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Leucocytes
Kinds of Leucocytes Terms modified by Leucocytes Selected AbstractsFAS LIGAND TRANSFECTION OF RENAL TUBULAR CELLS INDUCES APOPTOSIS OF ACTIVATED LEUCOCYTESNEPHROLOGY, Issue 3 2000Wang Yp [source] Total and Differential Leucocyte Counts and Lymphocyte Subpopulations in Lymph, Afferent and Efferent to the Supramammary Lymph Node, During Endotoxin-Induced Bovine MastitisREPRODUCTION IN DOMESTIC ANIMALS, Issue 2 2007S Lun Contents Leucocyte trafficking in afferent and efferent mammary lymph and the supramammary lymph node in cows was examined during 4 h after intramammary infusion of endotoxin from Escherichia coli. Total and differential leucocyte counts were measured in milk, blood and lymph. The proportions of CD4+, CD8+, major histocompatibility complex (MHC) class II+ and IgM+ lymphocytes were examined in the lymph and lymph node. At post-infusion hour (PIH) 4, the flow rates of both lymph fluids had increased approximately eightfold. Total leucocyte concentration increased in afferent lymph, but decreased in efferent lymph. Neutrophils increased in afferent lymph at PIH 2 and in efferent lymph and milk at PIH 4. The predominant cell type in afferent lymph shifted from lymphocyte to neutrophil while lymphocyte was still at PIH 4 the predominant type in efferent lymph. Among the lymphocytes, B cells were predominant in afferent lymph and lymph node at PIH 4 while T cells, mainly CD4+ cells, were predominant in efferent lymph both at PIH 0 and PIH 4. The CD4 : CD8 ratio was higher in efferent lymph and the challenged lymph node than in afferent lymph and the control node, respectively. There was a significant difference in proportions of each lymphocyte subpopulation except for IgM+ cells, between afferent and efferent lymph after infusion. According to the results, there was already during the first hours of the immune response, a non-random trafficking of neutrophils and lymphocyte subpopulations resulting in a changed distribution of cells in afferent and efferent lymph and a difference in lymphocyte reactivity between the two lymph fluids. [source] Microcystin-LR modulates selected immune parameters and induces necrosis/apoptosis of carp leucocytes,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010Anna Rymuszka Abstract Microcystins (MCs) are potent hepatotoxins acting by the inhibition of protein phosphatase 1 and 2A, and may promote liver tumors. Moreover, studies also suggest they are nephrotoxic. The aim of the present study was to assess possible in vitro effects of microcystin-LR (which contains the amino acids leucine and arginine, the most widely studied and distributed variant of all microcystins) on the selected immune functions of the cells isolated from the head kidney of carp. In the experiments, pure microcystin-LR (MC-LR), was used at concentrations of 0.01, 0.1, 0.5, and 1,µg/ml RPMI-1640 medium. Leucocytes (lymphocytes and phagocytes) were isolated by centrifugation on a density gradient. Lymphocyte proliferation, intracellular production of reactive oxygen species by phagocytes, and the presence of apoptotic and/or necrotic cells were assessed. The respiratory burst activity of phagocytic cells was increased at the lowest toxin concentration used in the study, but it was decreased at higher concentrations. Using a sensitive luminescent immunoassay, MC-LR was observed to have no influence on the T-cell proliferation but decreased the proliferation of B lymphocytes. Moreover, it was noted that MC-LR induced necrosis to a higher degree than apoptosis in fish leucocytes. The results of the present study suggest the modulatory potency of microcystin-LR on fish leucocytes. Environ. Toxicol. Chem. 2010;29:569,574. © 2009 SETAC [source] Immunocytochemical investigation of immune cells within human primary and permanent tooth pulpINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2006H. D. RODD Summary. Aim., The aim of this study was to determine whether there are any differences in the number and distribution of immune cells within human primary and permanent tooth pulp, both in health and disease. Design., The research took the form of a quantitative immunocytochemical study. One hundred and twenty-four mandibular first permanent molars and second primary molars were obtained from children requiring dental extractions under general anaesthesia. Following exodontia, 10-µm-thick frozen pulp sections were processed for