranianos. São tumores agressivos com prognóstico reservado e a maioria é tratada com ressecção radical. RELATO: Homem, 29 anos, com episódios de crises convulsivas e diagnóstico de hemorragia intraparenquimatosa. Durante a cirurgia, foi identificada lesão bem delimitada. A histologia demonstrou neoplasia fusocelular com atipias e numerosas mitoses. Os únicos marcadores imuno-histoquímicos positivos foram vimentina e S-100. O diagnóstico foi de sarcoma indiferenciado de alto grau. CONCLUSÃO: No diagnóstico diferencial de sarcomas de SNC, devem-se excluir lesões metastáticas e gliossarcoma.INTRODUCTION: The central nervous system (CNS sarcoma is a rare neoplasm with an incidence of 0.1% to 4.3% in intracranial tumors. They are aggressive with poor prognosis, and mostly treated with radical resection. REPORT: 29 year-old male patient with episodes of seizures and diagnosed with intraparenchymal hemorrhage. During the surgery a well-defined lesion was identified. Histology showed a spindle cell neoplasm with atypia and numerous mitoses. The immunohistochemical markers were positive only for vimentin and S-100. The diagnosis was high-grade undifferentiated sarcoma. CONCLUSION: Metastatic lesions and gliosarcoma should be excluded in the differential diagnosis of CNS sarcomas.

  16. Peripheral facial nerve palsy after therapeutic endoscopy.

    Science.gov (United States)

    Kim, Eun Jeong; Lee, Jun; Lee, Ji Woon; Lee, Jun Hyung; Park, Chol Jin; Kim, Young Dae; Lee, Hyun Jin

    2015-03-01

    Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the peripheral part of the facial nerve. Primary causes of peripheral FNP remain largely unknown, but detectable causes include systemic infections (viral and others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in relation to extrinsic compression has rarely been described in case reports. Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP following endoscopic submucosal dissection. This case is the first report of the development of peripheral FNP in a patient undergoing therapeutic endoscopy. We emphasize the fact that physicians should be attentive to the development of peripheral FNP following therapeutic endoscopy.

  17. Peripheral Facial Nerve Palsy after Therapeutic Endoscopy

    OpenAIRE

    Kim, Eun Jeong; Lee, Jun; Lee, Ji Woon; Lee, Jun Hyung; Park, Chol Jin; Kim, Young Dae; Lee, Hyun Jin

    2015-01-01

    Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the peripheral part of the facial nerve. Primary causes of peripheral FNP remain largely unknown, but detectable causes include systemic infections (viral and others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in relation to extrinsic compression has rarely been described in case reports. Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP following endoscopic submucosal...

  18. Contrast-enhanced peripheral MRA

    DEFF Research Database (Denmark)

    Nielsen, Yousef W; Thomsen, Henrik S

    2012-01-01

    -state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged......In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast...... MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic...

  19. The relative composition of the inflammatory infiltrate as an additional tool for synovial tissue classification.

    Directory of Open Access Journals (Sweden)

    Cristina Della Beffa

    Full Text Available OBJECTIVES: Traditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm² have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies. METHODS: Synovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11 were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC analysis and naïve Bayes classifier were used to compare the abilities of (1 the absolute densities of cells expressing a given marker (absolute method with (2 the percentages of these cells in the inflammatory cell population (relative method to differentiate among the six tissue classes. RESULTS: The inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm². CONCLUSIONS: This exploratory investigation featuring a variety of joint disorders revealed that measuring the relative

  20. Pelvic Inflammatory Disease

    Science.gov (United States)

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  1. Chronic inflammatory demyelinative polyneuropathy

    DEFF Research Database (Denmark)

    Said, Gérard; Krarup, Christian

    2013-01-01

    Chronic inflammatory demyelinative polyneuropathy (CIDP) is an acquired polyneuropathy presumably of immunological origin. It is characterized by a progressive or a relapsing course with predominant motor deficit. The diagnosis rests on the association of non-length-dependent predominantly motor ...

  2. Inflammatory Breast Cancer

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... with inflammatory breast cancer, but, due to the importance of radiation therapy in treating this disease, experts ...

  3. A comparison of florfenicol and tilmicosin for the treatment of undifferentiated fever in feedlot calves in western Canada.

    Science.gov (United States)

    Jim, G K; Booker, C W; Guichon, P T; Schunicht, O C; Wildman, B K; Johnson, J C; Lockwood, P W

    1999-01-01

    A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of florfenicol and tilmicosin for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feedlot. One thousand and eighty recently weaned, auction market derived, crossbred beef calves suffering from UF were allocated to one of 2 experimental groups as follows: florfenicol, which was intramuscular (i.m.) florfenicol administered at the rate of 20 mg/kg body weight (BW) at the time of allocation (Day 0) and again 48 h later, or tilmicosin, which was subcutaneous (s.c.) tilmicosin administered once at the rate of 10 mg/kg BW on day 0. Five hundred and forty-four animals were allocated to the florfenicol group and 536 animals were allocated to the tilmicosin group. The chronicity, wastage, overall mortality, and bovine respiratory disease (BRD) mortality rates were significantly (P florfenicol group than in the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, hemophilosis mortality, or miscellaneous mortality rates between the florfenicol and tilmicosin groups. Average daily gain (ADG) from arrival at the feedlot to the time of implanting and ADG from allocation to the time of implanting were significantly (P florfenicol group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in arrival weight, allocation weight, implanting weight, or ADG from arrival to allocation between the experimental groups. In the economic analysis, there was an advantage of $18.83 CDN per animal in the florfenicol group. The results of this study indicate that florfenicol is superior to tilmicosin for the treatment of UF because of lower chronicity, wastage, overall mortality, and BRD mortality rates. However, interpretation of these observations must take into consideration the fact that these calves received meta

  4. Subcellular Distribution of S-Nitrosylated H-Ras in Differentiated and Undifferentiated PC12 Cells during Hypoxia.

    Science.gov (United States)

    Barbakadze, Tamar; Goloshvili, Galina; Narmania, Nana; Zhuravliova, Elene; Mikeladze, David

    2017-10-01

    Hypoxia or exposure to excessive reactive oxygen or nitrogen species could induce S-nitrosylation of various target proteins, including GTPases of the Ras-superfamily. Under hypoxic conditions, the Ras-protein is translocated to the cytosol and interacts with the Golgi complex, endoplasmic reticulum, mitochondria. The mobility/translocation of Ras depend on the cells oxidative status. However, the importance of relocated Snitrosylated- H-Ras (NO-H-Ras) in proliferation/differentiation processes is not completely understood. We have determined the content of soluble- and membrane-bound-NO-HRas in differentiated (D) and undifferentiated (ND) rat pheochromocytoma (PC12) cells under hypoxic and normoxic conditions. In our experimental study, we analyzed NO-H-Ras levels under hypoxic/normoxic conditions in membrane and soluble fractions of ND and D PC12 cells with/without nitric oxide donor, sodium nitroprusside (SNP) treatment. Cells were analyzed by the S-nitrosylated kit, immunoprecipitation, and Western blot. We assessed the action of NO-H-Ras on oxidative metabolism of isolated mitochondria by determining mitochondrial hydrogen peroxide generation via the scopoletin oxidation method and ATPproduction as estimated by the luminometric method. Hypoxia did not influence nitrosylation of soluble H-Ras in ND PC12 cells. Under hypoxic conditions, the nitrosylation of soluble-H-Ras greatly decreased in D PC12 cells. SNP didn't change the levels of nitrosylation of soluble-H-Ras, in either hypoxic or normoxic conditions. On the other hand, hypoxia, per se, did not affect the nitrosylation of membrane-bound-H-Ras in D and ND PC12 cells. SNP-dependent nitrosylation of membrane-bound-H-Ras greatly increased in D PC12 cells. Both unmodified normal and mutated H-Ras enhanced the mitochondrial synthesis of ATP, whereas the stimulatory effects on ATP synthesis were eliminated after S-nitrosylation of H-Ras. According to the results, it may be proposed that hypoxia can decrease S

  5. Awareness of malaria and treatment-seeking behaviour among persons with acute undifferentiated fever in the endemic regions of Myanmar.

    Science.gov (United States)

    Naing, Phyo Aung; Maung, Thae Maung; Tripathy, Jaya Prasad; Oo, Tin; Wai, Khin Thet; Thi, Aung

    2017-01-01

    Myanmar has a high burden of malaria with two-third of the population at risk of malaria. One of the basic elements of the Roll Back Malaria Initiative to fight against malaria is early diagnosis and treatment within 24 h of fever. Public awareness about malaria is a key factor in malaria prevention and control and in improving treatment-seeking behaviour. A large community-based survey was carried out in 27 townships of malaria endemic regions in Myanmar in 2015 which reported on the knowledge, behaviour and practices around malaria in the general population. We used the data already collected in this survey to assess (i) general public awareness of malaria and (ii) treatment-seeking behaviour and associated factors among persons with acute undifferentiated fever. A total of 6597 respondents from 6625 households were interviewed (response rate of 99.5%). About 85% of the respondents were aware that mosquito bite was the mode of transmission of malaria and 90% mentioned that malaria was preventable. However, only 16% of the respondents knew about anti-malaria drug resistance. There were certain misconceptions about the transmission of malaria such as dirty water, same blood group, sharing shelter, sleeping/eating together and poor hygiene. Health facility staff were the most common source of information about malaria (80%). Nearly one-fourth (23%) of the respondents with fever resorted to self-medication. Around 28% of the respondents with fever underwent blood testing, less than half of whom (44%) were tested within 24 h. Elderly age group, females, those with poor knowledge about malaria and those residing in non-Regional Artemisinin Resistance Initiative townships were associated with poor treatment-seeking behaviour in case of fever. Although there is fair knowledge on mosquito bite as a mode of transmission and prevention of malaria, there are some misconceptions about transmission of malaria. Those having poor knowledge about malaria have poor treatment

  6. Acute undifferentiated febrile illness in patients presenting to a Tertiary Care Hospital in South India: clinical spectrum and outcome

    Directory of Open Access Journals (Sweden)

    Kundavaram Paul Prabhakar Abhilash

    2016-01-01

    Full Text Available Background: Acute undifferentiated febrile illness (AUFI may have similar clinical presentation, and the etiology is varied and region specific. Materials and Methods: This prospective observational study was conducted in a tertiary hospital in South India. All adult patients presenting with AUFI of 3-14 days duration were evaluated for etiology, and the differences in presentation and outcome were analyzed. Results: The study cohort included 1258 patients. A microbiological cause was identified in 82.5% of our patients. Scrub typhus was the most common cause of AUFI (35.9% followed by dengue (30.6%, malaria (10.4%, enteric fever (3.7%, and leptospirosis (0.6%. Both scrub typhus and dengue fever peaked during the monsoon season and the cooler months, whereas no seasonality was observed with enteric fever and malaria. The mean time to presentation was longer in enteric fever (9.9 [4.7] days and scrub typhus (8.2 [3.2] days. Bleeding manifestations were seen in 7.7% of patients, mostly associated with dengue (14%, scrub typhus (4.2%, and malaria (4.6%. The requirement of supplemental oxygen, invasive ventilation, and inotropes was higher in scrub typhus, leptospirosis, and malaria. The overall mortality rate was 3.3% and was highest with scrub typhus (4.6% followed by dengue fever (2.3%. Significant clinical predictors of scrub typhus were breathlessness (odds ratio [OR]: 4.96; 95% confidence interval [CI]: 3.38-7.3, total whole blood cell count >10,000 cells/mm 3 (OR: 2.31; 95% CI: 1.64-3.24, serum albumin <3.5 g % (OR: 2.32; 95% CI: 1.68-3.2. Overt bleeding manifestations (OR: 2.98; 95% CI: 1.84-4.84, and a platelet count of <150,000 cells/mm 3 (OR: 2.09; 95% CI: 1.47-2.98 were independent predictors of dengue fever. Conclusion: The similarity in clinical presentation and diversity of etiological agents demonstrates the complexity of diagnosis and treatment of AUFI in South India. The etiological profile will be of use in the development of

  7. Osteosclerotic Myeloma with Peripheral Neuropathy

    African Journals Online (AJOL)

    in a sheep-farming district, and worked as a carpenter. There was no history of heavy alcohol consumption and no known contact with any toxic substance. Examination. There were no general stigmata of disease, blood pressure was 185/85 mmHg, pulse 80/min, regular, and all peripheral pulses were present and equal.

  8. [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.

  9. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    sizes has been conducted. METHODS: Here, we performed a comprehensive review of meta-analyses of peripheral nongenetic biomarkers that could discriminate individuals with MDD from nondepressed controls. PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched through April 10, 2015. RESULTS: From 15...

  10. 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

  11. [Complications of peripheral regional anesthesia].

    Science.gov (United States)

    Neuburger, M; Büttner, J

    2011-11-01

    Peripheral regional anesthesia is a commonly used and safe procedure and eneral complications or side effects are generally rare. Nerve damage has an incidence allergies, dislocation of catheters and knotting or loops in catheters. Besides the general complications, there are some specific complications depending on the puncture site, such as pneumothorax or renal puncture.

  12. 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 ...

  13. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

    OpenAIRE

    Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2009-01-01

    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

  14. A comparison of the clinical field efficacy and safety of florfenicol and tilmicosin for the treatment of undifferentiated bovine respiratory disease of cattle in western Canada.

    Science.gov (United States)

    Hoar, B R; Jelinski, M D; Ribble, C S; Janzen, E D; Johnson, J C

    1998-01-01

    We compared the field efficacy of a new antibiotic, florfenicol, with tilmicosin in the treatment of naturally occurring undifferentiated bovine respiratory disease. Beef calves with rectal temperatures greater than 40.5 degrees C and signs compatible with undifferentiated bovine respiratory disease were entered into the trial. Calves were randomly assigned to receive either florfenicol (20 mg/kg bodyweight intramuscularly; 2 injections 48 h apart) or tilmicosin (10 mg/kg bodyweight subcutaneously; 1 injection). Clinical measures of efficacy included mortality, rectal temperature, illness index score, assessment of treatment success or failure, and the number of relapses or reinfections. Performance was assessed based on weight gains from day 0 to day 90. Two hundred and twenty calves entered the trial; 112 received florfenicol and 108 received tilmicosin. Seventeen deaths occurred between day 0 and day 90, but only 10 during the 28-day trial period. Seven calves receiving tilmicosin died, compared with 3 receiving florfenicol (P = 0.20). Of the 220 initial treatments, 45 (20%) were categorized as treatment failures; 27 in the tilmicosin group and 18 in the florfenicol group (P = 0.10). The number of calves experiencing a 2nd relapse was significantly different, with 17 of 30 (57%) calves on tilmicosin compared with 7 of 26 (27%) calves on florfenicol relapsing at least twice (P = 0.02). Average daily gains over 90 days were 1.55 kg/day for florfenicol-treated calves and 1.51 kg/day for tilmicosin-treated calves. No significant adverse reactions were noticed with either drug. Results indicate that florfenicol and tilmicosin are comparable in the treatment of undifferentiated bovine respiratory disease in western Canada. Images Figure 2. Figure 3. PMID:9524721

  15. Role of spinal microglia in rat models of peripheral nerve injury and inflammation.

    Science.gov (United States)

    Clark, Anna K; Gentry, Clive; Bradbury, Elizabeth J; McMahon, Stephen B; Malcangio, Marzia

    2007-02-01

    Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 h following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA-induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered.

  16. The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations

    International Nuclear Information System (INIS)

    Taga, Masataka; Shiraishi, Kazunori; Shimura, Tsutomu; Uematsu, Norio; Kato, Tomohisa; Niwa, Ohtsura; Nishimune, Yoshitake; Aizawa, Shinichi; Oshimura, Mitsuo

    2000-01-01

    The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53δ, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X-rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53-proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53δ cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/S arrest was not observed in X-ray and UV irradiated EC cells. X-rays induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated

  17. Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases.

    Directory of Open Access Journals (Sweden)

    Carla S B Viegas

    Full Text Available Calcification-related chronic inflammatory diseases are multifactorial pathological processes, involving a complex interplay between inflammation and calcification events in a positive feed-back loop driving disease progression. Gla-rich protein (GRP is a vitamin K dependent protein (VKDP shown to function as a calcification inhibitor in cardiovascular and articular tissues, and proposed as an anti-inflammatory agent in chondrocytes and synoviocytes, acting as a new crosstalk factor between these two interconnected events in osteoarthritis. However, a possible function of GRP in the immune system has never been studied. Here we focused our investigation in the involvement of GRP in the cell inflammatory response mechanisms, using a combination of freshly isolated human leucocytes and undifferentiated/differentiated THP-1 cell line. Our results demonstrate that VKDPs such as GRP and matrix gla protein (MGP are synthesized and γ-carboxylated in the majority of human immune system cells either involved in innate or adaptive immune responses. Stimulation of THP-1 monocytes/macrophages with LPS or hydroxyapatite (HA up-regulated GRP expression, and treatments with GRP or GRP-coated basic calcium phosphate crystals resulted in the down-regulation of mediators of inflammation and inflammatory cytokines, independently of the protein γ-carboxylation status. Moreover, overexpression of GRP in THP-1 cells rescued the inflammation induced by LPS and HA, by down-regulation of the proinflammatory cytokines TNFα, IL-1β and NFkB. Interestingly, GRP was detected at protein and mRNA levels in extracellular vesicles released by macrophages, which may act as vehicles for extracellular trafficking and release. Our data indicate GRP as an endogenous mediator of inflammatory responses acting as an anti-inflammatory agent in monocytes/macrophages. We propose that in a context of chronic inflammation and calcification-related pathologies, GRP might act as a novel

  18. 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...

  19. 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 ...

  20. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer.

    Science.gov (United States)

    Sullivan, Robert; Dailey, Travis; Duncan, Kelsey; Abel, Naomi; Borlongan, Cesario V

    2016-12-14

    Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

  1. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

    Directory of Open Access Journals (Sweden)

    Robert Sullivan

    2016-12-01

    Full Text Available Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

  2. MRI of pathology-proven peripheral nerve amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

    McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D. [Mayo Clinic, Department of Musculoskeletal Radiology, Rochester, MN (United States)

    2017-01-15

    To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

  3. Are human peripheral nerves sensitive to X-ray imaging?

    Directory of Open Access Journals (Sweden)

    Jonas Francisco Scopel

    Full Text Available Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures.

  4. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats.

    Science.gov (United States)

    Pyter, Leah M; El Mouatassim Bih, Sarah; Sattar, Husain; Prendergast, Brian J

    2014-03-13

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis that peripheral tumors likewise induce neuroinflammatory sensitization or priming. Female rats with chemically-induced mammary carcinomas were injected with either saline or lipopolysaccharide (LPS, 250μg/kg; i.p.), and expression of mRNAs involved in the pathway linking inflammation and depression (interleukin-1beta [Il-1β], CD11b, IκBα, indolamine 2,3-deoxygenase [Ido]) was quantified by qPCR in the hippocampus, hypothalamus, and frontal cortex, 4 or 24h post-treatment. In the absence of LPS, hippocampal Il-1β and CD11b mRNA expression were elevated in tumor-bearing rats, whereas Ido expression was reduced. Moreover, in saline-treated rats basal hypothalamic Il-1β and CD11b expression were positively correlated with tumor weight; heavier tumors, in turn, were characterized by more inflammatory, necrotic, and granulation tissue. Tumors exacerbated CNS proinflammatory gene expression in response to LPS: CD11b was greater in hippocampus and frontal cortex of tumor-bearing relative to tumor-free rats, IκBα was greater in hippocampus, and Ido was greater in hypothalamus. Greater neuroinflammatory responses in tumor-bearing rats were accompanied by attenuated body weight gain post-LPS. The data indicate that neuroinflammatory pathways are potentiated, or primed, in tumor-bearing rats, which may exacerbate future negative behavioral consequences. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. 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,…

  6. Inflammatory reaction in chondroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Yamamura, Sigeki [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sato, Keiji [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Sugiura, Hideshi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan); Iwata, Hisashi [Dept. of Orthopedic Surgery, Nagoya Univ. School of Medicine (Japan)

    1996-05-01

    The objective of this study was to evaluate the inflammatory reaction accompanying chondroblastoma and to define the value of the finding in clinical practice. We reviewed the clinical, radiographic, and magnetic resonance (MR) findings in six patients with histologically proven chondroblastoma. In all cases, MR imaging showered marrow and soft tissue edema. In four of six cases, periosteal reaction related to intra-osseous edema was more clearly demonstrated on MR imaging than on radiographs. Follow-up MR studies after surgery were available in three patients and all showed disappearance of inflammatory responses such as marrow and soft tissue edema, and reactive synovitis. We propose that these inflammatory reactions of chondroblastomas are inportant signs for detecting residual tumor in recurrences after surgery, as well as for making a precise diagnosis. The MR changes may also be valuable in demonstrating eradication of the tumor. (orig./MG)

  7. [Post-inflammatory hyperpigmentation].

    Science.gov (United States)

    Passeron, T

    2016-12-01

    Post-inflammatory hyperpigmentation (PIH) is a hyperpigmentation of the skin occurring after and sometimes during an inflammatory process. Although more frequent in dark skinned individuals, PIH can be observed in any type of skin and at all ages. In most case a strong impact on the quality of life of affected individuals is observed. The pathophysiology of PIH remains largely unknown. The activation of the melanocytes occurs in the first week following the inflammation emphasizing the crucial role of early preventive measures. Photoprotection with balanced UVA and UVB protection is required. Visible light could also play a role in PIH but this remains to be demonstrated. Healing topics with anti-inflammatory properties are of interest after a skin procedure. When the risk of PIH is high or when PIH occurs, topical steroids remains the gold standard approach. © 2016 Elsevier Masson SAS. Tous droits réservés.

  8. Peripheral neuromodulation in chronic migraine.

    Science.gov (United States)

    Perini, F; De Boni, A

    2012-05-01

    Patients with chronic migraines are often refractory to medical treatment. Therefore, they might need other strategies to modulate their pain, according to their level of disability. Neuromodulation can be achieved with several tools: meditation, biofeedback, physical therapy, drugs and electric neurostimulation (ENS). ENS can be applied to the central nervous system (brain and spinal cord), either invasively (cortical or deep brain) or non-invasively [cranial electrotherapy stimulation, transcranial direct current stimulation and transcranial magnetic stimulation]. Among chronic primary headaches, cluster headaches are most often treated either through deep brain stimulation or occipital nerve stimulation because there is a high level of disability related to this condition. ENS, employed through several modalities such as transcutaneous electrical nerve stimulation, interferential currents and pulsed radiofrequency, has been applied to the peripheral nervous system at several sites. We briefly review the indications for the use of peripheral ENS at the site of the occipital nerves for the treatment of chronic migraine.

  9. 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

  10. Diabetes and the peripheral nerve.

    Science.gov (United States)

    Obrosova, Irina G

    2009-10-01

    Diabetes-induced damage to peripheral nerve culminates in development of peripheral diabetic neuropathy (PDN), one of the most devastating complications of diabetes mellitus and a leading cause of foot amputation. The pathogenesis of PDN occurs as a consequence of complex interactions among multiple hyperglycemia-initiated mechanisms, impaired insulin signaling, inflammation, hypertension, and disturbances of fatty acid and lipid metabolism. This review describes experimental new findings in animal and cell culture models as well as clinical data suggesting the importance of 1) previously established hyperglycemia-initiated mechanisms such as increased aldose reductase activity, non-enzymatic glycation/glycooxidation, activation of protein kinase C, 2) oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation; 3) mitogen-activated protein kinase and cyclooxygenase-2 activation, impaired Ca(++) homeostasis and signaling, and several other mechanisms, in PDN.