indirect immunofluorescence. Triple-labelling regimes were employed using combinations of the following: (1) protein gene product 9·5, a general neuronal marker; (2) leucocyte common antigen (LCA); and (3) Ulex europaeus I lectin, a marker of vascular endothelium. Image analysis was then used to determine the percentage area of immunostaining for LCA. Results., Leucocytes were significantly more abundant in the pulp horn and mid-coronal region of intact and carious primary teeth, as compared to permanent teeth (P < 0·05, anova). Both dentitions demonstrated the presence of well-localized inflammatory cell infiltrates and marked aborization of pulpal nerves in areas of dense leucocyte accumulation. Conclusions., Primary and permanent tooth pulps appear to have a similar potential to mount inflammatory responses to gross caries The management of the compromised primary tooth pulp needs to be reappraised in the light of these findings. [source] Effects of Th2 pulmonary inflammation in mice with bleomycin-induced pulmonary fibrosisRESPIROLOGY, Issue 6 2008Hirokuni HIRATA Background and objective: Leucocytes, especially lymphocytes and neutrophils, as well as alveolar macrophages, that infiltrate into the lung are involved in the development of pulmonary fibrosis. However, the role of T helper (Th)2-type inflammation, mediated by Th2 cells and eosinophils, in fibrosis remains unknown. Transgenic mice deficient in the transcriptional repressor, Bcl6, display an attenuation of Th2 cytokine production. We studied the effects of Th2-type pulmonary inflammation on bleomycin-induced pulmonary fibrosis using Bcl6 transgenic mice. Methods: Bleomycin was administered to ovalbumin (OVA)-sensitized Bcl6 transgenic and wild-type mice by intratracheal instillation during sequential OVA antigen challenge. Concentrations of transforming growth factor-,1 in the BAL fluid were measured 2 weeks after bleomycin administration. At the same time lung tissue was examined histopathologically, and homogenized to assess collagen levels and Th1/Th2 cytokine mRNA expression. Results: Although OVA-sensitized, bleomycin-treated Bcl6 transgenic mice had markedly lower numbers of eosinophils in both BAL and lung tissue compared with OVA-sensitized, bleomycin-treated wild-type mice, the development of pulmonary fibrosis in response to bleomycin was similar in Bcl6 transgenic mice and wild-type mice. Conclusion: These results suggest that Th2-dominant inflammation in the lung is not essential for the development of bleomycin-induced pulmonary fibrosis. [source] ORIGINAL ARTICLE: Predictors of Inflammatory Breast Diseases During Lactation , Results of a Cohort StudyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Achim Wöckel Problem, Inflammatory breast diseases during lactation are major reasons for early weaning. Method of study, A prospective cohort study was performed to examine the association between stress and inflammatory breast diseases. Psychometric data, cytokine levels in breast milk and blood samples were analysed postpartum (T1). Psychometric data and course of breast feeding were evaluated twelve weeks later (T2). Patients were divided into case- and control-groups (according to the presence of breast diseases). Results, Mothers of the case group (n = 23) were significantly older and showed significantly increased stress levels between T1 and T2 compared with the control group (n = 43). Leucocytes in the postpartum blood count were significantly decreased in the case group. There were no significant differences between groups in the concentrations of Th-1- and Th-2-cytokines in breast milk postpartum. Conclusion, Higher maternal age, postpartum increase in stress perception and low number of leucocytes are associated with a higher incidence of inflammatory breast diseases. Further studies must examine the causality of this effect. [source] Leucocytes and intrinsic ROS production may be factors compromising sperm chromatin condensation statusANDROLOGIA, Issue 2 2010R. Henkel Summary Considering that the final protection of the DNA against major assaults in terms of chromatin condensation is finalised in the epididymis, it is not known how sperm production of reactive oxygen species (ROS) and inflammatory processes can contribute to protamine deficiency that is predetermined in the testes. Therefore, this study aimed at investigating relationships between poor chromatin condensation, morphology, ROS production, DNA damage and the impact of the presence of leucocytes. In 70 patients, sperm DNA status was determined using TUNEL and chromomycin A3 (CMA3) assays, and ROS-production by means of dihydroethidine. Morphology was evaluated according to strict criteria. The percentage of CMA3 -positive spermatozoa and leucocyte concentration (r = 0.178, P = 0.0377) as well as percentage of ROS-positive spermatozoa (r = 0.3010; P = 0.012) correlated significantly. Particularly, patients with leucocyte counts >0.5 × 106 ml,1 exhibited higher CMA3 positivity. No association was found between CMA3 positivity, TUNEL positivity and sperm morphology. While P- (poor prognosis: 0,4% normal morphology) and G-pattern (good prognosis: 5,14% normal morphology) morphology did not differ regarding chromatin condensation, P-pattern patients had a significantly higher percentage of DNA fragmentation (P = 0.0323). As oxidative stress is associated with disturbed chromatin condensation, results suggest that the idea that under-protamination of sperm DNA will automatically lead to DNA fragmentation might have to be revisited. [source] Melatonin Counteracts Alterations in Oxidative Metabolism and Cell Viability Induced by Intracellular Calcium Overload in Human Leucocytes: Changes with AgeBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Javier Espino In fact, the free radical theory of ageing proposes that deleterious actions of free radicals are responsible for the functional deterioration associated with ageing. Moreover, a close relationship exists between calcium homeostasis and oxidative stress. The current work was aimed at proving that intracellular calcium overload induced by N -formyl-methionyl-leucyl-phenylalanine (FMLP) and/or thapsigargin leads to oxidative stress. We additionally examined the effect of melatonin on the levels of reactive oxygen species (ROS) and cell viability in human leucocytes collected from young (20,30-year-old) and elderly (65,75-year-old) individuals under both basal and oxidative stress-induced conditions. Treatments with 10 nM FMLP and/or 1 ,M thapsigargin induced a transient increase in cytosolic free-calcium concentration ([Ca2 + ]c) in human leucocytes due to calcium release from internal stores, and led in turn to oxidative stress, as assessed by intracellular ROS measurement. Non-treated leucocytes from aged individuals exhibited higher ROS levels and lower rates of cell survival when compared to leucocytes from young individuals. Similar results were obtained in FMLP and/or thapsigargin-treated leucocytes from elderly individuals when compared to those from the young individuals. Melatonin treatment significantly reduced both hydrogen peroxide (H2O2) and superoxide anion levels, likely due to its free-radical scavenging properties, and enhanced leucocyte viability in both age groups. Therefore, melatonin may be a useful tool for the treatment of disease states and processes where an excessive production of oxidative damage occurs. [source] T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulationCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2010C. A. Pérez Novo Cite this as: C. A. Pérez Novo, M. Jedrzejczak-Czechowicz, A. Lewandowska-Polak, C. Claeys, G. Holtappels, P. Van Cauwenberge, M. L. Kowalski and C. Bachert, Clinical & Experimental Allergy, 2010 (40) 1323,1332. Summary Background Staphylococcal superantigens may modulate airway inflammatory disease. Objective We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. Methods Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of TH1/TH2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. Results After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c+CD14+ cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. Conclusion SEB induces both TH1 and TH2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors. [source] Involvement of 15-lipoxygenase and prostaglandin EP receptors in aspirin-triggered 15-hydroxyeicosatetraenoic acid generation in aspirin-sensitive asthmaticsCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2008M. Jedrzejczak-Czechowicz Summary Background The mechanism of aspirin (acetylsalicylic acid: ASA) hypersensitivity in asthmatic patients is related to arachidonic acid metabolism abnormalities, and specific triggering by ASA of 15-hydroxyeicosatetraenoic acid (15-HETE) generation was observed in leucocytes from aspirin-sensitive (AS) but not from aspirin-tolerant (AT) asthmatics. Objective The aim of this