  11. Close relationship qualities and maternal peripheral inflammation during pregnancy.

    Science.gov (United States)

    Ross, Kharah M; Miller, Gregory; Qadir, Sameen; Keenan-Devlin, Lauren; Leigh, Adam K K; Borders, Ann

    2017-03-01

    Close relationships are associated with pregnancy outcomes, but little is known about the mechanisms involved. This paper examines whether quality of women's close relationships, specifically with romantic partner (RP) and closest friend or family member (CF), is associated with inflammatory biomarkers during the third trimester of pregnancy. 90 pregnant women were assessed during the second and third trimester. At both visits they completed self-reports describing the positive and negative aspects of their RP and CF relationships. Peripheral blood was collected during these visits, and used to measure systemic levels of cytokines, including IFNγ, IL10, IL6, IL8 and IL13. An index of inflammatory regulation, as reflected by the ratio of IL6:IL10, was also computed. Positive (e.g. support, intimacy) and negative (e.g. conflict) aspects of the RP relationship interacted to predict third trimester cytokine values. Specifically, RP relationships relatively low in both positive and negative aspects were associated with lower third trimester anti-inflammatory (IL10, IL13) and anti-viral (IFNγ) cytokines, and a higher IL6:IL10 ratio, controlling for second trimester levels. These associations were independent of demographics, gestational age, weeks between assessment, parity, pre-pregnancy body mass index, maternal stress, distress, depressed mood and RP cohabitation. CF relationship aspects were not associated with inflammatory markers. RP relationships relatively low in both positive, e.g. support and intimacy, and negative, e.g. conflict, aspects were associated with a less anti- and more pro-inflammatory cytokine profile during the third trimester. These findings have implications for understanding the associations amongst close relationships, inflammation, and potentially pregnancy outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Familial congenital peripheral facial paralysis

    OpenAIRE

    Portillo Vallenas, Roberto; Aldave, Raquel; Reyes, Juan; Castañeda, César; Vera, José

    2014-01-01

    Objective: To study 29 individuals belonging to four familiar generations in whom 9 cases of facial paralysis was found in 2 generations. Setting: Neurophysiology Service, Guillermo Almenara Irigoyen National Hospital. Material and Methods: Neurological exam and electrophysiologic (EMG and VCN), otorrhinolaryngologic, radiologic, electroencephalographic, dermatoglyphic and laboratory studies were performed in 7 of the 9 patients (5 men and 2 women). Results: One case of right peripheral facia...

  13. 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

  14. Vasculitis and inflammatory arthritis.

    Science.gov (United States)

    Watts, Richard A; Scott, David G I

    2016-10-01

    Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. [Microbiota and inflammatory rheumatisms].

    Science.gov (United States)

    Jarlborg, Matthias; Alpizar-Rodriguez, Deshiré; Baillet, Athan; Finckh, Axel

    2018-03-07

    The microbiota and dysbiosis are involved in various diseases. Many studies in mice and humans demonstrate its influence on inflammatory rheumatisms. In rheumatoid arthritis (RA), Prevotella copri, a Gram-negative bacteria of the intestinal flora, is found to be more prevalent in the early stages of the disease. Specific antibodies against this germ have been identified in RA patients, suggesting a role of this bacteria in the initiation of the disease. Oral microorganisms involved in periodontitis have also been associated with the development and the activity of RA. These discoveries imply new targets in the management of inflammatory rheumatisms.

  16. Inflammation and peripheral venous disease. The San Diego Population Study.

    Science.gov (United States)

    Cushman, M; Callas, P W; Allison, M A; Criqui, M H

    2014-09-02

    The inflammatory response to healing in venous thrombosis might cause vein damage and post-thrombotic syndrome. Inflammation may also be involved in venous insufficiency apart from deep-vein thrombosis. We studied the association of inflammation markers with venous insufficiency in a general population sample. We characterised 2,404 men and women in a general population cohort for peripheral venous disease and its severity using physical exam, symptom assessment, and venous ultrasound. Inflammation markers, C-reactive protein (CRP), fibrinogen, interleukin 1-beta (IL-1-beta), IL-8, IL-10, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant-1 (MCP-1) and vascular endothelial cell growth factor (VEGF) were compared in 352 case participants with peripheral venous disease and 352 controls with no venous abnormalities frequency matched to cases by age, sex and race. Associations were also evaluated including a subset of 108 cases of severe venous disease, as previously defined. Odds ratios (95% CI), for peripheral venous disease for biomarkers in the top quartile (adjusting for age, race, sex, body mass index and history of venous thrombosis) were 1.8 (1.1-3.0), 1.6 (1.0-2.5) and 1.5 (0.9-2.3) for CRP, fibrinogen and IL-10, respectively. Associations were larger considering cases of severe venous disease, with odds ratios for these three analytes of 2.6 (1.2-5.9), 3.1 (1.3-7.3) and 2.2 (1.1-4.4), and for IL-8: 2.4 (1.1-5.2). There was no association of IL-1-beta, ICAM-1, VCAM-1, E-selectin, MCP-1 or VEGF with overall cases or severe venous disease. In conclusion, a subset of inflammation markers were associated with increased risk of peripheral venous disease, suggesting potential therapeutic targets for treatment.

  17. Renal inflammatory myofibroblastic tumor

    DEFF Research Database (Denmark)

    Heerwagen, S T; Jensen, C; Bagi, P

    2007-01-01

    Renal inflammatory myofibroblastic tumor (IMT) is a rare soft-tissue tumor of controversial etiology with a potential for local recurrence after incomplete surgical resection. The radiological findings in renal IMT are not well described. We report two cases in adults with a renal mass treated...

  18. Inflammatory pathways in spondyloarthritis

    NARCIS (Netherlands)

    Hreggvidsdottir, Hulda S.; Noordenbos, Troy; Baeten, Dominique L.

    2014-01-01

    Spondyloarthritis is the second most common form of chronic inflammatory arthritis and a unique hallmark of the disease is pathologic new bone formation. Several cytokine pathways have been genetically associated with ankylosing spondylitis (AS), the prototypic subtype of SpA, and additional

  19. Inflammatory bowel disease epidemiology

    DEFF Research Database (Denmark)

    Burisch, Johan; Munkholm, Pia

    2013-01-01

    The occurrence of inflammatory bowel disease (IBD) is increasing worldwide, yet the reasons remain unknown. New therapeutic approaches have been introduced in medical IBD therapy, but their impact on the natural history of IBD remains uncertain. This review will summarize the recent findings in t...... in the epidemiology of IBD....

  20. The Predictive Value of Inflammation-Related Peripheral Blood Measurements in Cancer Staging and Prognosis

    Directory of Open Access Journals (Sweden)

    Joanna L. Sylman

    2018-03-01

    Full Text Available In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel in silico frameworks to leverage this high-dimensional data.

  1. The OMERACT Magnetic Resonance Imaging Inflammatory Arthritis Group - advances and priorities

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; McQueen, Fiona; Bird, Paul

    2007-01-01

    This article updates the work and research priorities of the OMERACT working group on magnetic resonance imaging (MRI) in inflammatory arthritis, as presented to the OMERACT 8 meeting in Malta in May 2006. This work focused on testing the reliability of dedicated extremity MRI in rheumatoid...... arthritis and on the initial steps in the development of an MRI score for peripheral psoriatic arthritis....

  2. Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews

    NARCIS (Netherlands)

    Oaklander, Anne Louise; Lunn, Michael Pt; Hughes, Richard Ac; van Schaik, Ivo N.; Frost, Chris; Chalk, Colin H.

    2017-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population.

  3. [Development of peripheral nerve surgery].

    Science.gov (United States)

    Sames, M

    1998-03-01

    In the submitted review the author deals with the development of peripheral nerve surgery (PN) from ancient times to the present time incl. hithero unpublished details. He analyses in great detail the period of the last 40 years which is divided into three stages--the mechanical, biological period and the period of neurotrophism. From the Second World War to the sixties the period bears the term mechanical. The results of reinnervation during this period were not satisfactory as the nerves were connected without the use of a microscope, in major defects they were connected under considerable traction and the only criterion was the resistance against dehiscence. Significant improvement of results of regeneration of PN was recorded during the biological period. Mechanical ideas were overcome and biological and physiological reactions of the peripheral nerves were taken into account. Suture of nerves under traction was refuted and into clinical practice the surgical microscope, microsurgical technique and microsurgical autotransplantation with a nervous graft were introduced. The anatomical structure of the nerve with a plexiform pattern of the fascicles became however the limitation of surgical methods. After discovery of NGF (nerve growth factor) we can speak of the onset of a new period, neurotrophism. In laboratory experiments many substances are studied and theoretically new non-surgical possibilities how to promote regeneration lie ahead. However they cannot be applied yet in clinical practice. In injuries of peripheral nerves the only correct reconstruction method is still microsuture of the nerve and in case of losses microsurgical autotransplantation using a nerve graft.

  4. Inflammatory Bowel Disease (For Children)

    Science.gov (United States)

    ... For Kids / Inflammatory Bowel Disease Print en español Enfermedad inflamatoria del intestino What Is Inflammatory Bowel Disease? ... of IBD? There are two kinds of IBD: Crohn's disease and ulcerative colitis (say: UL-sur-uh- ...

  5. Pelvic Inflammatory Disease (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Pelvic Inflammatory Disease KidsHealth / For Parents / Pelvic Inflammatory Disease What's in this article? Symptoms Complications Prevention Treatment ...

  6. Pelvic inflammatory disease (PID) -- aftercare

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000710.htm Pelvic inflammatory disease (PID) - aftercare To use the sharing features on ... have just seen your health care provider for pelvic inflammatory disease (PID). PID refers to an infection of the ...

  7. Pelvic Inflammatory Disease (PID) Statistics

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Pelvic Inflammatory Disease (PID) Note: Javascript is disabled or is not supported ... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Pelvic Inflammatory Disease (PID) Statistics Recommend on Facebook Tweet Share Compartir ...

  8. Atypical idiopathic inflammatory demyelinating lesions

    DEFF Research Database (Denmark)

    Wallner-Blazek, Mirja; Rovira, Alex; Fillipp, Massimo

    2013-01-01

    Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be class...

  9. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    inflammatory cytokines such as interferon-g, IL-2, IL-3, tumour necrosis factor-a (TNF-a), and granulocyte macro- phage colony stimulating factor (GM-CSF...proliferation and density Gray et al., 198758 Animal (n Z 120) Vascular interpositional grafts Processed Grafts soft, pliable; no collapse of graft walls...T, Suzuki T, Sotozono C, Kinoshita S. Cultivated corneal epithelial stem cell transplantation in ocular surface disorders . Ophthalmology 2001;108

  10. Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

    OpenAIRE

    Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2012-01-01

    Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which w...

  11. Corneal ectasia secondary to peripheral endotheliopathy in a patient with classic pars planitis

    OpenAIRE

    Arellanes-Garcia, Lourdes; Preciado-Delgadillo, Maricarmen; Hernandez-Quintela, Everardo; Garza-Leon, Manuel

    2010-01-01

    Purpose To report a case of corneal ectasia secondary to pars planitis corneal endotheliopathy Methods Clinical case description and proposed hypothesis regarding development of corneal ectasia Results Eight-year-old male presented with 360° peripheral corneal endotheliopathy and edema, granulomatous keratic precipitates, and mild iritis OD. A progressive corneal ectasia then developed. Twenty months later, OS presented similarly and anterior chamber inflammatory cells, vitreous snowballs, an...

  12. Acute injury in the peripheral nervous system triggers an alternative macrophage response

    Directory of Open Access Journals (Sweden)

    Ydens Elke

    2012-07-01

    Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

  13. Interstitial mononuclear cell infiltrates in chronic rejection of the kidney and correlation with peripheral blood.

    OpenAIRE

    Jeong, H. J.; Hong, S. W.; Kim, Y. S.; Kim, M. S.; Choi, I. H.; Park, K.; Choi, I. J.

    1996-01-01

    To investigate the characteristics of interstitial inflammatory cells and possible involvement of nudelta T cells, 16 renal allograft biopsies showing chronic rejection were stained by immunohistochemical method and correlated with the data of peripheral blood evaluated by flow cytometry. For immunophenotyping, fresh frozen sections were stained with monoclonal antibodies against CD3, CD4, CD8, CD68, CD56, TCRdelta1 and HLA DR. Paraffin embedded tissue was stained with CD45RO, CD20-Cy and CD6...

  14. Evaluation of small peripheral pulmonary lesions with thin slice computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Kouzo (Nagasaki Univ. (Japan). School of Medicine)

    1992-12-01

    To evaluate the morphology of small peripheral pulmonary lesions, we studied thin-slice CT (TS-CT) images of 47 small peripheral pulmonary lesions (24 lung cancers, 23 benign lesions) in 47 patients. CT images were examined by two different window and level settings (window level; -600, window width; 1900 and window level; 50, window width; 300). In TS-CT images, findings of all lesions were classified into 3 different patterns (infiltrative type, solid with air-bronchogram type, homogeneous solid type) which were useful in diagnosing histology based on the growth pattern of the lesion. There was no lung cancer case in which calcification was diagnosed to be present on TS-CT. On the other hand, 5 of 9 inflammatory granulomas were recognized to contain calcium which was never seen on conventional CT. The results suggest that TS-CT may have a significant clinical role in diagnosing small peripheral pulmonary lesion by demonstrating macroscopic features and calcification. (author).

  15. The systemic inflammatory response syndrome.

    Science.gov (United States)

    Robertson, Charles M; Coopersmith, Craig M

    2006-04-01

    The systemic inflammatory response syndrome (SIRS) is the body's response to an infectious or noninfectious insult. Although the definition of SIRS refers to it as an "inflammatory" response, it actually has pro- and anti-inflammatory components. This review outlines the pathophysiology of SIRS and highlights potential targets for future therapeutic intervention in patients with this complex entity.

  16. Integrated Inflammatory Stress (ITIS) Model

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth O.; Hjorth, Poul G.; Olufsen, Mette S.

    2017-01-01

    maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing...

  17. Rheumatic manifestations of inflammatory bowel disease.

    Science.gov (United States)

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-11-28

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy.

  18. 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.

  19. Keratoconus: an inflammatory disorder?

    Science.gov (United States)

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-01-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition. PMID:25931166

  20. Inflammatory Bowel Disease.

    Science.gov (United States)

    Wehkamp, Jan; Götz, Martin; Herrlinger, Klaus; Steurer, Wolfgang; Stange, Eduard F

    2016-02-05

    Inflammatory bowel diseases are common in Europe, with prevalences as high as 1 in 198 persons (ulcerative colitis) and 1 in 310 persons (Crohn's disease). This review is based on pertinent articles retrieved by a search in PubMed and in German and European guidelines and Cochrane reviews of controlled trials. Typically, the main clinical features of inflammatory bowel diseases are diarrhea, abdominal pain, and, in the case of ulcerative colitis, peranal bleeding. These diseases are due to a complex immunological disturbance with both genetic and environmental causes. A defective mucosal barrier against commensal bowel flora plays a major role in their pathogenesis. The diagnosis is based on laboratory testing, ultrasonography, imaging studies, and, above all, gastrointestinal endoscopy. Most patients with Crohn's disease respond to budesonide or systemic steroids; aminosalicylates are less effective. Refractory exacerbations may be treated with antibodies against tumor necrosis factor (TNF) or, more recently, antibodies against integrin, a protein of the cell membrane. In ulcerative colitis, aminosalicylates are given first; if necessary, steroids or antibodies against TNF-α or integrin are added. Maintenance therapy to prevent further relapses often involves immunosuppression with thiopurines and/or antibodies. Once all conservative treatment options have been exhausted, surgery may be necessary. The treatment of chronic inflammatory bowel diseases requires individually designed therapeutic strategies and the close interdisciplinary collaboration of internists and surgeons.

  1. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Science.gov (United States)

    Farina, Antonietta R.; Di Ianni, Natalia; Cappabianca, Lucia; Ruggeri, Pierdomenico; Ragone, Marzia; Ianni, Giulia; Gulino, Alberto; Mackay, Andrew R.

    2013-01-01

    The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs) and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC. PMID:23841091

  2. A comparison of florfenicol-flunixin meglumine versus tulathromycin for the treatment of undifferentiated fever in fall-placed feedlot calves.

    Science.gov (United States)

    Van Donkersgoed, Joyce; Berg, Janice; Hendrick, Steven

    2009-01-01

    The purpose of this study was to compare the efficacy of a new combination drug, florfenicol-flunixin meglumine, with tulathromycin for initial treatment of undifferentiated fever (UF) in fall-placed calves that received metaphylactic tilmicosin on arrival at the feedlot. No significant differences were observed in UF relapses between the two drugs. Calves treated with florfenicol-flunixin had a lower crude case fatality rate (P = .0447) than calves treated with tulathromycin but did not have a significantly lower respiratory disease and histophilosis case fatality rate (P = .12). Whether the new florfenicol-flunixin product is more cost-effective than tulathromycin for the treatment of UF in fall-placed feedlot calves will depend on how the new product is priced in the marketplace relative to tulathromycin.

  3. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Antonietta R. Farina

    2013-01-01

    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

  4. Impact of copper oxide nanomaterials on differentiated and undifferentiated Caco-2 intestinal epithelial cells; assessment of cytotoxicity, barrier integrity, cytokine production and nanomaterial penetration.

    Science.gov (United States)

    Ude, Victor C; Brown, David M; Viale, Luca; Kanase, Nilesh; Stone, Vicki; Johnston, Helinor J

    2017-08-23

    Copper oxide nanomaterials (CuO NMs) are exploited in a diverse array of products including antimicrobials, inks, cosmetics, textiles and food contact materials. There is therefore a need to assess the toxicity of CuO NMs to the gastrointestinal (GI) tract since exposure could occur via direct oral ingestion, mucocillary clearance (following inhalation) or hand to mouth contact. Undifferentiated Caco-2 intestinal cells were exposed to CuO NMs (10 nm) at concentrations ranging from 0.37 to 78.13 μg/cm 2 Cu (equivalent to 1.95 to 250 μg/ml) and cell viability assessed 24 h post exposure using the alamar blue assay. The benchmark dose (BMD 20), determined using PROAST software, was identified as 4.44 μg/cm 2 for CuO NMs, and 4.25 μg/cm 2 for copper sulphate (CuSO 4 ), which informed the selection of concentrations for further studies. The differentiation status of cells and the impact of CuO NMs and CuSO 4 on the integrity of the differentiated Caco-2 cell monolayer were assessed by measurement of trans-epithelial electrical resistance (TEER), staining for Zonula occludens-1 (ZO-1) and imaging of cell morphology using scanning electron microscopy (SEM). The impact of CuO NMs and CuSO 4 on the viability of differentiated cells was performed via assessment of cell number (DAPI staining), and visualisation of cell morphology (light microscopy). Interleukin-8 (IL-8) production by undifferentiated and differentiated Caco-2 cells following exposure to CuO NMs and CuSO 4 was determined using an ELISA. The copper concentration in the cell lysate, apical and basolateral compartments were measured with Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES) and used to calculate the apparent permeability coefficient (P app ); a measure of barrier permeability to CuO NMs. For all experiments, CuSO 4 was used as an ionic control. CuO NMs and CuSO 4 caused a concentration dependent decrease in cell viability in undifferentiated cells. CuO NMs and CuSO 4

  5. The effect of comedication with conventional synthetic disease modifying antirheumatic drugs on TNF inhibitor drug survival in patients with ankylosing spondylitis and undifferentiated spondyloarthritis

    DEFF Research Database (Denmark)

    Lie, Elisabeth; Kristensen, Lars Erik; Forsblad-d'Elia, Helena

    2015-01-01

    OBJECTIVE: To assess the effect of comedication with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) on retention to tumour necrosis factor inhibitor (TNFi) therapy in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA). METHODS: Data...... on patients with a clinical diagnosis of AS or uSpA starting treatment with adalimumab, etanercept or infliximab as their first TNFi during 2003-2010 were retrieved from the Swedish national biologics register and linked to national population based registers. Five-year drug survival was analysed by Cox...... regression with age, sex, baseline csDMARD comedication, TNFi type, prescription year and covariates representing frailty and socioeconomic status. AS and uSpA were analysed separately. Sensitivity analyses included models with csDMARD as a time-dependent covariate and adjustments for additional potential...

  6. The state of «the pituitary gland - thyroid gland system» in the young men with undifferentiated dysplasia of the connective tissue

    Directory of Open Access Journals (Sweden)

    P. A. Yurchenko

    2013-01-01

    Full Text Available To investigate the state of «the pituitary gland-thyroid gland system» in the patients with undifferentiated dysplasia of the connective tissue (UDCT 83 young men of the call up age (18.2±0.4 y.o. were examined. The control group consisted of 26 practically healthy young men of the same age (18.5±0.2 y.o.. Autoimmune thyroiditis (AIT was diagnosed in 32.5 % of the men with UDCT. The rate of the internal (visceral phenotypical signs of UDCT in this group was significantly higher than in the men with UDCT but without thyroid problems.

  7. Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2017-08-01

    Full Text Available Arterial stiffness predicts an increased risk of cardiovascular events. Inflammation plays a major role in large arteries stiffening, related to atherosclerosis, arteriosclerosis, endothelial dysfunction, smooth muscle cell migration, vascular calcification, increased activity of metalloproteinases, extracellular matrix degradation, oxidative stress, elastolysis, and degradation of collagen. The present paper reviews main mechanisms explaining the crosstalk between inflammation and arterial stiffness and the most common inflammatory markers associated with increased arterial stiffness, considering the most recent clinical and experimental studies. Diverse studies revealed significant correlations between the severity of arterial stiffness and inflammatory markers, such as white blood cell count, neutrophil/lymphocyte ratio, adhesion molecules, fibrinogen, C-reactive protein, cytokines, microRNAs, and cyclooxygenase-2, in patients with a broad variety of diseases, such as metabolic syndrome, diabetes, coronary heart disease, peripheral arterial disease, malignant and rheumatic disorders, polycystic kidney disease, renal transplant, familial Mediterranean fever, and oral infections, and in women with preeclampsia or after menopause. There is strong evidence that inflammation plays an important and, at least, partly reversible role in the development of arterial stiffness, and inflammatory markers may be useful additional tools in the assessment of the cardiovascular risk in clinical practice. Combined assessment of arterial stiffness and inflammatory markers may improve non-invasive assessment of cardiovascular risk, enabling selection of high-risk patients for prophylactic treatment or more regular medical examination. Development of future destiffening therapies may target pro-inflammatory mechanisms.

  8. Anti-inflammatory profile of paricalcitol in kidney transplant recipients.

    Science.gov (United States)

    Donate-Correa, Javier; Henríquez-Palop, Fernando; Martín-Núñez, Ernesto; Hernández-Carballo, Carolina; Ferri, Carla; Pérez-Delgado, Nayra; Muros-de-Fuentes, Mercedes; Mora-Fernández, Carmen; Navarro-González, Juan F

    Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First‐in‐Human Study

    Science.gov (United States)

    Whitehouse, Michael R.; Howells, Nicholas R.; Parry, Michael C.; Austin, Eric; Kafienah, Wael; Brady, Kyla; Goodship, Allen E.; Eldridge, Jonathan D.; Blom, Ashley W.