study was to identify the enzymatic pathway involved in ASA-induced 15-HETE generation in AS asthmatics and to assess the regulatory role of prostaglandin EP receptors. Methods Peripheral blood leucocytes (PBLs) were isolated from AS (n=18) and AT (n=20) asthmatics and challenged with ASA, with and without pre-incubation with caffeic acid (CA) [15-lipoxygenase (15-LO) inhibitor] or prostaglandin receptor non-specific (misoprostol, sulprostone) and specific EP1,4 receptors agonists. Eicosanoids were measured in supernatants using specific immunoassays. Results Aspirin triggered 15-HETE generation in PBLs of AS asthmatics (mean increase 292%) but not in AT asthmatics and inhibited prostaglandin2 (PGE2) generation in both groups of patients to the same degree. Leucocytes from AS patients produced less PGE2, both before and after ASA incubation. Pre-incubation of PBLs with CA decreased basal 15-HETE production in all patients and completely inhibited ASA-induced 15-HETE generation in AS asthmatics. CA did not change basal PGE2 production but enhanced induced by ASA inhibition of PGE2. Non-specific agonists of EP receptors (misoprostol and sulprostone) did not affect basal 15-HETE production but inhibited in a dose-dependent manner the ASA-induced increase of 15-HETE generation in AS asthmatics. On the contrary, in AT asthmatics, pre-incubation of PBLs with misoprostol or sulprostone resulted in a significant increase in 15-HETE generation after addition of ASA (200 ,m). EP1,3 receptor agonists inhibited (range 72,94%) the ASA-induced 15-HETE production significantly. Conclusion Our study demonstrated that ASA-triggered 15-HETE generation involves the activation of 15-LO and is modulated by prostaglandin EP1,3 receptors. The relevance of these observations to the mechanism of in vivo ASA-induced asthmatic attack remains to be established. [source] Identification of wild type and variants of oestrogen receptors in polymorphonuclear and mononuclear leucocytesCLINICAL ENDOCRINOLOGY, Issue 1 2006Denis Stygar Summary Objective, ,Leucocytes play an important role in the pathogenesis of autoimmune and cardiovascular diseases. Clinical and epidemiological observations indicate that the sex steroid hormones, particularly oestrogens, may regulate leucocyte functions. The assumption that oestrogens have a direct effect on leucocytes has to be supported by identification of functional oestrogen receptors (ER) in leucocytes. This study aimed at investigating the presence of ER subtypes in different types of leucocytes isolated from peripheral blood of female and male donors. Design and patients, ,A total of nine men (age range 18,43 years) and nine women (age range 19,42 years) all healthy blood donors, were recruited for the study. The donors did not receive any medication or hormonal contraceptives for the last three months. Ten millilitres of peripheral blood was collected from each donor. Polymorphonuclear leucocytes (PMN) and peripheral blood mononuclear cells (PBMC) were purified by density gradient centrifugation. Measurements, ,ER, and ER, mRNA expression was measured by real-time reverse transcriptase,polymerase chain reaction (RT-PCR), and ER proteins were analysed by Western blot in the PBMC and PMN leucocyte populations. In addition, expression profiles of ER variant isoforms were characterized by conventional PCR using the splice-targeted primer approach. Results, ,Although we detected wild-type ER, and ER, mRNAs in PBMC but not in PMN cells, the ER, and ER, proteins were found in both cell types using Western blot. We observed that both ER, and ER, proteins differ in size between PMN and PBMC, suggesting that the two leucocyte populations contain diverse variant isoforms of ER, and ER,. RT-PCR analysis of exon-deleted ER splice variants revealed that PBMC express several exon-deleted variants of ER, and ER,, along with wild-type receptor, whereas the PMN cells only express exon-deleted variant isoforms and no wild-type ER, or ER,. Conclusions, ,Our study demonstrates the presence of ER, and ER, in PBMC and PMN cells from female and male donors. The ER, and ER, genes have complex transcriptional profiles, with many receptor variant isoforms being expressed. Considering the diversity of ER isoforms in leucocyte subtypes, we conclude that the expected effect of oestrogen would be highly cell type-specific. Further studies are needed to test the functional activity of ER isoforms and their relation to