    2016-01-01

    Abstract Meniscal cartilage tears are common and predispose to osteoarthritis (OA). Most occur in the avascular portion of the meniscus where current repair techniques usually fail. We described previously the use of undifferentiated autologous mesenchymal stem cells (MSCs) seeded onto a collagen scaffold (MSC/collagen‐scaffold) to integrate meniscal tissues in vitro. Our objective was to translate this method into a cell therapy for patients with torn meniscus, with the long‐term goal of delaying or preventing the onset of OA. After in vitro optimization, we tested an ovine‐MSC/collagen‐scaffold in a sheep meniscal cartilage tear model with promising results after 13 weeks, although repair was not sustained over 6 months. We then conducted a single center, prospective, open‐label first‐in‐human safety study of patients with an avascular meniscal tear. Autologous MSCs were isolated from an iliac crest bone marrow biopsy, expanded and seeded into the collagen scaffold. The resulting human‐MSC/collagen‐scaffold implant was placed into the meniscal tear prior to repair with vertical mattress sutures and the patients were followed for 2 years. Five patients were treated and there was significant clinical improvement on repeated measures analysis. Three were asymptomatic at 24 months with no magnetic resonance imaging evidence of recurrent tear and clinical improvement in knee function scores. Two required subsequent meniscectomy due to retear or nonhealing of the meniscal tear at approximately 15 months after implantation. No other adverse events occurred. We conclude that undifferentiated MSCs could provide a safe way to augment avascular meniscal repair in some patients. Registration: EU Clinical Trials Register, 2010‐024162‐22. Stem Cells Translational Medicine 2017;6:1237–1248 PMID:28186682

  10. Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    El-Akabawy Gehan

    2012-08-01

    Full Text Available Abstract Background Cell therapy is a potential therapeutic approach for several neurodegenetative disease, including Huntington Disease (HD. To evaluate the putative efficacy of cell therapy in HD, most studies have used excitotoxic animal models with only a few studies having been conducted in genetic animal models. Genetically modified animals should provide a more accurate representation of human HD, as they emulate the genetic basis of its etiology. Results In this study, we aimed to assess the therapeutic potential of a human striatal neural stem cell line (STROC05 implanted in the R6/2 transgenic mouse model of HD. As DARPP-32 GABAergic output neurons are predominately lost in HD, STROC05 cells were also pre-differentiated using purmorphamine, a hedgehog agonist, to yield a greater number of DARPP-32 cells. A bilateral injection of 4.5x105 cells of either undifferentiated or pre-differentiated DARPP-32 cells, however, did not affect outcome compared to a vehicle control injection. Both survival and neuronal differentiation remained poor with a mean of only 161 and 81 cells surviving in the undifferentiated and differentiated conditions respectively. Only a few cells expressed the neuronal marker Fox3. Conclusions Although the rapid brain atrophy and short life-span of the R6/2 model constitute adverse conditions to detect potentially delayed treatment effects, significant technical hurdles, such as poor cell survival and differentiation, were also sub-optimal. Further consideration of these aspects is therefore needed in more enduring transgenic HD models to provide a definite assessment of this cell line’s therapeutic relevance. However, a combination of treatments is likely needed to affect outcome in transgenic models of HD.

  11. Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid arthritis and its change in the course of therapy. Move toward personalized medicine.

    Science.gov (United States)

    Brzustewicz, Edyta; Bzoma, Izabella; Daca, Agnieszka; Szarecka, Maria; Bykowska, Malgorzata Sochocka; Witkowski, Jacek M; Bryl, Ewa

    2017-09-01

    To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups. Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA→RA) (n=16) and healthy controls (n=16) were enrolled into the study. UA→RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1β, IL-2 in sera and mononuclear cell supernatants in 72h and 120h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array. The cytokine profile of UA→RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA→RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supernatants of PBMC stimulated anti-CD3 for 72h and 120h are very similar. The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. INFLAMMATORY REACTIONS IN EXPERIMENTAL MYOCARDIAL DAMAGE

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    L. D. Khidirova

    2015-12-01

    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  13. INFLAMMATORY REACTIONS IN EXPERIMENTAL MYOCARDIAL DAMAGE

    Directory of Open Access Journals (Sweden)

    L. D. Khidirova

    2012-01-01

    Full Text Available Aim. To study the role of hormonal and metabolic changes specific to myocardial infarction in the development of inflammatory reactions in the experimental non-coronarogenic myocardial damage. Material and methods. Wistar male rats weighing 180–220 g (n=80 were used in the study. Metabolic myocardial infarction in intact rats and rats with alloxan diabetes was induced by epinephrine injected subcutaneously as single dose or daily (7 days. Myocardial infarction was verified by ECG analysis, and by histological control. Nitroblue tetrazolium test (NBT-test both spontaneous and zymosan induced NBT-test was used to determine the oxygen-dependent functional activity of neutrophils and their biocidal reserve. Determination of cationic proteins in neutrophils of peripheral blood was performed using lysosomal-cationic test. Results. Increase in oxygen-dependent neutrophil biocidal activity was found as well as reduction in biocidal reserves. Indicators of zymosan induced NBT-test raised according to aggravation of hormonal changes much slower: alloxan increased them by 10% only , epinephrine single dose — by 35%, long-term epinephrine administration simultaneously with alloxan — by 54%. At the same time oxygen-independent neutrophil activity determined by intra-neutrophil cationic proteins level was significantly reduced. Blood levels of pro-inflammatory cytokines raised according to progression of the changes in myocardium: tumor necrosis factor-α (from 5.5±0.03 to 12.6±1.23 pg/ml and interleukin-1β (from 6.0±0.18 to 11.1±0.78 pg/ml. Conclusion. Experimental model of hormonal changes specific to myocardial infarction detected a relationship between inflammatory reactions accompanying myocardial damage and increased catecholamine production.

  14. Solitary peripheral osteomas of the jaws

    OpenAIRE

    de França, Talita Ribeiro Tenório; Gueiros, Luiz Alcino Monteiro; de Castro, Jurema Freire Lisboa; Catunda, Ivson; Leão, Jair Carneiro; da Cruz Perez, Danyel Elias

    2012-01-01

    Osteoma is a benign osteogenic tumor composed of cancellous or compact bone, classified as peripheral, central, or extraskeletal. Peripheral osteomas are uncommon. Excluding the maxillary sinuses, the maxilla is a rare site for osteomas. The purpose of this report was to describe clinicopathological and radiological features of two peripheral osteomas occurring in the jaws, one located in the mandible and another in the edentulous maxillary alveolar ridge. The tumors were asymptomatic and wer...

  15. Pattern of peripheral arthritis in 15 patients with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Aref Hosseinian Amiri

    2015-01-01

    Full Text Available Background: Inflammatory bowel disease (IBD including ulcerative colitis (UC and Crohn′s disease is an immune-mediated chronic intestinal condition. The arthritis accompanying the IBDs are included in the family of spondyloarthritis. Peripheral arthritis develops in about 15-20% of IBD patients. Asymmetric oligoarthicular large joint involvements have inflammatory characteristics at these patients and occur in upper and lower extremities. Aim: The aim of the study was to analyze the pattern of joint involvement in 15 patients with UC during 2 years from January 2011 to December 2013. Subjects and Methods: This is a retrospective study of UC patients with acute and chronic arthritis during 2 years from January 2011 to December 2013 that refers to rheumatologic Clinic of Mazandaran University of Medical Sciences. Data were analyzed using the SPSS version 20. Variables analyzed include age, sex, presence of arthritis/periarthritis, the number of involved joints, kind and pattern of arthritis. Results: In these study 15 patients with UC and acute arthritis refers to BAGHBAN rheumatologic clinic. All of the patients were adults between 18 and 42-year-old with median age of 31.5 years old. Ten patients (66% were female, and five patients (33% were male. The media duration of UC was 3.9 years. Periarthrtis occurred in 7 (46% patients in association with arthritis. The most commonly involved join was ankle in 11 (73% cases. Another involved joints were knee in 5 (33%, wrist in 2 (12%, MTPs in 3 (20%, MCPs in 1 (6% and hip in 1 (6% of cases. In 4 (27% patients arthritis were monoarthicular, and eight (53% of patient′s arthritis were oligoathicular in 3 (20% cases, arthritis was polyarthicular. All of the arthritis were inflammatory. In 2 (13% of patients, arthritis were symmetric and in 9 (60% of cases were asymmetric. Conclusion: Inflammatory joint disease including arthritis and periarthrtis are important findings in UC. Asymmetric lower extremity

  16. Solitary peripheral osteomas of the jaws.

    Science.gov (United States)

    de França, Talita Ribeiro Tenório; Gueiros, Luiz Alcino Monteiro; de Castro, Jurema Freire Lisboa; Catunda, Ivson; Leão, Jair Carneiro; da Cruz Perez, Danyel Elias

    2012-06-01

    Osteoma is a benign osteogenic tumor composed of cancellous or compact bone, classified as peripheral, central, or extraskeletal. Peripheral osteomas are uncommon. Excluding the maxillary sinuses, the maxilla is a rare site for osteomas. The purpose of this report was to describe clinicopathological and radiological features of two peripheral osteomas occurring in the jaws, one located in the mandible and another in the edentulous maxillary alveolar ridge. The tumors were asymptomatic and were fully excised without any complications or recurrence. The lesions were submitted to histopathological analysis and diagnosed as peripheral osteoma, compact type.

  17. Peripheral visual performance enhancement by neurofeedback training.

    Science.gov (United States)

    Nan, Wenya; Wan, Feng; Lou, Chin Ian; Vai, Mang I; Rosa, Agostinho

    2013-12-01

    Peripheral visual performance is an important ability for everyone, and a positive inter-individual correlation is found between the peripheral visual performance and the alpha amplitude during the performance test. This study investigated the effect of alpha neurofeedback training on the peripheral visual performance. A neurofeedback group of 13 subjects finished 20 sessions of alpha enhancement feedback within 20 days. The peripheral visual performance was assessed by a new dynamic peripheral visual test on the first and last training day. The results revealed that the neurofeedback group showed significant enhancement of the peripheral visual performance as well as the relative alpha amplitude during the peripheral visual test. It was not the case in the non-neurofeedback control group, which performed the tests within the same time frame as the neurofeedback group but without any training sessions. These findings suggest that alpha neurofeedback training was effective in improving peripheral visual performance. To the best of our knowledge, this is the first study to show evidence for performance improvement in peripheral vision via alpha neurofeedback training.

  18. Solitary peripheral osteomas of the jaws

    Energy Technology Data Exchange (ETDEWEB)

    Franca, Talita Ribeiro Tenorio de; Gueiros, Luiz Alcino Monteiro; Castro, Jurema Freire Lisboa de; Leao, Jair Carneiro; Cruz Perez, Danyel Elias da [Oral Pathology Unit, Federal University of Pernambuco, Recife (Brazil); Catunda, Ivson [Hospital Geral de Areas, Recife (Brazil)

    2012-06-15

    Osteoma is a benign osteogenic tumor composed of cancellous or compact bone, classified as peripheral, central, or extraskeletal. Peripheral osteomas are uncommon. Excluding the maxillary sinuses, the maxilla is a rare site for osteomas. The purpose of this report was to describe clinicopathological and radiological features of two peripheral osteomas occurring in the jaws, one located in the mandible and another in the edentulous maxillary alveolar ridge. The tumors were asymptomatic and were fully excised without any complications or recurrence. The lesions were submitted to histopathological analysis and diagnosed as peripheral osteoma, compact type.

  19. Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain.

    Science.gov (United States)

    Rahman, Wahida; Dickenson, Anthony H

    2013-12-17

    The inflammatory response is a natural response of the body that occurs immediately following tissue damage, which may be due to injury, infection or disease. The acute inflammatory response is an essential mechanism that promotes healing and a key aspect is the ensuing pain, which warns the subject to protect the site of injury. Thus, it is common to see a zone of primary sensitization as well as consequential central sensitization that generally, is maintained by a peripheral drive from the zone of tissue injury. Inflammation associated with chronic pain states, such as rheumatoid and osteoarthritis, cancer and migraine etc. is deleterious to health and often debilitating for the patient. Thus there is a large unmet clinical need. The mechanisms underlying both acute and chronic inflammatory pain are extensive and complex, involving a diversity of cell types, receptors and proteins. Among these the contribution of voltage gated sodium and calcium channels on peripheral nociceptors is critical for nociceptive transmission beyond the peripheral transducers and changes in their distribution, accumulation, clustering and functional activities have been linked to both inflammatory and neuropathic pain. The latter has been the main area for trials and use of drugs that modulate ion channels such as carbamazepine and gabapentin, but given the large peripheral drive that follows tissue damage, there is a clear rationale for blocking voltage gated sodium and calcium channels in these pain states. It has been hypothesized that pain of inflammatory origin may evolve into a condition that resembles neuropathic pain, but mixed pains such as low back pain and cancer pain often include elements of both pain states. This review considers the therapeutic potential for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms.

    Science.gov (United States)

    Assaf, Areej M; Amro, Bassam I; Mashallah, Sundus; Haddadin, Randa N

    2016-05-31

    Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL-6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity.

  1. Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination.

    Science.gov (United States)

    Lin, Hsin-Pin; Oksuz, Idil; Svaren, John; Awatramani, Rajeshwar

    2018-02-28

    Recent studies have elucidated the crucial role for microRNAs in peripheral nerve myelination by ablating components of the microRNA synthesis machinery. Few studies have focused on the role of individual microRNAs. To fill this gap, we focused this study on miR-138, which was shown to be drastically reduced in Dicer1 and Dgcr8 knockout mice with hypomyelinating phenotypes and to potentially target the negative regulators of Schwann cell differentiation. Here, we show that of two miR-138 encoding loci, mir-138-1 is the predominant locus transcribed in Schwann cells. mir-138-1 is transcriptionally upregulated during myelination and downregulated upon nerve injury. EGR2 is required for mir-138-1 transcription during development, and both SOX10 and EGR2 bind to an active enhancer near the mir-138-1 locus. Based on expression analyses, we hypothesized that miR-138 facilitates the transition between undifferentiated Schwann cells and myelinating Schwann cells. However, in conditional knockouts, we could not detect significant changes in Schwann cell proliferation, cell cycle exit, or myelination. Overall, our results demonstrate that miR-138 is an Egr2-dependent microRNA but is dispensable for Schwann cell myelination.

  2. Characterization of the translocation breakpoint sequences of two DEK-CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in a case of acute undifferentiated leukemia

    NARCIS (Netherlands)

    von Lindern, M.; Breems, D.; van Baal, S.; Adriaansen, H.; Grosveld, G.

    1992-01-01

    The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to generate a fusion between the 3' part of the CAN gene on chromosome 9 and the 5' part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to be involved in a case of acute undifferentiated leukemia

  3. Diffusion-Weighted Imaging Using a Readout-Segmented, Multishot EPI Sequence at 3 T Distinguishes between Morphologically Differentiated and Undifferentiated Subtypes of Thyroid Carcinoma—A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Stefan Schob

    2016-10-01

    Full Text Available BACKGROUND: Thyroid carcinomas represent the most frequent endocrine malignancies. Recent studies were able to distinguish malignant from benign nodules of the thyroid gland with diffusion-weighted imaging (DWI. Although this differentiation is undoubtedly helpful, presurgical discrimination between well-differentiated and undifferentiated carcinomas would be crucial to define the optimal treatment algorithm. Therefore, the aim of this study was to investigate if readout-segmented multishot echo planar DWI is able to differentiate between differentiated and undifferentiated subtypes of thyroid carcinomas. PATIENTS AND METHODS: Fourteen patients with different types of thyroid carcinomas who received preoperative DWI were included in our study. In all lesions, apparent diffusion coefficient (ADCmin, ADCmean, ADCmax, and D were estimated on the basis of region of interest measurements after coregistration with T1-weighted, postcontrast images. All tumors were resected and analyzed histopathologically. Ki-67 index, p53 synthesis, cellularity, and total and average nucleic areas were estimated using ImageJ version 1.48. RESULTS: Analysis of variance revealed a statistically significant difference in ADCmean values between differentiated and undifferentiated thyroid carcinomas (P = .022. Spearman Rho calculation identified significant correlations between ADCmax and cell count (r = 0.541, P = .046 as well as between ADCmax and total nuclei area (r = 0.605, P = .022. CONCLUSION: DWI can distinguish between differentiated and undifferentiated thyroid carcinomas.

  4. Taxane-Induced Peripheral Neurotoxicity.

    Science.gov (United States)

    Velasco, Roser; Bruna, Jordi

    2015-04-28

    Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  5. Peripheral dose from megavolt beams

    International Nuclear Information System (INIS)

    Fraass, B.A.; van de Geijn, J.

    1983-01-01

    The peripheral dose (PD), defined as the dose outside of therapeutic radiation beams, has been investigated for 60 Co, 4-, 6-, and 10-MV x-ray machines. The measurements have been carried out down to dose levels of about 0.1% of the peak dose in the beam, since that dose level may be of clinical importance in some situations. The PD measurements for the various machines are qualitatively similar, which allows the identification of a simple basic data set which can characterize the PD for any particular machine. The PD has been separated into two components: in-phantom scatter dose and transmission (leakage) dose. Knowledge of the two components is important clinically when shielding is considered

  6. Novel environment influences the effect of paradoxical sleep deprivation upon brain and peripheral cytokine gene expression.

    Science.gov (United States)

    Ashley, Noah T; Sams, David W; Brown, Audrey C; Dumaine, Jennifer E

    2016-02-26

    Sleep loss increases inflammatory mediators in brain and peripheral tissues, but the mechanisms underlying this association are not fully understood. Male C57BL/6j mice were exposed to paradoxical sleep deprivation (PSD) for 24h using the modified multiple platform (MMP) technique (platforms over water) or two different controls: home cage or a dry platform cage, which constituted a novel environment. PSD mice exhibited increased IL-1β and TNF-α pro-inflammatory gene expression in brain (hypothalamus, hippocampus, pre-frontal cortex), as well as in peripheral tissues (liver, spleen), when compared with home-cage controls. In addition, among PSD mice, TGFβ1, an anti-inflammatory cytokine, was increased in pre-frontal cortex, liver, and spleen in conjunction with elevated serum corticosterone concentration relative to home-cage controls. However, these differences were nearly abolished when PSD mice were compared with control mice subjected to a dry MMP cage, suggesting that simply exposing mice to a novel environment can induce an acute inflammatory response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case

    Directory of Open Access Journals (Sweden)

    Saede Atarbashi Moghadam

    2016-01-01

    Full Text Available Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment.

  8. Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model.

    Science.gov (United States)

    Serpe, Loredana; Canaparo, Roberto; Daperno, Marco; Sostegni, Raffaello; Martinasso, Germana; Muntoni, Elisabetta; Ippolito, Laura; Vivenza, Nicoletta; Pera, Angelo; Eandi, Mario; Gasco, Maria Rosa; Zara, Gian Paolo

    2010-03-18

    Standard treatment for inflammatory bowel diseases (IBD) necessitates frequent intake of anti-inflammatory and/or immunosuppressive drugs, leading to significant adverse events. To evaluate the role solid lipid nanoparticles (SLN) play as drug delivery system in enhancing anti-inflammatory activity for drugs such as dexamethasone and butyrate in a human inflammatory bowel diseases whole-blood model. ELISA assay and the peripheral blood mononuclear cell (PBMC) cytokine mRNA expression levels were evaluated by quantitative SYBR Green real-time RT-PCR to determine the IL-1beta, TNF-alpha, IFN-gamma and IL-10 secretion in inflammatory bowel diseases patients' PBMC culture supernatants. There was a significant decrease in IL-1beta (p<0.01) and TNF-alpha (p<0.001) secretion, whilst IL-10 (p<0.05) secretion significantly increased after cholesteryl butyrate administration, compared to that of butyrate alone at the highest concentration tested (100 microM), at 24h exposure. There was a significant decrease in IL-1beta (p<0.01), TNF-alpha (p<0.001) and IL-10 (p<0.001) secretion after dexamethasone loaded SLN administration, compared to dexamethasone alone at the highest concentration tested (250 nM) at 24h exposure. No IFN-gamma was detected under any conditions and no cytotoxic effects observed even at the highest concentration tested. The incorporation of butyrate and dexamethasone into SLN has a significant positive anti-inflammatory effect in the human inflammatory bowel disease whole-blood model. Copyright 2010 Elsevier B.V. All rights reserved.

  9. Peripheral Exophytic Oral Lesions: A Clinical Decision Tree

    Directory of Open Access Journals (Sweden)

    Hamed Mortazavi

    2017-01-01

    Full Text Available Diagnosis of peripheral oral exophytic lesions might be quite challenging. This review article aimed to introduce a decision tree for oral exophytic lesions according to their clinical features. General search engines and specialized databases including PubMed, PubMed Central, Medline Plus, EBSCO, Science Direct, Scopus, Embase, and authenticated textbooks were used to find relevant topics by means of keywords such as “oral soft tissue lesion,” “oral tumor like lesion,” “oral mucosal enlargement,” and “oral exophytic lesion.” Related English-language articles published since 1988 to 2016 in both medical and dental journals were appraised. Upon compilation of data, peripheral oral exophytic lesions were categorized into two major groups according to their surface texture: smooth (mesenchymal or nonsquamous epithelium-originated and rough (squamous epithelium-originated. Lesions with smooth surface were also categorized into three subgroups according to their general frequency: reactive hyperplastic lesions/inflammatory hyperplasia, salivary gland lesions (nonneoplastic and neoplastic, and mesenchymal lesions (benign and malignant neoplasms. In addition, lesions with rough surface were summarized in six more common lesions. In total, 29 entities were organized in the form of a decision tree in order to help clinicians establish a logical diagnosis by a stepwise progression method.

  10. Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.

    Science.gov (United States)

    Grässel, Susanne; Muschter, Dominique

    2017-04-28

    The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.

  11. The Biochemical Origin of Pain: The origin of all Pain is Inflammation and the Inflammatory Response. PART 2 of 3 –Inflammatory Profile of Pain Syndromes

    Science.gov (United States)

    2009-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome / reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing

  12. Role of Schwann cells in the regeneration of penile and peripheral nerves

    Directory of Open Access Journals (Sweden)

    Lin Wang

    2015-01-01

    Full Text Available Schwann cells (SCs are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED. Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1 the origin and development of SCs in the peripheral and penile nerve system; (2 Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3 how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4 and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.

  13. Beauty and cuteness in peripheral vision

    Science.gov (United States)

    Kuraguchi, Kana; Ashida, Hiroshi

    2015-01-01

    Guo et al. (2011) showed that attractiveness was detectable in peripheral vision. Since there are different types of attractiveness (Rhodes, 2006), we investigated how beauty and cuteness are detected in peripheral vision with a brief presentation. Participants (n = 45) observed two Japanese female faces for 100 ms, then were asked to respond which face was more beautiful (or cuter). The results indicated that both beauty and cuteness were detectable in peripheral vision, but not in the same manner. Discrimination rates for judging beauty were invariant in peripheral and central vision, while discrimination rates for judging cuteness declined in peripheral vision as compared with central vision. This was not explained by lower resolution in peripheral vision. In addition, for male participants, it was more difficult to judge cuteness than beauty in peripheral vision, thus suggesting that gender differences can have a certain effect when judging cuteness. Therefore, central vision might be suitable for judging cuteness while judging beauty might not be affected by either central or peripheral vision. This might be related with the functional difference between beauty and cuteness. PMID:25999883

  14. Beauty and Cuteness in Peripheral Vision

    Directory of Open Access Journals (Sweden)

    Kana eKuraguchi

    2015-05-01

    Full Text Available Guo, Liu, & Roebuck (2011 showed that attractiveness was detectable in peripheral vision. Since there are different types of attractiveness (Rhodes, 2006, we investigated how beauty and cuteness are detected in peripheral vision with a brief presentation. Participants (n = 45 observed two Japanese female faces for 100 ms, then were asked to respond which face was more beautiful (or cuter. The results indicated that both beauty and cuteness were detectable in peripheral vision, but not in the same manner. Discrimination rates for judging beauty were invariant in peripheral and central vision, while discrimination rates for judging cuteness declined in peripheral vision as compared with central vision. This was not explained by lower resolution in peripheral vision. In addition, for male participants, it was more difficult to judge cuteness than beauty in peripheral vision, thus suggesting that gender differences can have a certain effect when judging cuteness. Therefore, central vision might be suitable for judging cuteness while judging beauty might not be affected by either central or peripheral vision. This might be related with the functional difference between beauty and cuteness.

  15. Relapses in inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Blas J. Larrauri

    2016-12-01

    Full Text Available Most studies about treatment of inflammatory myopathies consist of cross-sectional analyses that do not assess long-term efficacy. In the present study we describe the follow-up of seven patients with inflammatory myopathies, 5 polymyositis and 2 dermatomyositis. We describe their clinical features, follow-up, muscle enzyme levels, and treatment responses. We define the latter as treatment cycles, every one of which end when steroid doses need to be increased or a new immunosuppressive drug has to be added because of clinical worsening or sustained increases in muscle enzyme levels. Treatment can cause remission, partially control, or fail in achieving myositis improvement when it normalizes, stabilizes, or does not affect muscle enzymes or clinical features, respectively. We analyzed 20 cycles, in which remission was achieved in 14 cases, partial control in 5 instances, and treatment failure in one case. Remission occurred after an average of 139 ± 98 days, whereas partial control took place in 160 ± 100 days. Except in one case, all treatment cycles controlled or remitted the symptoms. However, in all patients the illness recurred with time.

  16. Whole-body magnetic resonance imaging in inflammatory arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Eshed, Iris; Althoff, Christian E.

    2017-01-01

    with reproducibility data). The Working Group decided on inflammation in peripheral joints and entheses as primary focus areas, and then developed consensus MRI definitions for these pathologies, selected anatomical locations for assessment, agreed on a core set of MRI sequences and imaging planes for the different...... was to perform a systematic literature review (SLR) and to develop consensus definitions of key pathologies, anatomical locations for assessment, a set of MRI sequences and imaging planes for the different body regions, and a preliminary scoring system for WB-MRI in inflammatory arthritis. Methods: An SLR...

  17. Peripheral Neuropathy in Chlamydia Reactive Arthritis

    Directory of Open Access Journals (Sweden)

    O.V. Syniachenko

    2016-09-01

    Full Text Available Relevance. Peripheral neuropathy (PNP in urogenital chlamydia reactive arthritis (CRA is described as single observations, and many clinical and pathogenetic aspects of this lesion of the nervous system remain unclear. Objective of the study: to evaluate the incidence and nature of the clinical course of PNP in CRA, the connection of the nerve and joint injuries, to explore the questions of pathogenetic constructions of this neuropathy, to identify risk factors. Material and methods. We observed 101 patients with CRA, mean age of them was 32 years, disease duration — 4 years, and the male to female ratio — 1 : 1. In 90 % of CRA cases, Chlamydia trochamatis was found in prostatic secretions, in scraps from the urethra, the cervix, the vaginal wall, in 83 % — positive serologic tests for chlamydia infection. Results. Signs of PNP in CRA were in 19 % of patients in the ratio of mononeuropathy to polyneuropathy as 1 : 1, with motor, sensory and mixed disorders in a ratio of 1 : 3 : 6, the presence of autonomic changes in every second patient and more frequent distal localization of the process in the hands, which is influenced by the severity of the articular syndrome, high levels of antichlamydia antibodies in the blood, and the axonal and demyelinating indicators of electroneuromyography — by the severity of urogenital lesions and the presence of Guillain-Barre syndrome. A high rate of arthritis progression is a prognosis-negative sign of PNP course in patients with CRA. The pathogenic constructions of PNP involve the inflammatory immune proteins, disturbances of vascular endothelial function and physicochemical surface rheological pro­perties of the serum. Conclusion. PNP takes place in every fifth patient with CRA, correlates with clinical and laboratory signs of joint disease, and in the future will be useful to identify actively this pathology of the nervous system for the subsequent timely rehabilitation, and CRA

  18. Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

    Directory of Open Access Journals (Sweden)

    Stéphane Mathis

    2016-01-01

    Full Text Available Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies. For each patient, we carried out a pathological analysis (nerve and muscle and an electrophysiological study (and follow-up. To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders.

  19. Cryoplasty for peripheral arterial disease.

    Science.gov (United States)

    McCaslin, James E; Andras, Alina; Stansby, Gerard

    2013-08-11

    Percutaneous balloon angioplasty is an endovascular technique for restoring blood flow through an artery that has become narrowed or blocked by atherosclerosis. Narrowing of the artery following angioplasty (restenosis) is the major cause of long-term failure. Cryoplasty offers a different approach to improving long-term angioplasty results. It combines the dilation force of balloon angioplasty with cooling of the vessel wall. This systematic review evaluated cryoplasty in peripheral arterial disease and provides focus for further research in the field. This is an update of a review first published in 2007. To assess the efficacy of, and complications associated with, cryoplasty for maintaining patency in the iliac, femoropopliteal and crural arteries in the short and medium term. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 10). Trial databases were searched for ongoing or unpublished studies. We also searched the reference lists of relevant articles. All randomised controlled trials in which participants with peripheral arterial disease (PAD) of the lower limbs, or lower limb bypass graft stenoses, were randomised to cryoplasty with or without another procedure versus a procedure without cryoplasty were considered. This included trials where all participants received angioplasty and the randomisation was for cryoplasty versus no cryoplasty and trials where cryoplasty was used as an adjunct to conventional treatment (for example stenting) against a control. Two review authors independently reviewed, assessed and selected trials, extracted data and assessed risk of bias. Seven trials (six primary cryoplasty and one adjunctive cryoplasty trial) with a combined total of 478 patients were included in this review. The trials reported patency and restenosis either by participant, lesion or vessel location. Follow-up ranged from 30 days to

  20. Inflammatory mediators of neuropathic pain

    OpenAIRE

    Oliveira Júnior, José Oswaldo de; Portella Junior, Caio Sander Andrade; Cohen, Cláudia Panossian

    2016-01-01

    ABSTRACT BACKGROUND AND OBJECTIVES: Pro-inflammatory chemical mediators and algogenic substances seem to be confused by the sharing of their actions and by interactions in painful and inflammatory presentation. This study aimed at presenting a review of major inflammatory chemical mediators and place them in neuropathic pain pathophysiology. CONTENTS: Inflammation is the homeostatic response of vascularized tissues to remove harmful agents and restore their normal functions. Nervous system ...

  1. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    DEFF Research Database (Denmark)

    Lukács, M; Haanes, K A; Majláth, Zs

    2015-01-01

    BACKGROUND: Migraine is a painful disorder with a huge impact on individual and public health. We hypothesize that migraine pain originates from a central mechanism that results secondarily in hypersensitivity in peripheral afferents associated with the cerebral and cranial blood vessels. It has...... in the satellite glial cells, while IL-1β reactivity was observed in the neuronal cytoplasm, close to the cell membrane, seemingly as sign of neuro-glial interaction. The CGRP expression in the neurons and nerve fibres was enhanced after the application of either inflammatory agent. Myography resulted in a strong...

  2. Enzymatic Activities of Bovine Peripheral Blood Leukocytes and Milk Polymorphonuclear Neutrophils during Intramammary Inflammation Caused by Lipopolysaccharide

    Science.gov (United States)

    Prin-Mathieu, C.; Le Roux, Y.; Faure, G. C.; Laurent, F.; Béné, M. C.; Moussaoui, F.

    2002-01-01

    Leukocytes are recruited from peripheral blood into milk as part of the inflammatory response to mastitis. However, excessive accumulation of inflammatory cells alters the quality of milk and the proteases produced by polymorphonuclear neutrophils (PMNs) and macrophages may lead to mammary tissue damage. To investigate PMN recruitment and the kinetics of their intracytoplasmic enzymes in inflammation, we generated mastitis in six cows by intramammary infusion of lipopolysaccharide (LPS). Clinical signs of acute mastitis were observed in all of the cows, and normal status was resumed by 316 h. Intracytoplasmic elastase, collagenase, and cathepsin activities were measured within live cells by flow cytometry in peripheral blood leukocytes and milk PMNs before and during the inflammatory process (at 10 time points between 4 and 316 h). The proportion of immature PMNs was appreciated by CD33 surface labeling measured in flow cytometry. Leukopenia was observed in the peripheral blood 4 h postinfusion, concomitant to an increase in somatic cell counts in milk. CD33+ PMNs were preferentially recruited from the peripheral blood to milk. Enzymatic activities were detected in PMNs, lymphocytes, and monocytes at levels depending on the cell type, sample nature, and time of collection. Milk PMNs had lower enzymatic activities than peripheral blood PMNs. This study showed that milk PMNs recruited during LPS-induced experimental mastitis have an immature phenotype and significantly lower enzymatic activities than peripheral blood PMNs. This suggests that CD33, an adhesion molecule, may be involved in the egress from blood to milk and that the enzymatic contents of PMNs are partly used during this process. PMID:12093678

  3. The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review.

    Science.gov (United States)

    Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L

    2015-12-01

    Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important

  4. Neuroimmune regulation of inflammatory responses in inflammatory bowel disease

    NARCIS (Netherlands)

    Rijnierse, Anneke

    2006-01-01

    The term inflammatory bowel disease (IBD) is used to describe chronic inflammatory conditions of the gastro-intestinal tract. Patients suffer from abdominal pain, diarrhea, rectal bleeding and a substantial personal burden. The etiology of IBD is gradually being unraveled but remains a complex

  5. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...... in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were...

  6. Fatal inflammatory hypophysitis.

    Science.gov (United States)

    McIntyre, Elizabeth A; Perros, Petros

    2007-01-01

    A young female patient presented as an acute medical emergency with hypoglycaemia. Investigations revealed panhypopituitarism and an inflammatory pituitary mass. An antibody screen was negative for anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution (cANCA). Pituitary histology showed lymphocytic infiltration and a few Langerhan's cells. The pituitary mass rapidly expanded to involve the optic nerves and led to bilateral blindness. Later, the patient developed diarrhoea, a vasculitis rash, scleritis, and proteinuria. In subsequent investigations cANCA became positive. The patient responded to steroids and cyclophosphamide treatment and remained in partial remission for six months before dying of severe sepsis. This is the first description of Wegener's granulomatosis presenting with acute anterior pituitary failure in the absence of other organ involvement and negative serology.

  7. Inflammatory response after nailing.

    Science.gov (United States)

    Kanakaris, Nikolaos K; Anthony, Christopher; Papasotiriou, Antonios; Giannoudis, Peter V

    2017-06-01

    Intramedullary nailing, as the gold standard stabilisation method of most long bones, has been tailed by its extensive use as the basic tool of investigating the immune response to trauma in many large and small animal models, as well as at the clinical setting. Over the last few decades a complex map of interactions between pro and anti-inflammatory pathways has been the result of these significant global research efforts. Parallel to the evolution of modern nailing and reaming techniques, significant developments at the fields of other disciplines relevant to trauma care, has improved the contemporary management of injured patients, challenging previous concepts and altering clinical barriers. The current article aims to summarise the current understanding of the effect of instrumenting the medullary canal after trauma, and hint on potential future directions. Copyright © 2017. Published by Elsevier Ltd.

  8. Regulation of inflammatory gene expression in PBMCs by immunostimulatory botanicals.

    Directory of Open Access Journals (Sweden)

    Karen L Denzler

    Full Text Available Many hundreds of botanicals are used in complementary and alternative medicine for therapeutic use as antimicrobials and immune stimulators. While there exists many centuries of anecdotal evidence and few clinical studies on the activity and efficacy of these botanicals, limited scientific evidence exists on the ability of these botanicals to modulate the immune and inflammatory responses. Using botanogenomics (or herbogenomics, this study provides novel insight into inflammatory genes which are induced in peripheral blood mononuclear cells following treatment with immunomodulatory botanical extracts. These results may suggest putative genes involved in the physiological responses thought to occur following administration of these botanical extracts. Using extracts from immunostimulatory herbs (Astragalus membranaceus, Sambucus cerulea, Andrographis paniculata and an immunosuppressive herb (Urtica dioica, the data presented supports previous cytokine studies on these herbs as well as identifying additional genes which may be involved in immune cell activation and migration and various inflammatory responses, including wound healing, angiogenesis, and blood pressure modulation. Additionally, we report the presence of lipopolysaccharide in medicinally prepared extracts of these herbs which is theorized to be a natural and active component of the immunostimulatory herbal extracts. The data presented provides a more extensive picture on how these herbs may be mediating their biological effects on the immune and inflammatory responses.

  9. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype

    Science.gov (United States)

    Mathey, Emily K; Park, Susanna B; Hughes, Richard A C; Pollard, John D; Armati, Patricia J; Barnett, Michael H; Taylor, Bruce V; Dyck, P James B; Kiernan, Matthew C; Lin, Cindy S-Y

    2015-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP. PMID:25677463

  10. Production of deoxyschizandrin and γ-schizandrin in shoot-differentiating and undifferentiating callus cultures of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine).

    Science.gov (United States)

    Szopa, Agnieszka; Ekiert, Halina

    2013-06-10

    Shoot-differentiating and undifferentiating callus cultures of Schisandra chinensis were cultured, respectively, on six and two variants of the Murashige and Skoog (MS) medium, differing in the concentration of cytokinin, 6-benzyladenine (BA) and auxin, α-naphthaleneacetic acid (NAA). In methanolic extracts from the biomass of both types of culture the amounts of two lignans: deoxyschizandrin and γ-schizandrin were estimated using the HPLC method. The levels of both compounds in the shoot-differentiating callus extracts were dependent on the concentration of BA and NAA in the MS medium variants. The amounts of deoxyschizandrin were high and varied over a wide range from 34.23 to 308.51 mg 100 g(-1) dry weight (DW); the amounts of γ-schizandrin were of a different order and ranged from 1.07 to 22.09 mg 100 g(-1) DW. In the extracts from undifferentiating callus the amounts of both compounds were lower and almost identical on the tested variants of the MS medium, equal, respectively, to about 18.5 mg 100 g(-1) DW deoxyschizandrin, and about 1.0 mg 100 g(-1) DW γ-schizandrin. The maximum amounts of deoxyschizandrin were obtained on the MS medium variant containing 3 mg l(-1) BA and 1 mg l(-1) NAA. These amounts were 7.5 and 5.1 times higher, respectively, than in the extracts from the leaves (41.01 mg 100 g(-1) DW) and fruits (60.72 mg 100 g(-1) DW) of native plant, analyzed for comparison. The maximum amount of γ-schizandrin in shoot-differentiating callus (22.09 mg 100 g(-1) DW) was comparable with its amount in the leaves (22.27 mg 100 g(-1) DW), but 3 times lower than in the fruits (66.50 mg 100 g(-1) DW). The obtained high amounts of deoxyschizandrin in the extracts of shoot-differentiating callus are of interest from the practical perspective. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Comparative study of two boron compounds (BPA and BOPP) for the application of BNCT to an animal model of undifferentiated thyroid cancer

    International Nuclear Information System (INIS)

    Dagrosa, Maria A.; Viaggi, Mabel; Juvenal, Guillermo; Pisarev, Mario A.

    2003-01-01

    Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron compounds by tumors. Once the uptake, relative to normal tissues, is equal of greater than 3, the tumoral area is irradiated with an appropriate neutron beam. The 10 B is then converted into 11 B and this decays releasing an atom of Li, gamma rays and alpha particles. These latter have a high linear energy transfer (LET) and will cause local damage, eventually killing the tumoral cells. At the present time several clinical trials are being conducted in different countries to treat patients with glioblastoma multiform and melanomas. So far the results obtained, specially with this last disease, are quite encouraging. Undifferentiated thyroid cancer (UTC) is a very aggressive tumor which does not respond to the therapies available at the present. Usually it has a very bad prognosis with a very short survival period. We have previously shown that the human UTC cell line ARO has an uptake of borophenylanine (BPA) significantly greater than normal thyroid or than human follicular adenoma cells in culture. Moreover, an animal model for UTC was developed in our laboratory by transplanting the human ARO cells into nude mice. This model closely resembles the evolution of human disease and even produces lung metastasis, like the human. In the present studies we have compared the uptake of two boron compounds: BPA and boronated porphyrin (BOPP). BPA was administered via ip in a dose of 600 mg/kg body weight, while BOPP was given either ip or iv, in doses of 10 and 100 mg/kg body weight. The animals were sacrificed at different times after the injection: up to 150 min for BPA and after 24 h with BOPP. The concentration of boron was determined by ICP-AES. The results obtained showed that the uptake of BPA was significantly greater in the tumoral area and in the infiltrated surrounding skin than in the other organs examined (liver, kidney, lung, mice thyroid, blood, spleen and distal skin

  12. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

    Directory of Open Access Journals (Sweden)

    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  13. Investigations of peripheral dose for helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lissner, Steffen; Schubert, Kai; Sterzing, Florian; Herfarth, Klaus; Sroka-Perez, Gabriele; Debus, Juergen [University Hospital Heidelberg (Germany). Dept. of Radiation Oncology; Wiezorek, Tilo [University Hospital Jena (Germany). Dept. of Radiotherapy

    2013-07-01

    Purpose: Whenever treating a patient with percutaneous radiotherapy, a certain amount of dose is inevitably delivered to healthy tissue. This is mainly due to beam's entry and exit in the region of the target volume. In regions distant from the target volume, dose is delivered by leakage from the MLC and head scatter from the accelerator head and phantom scatter from the target volume (peripheral dose). Helical tomotherapy is a form of radiation therapy with a uniquely designed machine and delivery pattern which influence the peripheral dose. The goal of this work was to investigate peripheral dose in helical tomotherapy. The experiments were used to establish a complex characterization of the peripheral dose. Materials and methods: A 30*30*60cm{sup 3} slab phantom and TLD-100 (Lithium fluoride) were used for the experiments. Treatment procedures were generated with the tomotherapy planning system (TPS). Additionally, procedures were created on the Operator Station of the tomotherapy system without a calculation of the dose distribution. The peripheral dose which was produced by a typical tomotherapy treatment plan was measured. Furthermore, these procedures were used to differentiate the parts of the peripheral dose in phantom scatter dose and head scatter and leakage dose. Additionally, the relation between peripheral dose and treatment time and between peripheral dose and delivered dose was investigated. Additionally, the peripheral dose was measured in an Alderson phantom. Results: Distances of 30cm or more resulted in a decrease of the peripheral dose to less than 0.1% of the target dose. The measured doses have an offset of approximately 1cGy in comparison to the calculated doses from the TPS. The separated head scatter and leakage dose was measured in the range of 1cGy for typical treatments. Furthermore, the investigations show a linear correlation between head scatter leakage dose and treatment time and between scatter dose parts and delivered dose. A

  14. CT characteristics of peripheral organizing pneumonia

    International Nuclear Information System (INIS)

    Yang, Seong Oh; Choi, Chul Soon; Kim, Myung Joon; Lee, Kyung Soo; Choi, Hyung Sik; Jun, Young Hwan; Park, Yong Koo

    1988-01-01

    Diagnostic dilemma of persistent mass-forming parenchymal opacity in the lung periphery occurs occasionally in the realm of diagnostic radiology. Until recently, literature on the role of computed tomography in peripheral organizing pneumonia, which is difficult to differentiate from malignancy, has little been published. We experienced one case of pathologically proven organizing pneumonia diagnosed preoperatively by chest CT. When it comes to solitary peripheral mass density in the lung, we think that CT can be proved useful in the diagnosis of benign organizing pneumonia by showing regular and smoothly corrugate margin, peripheral contrast enhancement with inner low density, and air-trapping by intervening normal lung parenchyma.

  15. Current and future peripherally-acting antitussives.

    Science.gov (United States)

    Dicpinigaitis, Peter V

    2006-07-28

    Cough is among the most common complaints for which medical evaluation is sought. The clinical significance of this problem is evidenced by the enormous financial expenditure on prescription and non-prescription cough remedies worldwide. Centrally-acting antitussive agents, such as opiates, are often associated with undesirable or intolerable side effects, including sedation, nausea, and constipation. Therefore, safe and effective peripherally-acting antitussive agents are particularly desirable. Relatively few commercially-available products suppress cough through a peripheral mechanism of action. Recent research in the field of cough has resulted in the development of several new classes of compounds that may prove to be clinically useful peripherally-acting antitussives.

  16. Guillain-Barré syndrome, tuberculosis and inflammatory bowel disease: a multiple association

    Directory of Open Access Journals (Sweden)

    de la Torre Ricardo

    2010-07-01

    Full Text Available Abstract Guillain-Barré syndrome (GBS has been associated with both infective or non-infective aetiologies. GBS is usually preceded by acute respiratory or gastrointestinal infection but its association with tuberculosis has been exceptionally reported. Inflammatory bowel disease (IBD is associated with clinical manifestations involving the neurological system, peripheral neuropathy is known to be related to IBD and, either demyelinating or axonal involvement of peripheral nerves have been described. We report an unusual case of GBS associated with lymph node tuberculosis and ulcerative colitis.

  17. Systems and methods to control multiple peripherals with a single-peripheral application code

    Science.gov (United States)

    Ransom, Ray M.

    2013-06-11

    Methods and apparatus are provided for enhancing the BIOS of a hardware peripheral device to manage multiple peripheral devices simultaneously without modifying the application software of the peripheral device. The apparatus comprises a logic control unit and a memory in communication with the logic control unit. The memory is partitioned into a plurality of ranges, each range comprising one or more blocks of memory, one range being associated with each instance of the peripheral application and one range being reserved for storage of a data pointer related to each peripheral application of the plurality. The logic control unit is configured to operate multiple instances of the control application by duplicating one instance of the peripheral application for each peripheral device of the plurality and partitioning a memory device into partitions comprising one or more blocks of memory, one partition being associated with each instance of the peripheral application. The method then reserves a range of memory addresses for storage of a data pointer related to each peripheral device of the plurality, and initializes each of the plurality of peripheral devices.

  18. T Cell Repertoire and Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Kenneth Croitoru

    1996-01-01

    Full Text Available The diversity of the T cell receptor repertoire is generated through rearrangement of the variable, junctional and constant region genes. Selection processes in the thymus and periphery serve to eliminate self-reacting T cells, thereby preventing autoimmune disease. The possibility that inflammatory bowel disease (IBD is an autoimmune disease has led to the search for an auto-antigen. In addition, studies are exploring the T cell receptor repertoire in IBD patients for changes that may provide clues regarding etiopathogenesis. Using monoclonal antibodies to T cell receptor variable-gene products or polymerase chain reaction analysis of variable-gene mRNA expression, the mucosal T cell repertoire has been examined in humans. The intestinal intraepithelial lymphocytes show a significant degree of oligoclonal expansion that may represent local antigen exposure or unique selection processes. This is in keeping with studies that show that murine intestinal intraepithelial lymphocytes undergo positive and possibly negative selection independent of the thymus. In the inflamed human gut, shifts in the T cell receptor repertoire may also reflect recruitment of peripheral T cells to the gut. In one study, a subset of Crohn’s disease patients was shown to have an increase in the proportion of variable β8 peripheral blood lymphocyte and mesenteric lymph node cells, suggesting a superantigen effect. The authors hypothesized that changes in the functional T cell receptor repertoire can also occur which might be independent of changes in the distribution of T cells expressing variable β T cell receptors. In fact, the authors have shown there is a selective decrease in the cytotoxic function of peripheral variable β8 T cells in Crohn’s disease. Furthermore, stimulation with the variable β8 selective bacterial enterotoxin staphylococcal enterotoxin E failed to increase the cytotoxic function in this subset of Crohn’s disease patients compared with

  19. Systemic inflammatory responses in asthma

    NARCIS (Netherlands)

    Hove, W. ten

    2007-01-01

    In asthma, inflammatory cells undergo a process referred to as priming. During priming responses, cells are not directly activated by inflammatory stimuli, but acquire increased responsiveness towards heterologous stimuli. The focus of the studies presented in the thesis of Willem ten Hove was

  20. Vitamin D in inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Thea K Wöbke

    2014-07-01

    Full Text Available Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, atherosclerosis or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signalling modulates many inflammatory responses on several levels. This includes i the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, ii the interference with transcription factors, such as NF-kB, which regulate the expression of inflammatory genes and iii the activation of signalling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signalling and other signalling cascades involved in inflammation.An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP, ChIP-seq and FAIRE-seq.