disease. [source] n-3 polyunsaturated fatty acid supplementation, monocyte adhesion molecule expression and pro-inflammatory mediators in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 1 2001M. J. Sampson SUMMARY Aims To examine the effect of n-3 polyunsaturated fatty acid supplements on the monocyte surface expression of adhesion molecules involved in pro-atherogenic monocyte,endothelial interactions, and on pro-inflammatory mediators in Type 2 diabetes mellitus. Methods Twenty-nine subjects with Type 2 diabetes and 21 controls without diabetes were studied. Monocyte expression of leucocyte function-associated antigens 1 and 3, intercellular adhesion molecule-1, and the major histocompatibility complex class II molecule HLA-DR were measured using a laser flow cytometric method. Supplementation with 2.08 g n-3 fatty acids for 21 days was undertaken and measurements repeated. Plasma soluble adhesion molecule concentrations, plasminogen activator inhibitor-1 activity and antigen and pro-inflammatory mediators (cysteinyl leukotriene and monocyte leukotriene B4) were also measured. Results Groups did not differ in monocyte expression of adhesion molecules or HLA-DR, or in leukotriene production although plasma soluble adhesion molecule concentrations were higher in the diabetes groups (P < 0.05). n-3 fatty acid supplementation influenced neither the expression of these molecules nor plasma soluble adhesion molecule concentrations or leukotriene production. Conclusions This study does not support increased monocyte adhesion molecule expression or abnormal monocyte production of pro-inflammatory mediators as mechanisms for increased atherogenic risk in Type 2 diabetes. Cardioprotective actions of n-3 fatty acids may not be mediated through these mechanisms. [source] Effect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitisEQUINE VETERINARY JOURNAL, Issue 3 2010J. M. WILLIAMS Summary Reasons for performing study: Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1,, IL-6), COX-2, chemokines (i.e. IL-8) and endothelial adhesion molecules (i.e. ICAM-1 and E-selectin). In models of human sepsis, i.v. lidocaine has been reported to decrease leucocyte and endothelial activation, and the expression of proinflammatory cytokines and chemokines. Objectives: To evaluate the effect of i.v. lidocaine therapy on the inflammatory processes documented to occur in the BWE model of laminitis. Methods: Twelve horses were administered BWE and treated immediately with either lidocaine (1.3 mg/kg bwt bolus, followed by 0.05 mg/kg bwt/min CRI, n = 6) or saline (n = 6) for 10 h. At 10 h post BWE administration, laminar samples were obtained under general anaesthesia for assessment of proinflammatory gene expression (using RT-qPCR) and leucocyte emigration (via CD13 immunohistochemistry). At 0, 3 and 10 h post BWE administration, skin samples were obtained for assessment of leucocyte emigration (via calprotectin immunohistochemistry). Results: No significant differences between groups were noted for inflammatory gene mRNA concentrations (IL-1,, IL-6, IL-8, COX-2) or for number of leucocytes present within the laminar interstitium or skin dermis. Increased (P<0.05) laminar E-selectin mRNA concentrations were present in the LD group (vs. SAL group). Conclusions: Continuous administration of i.v. lidocaine does not inhibit inflammatory events in either the laminae or skin in the horse administered black walnut extract. Potential relevance: This work questions the use of continuous i.v. administration of lidocaine as an effective anti-inflammatory therapy for systemic inflammation. [source] Parabolic flight primes cytotoxic capabilities of polymorphonuclear leucocytes in humansEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2009I. Kaufmann Abstract Background, Previously performed in vitro studies suggested that gravitational stress may alter functions of immune cells. This study investigated the in vivo effects of parabolic flight manoeuvres as a short-term model of micro- and hypergravity on the cytotoxic and microbicidal polymorphonuclear leucocyte (PMN) functions as the key element of innate immunity. Material and methods, Twenty-one healthy male volunteers underwent 30 subsequent parabolic flight manoeuvres. Each manoeuvre produced 22-s periods of nearly weightlessness close to «0g», with each parabola starting with a pull-up and ending with a pull-out (hypergravity) at 1·8 g for about 20 s each. Blood samples were drawn 