  1. Relationship between inflammatory response and postoperative cognitive complications: Advance in research

    Directory of Open Access Journals (Sweden)

    Ya-wei LI

    2014-10-01

    Full Text Available Postoperative cognitive complications (including delirium and cognitive dysfunction are common in elderly patients after an operation, and they are usually accompanied by a poor prognosis. Although the mechanism of postoperative cognitive complications remains unclear, previous studies suggest that inflammatory reaction of central neural system (CNS may play an important role in its development. Peripheral inflammatory reaction could be spread to CNS in several ways, and inflammatory reaction of CNS may interfere its function, inhibit the regeneration of neurons, and induce apoptosis of neurons, finally resulting in cognitive impairment and complications. Intraoperative administration of single, high-dose glucocorticoid (dexamethasone and perioperative non-stero idal anti-inflammatory drugs (NSAIDs may be helpful to decrease the incidence of postoperative cognitive complications. The influence of perioperative prophylactic usage of ulinastatin and anesthetic technique in prevention of postoperative cognitive complications calls for further investigation. DOI: 10.11855/j.issn.0577-7402.2014.08.17

  2. Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

    Science.gov (United States)

    González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

    2015-01-01

    Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

  3. The impact of MRI on the clinical management of inflammatory arthritides

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Ulrich [University of Alberta, Department of Medicine, Division of Rheumatology, Edmonton, AB (Canada); Balgrist University Hospital, Department of Rheumatology, Zurich (Switzerland); Oestergaard, Mikkel [Copenhagen University Hospital at Glostrup, Department of Rheumatology, Copenhagen (Denmark); Lambert, Robert G.W. [University of Alberta, Department of Radiology and Diagnostic Imaging, Edmonton, AB (Canada); Maksymowych, Walter P. [University of Alberta, Department of Medicine, Division of Rheumatology, Edmonton, AB (Canada)

    2011-09-15

    In the past two decades, MRI has gained a major role in research and clinical management of patients with inflammatory arthritides, particularly in spondyloarthritis (SpA), rheumatoid arthritis (RA), and osteoarthritis (OA). MRI is regarded as the most sensitive imaging modality for detecting early SpA in young patients with inflammatory back pain and normal radiographs of the sacroiliac joints. The recently published Assessment of SpondyloArthritis International Society classification criteria for axial SpA include for the first time a positive MRI demonstrating sacroiliitis as an imaging criterion indicative of SpA together with at least one clinical feature of SpA. Recent data show that systematic assessment of sacroiliitis displayed on MRI has much greater diagnostic utility than previously reported and highlight the diagnostic relevance of structural lesions. In RA, MRI has predictive value for the development of disease in new onset undifferentiated arthritis, and MR pathology at disease onset is a highly significant predictor of radiographic erosions. Consequently MRI has been credited with an important role in the new ACR/EULAR 2010 classification criteria for RA. In OA, bone marrow edema (BME) and synovitis may serve as biomarkers in interventional trials. Treatment interventions targeting BME and synovitis observed on MRI in inflammatory arthritides may have a disease-modifying effect as these lesions are potentially reversible and have been shown to be associated with structural progression. Research should focus on the prognostic significance of MRI lesions in larger cohorts and whether adding MRI to routine care improves clinical and radiographic outcome in patients with inflammatory arthritides. (orig.)

  4. Non-conventional features of peripheral serotonin signalling - the gut and beyond.

    Science.gov (United States)

    Spohn, Stephanie N; Mawe, Gary M

    2017-07-01

    Serotonin was first discovered in the gut, and its conventional actions as an intercellular signalling molecule in the intrinsic and extrinsic enteric reflexes are well recognized, as are a number of serotonin signalling pharmacotherapeutic targets for treatment of nausea, diarrhoea or constipation. The latest discoveries have greatly broadened our understanding of non-conventional actions of peripheral serotonin within the gastrointestinal tract and in a number of other tissues. For example, it is now clear that bacteria within the lumen of the bowel influence serotonin synthesis and release by enterochromaffin cells. Also, serotonin can act both as a pro-inflammatory and anti-inflammatory signalling molecule in the intestinal mucosa via activation of serotonin receptors (5-HT 7 or 5-HT 4 receptors, respectively). For decades, serotonin receptors have been known to exist in a variety of tissues other than the gut, but studies have now provided strong evidence for physiological roles of serotonin in several important processes, including haematopoiesis, metabolic homeostasis and bone metabolism. Furthermore, evidence for serotonin synthesis in peripheral tissues outside of the gut is emerging. In this Review, we expand the discussion beyond gastrointestinal functions to highlight the roles of peripheral serotonin in colitis, haematopoiesis, energy and bone metabolism, and how serotonin is influenced by the gut microbiota.

  5. Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

    Directory of Open Access Journals (Sweden)

    Alessandra Menon

    2018-01-01

    Full Text Available Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21% has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF, the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.

  6. Field study of the comparative efficacy of gamithromycin and tulathromycin for the treatment of undifferentiated bovine respiratory disease complex in beef feedlot calves.

    Science.gov (United States)

    Torres, Siddartha; Thomson, Dan U; Bello, Nora M; Nosky, Bruce J; Reinhardt, Chris D

    2013-06-01

    To compare the efficacy of gamithromycin with that of tulathromycin for the treatment of undifferentiated bovine respiratory disease complex (BRDC) in feedlot calves. 1,049 weaned crossbred beef calves. At each of 6 feedlots, newly arrived calves with BRDC were administered a single dose of gamithromycin (6.0 mg/kg, SC; n = 523) or tulathromycin (2.5 mg/kg, SC; 526). Case-fatality and BRDC retreatment rates during the first 120 days after treatment, final body weight, and average daily gain (ADG), were compared between treatments. At 2 feedlots, calves were assigned clinical scores for 10 days after treatment to determine recovery rates for each treatment. Bioequivalence limits for gamithromycin and tulathromycin were calculated for outcomes for which there was no significant difference between treatments. Mean BRDC retreatment rate (17.7%) for calves administered gamithromycin was greater than that (9.0%) for calves administered tulathromycin. Mean case-fatality rate, final body weight, ADG, and clinical score 10 days after treatment did not differ significantly between treatments. Limits for mean differences within which gamithromycin was bioequivalent to tulathromycin were ± 2.4% for case-fatality rate, ± 13 kg for final body weight, and ± 0.1 kg/d for ADG. Calves administered gamithromycin had a higher BRDC retreatment rate than did calves administered tulathromycin; otherwise, the clinical efficacy did not differ between the 2 treatments for the treatment of BRDC in feedlot calves.

  7. Efficacy of a florfenicol-flunixin meglumine combination product versus tulathromycin or ceftiofur crystalline free acid for the treatment of undifferentiated fever in feedlot calves.

    Science.gov (United States)

    Hannon, Sherry J; Perrett, Tye; Wildman, Brian K; Schunicht, Oliver C; Vogstad, Amanda R; Fenton, R Kent; Borciaga-Robles, Luis O; Pollock, Colleen M; Jim, G Kee; Berg, Janice; Booker, Calvin W

    2009-01-01

    In this field trial, a new combination product containing florfenicol and flunixin meglumine (FLOR-FM) was compared with commercially available products that contained only tulathromycin (TULA) or ceftiofur crystalline free acid (CCFA) for the treatment of undifferentiated fever (UF; rectal temperature >/=105.0 degrees F) in beef calves that received long-acting oxytetracycline at feedlot arrival. The overall mortality rate of the FLOR FM group (2.0%) was significantly (P less than .050) lower than the rates in the TULA and CCFA groups (10.0% and 20.0%, respectively; 50 animals/group), even though the first UF relapse rate of the FLOR FM group was significantly (P less than .050) higher than that of the TULA group. In the FLOR FM group, this resulted in per-animal economic advantages of Can$46.23 (versus TULA) and Can$108.77 (versus CCFA) based on equal costs for initial UF therapy. These results demonstrate that it is more cost-effective to administer FLOR FM than TULA or CCFA for initial UF therapy in feedlot calves at high risk for bovine respiratory disease that receive metaphylactic long-acting oxytetracycline at feedlot arrival.

  8. A case of a resected benign myxoma-like hemorrhagic cyst, which later recurred as undifferentiated pleomorphic sarcoma in the left atrium.

    Science.gov (United States)

    Kim, Eunju; Choi, Seo-Won; Min, Daniel; Kim, Sang Hoon; Yang, Woo-In; Moon, Jae Youn; Sung, Jung Hoon; Kim, In Jai; Lim, Sang-Wook; Cha, Dong-Hun; Moon, Byung; Cho, Sang-Ho; Kim, Won-Jang

    2017-04-01

    An intracardiac cystic mass is a rare type of mass found in the left atrium. The differential diagnosis of an intracardiac cystic mass includes hydatid cysts, bronchogenic cysts, intracardiac varices, and hemorrhages in some tumor types, including myxoma. We present the case of a 68-year-old woman who presented with episodic dyspnea. Transthoracic echocardiography (TTE) revealed the presence of a left atrial mass mimicking myxoma. However, in postoperative findings, it was determined that the mass was actually a hemorrhagic cyst. Eighteen months later, the patient presented with recurrent exertional dyspnea and TTE revealed the recurrence of a left atrial mass. Computed tomography showed that the mass extended into the right atrium, inferior vena cava, and coronary sinus. After re-operation, the final histological diagnosis was determined to be an undifferentiated pleomorphic sarcoma in the left atrium. An intracardiac hemorrhagic cyst was suspected during the operation of a benign-looking LA mass. As such, we recommend that other rare etiologies be considered and more biopsies be performed when possible.

  9. The osteogenic response of undifferentiated human mesenchymal stem cells (hMSCs) to mechanical strain is inversely related to body mass index of the donor.

    Science.gov (United States)

    Friedl, Gerald; Windhager, Reinhard; Schmidt, Helena; Aigner, Reingard

    2009-08-01

    While the importance of physical factors in the maintenance and regeneration of bone tissue has been recognized for many years and the mechano-sensitivity of bone cells is well established, there is increasing evidence that body fat constitutes an independent risk factor for complications in bone fracture healing and aseptic loosening of implants. Although mechanical causes have been widely suggested, we hypothesized that the osteogenic mechano-response of human mesenchymal stem cells (hMSCs) may be altered in obese patients. We determined the phenotypic and genotypic response of undifferentiated hMSCs of 10 donors to cyclic tensile strain (CTS) under controlled in vitro conditions and analyzed the potential relationship relevant to the donor's anthropomorphometric and biochemical parameters related to donor's fat and bone metabolism. The osteogenic marker genes were all statistically significantly upregulated by CTS, which was accompanied by a significant increase in cell-based ALP activity. Linear correlation analysis revealed that there was a significant correlation between phenotypic CTS response and the body mass index of the donor (r = -0.91, p < 0.001) and phenotypic CTS response was also significantly related to leptin levels (r = -0.68) and estradiol levels (r = 0.67) within the bone marrow microenvironment of the donor. Such an upstream imprinting process mediated by factors tightly related to the donor's fat metabolism, which hampers the mechanosensitivity of hMSCs in obese patients, may be of pathogenetic relevance for the complications associated with obesity that are seen in orthopedic surgery.

  10. [A Case of Resection for Lymph Node Recurrence around the Inferior Vena Cava after Radical Surgery of Undifferentiated Carcinoma of the Pancreatic Head Region].

    Science.gov (United States)

    Kubo, Masahiko; Yamada, Daisaku; Eguchi, Hidetoshi; Iwagami, Yoshifumi; Noda, Takehiro; Asaoka, Tadafumi; Wada, Hiroshi; Kawamoto, Kouichi; Gotoh, Kunihito; Kobayashi, Shogo; Mori, Masaki; Doki, Yuichiro

    2018-02-01

    A 60-year-old man underwent palliative surgery with a diagnosis of unresectable cancer, and he visited our hospital for further treatment. Since the cancer was unresectable and multiple hepatic tumors were revealed in CT images that were not metastases, we decided to perform curative surgery for the pancreatic cancer accompanied by partial liver invasion. Pancreaticoduodenectomy plus partial hepatectomy were performed, and 2 tumors were detected in the resected specimen: one in the pancreas-duodenum region and a submucosal tumor in the duodenum bulb. The large tumor that occupied the pancreasduodenum region was histologically diagnosed as an undifferentiated carcinoma, and the duodenal submucosal tumor was consistent with findings of a poorly differentiated adenocarcinoma. Two years after surgery, CT examination revealed a mass extending into the inferior vena cava(IVC)from near the right renal vein. We eventually diagnosed lymph node recurrence with tumor thrombosis inthe IVC and started chemotherapy(FOLFIRINOX). After the tumor decreased, we performed salvage surgery involving resection of the lymph node, thrombectomy, and right nephrectomy. The tumor revealed atypical cells in the region of thrombosis, and the pathological findings were not in conflict with the findings of metastases from pancreatic cancer 2 years prior. After the treatment, chemotherapy was administered and he survived without any recurrence for 15 months after surgery.

  11. Panuveíte em artrite indiferenciada HLA-B27 positiva Panuveitis in HLA-B27 positive undifferentiated arthritis

    Directory of Open Access Journals (Sweden)

    Mário Sérgio Ferreira Santos

    2008-10-01

    Full Text Available Entre os vários tipos de inflamação ocular associados às doenças reumatológicas, a uveíte anterior é particularmente comum nas espondiloartropatias, em especial quando associada à presença do genótipo HLA-B27. Relatou-se o caso de um paciente com artrite indiferenciada HLA-B27 positivo, complicado com panuveíte e vasculite da retina, refratária ao tratamento imunossupressor tradicional, que obteve boa resposta clínica ao uso de anti-TNF-alfa.Among the several types of ocular inflammation associated to the rheumatic diseases, anterior uveitis is particularly common in the spondyloarthropathies, especially when associated to the presence of the HLA-B27 genotype. We report the case of HLA-B27 positive patient with undifferentiated arthritis, complicated with panuveitis and retinal vasculitis, that was refractory to the traditional imunossupressive treatment, and had a good clinical response with anti-TNF-alpha therapy.

  12. A Trp53fl/flPtenfl/fl mouse model of undifferentiated pleomorphic sarcoma mediated by adeno-Cre injection and in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Marisa R Buchakjian

    Full Text Available Genetic mouse models of soft tissue sarcoma provide critical insights into disease pathophysiology, which are oftentimes unable to be extracted from human tumor samples or xenograft models. In this study we describe a mouse model of soft tissue sarcoma mediated by adenoviral-Cre recombinase injection into Trp53fl/fl/Ptenfl/fl lox-stop-lox luciferase mice. Injection of adenovirus expressing Cre recombinase, either subcutaneously or intramuscularly in two experimental groups, results in viral infection and gene recombination with 100% penetrance within the first 24 hours following injection. Luciferase expression measured by real-time bioluminescence imaging increases over time, with an initial robust increase following viral injection, followed by a steady rise over the next several weeks as primary tumors develop and grow. Intramuscular injections were more commonly associated with evidence of systemic viral distribution than subcutaneous injections. All mice developed soft tissue sarcomas at the primary injection site, with histological examination identifying 93% of tumors as invasive pleomorphic sarcomas based on microscopic morphology and immunohistochemical expression of sarcoma markers. A lymphocytic infiltrate was present in 64% of the sarcomas in this immunocompetent model and 71% of tumors expressed PD-L1. This is the first report of a viral-Cre mediated Trp53/Pten mouse model of undifferentiated pleomorphic sarcoma. The bioluminescence imaging feature, along with high penetrance of the model and its immunological characteristics, makes it suited for pre-clinical studies of soft tissue sarcoma.

  13. An Item Analysis of the French Version of the Test for Reception of Grammar Among Children and Adolescents With Down Syndrome or Intellectual Disability of Undifferentiated Etiology.

    Science.gov (United States)

    Facon, Bruno; Magis, David

    2016-10-01

    An item analysis of Bishop's (1983) Test for Reception of Grammar (TROG) in its French version (F-TROG; Lecocq, 1996) was conducted to determine whether the difficulty of items is similar for participants with or without intellectual disability (ID). In Study 1, responses to the 92 F-TROG items by 55 participants with Down syndrome (DS), 55 with ID of undifferentiated etiology (UND), and 55 typical children (TYP) matched on their F-TROG total score were compared using the transformed item difficulties method, a statistical approach designed to detect differential item functioning (DIF) between groups. In Study 2, an additional comparison involving 526 TYP participants and 526 participants with UND was conducted to increase the statistical power of the analysis. The difficulty of items was highly similar whatever the sample size or clinical status of participants. Fewer than 3.5% of the items were flagged as showing DIF. Tests such as the TROG can be used with confidence in clinical practice as well as in research studies comparing participants with or without ID. Methods designed for investigating potential internal test bias-such as done here-should be more regularly employed in the developmental disability field to affirm the absence of DIF.

  14. Pleomorphic malignant fibrous histiocytoma/undifferentiated high-grade pleomorphic sarcoma of the scrotum in a patient presenting as fournier gangrene: a case report.

    Science.gov (United States)

    Guo, Juan; Zhou, Shengmei; Rao, Nagesh P; Pez, Gholam H

    2010-10-01

    Pleomorphic malignant fibrous histiocytoma (MFH), also known as undifferentiated high-grade pleomorphic sarcoma according to the latest World Health Organization classification, is a diagnosis of exclusion and extremely rare in adult scrotal/paratesticular region. Clinical presentation of scrotal/paratesticular pleomorphic MFH is usually a painless and gradual scrotal swelling. We report a case of scrotal MFH in a 63-year-old man who presented as Fournier gangrene after 10-month painful scrotal swelling and multiple procedures. The specimen of emergent debridement was submitted for pathologic and bacteriologic examination. Microscopically, the lesion had marked architectural and cytologic pleomorphism. The neoplastic cells were positive for vimentin, but negative for all lineage-specific markers. Fluorescence in-situ hybridization showed an aneuploid karyotype and negative results for lipomatous tumor abnormalities. Bacterial cultures of the specimen showed extensive growth of virulent polymicrobes. The diagnosis of scrotal/paratesticular pleomorphic MFH with concurrent Fournier gangrene was made. Thoracic computed tomography scan showed bilateral multiple pulmonary nodules. The patient died 1 month later.

  15. Dopaminergic Receptors and Tyrosine Hydroxylase Expression in Peripheral Blood Mononuclear Cells: A Distinct Pattern in Central Obesity.

    Science.gov (United States)

    Leite, Fernanda; Lima, Margarida; Marino, Franca; Cosentino, Marco; Ribeiro, Laura

    2016-01-01

    Dopamine (DA) may be involved in central obesity (CO), an inflammatory condition, through its role in the central nervous system and in periphery, where it may affect immune cell function through five different DA receptors (DR). Whether dopaminergic pathways in peripheral immune cells are implicated in the inflammatory condition linked to CO is however unknown. In a cohort of blood donors with and without CO, categorized by waist circumference (WC) (CO: WC ≥ 0.80 m in women and ≥ 0.94 m in men), we studied the expression of DR and tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of DA, in peripheral blood mononuclear cells (PBMCs) and their relation with anthropometric and metabolic/endocrine and inflammatory parameters. DR D1-5 and TH expression was assessed by semi quantitative real-time PCR. As inflammatory markers we investigated the immunophenotype of monocyte subsets by flow cytometry, staining for CD14, CD16, CD11b and CD36. CO individuals showed higher plasma levels of leptin and higher inflammatory pattern of monocytes compared with non-CO. PBMC expression of DR D2, DR D4 and DR D5 as well as of TH were lower in CO in comparison with non-CO. DR D2, and DR D5 expression correlated with lower WC and weight, and with lower inflammatory pattern of monocytes, and TH expression correlated with lower WC. DR D4 expression correlated with lower plasma levels of glycosylated hemoglobin, and DR D2 expression correlated with lower CO. Results show that CO is associated with peripheral inflammation and downregulation of dopaminergic pathways in PBMCs, possibly suggesting DR expressed on immune cells as pharmacological targets in obesity for better metabolic outcome.

  16. Anti-inflammatory properties of desipramine and fluoxetine

    Directory of Open Access Journals (Sweden)

    Portet Karine

    2007-05-01

    Full Text Available Abstract Background Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. Methods The antidepressants desipramine and fluoxetine were compared in vivo to the glucocorticoid prednisolone, an anti-inflammatory drug of reference. In a murine model of lipopolysaccharides (LPS-induced septic shock, animals received the drugs either before or after injection of LPS. Circulating levels of tumour necrosis factor (TNF-α and mortality rate were measured. In ovalbumin-sensitized rats, the effect of drug treatment on lung inflammation was assessed by counting leukocytes in bronchoalveolar lavages. Bronchial hyperreactivity was measured using barometric plethysmography. In vitro production of TNF-α and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES from activated monocytes and lung epithelial cells, respectively, was analysed by immunoassays. Reporter gene assays were used to measure the effect of antidepressants on the activity of nuclear factor-κB and activator protein-1 which are involved in the control of TNF-α and RANTES expression. Results In the septic shock model, all three drugs given preventively markedly decreased circulating levels of TNF-α and mortality (50% mortality in fluoxetine treated group, 30% in desipramine and prednisolone treated groups versus 90% in controls. In the curative trial, antidepressants had no statistically significant effect, while prednisolone still decreased mortality (60% mortality versus 95% in controls. In ovalbumin-sensitized rats, the three drugs decreased lung inflammation, albeit to different degrees. Prednisolone and fluoxetine reduced the number of macrophages, lymphocytes

  17. Effect of radiosynovectomy in patients with inflammatory joint disorders not caused by rheumatoid arthritis

    International Nuclear Information System (INIS)

    Kroeger, S.; Klutmann, S.; Bohuslavizki, K.H.; Clausen, M.; Sawula, J.A.; Brenner, W.; Henze, E.

    1999-01-01

    Aim: Effect of radiosynovectomy (RS) should be evaluated both by subjective and objective parameters in patients with osteoarthritis and in patients with inflammatory joint disorders not caused by rheumatoid arthritis. Methods: A total of 98 joints in 61 patients were investigated. Patients were divided into two groups. The first group included 35 patients with therapy-resistant effusions caused by severe osteoarthritis (46 joints). The second group consisted of 26 patients (52 joints) with ankylosing spondylitis, reactive arthritis, undifferentiated spondylarthropathy, psoriatic arthritis, pigmented villo-nodular synovitis, and recurrent synovitis following surgery. Effect of RS was evaluated by a standardized questionnaire and quantified by T/B-ratios derived from blood pool images prior to and after RS. Results: Within the first patient group suffering from osteoarthritis, 40% showed a good or excellent improvement of clinical symptoms, 51% were unchanged, and in 9% symptoms worsened. Similar results were found in the second patient group. The majority of unchanged results were small finger joints. In contrast, wrist and knee joints showed a better improvement. Good correlation between results of bone scan and patients subjective impression was found in 38% and 67% in the first and the second patient group, respectively. Conclusion: Radiosynovectomy might be an effective treatment in osteoarthritis and inflammatory joint disorders not caused by rheumatoid arthritis. (orig.) [de

  18. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  19. Side Effects: Nerve Problems (Peripheral Neuropathy)

    Science.gov (United States)

    Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

  20. Peripheral Vestibular System Disease in Vestibular Schwannomas

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

    2015-01-01

    with VS. METHODS: Retrospective analysis of vestibular system histopathology in temporal bones from 17 patients with unilateral VS. The material was obtained from The Copenhagen Temporal Bone Collection. RESULTS: Vestibular schwannomas were associated with atrophy of the vestibular ganglion, loss of fiber...... 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...

  1. Pharmacological Treatment Of Diabetic Peripheral Neuropathy

    OpenAIRE

    Cohen, Kenneth; Shinkazh, Nataliya; Frank, Jerry; Israel, Igor; Fellner, Chris

    2015-01-01

    Pain modulation is a key treatment goal for diabetic peripheral neuropathy patients. Guidelines have recommended antidepressant, anticonvulsant, analgesic, and topical medications—both approved and off-label—to reduce pain in this population.

  2. Allogeneic Peripheral Blood Stem Cell Harvest

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

  3. Neurophysiological approach to disorders of peripheral nerve

    DEFF Research Database (Denmark)

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves...

  4. Peripheral myelin protein 22 alters membrane architecture

    Science.gov (United States)

    Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

    2017-01-01

    Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

  5. Peripherally inserted central catheter - dressing change

    Science.gov (United States)

    PICC - dressing change ... You have a peripherally inserted central catheter (PICC). This is a tube that goes into a vein in your arm. It carries nutrients and medicines into your body. It may also ...

  6. Peripheral Arterial Disease Can Be a Killer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Special Section Peripheral Arterial Disease Can Be a Killer Past Issues / ... Color changes in skin, paleness, or blueness Lower temperature in one leg compared to the other leg ...

  7. Photoacoustic and ultrasound dual-modality imaging for inflammatory arthritis

    Science.gov (United States)

    Xu, Guan; Chamberland, David; Girish, Gandikota; Wang, Xueding

    2014-03-01

    Arthritis is a leading cause of disability, affecting 46 million of the population in the U.S. Rendering new optical contrast in articular tissues at high spatial and temporal resolution, emerging photoacoustic imaging (PAI) combined with more established ultrasound (US) imaging technologies provides unique opportunities for diagnosis and treatment monitoring of inflammatory arthritis. In addition to capturing peripheral bone and soft tissue images, PAI has the capability to quantify hemodynamic properties including regional blood oxygenation and blood volume, both abnormal in synovial tissues affected by arthritis. Therefore, PAI, especially when performed together with US, should be of considerable help for further understanding the pathophysiology of arthritis as well as assisting in therapeutic decisions, including assessing the efficacy of new pharmacological therapies. In this paper, we will review our recent work on the development of PAI for application to the diagnostic imaging and therapeutic monitoring of inflammatory arthritis. We will present the imaging results from a home-built imaging system and another one based on a commercial US. The performance of PAI in evaluating pharmacological therapy on animal model of arthritis will be shown. Moreover, our resent work on PAI and US dual-modality imaging of human peripheral joints in vivo will also be presented.

  8. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.

    Science.gov (United States)

    Glocker, Erik-Oliver; Kotlarz, Daniel; Boztug, Kaan; Gertz, E Michael; Schäffer, Alejandro A; Noyan, Fatih; Perro, Mario; Diestelhorst, Jana; Allroth, Anna; Murugan, Dhaarini; Hätscher, Nadine; Pfeifer, Dietmar; Sykora, Karl-Walter; Sauer, Martin; Kreipe, Hans; Lacher, Martin; Nustede, Rainer; Woellner, Cristina; Baumann, Ulrich; Salzer, Ulrich; Koletzko, Sibylle; Shah, Neil; Segal, Anthony W; Sauerbrey, Axel; Buderus, Stephan; Snapper, Scott B; Grimbacher, Bodo; Klein, Christoph

    2009-11-19

    The molecular cause of inflammatory bowel disease is largely unknown. We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient. In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10-induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor alpha and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10-dependent "negative feedback" regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful. Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient. 2009 Massachusetts Medical Society

  9. Association between polyunsaturated fatty acid-derived oxylipid biosynthesis and leukocyte inflammatory marker expression in periparturient dairy cows.

    Science.gov (United States)

    Raphael, W; Halbert, L; Contreras, G A; Sordillo, L M

    2014-01-01

    Peripheral blood mononuclear leukocytes from periparturient cows can have exacerbated inflammatory responses that contribute to disease incidence and severity. Oxylipids derived from the oxygenation of polyunsaturated fatty acids (PUFA) can regulate the magnitude and duration of inflammation. Although PUFA substrate for oxylipid biosynthesis in leukocytes is known to change across the periparturient period, the plasma oxylipid profile and how this profile relates to leukocyte inflammatory phenotype is not clear. The objective of this study was to determine if a relationship exists between the profile of pro- and antiinflammatory plasma oxylipids and the inflammatory phenotype of peripheral blood leukocytes during the periparturient period. Seven multiparous Holsteins were sampled from the prepartum period through peak lactation. Plasma oxylipids were measured by liquid chromatography-mass spectrometry, peripheral leukocyte mRNA expression was measured by quantitative PCR, and PUFA content of peripheral blood mononuclear cells was measured by gas chromatography-mass spectrometry. Concentrations of several hydroxyl products of linoleic and arachidonic acid changed over time. Linoleic acid and arachidonic acid concentrations in leukocytes increased during early lactation, suggesting that substrate availability for hydroxyoctadecadienoic and hydroxyeicosatetraenoic acid biosynthesis may influence the oxylipid profile. Leukocyte mRNA expressions of IL-12B, IL-1B, inducible nitric oxide synthase 2, and cyclooxygenase 2 were correlated with several plasma oxylipids. These are the first observations linking leukocyte inflammatory gene responses to shifts in oxylipid biosynthesis in periparturient dairy cows. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Dry needling — peripheral and central considerations

    OpenAIRE

    Dommerholt, Jan

    2011-01-01

    Dry needling is a common treatment technique in orthopedic manual physical therapy. Although various dry needling approaches exist, the more common and best supported approach targets myofascial trigger points. This article aims to place trigger point dry needling within the context of pain sciences. From a pain science perspective, trigger points are constant sources of peripheral nociceptive input leading to peripheral and central sensitization. Dry needling cannot only reverse some aspects...

  11. Management of peripheral facial nerve palsy

    OpenAIRE

    Finsterer, Josef

    2008-01-01

    Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell?s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the...

  12. Myopia onset and role of peripheral refraction

    Directory of Open Access Journals (Sweden)

    Rotolo M

    2017-06-01

    Full Text Available Maurilia Rotolo,1,2 Giancarlo Montani,2 Raul Martin1,3 1Optometry Research Group, IOBA Eye Institute, School of Optometry, Universidad de Valladolid, Valladolid, Spain; 2Optics and Optometry, Corso di Ottica e Optometria, Universita del Salento, Lecce, Italy; 3Faculty of Health and Human Sciences, School of Health Professions, Plymouth University, Peninsula Allied Health Centre, Plymouth, UK Background: To determine the peripheral refraction characteristics related to 18-month changes in refraction in Caucasian (Mediterranean children.Methods: Non-cycloplegic peripheral refraction at 10° intervals over the central ±30° of horizontal visual field over 18 months (baseline, 12 months, and 18 months of follow-up was conducted in 50 healthy children who were 8 years old. Axial length (AL was also recorded. Relative peripheral refraction (RPR was calculated and eyes were divided into three study groups: non-myopic eyes, myopic eyes, and eyes that develop myopia.Results: Myopic eyes showed hyperopic RPR and emetropic and hyperopic eyes showed myopic RPR. Univariate analysis of variance did not find any statistically significant effect of peripheral refraction (F36=0.13; P=1.00 and RPR (F36=0.79; P=0.80 on myopia onset (eyes that developed myopia along the study. All the studied groups showed an increase of AL, without statistically significant differences between the studied groups (F6=0.09; P=0.99.Conclusion: Hyperopic relative peripheral shift change in eyes that develop myopia has been found with differences in RPR between myopic (hyperopic RPR and hyperopic or emmetropic eyes (with myopic RPR. The results suggest that RPR cannot predict development or progression of myopia in Caucasian (Mediterranean children and the efficacy in slowing myopia progression obtained with treatments that manipulate the peripheral refraction is not just driven with RPR. Keywords: myopia, refractive errors, myopia onset, peripheral refraction, relative peripheral

  13. Passive Scalar Evolution in Peripheral Region

    OpenAIRE

    Lebedev, V. V.; Turitsyn, K. S.

    2003-01-01

    We consider evolution of a passive scalar (concentration of pollutants or temperature) in a chaotic (turbulent) flow. A universal asymptotic behavior of the passive scalar decay (homogenization) related to peripheral regions (near walls) is established. The passive scalar moments and its pair correlation function in the peripheral region are analyzed. A special case investigated in our paper is the passive scalar decay along a pipe.

  14. Case of Unilateral Peripheral Cone Dysfunction

    OpenAIRE

    Yujin Mochizuki; Kei Shinoda; Celso Soiti Matsumoto; Gerd Klose; Emiko Watanabe; Keisuke Seki; Itaru Kimura; Atsushi Mizota

    2012-01-01

    Purpose: Peripheral cone dystrophy is a subgroup of cone dystrophy, and only 4 cases have been reported. We present a patient with unilateral peripheral cone dysfunction and report the functional changes determined by electrophysiological tests and ultrastructural changes determined by spectral domain optical coherence tomography (SD-OCT). Case: A 34-year-old woman complained of blurred vision in both eyes. Our examination showed that her visual acuity was 0.05 OD and 0.2 OS. A relative affer...

  15. Peripheral inflammatory biomarkers for myocardial infarction risk: a prospective community-based study

    Science.gov (United States)

    BACKGROUND: Most previous studies regarding chronic inflammation and risk of myocardial infarction (MI) have lacked repeated measures of high-sensitivity C-reactive protein (hs-CRP) and/or white blood cell (WBC) count over time. We examined whether cumulative average and longitudinal changes in thes...

  16. IGF1 potentiates the pro-inflammatory response in human peripheral blood mononuclear cells via MAPK

    NARCIS (Netherlands)

    Wolters, T.L.C.; Netea, M.G.; Hermus, A.R.M.M.; Smit, J.W.A.; Netea-Maier, R.T.

    2017-01-01

    Acromegaly is characterized by growth hormone (GH) and insulin-like growth factor 1 (IGF1) excess and is accompanied by an increased cardiovascular diseases (CVD) risk. As innate immune responses are crucial in CVD development, and IGF1 is linked to subclinical inflammation, we hypothesized that

  17. Peripheral Circulatory Features during High-Frequency Jet Ventilation

    Directory of Open Access Journals (Sweden)

    M. B. Kontorovich

    2010-01-01

    Full Text Available The paper gives the results of a study of peripheral circulatory features during high-frequency jet ventilation (HFJV. The main specific features of peripheral circulation and oxygen transport during HFJV are formulated on the basis of a study of cardiac output (impedance cardiography, peripheral vascular resistance, peripheral vascular blood filling (photoplethysmogram analysis, adaptive peripheral blood flow reactions (spectral analysis of peripheral vascular pulsation. HFJV gives rise to the peculiar pattern of peripheral hemodynamics and tissue gas exchange, which is characterized by higher oxygen uptake without a decrease in mixed venous blood saturation, with normal extraction coefficient and preserved low peripheral vascular resistance. During HFJV, unlike traditional ventilation, the main peripheral hemodynamic feature is the increased capillary bed blood volume caused by the blood flow involvement of reserve capillaries under control of volume (parasympathetic regulation of adaptive peripheral hemodynamic reactions. Key words: high-frequency jet ventilation, oxygen transport, peripheral hemodynamics.

  18. Expression profiling feline peripheral blood monocytes identifies a transcriptional signature associated with type two diabetes mellitus.

    Science.gov (United States)

    O'Leary, Caroline A; Sedhom, Mamdouh; Reeve-Johnson, Mia; Mallyon, John; Irvine, Katharine M

    2017-04-01

    Diabetes mellitus is a common disease of cats and is similar to type 2 diabetes (T2D) in humans, especially with respect to the role of obesity-induced insulin resistance, glucose toxicity, decreased number of pancreatic β-cells and pancreatic amyloid deposition. Cats have thus been proposed as a valuable translational model of T2D. In humans, inflammation associated with adipose tissue is believed to be central to T2D development, and peripheral blood monocytes (PBM) are important in the inflammatory cascade which leads to insulin resistance and β-cell failure. PBM may thus provide a useful window to study the pathogenesis of diabetes mellitus in cats, however feline monocytes are poorly characterised. In this study, we used the Affymetrix Feline 1.0ST array to profile peripheral blood monocytes from 3 domestic cats with T2D and 3 cats with normal glucose tolerance. Feline monocytes were enriched for genes expressed in human monocytes, and, despite heterogeneous gene expression, we identified a T2D-associated expression signature associated with cell cycle perturbations, DNA repair and the unfolded protein response, oxidative phosphorylation and inflammatory responses. Our data provide novel insights into the feline monocyte transcriptome, and support the hypothesis that inflammatory monocytes contribute to T2D pathogenesis in cats as well as in humans. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Feto-maternal interactions in pregnancies: placental microparticles activate peripheral blood monocytes.

    Science.gov (United States)

    Messerli, M; May, K; Hansson, S R; Schneider, H; Holzgreve, W; Hahn, S; Rusterholz, C

    2010-02-01

    Normal pregnancy is associated with a systemic maternal inflammatory reaction, including the activation of peripheral blood monocytes. This reaction is exaggerated in pre-eclampsia, a severe placenta-dependent disorder of pregnancy specific to humans. It has been suggested that placental syncytiotrophoblast membrane microparticles (STBM), which are released into the peripheral blood, may contribute to the maternal response. The aim of this study was to investigate the inflammatory properties of STBM generated by four different approaches on primary human monocytes in vitro. Cellular viability, phenotype and functional response were analysed. STBM isolated by mechanical dissection and STBM generated from villous explant cultures incubated in hypoxic conditions had only minor influences on the monocytic phenotype and failed to induce a proinflammatory response. By contrast, STBM washed from the maternal side of a placental cotyledon and STBM shed by explants cultured in air up-regulated cell surface expression of the adhesion molecule CD54 and induced the production of interleukin (IL)-8, IL-6 and IL-1beta. Cytokine production was time- and dose-dependent. Our study, therefore, suggests that monocyte activation in normal pregnancy and pre-eclampsia may be induced by STBM released by the placenta. The higher amounts of STBM circulating in maternal blood in pre-eclampsia might lead to the excessive maternal inflammatory reaction. 2009 Elsevier Ltd. All rights reserved.

  20. Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins

    Science.gov (United States)

    Lozano-Ojalvo, Daniel; Molina, Elena; López-Fandiño, Rosina

    2016-01-01

    The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid) was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs), as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs). The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit. PMID:27007699

  1. Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins.

    Directory of Open Access Journals (Sweden)

    Daniel Lozano-Ojalvo

    Full Text Available The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs, as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs. The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit.

  2. Role of the peripheral innate immune system in the development of Alzheimer's disease.

    Science.gov (United States)

    Le Page, Aurélie; Dupuis, Gilles; Frost, Eric H; Larbi, Anis; Pawelec, Graham; Witkowski, Jacek M; Fulop, Tamas

    2017-12-21

    Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice.

    Science.gov (United States)

    Bernardy, Catia C F; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Calixto-Campos, Cássia; Carvalho, Thacyana T; Fattori, Victor; Borghi, Sergio M; Casagrande, Rubia; Verri, Waldiceu A

    2017-01-01

    The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10-100 mg/kg) 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO 2 , 30  μ g). Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNF α , IL-1 β , IL-10, COX-2, preproET-1, gp91 phox , Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO 2 -induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO 2 were successfully inhibited by tempol. KO 2 -induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO 2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

  4. Tempol, a Superoxide Dismutase Mimetic Agent, Inhibits Superoxide Anion-Induced Inflammatory Pain in Mice

    Directory of Open Access Journals (Sweden)

    Catia C. F. Bernardy

    2017-01-01

    Full Text Available The present study evaluated the anti-inflammatory and analgesic effects of the superoxide dismutase mimetic agent tempol in superoxide anion-induced pain and inflammation. Mice were treated intraperitoneally with tempol (10–100 mg/kg 40 min before the intraplantar injection of a superoxide anion donor, potassium superoxide (KO2, 30 μg. Mechanical hyperalgesia and thermal hyperalgesia, paw edema, and mRNA expression of peripheral and spinal cord mediators involved in inflammatory pain, TNFα, IL-1β, IL-10, COX-2, preproET-1, gp91phox, Nrf2, GFAP, and Iba-1, were evaluated. Peripheral and spinal cord reductions of antioxidant defenses and superoxide anion were also assessed. Tempol reduced KO2-induced mechanical hyperalgesia and thermal hyperalgesia and paw edema. The increased mRNA expression of the evaluated mediators and oxidative stress in the paw skin and spinal cord and increased mRNA expression of glial markers in the spinal cord induced by KO2 were successfully inhibited by tempol. KO2-induced reduction in Nrf2 mRNA expression in paw skin and spinal cord was also reverted by tempol. Corroborating the effect of tempol in the KO2 model, tempol also inhibited carrageenan and CFA inflammatory hyperalgesia. The present study demonstrates that tempol inhibits superoxide anion-induced molecular and behavioral alterations, indicating that tempol deserves further preclinical studies as a promising analgesic and anti-inflammatory molecule for the treatment of inflammatory pain.

  5. Conditional gene deletion reveals functional redundancy of GABAB receptors in peripheral nociceptors in vivo

    Directory of Open Access Journals (Sweden)

    Bettler Bernhard

    2009-11-01

    Full Text Available Abstract Background γ-aminobutyric acid (GABA is an important inhibitory neurotransmitter which mainly mediates its effects on neurons via ionotropic (GABAA and metabotropic (GABAB receptors. GABAB receptors are widely expressed in the central and the peripheral nervous system. Although there is evidence for a key function of GABAB receptors in the modulation of pain, the relative contribution of peripherally- versus centrally-expressed GABAB receptors is unclear. Results In order to elucidate the functional relevance of GABAB receptors expressed in peripheral nociceptive neurons in pain modulation we generated and analyzed conditional mouse mutants lacking functional GABAB(1 subunit specifically in nociceptors, preserving expression in the spinal cord and brain (SNS-GABAB(1-/- mice. Lack of the GABAB(1 subunit precludes the assembly of functional GABAB receptor. We analyzed SNS-GABAB(1-/- mice and their control littermates in several models of acute and neuropathic pain. Electrophysiological studies on peripheral afferents revealed higher firing frequencies in SNS-GABAB(1-/- mice compared to corresponding control littermates. However no differences were seen in basal nociceptive sensitivity between these groups. The development of neuropathic and chronic inflammatory pain was similar across the two genotypes. The duration of nocifensive responses evoked by intraplantar formalin injection was prolonged in the SNS-GABAB(1-/- animals as compared to their control littermates. Pharmacological experiments revealed that systemic baclofen-induced inhibition of formalin-induced nociceptive behaviors was not dependent upon GABAB(1 expression in nociceptors. Conclusion This study addressed contribution of GABAB receptors expressed on primary afferent nociceptive fibers to the modulation of pain. We observed that neither the development of acute and chronic pain nor the analgesic effects of a systematically-delivered GABAB agonist was significantly

  6. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  7. Vascular access in neonatology: peripherally inserted central catheter and peripheral venous catheter

    Directory of Open Access Journals (Sweden)

    Marcia Lienemann

    2014-04-01

    The objective of this paper is to present aspects of peripherally inserted central catheter and peripheral venous catheter, highlighting important points in choosing the type of access. For the passage of peripherally inserted central catheter is previously performing specific course necessary, while the primary indication occurs when it is necessary to access the patient's stay for a long period of time. Whereas peripheral venipuncture is the most appropriate in cases of needing an IV line quickly and safely, for the administration of fluids, blood collection, blood transfusion and other.

  8. Cefotaxime Treatment of Pelvic Inflammatory Disease

    OpenAIRE

    Monson, Thomas P.; Miller, Timothy T.; Nolan, Charles M.

    1981-01-01

    We studied cefotaxime in the treatment of gonococcal and nongonococcal pelvic inflammatory disease. Cefotaxime was uniformly effective against gonococcal pelvic inflammatory disease. However, 4 of 11 patients with nongonococcal pelvic inflammatory disease had a suboptimal response.

  9. Development of Spontaneous Autoimmune Peripheral Polyneuropathy in B7-2–Deficient Nod Mice

    Science.gov (United States)

    Salomon, Benoît; Rhee, Lesley; Bour-Jordan, Helene; Hsin, Honor; Montag, Anthony; Soliven, Betty; Arcella, Jennifer; Girvin, Ann M.; Miller, Stephen D.; Bluestone, Jeffrey A.

    2001-01-01

    An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is protected from diabetes but develops a spontaneous autoimmune peripheral polyneuropathy. All the female and one third of the male mice exhibited limb paralysis with histologic and electrophysiologic evidence of severe demyelination in the peripheral nerves beginning at 20 wk of age. No central nervous system lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic cells, CD4+, and CD8+ T cells. Finally, CD4+ T cells isolated from affected animals induced the disease in NOD.SCID mice. Thus, the B7-2–deficient NOD mouse constitutes the first model of a spontaneous autoimmune disease of the peripheral nervous system, which has many similarities to the human disease, chronic inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that NOD mice have “cryptic” autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway. PMID:11535635

  10. Extracellular vesicles: Pharmacological modulators of the peripheral and central signals governing obesity.

    Science.gov (United States)

    Milbank, Edward; Martinez, M Carmen; Andriantsitohaina, Ramaroson

    2016-01-01

    Obesity and its metabolic resultant dysfunctions such as insulin resistance, hyperglycemia, dyslipidemia and hypertension, grouped as the "metabolic syndrome", are chronic inflammatory disorders that represent one of the most severe epidemic health problems. The imbalance between energy intake and expenditure, leading to an excess of body fat and an increase of cardiovascular and diabetes risks, is regulated by the interaction between central nervous system (CNS) and peripheral signals in order to regulate behavior and finally, the metabolism of peripheral organs. At present, pharmacological treatment of obesity comprises actions in both CNS and peripheral organs. In the last decades, the extracellular vesicles have emerged as participants in many pathophysiological regulation processes. Whether used as biomarkers, targets or even tools, extracellular vesicles provided some promising effects in the treatment of a large variety of diseases. Extracellular vesicles are released by cells from the plasma membrane (microvesicles) or from multivesicular bodies (exosomes) and contain lipids, proteins and nucleic acids, such as DNA, protein coding, and non-coding RNAs. Owing to their composition, extracellular vesicles can (i) activate receptors at the target cell and then, the subsequent intracellular pathway associated to the specific receptor; (ii) transfer molecules to the target cells and thereby change their phenotype and (iii) be used as shuttle of drugs and, thus, to carry specific molecules towards specific cells. Herein, we review the impact of extracellular vesicles in modulating the central and peripheral signals governing obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The influence of inflammatory cytokines in physiopathology of suicidal behavior.

    Science.gov (United States)

    Miná, V A L; Lacerda-Pinheiro, S F; Maia, L C; Pinheiro, R F F; Meireles, C B; de Souza, S I R; Reis, A O A; Bianco, B; Rolim, M L N

    2015-02-01

    Based on the urgent need for reliable biomarkers in relation to suicide risk both for more accurate prediction as well as for new therapeutic opportunities, several researchers have been studied evidences of the potential participation of inflammatory processes in the brain, in particular cytokines, in suicide. The purpose of this review was to analyze the associations between inflammation markers and suicide. To achieve this goal, a systematic review of literature was conducted via electronic database Scopus using the Medical Subject Headings (MeSH) terms: "cytokines", "suicide" and "inflammation". Through this search it was found 54 articles. After analyzing them 15 met the eligibility criteria and were included in the final sample. One of the most mentioned inflammatory markers was Interferon-α (IFN-α), a pro-inflammatory cytokine which has been shown to increase serum concentrations of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-a (TNF- α) and IFN-ϒ, which are factors increased suicide victims and attempters. In this line, IL-6 is not only found to be elevated in the cerebrospinal fluid of suicide attempters, even its levels in the peripheral blood have been proposed as a biological suicide marker. Another study stated that increased levels of IL-4 and IL-13 transcription in the orbitofrontal cortex of suicides suggest that these cytokines may affect neurobehavioral processes relevant to suicide. A lack of studies and great amount of cross-sectional studies. Inflammation may play an important role in the pathophysiology of suicide, especially, levels of some specific inflammatory cytokines. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Leukocyte Profile in Peripheral Blood and Neutrophil-Lymphocyte Ratio in Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Ring, Hans Christian; Prens, Errol P.