24 h prior to take off (T0), after 25,30 parabolas (T1), and 24 h (T2) and 48 h (T3) after flight for determination of (i) leucocyte number and subpopulations, (ii) PMNs' capabilities to produce hydrogen peroxide (H2O2) and to adhere and phagocytose particles and (iii) plasma cytokines known to prime PMN functions [interleukin-8 (IL-8), tumour necrosis factor-, (TNF-,), granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)]. Results, Parabolic flight induced an increase in leucocyte number with a significant elevation of the PMN fraction. The spontaneous H2O2 production by PMNs did not change; however, the capability of PMNs to produce H2O2 in response to soluble stimuli [N -formyl-methionyl-leucyl-phenylalanine (fMLP), fMLP and TNF-,, calcium ionophore (A23187), phorbol myristate acetate (PMA)] was increased. Adhesive and phagocytic properties of PMNs were not altered. Regarding priming cytokines, IL-8 and G-CSF were significantly elevated. Conclusions, Our data indicate that parabolic flight induces priming of the cytotoxic capabilities of PMNs without affecting microbicidal functions. [source] ,(1,2)-Fucosylation prevents sialyl Lewis x expression and E-selectin-mediated adhesion of fucosyltransferase VII-transfected cellsFEBS JOURNAL, Issue 1 2000Mourad Zerfaoui E-selectin is a cytokine-inducible, calcium-dependent endothelial cell adhesion molecule that plays a critical role in the leucocyte,endothelium interaction during inflammation and is thought to contribute to the metastatic dissemination of tumour cells. Like the other selectins, E-selectin binds to ligands carrying the tetrasaccharide sialyl-Lewis x (NeuAc,2,3Gal,1,4[Fuc,1,3]GlcNAc)1 or its isomer sialyl-Lewis a (NeuAc,2, 3Gal,1,3[Fuc,1,4]GlcNAc). We examined the effect of expressing the H-type ,(1,2)-fucosyltransferase or the ,(2,6)-sialyltransferase on the synthesis of sialyl-Lewis x by ,(1,3)fucosyltransferase. We found that H-type ,(1,2)-fucosyltransferase but not ,(2,6)-sialyltransferase, strongly inhibited sialyl-Lewis x expression and E-selectin adhesion. We assume that H-type ,(1,2)-fucosyltransferase competes with the endogenous ,(2,3)-sialyltransferase for the N -acetyllactosamine structures assigned to further serve as acceptors for ,(1,3)fucosyltransferase. [source] ,1 -antitrypsin prevents polymorphonuclear leucocyte-elastase effects on spermatozoa qualityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2010J. Leßig Summary Elevated levels of polymorphonuclear leucocyte (PMN)-derived elastase, which is suggested as marker for inflammations in the male genital tract, correlate well with spermatozoa deterioration. PMN elastase caused a time- and concentration-dependent (up to a elastase concentration of 0.5 ,g/mL) externalization of phosphatidylserine and intercalation of propidium iodide on human spermatozoa. There are apparently a limited number of target sites for elastase on spermatozoa surface, because the further enhancement of elastase amount did not fasten alterations in spermatozoa parameters. Analysis of flow cytometry data revealed that most spermatozoa were in a necrotic state after an exposure with elastase for 22 h. Some apoptotic cells were only detected at shorter incubation periods. Seminal plasma prevented in a concentration-dependent manner the PMN elastase-mediated loss of vitality of spermatozoa. We detected by blotting techniques large amounts of ,1 -antitrypsin in seminal plasma. This antiproteinase is known to inactivate elastase at inflammatory sites. Increasing concentrations of ,1 -antitrypsin prevented gradually spermatozoa deterioration induced by elastase. Thus, ,1 -antitrypsin contributes to an efficient protease/antiproteinase balance in seminal plasma. A disturbed balance will promote the development of chronic inflammations which can also be the reason for male infertility problems. [source] Side Effects of Cardiopulmonary Bypass:JOURNAL OF CARDIAC SURGERY, Issue 6 2004What Is the Reality? This is due, in part, to lack of suitable control group against which bypass and cardioplegic arrest can be compared. The recent success of beating heart coronary artery bypass grafting has, however, for the first time, provided an opportunity to compare the same operation, in similar patient groups, with, or without CPB and cardioplegic arrest. CPB is associated with an acute phase reaction of protease cascades, leucocyte, and platelet activation that result in tissue injury. This is largely manifest