    2016-01-01

    .0001) and monocyte (p = 0.0014, p = 0.0004) levels in the HS groups compared with controls. Conclusion: The hs-CRP levels associated with HS appear to be intermediate (2.2-5.1 mg/l), implying systemic inflammation rather than infection. The peripheral blood leukocytosis in HS was dominated by neutrophils...... to the inflammatory state in HS. Objective: To investigate the status of inflammation and leukocyte profile in the peripheral blood of HS patients. Materials and Methods: Using a comparative cross-sectional study design, we investigated blood samples of high-sensitivity C-reactive protein (hs-CRP) and leukocyte...... odds of leukocytosis when compared to controls with an odds ratio for the HS-HOSP group of 4.38 (95% CI = 2.18-8.80; p neutrophil (p

  13. Case report of a patient with peripheral facial nerve palsy

    OpenAIRE

    Rysová, Jana

    2013-01-01

    Title of bachelor's thesis: Case report of a patient with peripheral facial nerve palsy Summary: Teoretical part of bachelor's thesis contains theoretical foundation of peripheral facial nerve palsy. Practical part of bachelor's thesis contains physiotherapeutic case report of patient with peripheral facial nerve palsy. Key words: peripheral facial nerve palsy, casuistry, rehabilitation

  14. Airway Humidification Reduces the Inflammatory Response During Mechanical Ventilation.

    Science.gov (United States)

    Jiang, Min; Song, Jun-Jie; Guo, Xiao-Li; Tang, Yong-Lin; Li, Hai-Bo

    2015-12-01

    Currently, no clinical or animal studies have been performed to establish the relationship between airway humidification and mechanical ventilation-induced lung inflammatory responses. Therefore, an animal model was established to better define this relationship. Rabbits (n = 40) were randomly divided into 6 groups: control animals, sacrificed immediately after anesthesia (n = 2); dry gas group animals, subjected to mechanical ventilation for 8 h without humidification (n = 6); and experimental animals, subjected to mechanical ventilation for 8 h under humidification at 30, 35, 40, and 45°C, respectively (n = 8). Inflammatory cytokines in the bronchi alveolar lavage fluid (BALF) were measured. The integrity of the airway cilia and the tracheal epithelium was examined by scanning and transmission electron microscopy, respectively. Peripheral blood white blood cell counts and the wet to dry ratio and lung pathology were determined. Dry gas group animals showed increased tumor necrosis factor alpha levels in BALF compared with control animals (P humidification temperature was increased to 40°C. Scanning and transmission electron microscopy analysis revealed that cilia integrity was maintained in the 40°C groups. Peripheral white blood cell counts were not different among those groups. Compared with control animals, the wet to dry ratio was significantly elevated in the dry gas group (P humidification at 40°C resulted in reduced pathologic injury compared with the other groups based on the histologic score. Pathology and reduced inflammation observed in animals treated at 40°C was similar to that observed in the control animals, suggesting that appropriate humidification reduced inflammatory responses elicited as a consequence of mechanical ventilation, in addition to reducing damage to the cilia and reducing water loss in the airway. Copyright © 2015 by Daedalus Enterprises.

  15. New Morphine Analogs Produce Peripheral Antinociception within a Certain Dose Range of Their Systemic Administration.

    Science.gov (United States)

    Lackó, Erzsébet; Riba, Pál; Giricz, Zoltán; Váradi, András; Cornic, Laura; Balogh, Mihály; Király, Kornél; Csekő, Kata; Mousa, Shaaban A; Hosztafi, Sándor; Schäfer, Michael; Zádori, Zoltán Sándor; Helyes, Zsuzsanna; Ferdinandy, Péter; Fürst, Susanna; Al-Khrasani, Mahmoud

    2016-10-01

    Growing data support peripheral opioid antinociceptive effects, particularly in inflammatory pain models. Here, we examined the antinociceptive effects of subcutaneously administered, recently synthesized 14-O-methylmorphine-6-O-sulfate (14-O-MeM6SU) compared with morphine-6-O-sulfate (M6SU) in a rat model of inflammatory pain induced by an injection of complete Freund's adjuvant and in a mouse model of visceral pain evoked by acetic acid. Subcutaneous doses of 14-O-MeM6SU and M6SU up to 126 and 547 nmol/kg, respectively, produced significant and subcutaneous or intraplantar naloxone methiodide (NAL-M)-reversible antinociception in inflamed paws compared with noninflamed paws. Neither of these doses significantly affected thiobutabarbital-induced sleeping time or rat pulmonary parameters. However, the antinociceptive effects of higher doses were only partially reversed by NAL-M, indicating contribution of the central nervous system. In the mouse writhing test, 14-O-MeM6SU was more potent than M6SU after subcutaneous or intracerebroventricular injections. Both displayed high subcutaneous/intracerebroventricular ED50 ratios. The antinociceptive effects of subcutaneous 14-O-MeM6SU and M6SU up to 136 and 3043 nmol/kg, respectively, were fully antagonized by subcutaneous NAL-M. In addition, the test compounds inhibited mouse gastrointestinal transit in antinociceptive doses. Taken together, these findings suggest that systemic administration of the novel compound 14-O-MeM6SU similar to M6SU in specific dose ranges shows peripheral antinociception in rat and mouse inflammatory pain models without central adverse effects. These findings apply to male animals and must be confirmed in female animals. Therefore, titration of systemic doses of opioid compounds with limited access to the brain might offer peripheral antinociception of clinical importance. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Chronic inflammatory demyelinating polyneuropathy in adults: diagnostic approaches and first line therapy

    Directory of Open Access Journals (Sweden)

    N. А. Suponevа

    2016-01-01

    Full Text Available Chronic inflammatory demyelinating polyneuropathy (CIDP is among the key reasons of chronic polyneuropathies in adults. Diagnostic algorithm of CIDP in adults is presented. Diagnosis of CIDP is based on clinical and electrodiagnostic criteria of European Federation of Neurological Societies/Peripheral Nervous System in 2010. Principles of CIDP treatment are discussed, including modern trends of standard and 10 % IVIG solutions. 

  17. Characterization of inflammatory markers associated with systemic lupus erythematosus patients undergoing treatment

    OpenAIRE

    Timóteo, Rodolfo Pessato; Micheli, Douglas Cobo; Teodoro, Reginaldo Botelho; Freire, Marlene; Bertoncello, Dernival; Murta, Eddie Fernando Candido; Tavares-Murta, Beatriz Martins

    2016-01-01

    ABSTRACT Objective: To characterize the inflammatory profiles of patients with systemic lupus erythematosus receiving standard treatment compared to healthy controls. Patients and methods: Peripheral venous blood was collected from systemic lupus erythematosus patients (n = 14) and controls (n = 18) at enrollment. Blood samples were used for quantification, by flow cytometry, of CD11b (integrin) and Chemokine receptor CXCR2 expression surface antigen in neutrophils and lymphocytes, while cy...

  18. Activation of monocytes and cytokine production in patients with peripheral atherosclerosis obliterans

    Directory of Open Access Journals (Sweden)

    Lastória Sidney

    2011-08-01

    Full Text Available Abstract Background Arterial peripheral disease is a condition caused by the blocked blood flow resulting from arterial cholesterol deposits within the arms, legs and aorta. Studies have shown that macrophages in atherosclerotic plaque are highly activated, which makes these cells important antigen-presenting cells that develop a specific immune response, in which LDLox is the inducing antigen. As functional changes of cells which participate in the atherogenesis process may occur in the peripheral blood, the objectives of the present study were to evaluate plasma levels of anti-inflammatory and inflammatory cytokines including TNF-α, IFN-γ, interleukin-6 (IL-6, IL-10 and TGF-β in patients with peripheral arteriosclerosis obliterans, to assess the monocyte activation level in peripheral blood through the ability of these cells to release hydrogen peroxide (H2O2 and to develop fungicidal activity against Candida albicans (C. albicans in vitro. Methods TNF-α, IFN-γ, IL-6, IL-10 and TGF-β from plasma of patients were detected by ELISA. Monocyte cultures activated in vitro with TNF-alpha and IFN-gamma were evaluated by fungicidal activity against C. albicans by culture plating and Colony Forming Unit (CFU recovery, and by H2O2 production. Results Plasma levels of all cytokines were significantly higher in patients compared to those detected in control subjects. Control group monocytes did not release substantial levels of H2O2 in vitro, but these levels were significantly increased after activation with IFN-γ and TNF-α. Monocytes of patients, before and after activation, responded less than those of control subjects. Similar results were found when fungicidal activity was evaluated. The results seen in patients were always significantly smaller than among control subjects. Conclusions: The results revealed an unresponsiveness of patient monocytes in vitro probably due to the high activation process occurring in vivo as corroborated by high

  19. Transcompartmental Inflammatory Responses in Humans

    DEFF Research Database (Denmark)

    Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A

    2014-01-01

    OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysacchar......OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following...

  20. Desquamative Inflammatory Vaginitis: The Unknown

    OpenAIRE

    María Trinidad Alumbreros Andújar; Ana González López; Celia Pérez Parra; Rafael López Pérez; Carmen Céspedes Casas; María Mercedes Ramírez Gómez; Castor Martin Francisco; Francisco Javier Haya Palazuelos

    2015-01-01

    Introduction: Desquamative inflammatory vaginitis (DIV) is a chronic inflammatory process of unknown etiology, characterized by genital pain and profuse vaginal discharge, mainly affecting perimenopausal women. It is an entity little known by clinicians, leading to a delay in diagnosis and the consequent alteration of the patients’ quality of life. The aim in this manuscript is to analyze DIV through the review of a case and the scientific literature. Case presentation: We report the case ...

  1. Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren’s syndrome: a clinical study of 81 pregnancies in 41 patients

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: To study the incidence and the features of congenital heart block (CHB in patients with undifferentiated connective tissue disease (UCTD and primary Sjögren’s syndrome (pSS. Methods: We studied 81 pregnancies of 41 women attending the Outpatients’ Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61% were affected with UCTD and 16 (39% with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. Results: CHB was found in 2 out of the 46 (4,3% pregnancies followed by our Staff and in 2 out of the 35 (5,7% included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0,026. Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. Conclusion: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.

  2. IL10 GGC haplotype is positively and HLA-DQA1*05-DQB1*02 is negatively associated with radiographic progression in undifferentiated arthritis.

    Science.gov (United States)

    Ursum, Jennie; van der Weijden, Mignon A C; van Schaardenburg, Dirkjan; Prins, Arend P A; Dijkmans, Ben A C; Twisk, Jos W R; Crusius, Jakob B A; van der Horst-Bruinsma, Irene E

    2010-07-01

    In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA. Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score > or = 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) -1031, -863, -857, -308, -238; lymphotoxin-alpha (LTA) +368, +252; interleukin 10 (IL10) -2849, -1082, -819; IL1A -889, IL1B -31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression. Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0-13.1, p HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1-0.8, p = 0.013) and with allele TNF -308A (OR 0.4, 95% CI, 0.2-0.9, p = 0.02). The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF -308A allele, which are associated with mild radiographic progression in early UA.

  3. Acetylcholinesterase-positive innervation is present at undifferentiated stages of the sea turtle Lepidochelis olivacea embryo gonads: implications for temperature-dependent sex determination.

    Science.gov (United States)

    Gutiérrez-Ospina, G; Jiménez-Trejo, F J; Favila, R; Moreno-Mendoza, N A; Granados Rojas, L; Barrios, F A; Díaz-Cintra, S; Merchant-Larios, H

    1999-07-19

    In embryos of different reptile species, incubation temperature triggers a cascade of endocrine events that lead to gonad sex differentiation. The cellular and molecular mechanisms by which temperature sets in motion this process are still controversial. Here, we begin evaluating the possible participation of the nervous system in temperature-dependent sex determination by showing the existence and origin of acetylcholinesterase (AchE)-positive nerve fibers in undifferentiated gonads of the Lepidochelys olivacea (L. olivacea) sea turtle putative male and female embryos, along the thermosensitive period for sex determination (TPSD; stages 20-27). AChE-positive nerve bundles and fibers were readily visualized until developmental stage 24 and thereafter. DiI injections and confocal imaging showed that some of these gonadal nerves arise from the lower thoracic and upper lumbar spinal cord levels, and might thus be sensory in nature. Because the vertebrate spinal cord is capable of integrating by itself thermoregulatory responses with no intervention of uppermost levels of the central nervous system, we also evaluated spinal cord maturation during the TPSD. The maturation of the spinal cord was more advanced in putative female than in male embryos, when sex determination is taking place for each sex; this process starts and ends earlier in male than in female embryos. Together these observations open the possibility that the spinal cord and the innervation derived from it could play a direct role in driving or modulating the process of temperature-dependent gonad sex determination and/or differentiation, particularly in female L. olivacea embryos.

  4. Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy: Rationale for combination neoadjuvant immune checkpoint inhibition and radiotherapy.

    Science.gov (United States)

    Keung, Emily Z; Tsai, Jen-Wei; Ali, Ali M; Cormier, Janice N; Bishop, Andrew J; Guadagnolo, B Ashleigh; Torres, Keila E; Somaiah, Neeta; Hunt, Kelly K; Wargo, Jennifer A; Lazar, Alexander J; Wang, Wei-Lien; Roland, Christina L

    2018-01-01

    Background : Undifferentiated pleomorphic sarcoma of the extremity and trunk (ET-UPS) presents a unique therapeutic challenge. Although immunotherapy has recently been employed in advanced soft tissue sarcoma, there is limited data characterizing the immune infiltrate in ET-UPS. Radiotherapy (RT) has been shown in other tumor types to promote tumor antigen release and enhance tumor-specific targeting by the adaptive immune system. The aim of this study was to 1) characterize the baseline immune infiltrate and 2) evaluate the effect of preoperative RT on the histologic appearance of and the immune infiltrate in ET-UPS. Methods : We identified 17 matched ET-UPS samples before and after RT. Immunohistochemistry was performed with CD8, CD4, PD-L1, PD1, CD3, CD163 and FoxP3 positive cells identified in all samples. Changes in the immune infiltrate following RT were examined. Results : There was a trend towards increased density of tumor infiltrating immune cells in ET-UPS following RT, with increases in median number of CD3 (158 vs 219 cells/mm 2 , p = 0.06), CD4 (3 vs 13 cells/mm 2 , p = 0.01), CD8 (55 vs 111 cells/mm 2 , p = 0.17), and FOXP3 (14 vs 25 cells/mm 2 , p = 0.23) positive cells. Interestingly, although PD-L1 was not expressed in any ET-UPS tumor at baseline, positive PD-L1 expression was observed in 21% (3/14) of tumors after RT (p = 0.07). Conclusion : An immune infiltrate is present in ET-UPS at the time of diagnosis, with a trend towards increased density of immune infiltrate and PD-L1 expression after RT. These data support prospectively evaluating immune checkpoint inhibitors with standard of care RT in the treatment of ET-UPS.

  5. A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

    Science.gov (United States)

    Ahmad, S; Dhar, M; Mittal, G; Bhat, N K; Shirazi, N; Kalra, V; Sati, H C; Gupta, V

    2016-04-01

    Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection.

  6. Human colon cancer profiles show differential microRNA expression depending on mismatch repair status and are characteristic of undifferentiated proliferative states

    International Nuclear Information System (INIS)

    Sarver, Aaron L; Cunningham, Julie M; Subramanian, Subbaya; Wang, Liang; Smyrk, Tom C; Rodrigues, Cecilia MP; Thibodeau, Stephen N; Steer, Clifford J; French, Amy J; Borralho, Pedro M; Thayanithy, Venugopal; Oberg, Ann L; Silverstein, Kevin AT; Morlan, Bruce W; Riska, Shaun M; Boardman, Lisa A

    2009-01-01

    Colon cancer arises from the accumulation of multiple genetic and epigenetic alterations to normal colonic tissue. microRNAs (miRNAs) are small, non-coding regulatory RNAs that post-transcriptionally regulate gene expression. Differential miRNA expression in cancer versus normal tissue is a common event and may be pivotal for tumor onset and progression. To identify miRNAs that are differentially expressed in tumors and tumor subtypes, we carried out highly sensitive expression profiling of 735 miRNAs on samples obtained from a statistically powerful set of tumors (n = 80) and normal colon tissue (n = 28) and validated a subset of this data by qRT-PCR. Tumor specimens showed highly significant and large fold change differential expression of the levels of 39 miRNAs including miR-135b, miR-96, miR-182, miR-183, miR-1, and miR-133a, relative to normal colon tissue. Significant differences were also seen in 6 miRNAs including miR-31 and miR-592, in the direct comparison of tumors that were deficient or proficient for mismatch repair. Examination of the genomic regions containing differentially expressed miRNAs revealed that they were also differentially methylated in colon cancer at a far greater rate than would be expected by chance. A network of interactions between these miRNAs and genes associated with colon cancer provided evidence for the role of these miRNAs as oncogenes by attenuation of tumor suppressor genes. Colon tumors show differential expression of miRNAs depending on mismatch repair status. miRNA expression in colon tumors has an epigenetic component and altered expression that may reflect a reversion to regulatory programs characteristic of undifferentiated proliferative developmental states

  7. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

    Science.gov (United States)

    Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

    2014-06-15

    Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  8. Beta secretase activity in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Carolyn Tallon

    2017-01-01

    Full Text Available While the peripheral nervous system has the capacity to regenerate following a nerve injury, it is often at a slow rate and results in unsatisfactory recovery, leaving patients with reduced function. Many regeneration associated genes have been identified over the years, which may shed some insight into how we can manipulate this intrinsic regenerative ability to enhance repair following peripheral nerve injuries. Our lab has identified the membrane bound protease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1, or beta secretase, as a potential negative regulator of peripheral nerve regeneration. When beta secretase activity levels are abolished via a null mutation in mice, peripheral regeneration is enhanced following a sciatic nerve crush injury. Conversely, when activity levels are greatly increased by overexpressing beta secretase in mice, nerve regeneration and functional recovery are impaired after a sciatic nerve crush injury. In addition to our work, many substrates of beta secretase have been found to be involved in regulating neurite outgrowth and some have even been identified as regeneration associated genes. In this review, we set out to discuss BACE1 and its substrates with respect to axonal regeneration and speculate on the possibility of utilizing BACE1 inhibitors to enhance regeneration following acute nerve injury and potential uses in peripheral neuropathies.

  9. Photoacoustic and ultrasound dual-modality imaging of human peripheral joints

    Science.gov (United States)

    Xu, Guan; Rajian, Justin R.; Girish, Gandikota; Kaplan, Mariana J.; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

    2013-01-01

    A photoacoustic (PA) and ultrasound (US) dual modality system, for imaging human peripheral joints, is introduced. The system utilizes a commercial US unit for both US control imaging and PA signal acquisition. Preliminary in vivo evaluation of the system, on normal volunteers, revealed that this system can recover both the structural and functional information of intra- and extra-articular tissues. Confirmed by the control US images, the system, on the PA mode, can differentiate tendon from surrounding soft tissue based on the endogenous optical contrast. Presenting both morphological and pathological information in joint, this system holds promise for diagnosis and characterization of inflammatory joint diseases such as rheumatoid arthritis.

  10. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-04-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  11. Coffee consumption modulates inflammatory processes in an individual fashion.

    Science.gov (United States)

    Muqaku, Besnik; Tahir, Ammar; Klepeisz, Philip; Bileck, Andrea; Kreutz, Dominique; Mayer, Rupert L; Meier, Samuel M; Gerner, Marlene; Schmetterer, Klaus; Gerner, Christopher

    2016-12-01

    Anti-inflammatory effects of coffee consumption have been reported to be caused by caffeine and adenosine receptor signaling. However, contradictory effects have been observed. Many kinds of chronic diseases are linked to inflammation; therefore a profound understanding of potential effects of coffee consumption is desirable. We performed ex vivo experiments with eight individuals investigating peripheral blood mononuclear cells isolated from venous blood before and after coffee consumption, as well as in vitro experiments applying caffeine on isolated cells. After in vitro inflammatory stimulation of the cells, released cytokines, chemokines, and eicosanoids were determined and quantified using targeted mass spectrometric methods. Remarkably, the release of inflammation mediators IL6, IL8, GROA, CXCL2, CXCL5 as well as PGA2, PGD2, prostaglandin E2 (PGE2), LTC4, LTE4, and 15S-HETE was significantly affected after coffee consumption. While in several individuals coffee consumption or caffeine treatment caused significant downregulation of most inflammation mediators, in other healthy individuals exactly the opposite effects were observed. Ruling out age, sex, coffee consumption habits, the metabolic kinetics of caffeine in blood and the individual amount of regulatory T cells or CD39 expression as predictive parameters, we demonstrated here that coffee consumption may have significant pro- or anti-inflammatory effects in an individual fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Citral reduces nociceptive and inflammatory response in rodents

    Directory of Open Access Journals (Sweden)

    Lucindo J. Quintans-Júnior

    2011-06-01

    Full Text Available Citral (CIT, which contains the chiral enantiomers, neral (cis and geranial (trans, is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001 against acetic acid (0.8% induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05 only at higher dose (200 mg/kg of CIT in the first phase of the test. CIT significantly reduce (p<0.001 nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg significantly reduced (p<0.001 the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

  13. Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages

    Directory of Open Access Journals (Sweden)

    Norikazu Kiguchi

    2017-11-01

    Full Text Available Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1 macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain.

  14. The TNF-alpha transgenic mouse model of inflammatory arthritis.

    Science.gov (United States)

    Li, Ping; Schwarz, Edward M

    2003-08-01

    Rheumatoid arthritis is a chronic inflammatory disorder that affects multiple peripheral joints. It is the most common form of inflammatory arthritis and is characterized by synovial hyperplasia, immune cell infiltration, cartilage destruction, and bone erosion. To gain insight into the etiology of the disease, a variety of animal models have been established. Twelve years ago George Kollias' laboratory generated a transgenic (Tg) mouse that over-expresses human TNF-alpha, and develops an erosive polyarthritis with many characteristics observed in rheumatoid arthritis patients. The phenotype of this mouse model validated the theory that TNF-alpha is at the apex of the pro-inflammatory cascade in rheumatoid arthritis, and foreshadowed the remarkable success of anti-TNF-alpha therapy that has transformed the effective management of this disease. As such, the TNF-Tg mice are very useful tools for dissecting the molecular mechanisms of the pathogenic process and evaluating the efficacy of novel therapeutic strategies for rheumatoid arthritis. In this review we (1) provide a brief summary of TNF-alpha biology and the role of this dominant cytokine in rheumatoid arthritis, (2) describe the various TNF-Tg models and their phenotypes, and (3) give examples of how this model has been used experimentally.

  15. Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

    Directory of Open Access Journals (Sweden)

    Wen Yeong-Ray

    2010-10-01

    Full Text Available Abstract Background Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood. Results A decrease in paw withdrawal latency (PWL after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1 and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK activity after reinflammation. Conclusions Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.

  16. Altered Cytokine Gene Expression in Peripheral Blood Monocytes across the Menstrual Cycle in Primary Dysmenorrhea: A Case-Control Study

    Science.gov (United States)

    Ma, Hongyue; Hong, Min; Duan, Jinao; Liu, Pei; Fan, Xinsheng; Shang, Erxin; Su, Shulan; Guo, Jianming; Qian, Dawei; Tang, Yuping

    2013-01-01

    Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥2-fold difference in expression (Pmenstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea. PMID:23390521

  17. Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study.

    Directory of Open Access Journals (Sweden)

    Hongyue Ma

    Full Text Available Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase, and the first (menstrual phase and the fifth (regenerative phase days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased, 14 (five increased and nine decreased, and 15 (seven increased and eight decreased genes with ≥ 2-fold difference in expression (P<0.05 in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8 were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea.

  18. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms

    Directory of Open Access Journals (Sweden)

    Joanna Balding

    2004-01-01

    Full Text Available THE mechanisms responsible for development of inflammatory bowel disease (IBD have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n=172 and healthy controls (n=389 for polymorphisms in genes encoding various cytokines (interleukin (IL-1β, IL-6, tumour necrosis factor (TNF, IL-10, IL-1 receptor antagonist. Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-α-308 polymorphism (p=0.0135. There was also variation in the frequency of IL-6-174 and TNF-α-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p=0.01. We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

  19. Intraoperative digital angiography: Peripheral vascular applications

    International Nuclear Information System (INIS)

    Bell, K.; Reifsteck, J.E.; Binet, E.F.; Fleisher, H.J.

    1986-01-01

    Intraoperative digital angiography is the procedure of choice for the peripheral vascular surgeon who wishes to evaluate his results before terminating anesthesia. Two operating suites at the John L. McClellan Memorial Veterans Hospital are equipped with permanent ceiling-mounted Philips C-arm fluoroscopes and share an ADAC 4100 digital angiographic system. In the last 18 months, 40 peripheral vascular intraoperative digital angiographic procedures have been performed, in all but two cases using direct arterial puncture. In 65% of cases, the intraoperative study showed no significant abnormality. In 12.5%, minor abnormalities not requiring reoperation were seen. In 22.5% of cases, the intraoperative digital angiogram revealed a significant abnormality requiring immediate operative revision. None of the patients who underwent reoperation experienced postoperative sequelae. Intraoperative digital angiography is useful in identifying complications of peripheral vascular operations

  20. Comparing modalities and feedback for peripheral interaction

    DEFF Research Database (Denmark)

    Hausen, Doris; Wagner, Christine; Boring, Sebastian

    2013-01-01

    When executing one task on a computer, we are frequently confronted with secondary tasks (e.g., controlling an audio player or changing the IM state) that require shifting our attention away from the actual task, thus increasing our cognitive load. Peripheral interaction aims at reducing that cog......When executing one task on a computer, we are frequently confronted with secondary tasks (e.g., controlling an audio player or changing the IM state) that require shifting our attention away from the actual task, thus increasing our cognitive load. Peripheral interaction aims at reducing...... of visual feedback. In a dual-task lab study we found that those additional modalities are fit for peripheral interaction. Also, feedback did not have a measurable influence, yet it assured participants in their actions....

  1. [Peripheral retinal degenerations--treatment recommendations].

    Science.gov (United States)

    Joussen, A M; Kirchhof, B

    2004-10-01

    This report reviews the clinical appearance of degenerative diseases of the peripheral retina in relationship to the risk of developing a rhegmatogenous retinal detachment. We present recommendations for preventive treatment in eyes at increased risk of developing retinal detachment. Retinal degenerations are common lesions involving the peripheral retina but most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and very rarely zonular traction tufts can result in rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic treatment; however, adequate studies have not been performed to date. Most of the peripheral retinal degenerations may not require treatment except in rare, high-risk situations. According to current knowledge there is no higher incidence of secondary pucker or other side effects after laser coagulation. Therefore, generous laser indication is recommended if risk factors apply.

  2. Comprehensive management of presbycusis: central and peripheral.

    Science.gov (United States)

    Parham, Kourosh; Lin, Frank R; Coelho, Daniel H; Sataloff, Robert T; Gates, George A

    2013-04-01

    The prevailing otolaryngologic approach to treatment of age-related hearing loss (ARHL), presbycusis, emphasizes compensation of peripheral functional deficits (ie, hearing aids and cochlear implants). This approach does not address adequately the needs of the geriatric population, 1 in 5 of whom is expected to consist of the "old old" in the coming decades. Aging affects both the peripheral and central auditory systems, and disorders of executive function become more prevalent with advancing age. Growing evidence supports an association between age-related hearing loss and cognitive decline. Thus, to facilitate optimal functional capacity in our geriatric patients, a more comprehensive management strategy of ARHL is needed. Diagnostic evaluation should go beyond standard audiometric testing and include measures of central auditory function, including dichotic tasks and speech-in-noise testing. Treatment should include not only appropriate means of peripheral compensation but also auditory rehabilitative training and counseling.

  3. TCRgamma gene rearrangement analysis in skin samples and peripheral blood of mycosis fungoides patients.

    Science.gov (United States)

    Kandolf Sekulović, L; Cikota, B; Stojadinović, O; Basanović, J; Skiljević, D; Medenica, Lj; Pavlović, M; Magić, Z

    2007-12-01

    Diagnosing mycosis fungoides (MF) can be challenging in the early stage of the disease because histopathological features may simulate a variety of benign inflammatory skin diseases. Assessment of T-cell clonality was found to be useful in diagnosis and follow-up of patients. In this study, PCR-based TCRgamma gene rearrangement analysis was performed in skin and peripheral blood samples of patients with MF treated at the two largest referral centers in Serbia, and the results obtained were correlated with clinical and follow-up data. Skin and peripheral blood samples were obtained with informed consent from 37 patients treated at the Department of Dermatology of the Military Medical Academy and the Medical Center of Serbia from 2001 to 2006. The median time of follow-up was 4 years. Multiplex PCR was used for TCRgamma gene rearrangement analysis in skin and peripheral blood samples. Clonality results were correlated with the clinical data and disease course data. Monoclonality was detected in skin samples of 30/37 patients (81%), in 2/5 patients with large-plaque parapsoriasis (LPP), in 28/32 (88%) patients with histologically proven MF, and in 1/16 (6%) patients with benign inflammatory dermatoses. A monoclonal pattern in both skin and peripheral blood was detected in 7/16 (44%) patients in the late stage of the disease, and in 1/7 (14%) patients in the early stage of the disease. A dominant clone was found in both skin and peripheral blood in 1/4 patients in remission, 2/5 with a stable disease, and 4/9 (44%) with disease progression. TCR-gamma gene rearrangement analysis can be regarded as a useful adjunct to diagnosis of epidermotropic lymphoproliferative disorders. The presence of a dominant clone in both the skin and peripheral blood was more frequently detected in late stages and in patients with disease progression, confirming the usefulness of clonality detection by TCR-gamma gene rearrangement analysis in follow-up of patients with primary cutaneous T

  4. Chronic obstructive pulmonary disease and peripheral neuropathy

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    Gupta Prem

    2006-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is the fourth leading cause of death world-wide and a further increase in the prevalence as well as mortality of the disease is predicted for coming decades. There is now an increased appreciation for the need to build awareness regarding COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its associated complication(s. Peripheral neuropathy in COPD has received scanty attention despite the fact that very often clinicians come across COPD patients having clinical features suggestive of peripheral neuropathy. Electrophysiological tests like nerve conduction studies are required to distinguish between axonal and demyelinating type of disorder that cannot be analyzed by clinical examination alone. However, various studies addressing peripheral neuropathy in COPD carried out so far have included patients with COPD having markedly varying baseline characteristics like severe hypoxemia, elderly patients, those with long duration of illness, etc. that are not uniform across the studies and make it difficult to interpret the results to a consistent conclusion. Almost one-third of COPD patients have clinical evidence of peripheral neuropathy and two-thirds have electrophysiological abnormalities. Some patients with no clinical indication of peripheral neuropathy do have electrophysiological deficit suggestive of peripheral neuropathy. The more frequent presentation consists of a polyneuropathy that is subclinical or with predominantly sensory signs, and the neurophysiological and pathological features of predominantly axonal neuropathy. The presumed etiopathogenic factors are multiple: chronic hypoxia, tobacco smoke, alcoholism, malnutrition and adverse effects of certain drugs.

  5. Role of IL-10 in Resolution of Inflammation and Functional Recovery after Peripheral Nerve Injury.

    Science.gov (United States)

    Siqueira Mietto, Bruno; Kroner, Antje; Girolami, Elizabeth I; Santos-Nogueira, Eva; Zhang, Ji; David, Samuel

    2015-12-16

    A rapid proinflammatory response after peripheral nerve injury is required for clearance of tissue debris (Wallerian degeneration) and effective regeneration. Unlike the CNS, this response is rapidly terminated in peripheral nerves starting between 2 and 3 weeks after crush injury. We examined the expression and role of the anti-inflammatory cytokine IL-10 in the resolution of inflammation and regeneration after sciatic nerve crush injury in mice. IL-10 mRNA increased over the first 7 d after injury, whereas at the protein level, immunofluorescence labeling showed IL-10(+) cells increased almost 3-fold in the first 3 weeks, with macrophages being the major cell type expressing IL-10. The role of IL-10 in nerve injury was assessed using IL-10-null mice. Increased numbers of macrophages were found in the distal segment of IL-10-null mice at early (3 d) and late (14 and 21 d) time points, suggesting that IL-10 may play a role in controlling the early influx and the later efflux of macrophages out of the nerve. A chemokine/cytokine PCR array of the nerve 24 h after crush showed a 2- to 4-fold increase in the expression of 10 proinflammatory mediators in IL-10(-/-) mice. In addition, myelin phagocytosis in vitro by LPS stimulated bone-marrow-derived macrophages from IL-10-null mice failed to downregulate expression of proinflammatory chemokines/cytokines, suggesting that IL-10 is required for the myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory/pro-repair phenotype. The failure to switch off inflammation in IL-10-null mice was accompanied by impaired axon regeneration and poor recovery of motor and sensory function. An appropriately regulated inflammatory response after peripheral nerve injury is essential for axon regeneration and recovery. The aim of this study was to investigate the expression and role of the anti-inflammatory cytokine IL-10 in terminating inflammation after sciatic nerve crush injury and promoting

  6. Classic Peripheral Signs of Subacute Bacterial Endocarditis

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    Yooyoung Chong

    2016-10-01

    Full Text Available A 50-year-old female patient with visual disturbances was referred for further evaluation of a heart murmur. Fundoscopy revealed a Roth spot in both eyes. A physical examination showed peripheral signs of infective endocarditis, including Osler nodes, Janeway lesions, and splinter hemorrhages. Our preoperative diagnosis was subacute bacterial endocarditis with severe aortic regurgitation. The patient underwent aortic valve replacement and was treated with intravenous antibiotics for 6 weeks postoperatively. The patient made a remarkable recovery and was discharged without complications. We report this case of subacute endocarditis with all 4 classic peripheral signs in a patient who presented with visual disturbance.

  7. [Degenerative lesions of the peripheral retina].

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    Conart, J-B; Baron, D; Berrod, J-P

    2014-01-01

    Degenerative lesions of the peripheral retina are present from teenage years onwards and increase with age. These abnormabilities are frequent, some of them being benign while others predispose to retinal tears and detachment. In the latter case, the lesions are rhegmatogenous and may justify prophylactic treatment by laser photocoagulation. We distinguish congenital lesions of the peripheral retina and intraretinal, chorioretinal and vitreoretinal degenerations. The holes and tears observed in 2% of the population consist of round atrophic holes, "horseshoe" tears, oral dialyses and giant tears. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Laser peripheral iridoplasty for angle-closure.

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    Ng, Wai Siene; Ang, Ghee Soon; Azuara-Blanco, Augusto

    2012-02-15

    Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations.   To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles (PACs), PAC and PACG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 January 2012. We included only randomised controlled trials (RCTs) in this review. Patients with narrow angles, PAC or PACG were eligible. We excluded studies that included only patients with acute presentations

  9. Peripheral Immune Alterations in Major Depression: The Role of Subtypes and Pathogenetic Characteristics

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    Frank Euteneuer

    2017-11-01

    Full Text Available Depression has been associated with peripheral inflammatory processes and alterations in cellular immunity. Growing evidence suggests that immunological alterations may neither be necessary nor sufficient to induce depression in general, but seem to be associated with specific features. Using baseline data from the Outcome of Psychological Interventions in Depression trial, this exploratory study examines associations between depression subtypes and pathogenetic characteristics (i.e., melancholic vs non-melancholic depression, chronic vs non-chronic depression, age of onset, cognitive-affective and somatic symptom dimensions with plasma levels of C-reactive protein (CRP, interleukin (IL-6, IL-10, and numbers of leukocyte subpopulations in 98 patients with major depression (MD and 30 age and sex-matched controls. Patients with MD exhibited higher CRP levels, higher neutrophil and monocyte counts, lower IL-10 levels, and an increased neutrophil to lymphocyte ratio (NLR than controls. Patient with later age of onset had higher levels of two inflammatory markers (CRP, NLR and lower cytotoxic T cell counts after adjusting for sociodemographics, lifestyle factors, and antidepressants. Furthermore, lower anti-inflammatory IL-10 levels were related to more severe somatic depressive symptoms. These results confirm and extend previous findings suggesting that increased levels of CRP are associated with a later onset of depression and demonstrate that also NLR as a subclinical inflammatory marker is related to a later onset of depression.

  10. Inflammatory pathways of importance for management of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Coskun, Mehmet; Soendergaard, Christoffer

    2014-01-01

    Inflammatory bowel disease (IBD) is a group of chronic disorders of the gastrointestinal tract comprising Crohn's disease (CD) and ulcerative colitis (UC). Their etiologies are unknown, but they are characterised by an imbalanced production of pro-inflammatory mediators, e.g., tumor necrosis factor...... includes the TNF inhibitors (TNFi), designed to target and neutralise the effect of TNF-α. TNFi have shown to be efficient in treating moderate to severe CD and UC. However, convenient alternative therapeutics targeting other immune pathways are needed for patients with IBD refractory to conventional...

  11. Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury

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    Yingjun Min

    2017-09-01

    Full Text Available While extensive studies report that neonatal hypoxia-ischemia (HI induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d rat pups to systemic hypoxia (3.5 h, a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg was injected intraperitoneally (i.p. 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS, indicated by presence of C-C chemokine receptor type 2 (CCR2+/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker. Interrupted blood-brain barrier (BBB, hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response.

  12. Minocycline-Suppression of Early Peripheral Inflammation Reduces Hypoxia-Induced Neonatal Brain Injury

    Science.gov (United States)

    Min, Yingjun; Li, Hongchun; Xu, Kaiyu; Huang, Yilong; Xiao, Jie; Wang, Weizhou; Li, Longjun; Yang, Ting; Huang, Lixuan; Yang, Ling; Jiang, Hong; Wang, Qian; Zhao, Min; Hua, HaiRong; Mei, Rong; Li, Fan

    2017-01-01

    While extensive studies report that neonatal hypoxia-ischemia (HI) induces long-term cognitive impairment via inflammatory responses in the brain, little is known about the role of early peripheral inflammation response in HI injury. Here we used a neonatal hypoxia rodent model by subjecting postnatal day 0 (P0d) rat pups to systemic hypoxia (3.5 h), a condition that is commonly seen in clinic neonates, Then, an initial dose of minocycline (45 mg/kg) was injected intraperitoneally (i.p.) 2 h after the hypoxia exposure ended, followed by half dosage (22.5 mg/kg) minocycline treatment for next 6 consecutive days daily. Saline was injected as vehicle control. To examine how early peripheral inflammation responded to hypoxia and whether this peripheral inflammation response was associated to cognitive deficits. We found that neonatal hypoxia significantly increased leukocytes not only in blood, but also increased the monocytes in central nervous system (CNS), indicated by presence of C-C chemokine receptor type 2 (CCR2+)/CD11b+CD45+ positive cells and CCR2 protein expression level. The early onset of peripheral inflammation response was followed by a late onset of brain inflammation that was demonstrated by level of cytokine IL-1β and ionized calcium binding adapter molecule 1(Iba-1; activated microglial cell marker). Interrupted blood-brain barrier (BBB), hypomyelination and learning and memory deficits were seen after hypoxia. Interestingly, the cognitive function was highly correlated with hypoxia-induced leukocyte response. Notably, administration of minocycline even after the onset of hypoxia significantly suppressed leukocyte-mediated inflammation as well as brain inflammation, demonstrating neuroprotection in systemic hypoxia-induced brain damage. Our data provided new insights that systemic hypoxia induces cognitive dysfunction, which involves the leukocyte-mediated peripheral inflammation response. PMID:28955196

  13. A community-based epidemiological study of peripheral neuropathies in Assiut, Egypt.

    Science.gov (United States)

    Kandil, Mahmoud R; Darwish, Esam S; Khedr, Eman M; Sabry, Mahmoud M; Abdulah, Mohamed A

    2012-12-01

    There is very little published information about the prevalence, patterns, and predictors of peripheral neuropathies. The current study is a community-based survey was conducted in the Assiut Governorate to estimate their prevalence and clinical profile. A door-to-door study was carried out on 42,223 persons from rural and urban communities in the Assiut Governorate, Egypt. There were 13,288 (31.5%) subjects from the urban and 28,935 (68·5%) from the rural area. All subjects filled in a questionnaire designed specifically for diagnosis of peripheral neuropathy. Positive cases were then given a complete medical and neurological examination, routine laboratory tests, neurophysiology, and neuroimaging (magnetic resonance). The crude prevalence rate (CPR) of peripheral neuropathy was 3181/100,000 inhabitants. There was a significantly higher prevalence in the rural compared with the urban population (3795 versus 1844/100,000) and in females than males (4473 versus 1943/100,000; Psyndrome (1686/100,000). Diabetic neuropathy was the most common non-compressive neuropathy with a CPR of 649/100,000. Type II diabetes was recorded in 241 patients with a CPR of 571/100,000. Compressive radiculopathy had a crude prevalence of 358/100,000; traumatic and iatrogenic radiculopathy had a prevalence rate of 149/100,000. Less common conditions were: uremic neuropathy (21/100,000) hepatic neuropathy (14/100,000), Bell's palsy (28/100,000), Guillian-Barre' syndrome (12/100,000), chronic inflammatory demyelinating polyneuropathy (12/100,000), hereditary sensory motor neuropathy (12/100,000), and idiopathic neuropathy (92/100,000). The overall prevalence of peripheral neuropathies was high in comparison to other studies. Entrapment neuropathy, diabetic neuropathy, and spondylotic radiculopathy were the most common. Overall, the prevalence of peripheral neuropathy was higher in the rural than in the urban population.

  14. Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis.

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    Mirko Manetti

    Full Text Available The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc remain unclear. Since the recently discovered angiogenic T cells (Tang may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+ were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC. Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC, and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further

  15. The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

    2017-03-01

    To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

  16. Peripheral endocannabinoid system dysregulation in first-episode psychosis.

    Science.gov (United States)

    Bioque, Miquel; García-Bueno, Borja; Macdowell, Karina S; Meseguer, Ana; Saiz, Pilar A; Parellada, Mara; Gonzalez-Pinto, Ana; Rodriguez-Jimenez, Roberto; Lobo, Antonio; Leza, Juan C; Bernardo, Miguel

    2013-12-01

    Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.

  17. Action of β-endorphin and nonsteroidal anti-inflammatory drugs, and the possible effects of nonsteroidal anti-inflammatory drugs on β-endorphin.

    Science.gov (United States)

    Luan, Yuan-Hang; Wang, Di; Yu, Qi; Chai, Xiao-Qing

    2017-02-01

    This study aimed to review research on the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on β-endorphin. NSAIDs are commonly used as anti-inflammatory and analgesic drugs. They are well known for inducing peripheral analgesia by inhibiting cyclooxygenase (COX). However, an increasing number of studies have shown that NSAIDs have an analgesic effect not only in the periphery but also at the center. It means that a central analgesic mechanism of the action of NSAIDs exists besides the peripheral mechanism, and the central mechanism likely involves β-endorphin. β-Endorphin is one of the most prominent endogenous peptides, existing in the hypophysis cerebri and hypothalamus. It plays an irreplaceable role in the central and peripheral analgesia in the human body mainly through three mechanisms including three parts, the spinal cord, the supraspinal cord, and peripheries. β-Endorphin plays an important role in the development of hyperalgesia. However, the specific signal transduction pathways between prostaglandin E 2 or NSAIDs and β-endorphin are still not quite clear. Whether NSAIDs can lead to the increased content of β-endorphin in all patients after any operation needs further investigation. Further studies should determine the optimal dose when NSAIDs and opioid drugs are used together, and also explore the existence of one NSAID that has the potential to replace the traditional opioid drugs and can achieve adequate analgesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effect of PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction

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    Li-Jun Deng

    2017-10-01

    Full Text Available Objective: To study the effect of probucol + aspirin + atorvastatin (PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction. Methods: Patients with acute cerebral infarction who were treated in Affiliated Hospital of Jianghan University between February 2015 and January 2015 were selected and randomly divided into the PAS group who received probucol + aspirin + atorvastatin triple therapy and the control group who received aspirin + atorvastatin double therapy. The markers of nerve injury, oxidative stress and inflammatory response were determined before treatment and 15 d after treatment. Results: 15 d after treatment, peripheral blood Keap-1 expression and serum GPX1 contents of both groups of patients were significantly higher than those before treatment while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those before treatment, and peripheral blood Keap-1 expression and serum GPX1 content of PAS group were significantly higher than those of control group while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those of control group. Conclusion: PAS triple therapy can reduce the nerve injury as well as oxidative stress response and inflammatory response in patients with cerebral infarction.

  19. Functional phenotype of synovial monocytes modulating inflammatory T-cell responses in rheumatoid arthritis (RA.

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    Bo Ruem Yoon

    Full Text Available Monocytes function as crucial innate effectors in the pathogenesis of chronic inflammatory diseases, including autoimmunity, as well as in the inflammatory response against infectious pathogens. Human monocytes are heterogeneous and can be classified into three distinct subsets based on CD14 and CD16 expression. Although accumulating evidence suggests distinct functions of monocyte subsets in inflammatory conditions, their pathogenic roles in autoimmune diseases remain unclear. Thus, we investigated the phenotypic and functional characteristics of monocytes derived from synovial fluid and peripheral blood in RA patients in order to explore the pathogenic roles of these cells. In RA patients, CD14+CD16+, but not CD14dimCD16+, monocytes are predominantly expanded in synovial fluid and, to a lesser degree, in peripheral blood. Expression of co-signaling molecules of the B7 family, specifically CD80 and CD276, was markedly elevated on synovial monocytes, while peripheral monocytes of RA and healthy controls did not express these molecules without stimulation. To explore how synovial monocytes might gain these unique properties in the inflammatory milieu of the synovial fluid, peripheral monocytes were exposed to various stimuli. CD16 expression on CD14+ monocytes was clearly induced by TGF-β, although co-treatment with IL-1β, TNF-α, or IL-6 did not result in any additive effects. In contrast, TLR stimulation with LPS or zymosan significantly downregulated CD16 expression such that the CD14+CD16+ monocyte subset could not be identified. Furthermore, treatment of monocytes with IFN-γ resulted in the induction of CD80 and HLA-DR expression even in the presence of TGF-β. An in vitro assay clearly showed that synovial monocytes possess the unique capability to promote Th1 as well as Th17 responses of autologous peripheral CD4 memory T cells. Our findings suggest that the cytokine milieu of the synovial fluid shapes the unique features of synovial

  20. Correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response

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    Yi He

    2017-06-01

    Full Text Available Objective: To study the correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response. Methods: Neonates who were born and diagnosed with pneumonia in Zigong Maternity and Child Healthcare Hospital between September 2015 and February 2017 were selected as pneumonia group, and neonates without infection were selected as control group. SP-A gene rs1059054 and rs1136454 loci polymorphism, the contents of inflammatory cytokines in serum as well as the expression of inflammatory transcription factors in peripheral blood were determined. Results: The constituent ratio of rs1059054 loci CC