as subclinical organ dysfunction that produces a clinical effect in those patients that generate an excessive inflammatory response or in those with limited functional reserve. The contribution of myocardial ischemia/reperfusion, secondary to aortic cross-clamping, and cardioplegic arrest, to the systemic inflammatory response and wider organ dysfunction is unknown, and requires further evaluation in clinical trials. [source] Antitumour Activity and Side Effects of Combined Treatment with Chitosan and Cisplatin in Sarcoma 180-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000YOSHIYUKI KIMURA We examined the possible modulation by chitosan of the antitumour effects and side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed that CDDP had potent antitumour activity when administered orally as well as intraperitoneally. We also compared the antitumour activity and side effects of orally administered CDDP plus orally administered chitosan versus intraperitoneally administered CDDP plus orally administered chitosan in sarcoma 180-bearing mice. When CDDP (1.25 mg kg,1 × 2 day,1) was intraperitoneally administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen urea level), immunotoxicity (the reduction of spleen and thymus weight) and a reduction in body weight resulted. These intraperitoneally administered CDDP-induced side effects were not prevented by oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1) for 14 consecutive days. On the other hand, the side effects such as the reductions of body and spleen weights induced by orally administered CDDP (1.25 mg kg,1 × 2 day,1) were prevented by the oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1). From these results, we conclude that the orally administered chitosan plus CDDP might be useful for the prevention of body weight reduction and immunotoxicity (the reduction of spleen weight) induced by the orally administered CDDP without diminishing antitumour activity. [source] Incidence of benign upper respiratory tract infections, HSV and HPV cutaneous infections in inflammatory bowel disease patients treated with azathioprineALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009P. SEKSIK Summary Background, There are few data on the incidence of benign infections (upper respiratory tract infections, herpes lesions and viral warts) during exposure to azathioprine. Aims, To determine the incidence of benign infections in IBD out-patients receiving azathioprine (AZA+) and to look at the influence of leucocyte counts in the onset of these events. Methods, A total of 230 patients were included in a prospective cohort and observed during 207 patient-years. Episodes of benign infections were collected and incidences of benign infections were compared between the AZA+ group and patients without AZA (AZA,). Results, The incidence of upper respiratory tract infections in the cohort was 2.1 ± 2.2 per observation-year. There was no difference between the AZA+ (n = 169) and AZA, (n = 61) groups (2.2 ± 2.3 vs. 2.1 ± 2.1, P = 0.77). The incidence of herpes flares was significantly increased in the AZA+ group compared to the AZA, group (1.0 ± 2.6 vs. 0.2 ± 0.8 per year, P = 0.04). Similarly, there were significantly more patients with appearance or worsening viral warts in the AZA+ group (17.2% (AZA+) vs. 3.3% (AZA,), P = 0.004). Conclusion, This study suggests that the incidence of herpes flares and the appearance or worsening of viral warts are increased in IBD patients receiving AZA. [source] Effects of etomidate on free intracellular amino acid concentrations in polymorphonuclear leucocytes in vitroACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2000J. Mühling Background: Previous studies have shown the inhibitory effects of etomidate on polymorphonuclear leucocyte (PMN) function. No reports exist, however, regarding free intracellular amino acid metabolism, although physiological cell metabolism and basic cell functions rely upon a balanced intracellular amino acid content and the cell membrane-mediated separation of cellular amino acids from the extracellular plasma amino acid pool. Thus, in the current study, we evaluated the effects of etomidate on free intracellular amino acid metabolism in PMN. Methods: With ethics committee approval, blood was withdrawn from 35 healthy volunteers and incubated (1 h) either with 0 ,g/ml, 0.0156 ,g/ml, 0.0625 ,g/ml or 0.5 ,g/ml of etomidate as well as with its additives (propylene glycol and Lipofundin MCT® 10%). The PMN were separated using standardized Percoll® -gradient and centrifugation procedure before deep-freezing and lyophilization techniques were employed. All PMN samples were dissolved in methanol/H2O, and the concentrations of free intracellular amino acids were monitored using both novel advanced PMN-separation and high-performance liquid chromatography techniques. Results: Etomidate influenced important free amino acid profiles in PMN in a dose-dependent manner, indicating complex changes of cellular amino acid turnover. Neither propylene glycol nor Lipofundin MCT® 10% changed free amino acid concentrations in PMN. Conclusions: For the first time, the effects of etomidate on free intracellular amino acid metabolism in PMN have been investigated. Our results draw attention to the biochemical pathways which may be involved in etomidate-induced alterations in PMN function and cellular immunocompetence. [source] Epidemiology and demographics of prostatitisANDROLOGIA, Issue 5 2003A. J. Schaefler Summary. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a multifactorial problem affecting men of all ages and demographics. Currently, there is a relative dearth of epidemiological information on CPPS. It is clear that patients with CPPS have a dismal quality of life and many have benefited only minimally from empiric, goal-directed therapy. Long-term follow-up of the CPPS cohort will answer important questions about the natural and treated history of this syndrome. Similarly, ongoing and future studies will provide community-based and prevalence estimates for CPPS, morbidity rates for men with CPPS, and the rates of symptom improvement and symptom deterioration for these men, as well as the probability of benefits and harm from different treatments. Although men with CP routinely receive antiinflammatory and antimicrobial therapy, recent studies suggest that leucocyte and bacterial counts do not correlate with severity of symptoms. These findings suggest that factors other than leucocytes and bacteria contribute to the symptoms associated with CPPS. The probability of benefits and harm from different treatments for CPPS, and reliable and valid measures to define these outcomes are eagerly awaited. [source] Decreased immunocompetence in a severely bottlenecked population of an endemic New Zealand birdANIMAL CONSERVATION, Issue 1 2007K. A. Hale Abstract Inbreeding resulting from severe population bottlenecks may impair an individual's immune system and render it more susceptible to disease. Although a reduced immune response could threaten the survival of highly endangered species, few studies have assessed the effect of population bottlenecks on immunocompetence. We compared the counts of leucocytes and external, blood and gastrointestinal parasite loads in two populations of the endemic New Zealand robin Petroica australis to assess the immunocompetence of birds in a severely bottlenecked population relative to its more genetically diverse source population. Despite similar parasite loads in both populations, robins in the severely bottlenecked population showed lower counts of both total leucocyte and total lymphocyte numbers. When the immune system was experimentally challenged using the phytohaemagglutinin skin test, robins in the severely bottlenecked population exhibited a significantly lower immune response than the source population, suggesting that birds passing through a severe bottleneck have a compromised immunocompetence. Our results confirm that severe bottlenecks reduce the immune response of birds and highlight the need to avoid severe bottlenecks in the recovery programmes of endangered species. [source] Quantitative trait loci for porcine white blood cells and platelet-related traits in a White Duroc × Erhualian F2 resource populationANIMAL GENETICS, Issue 3 2009S. Yang Summary White blood cell count and platelets are implicated as risk factors for common complex diseases. Genetic factors substantially affect these traits in humans and mice. However, little is known about the genetic architecture of these traits in pigs. To identify quantitative trait loci (QTL) for leucocyte- and platelet-related traits in pigs, the total leucocyte number and differential leucocyte counts including the fraction of basophils, eosinophils, lymphocytes, monocytes, neutrophils, and a series of platelet parameters including platelet count, mean platelet volume, platelet distribution width and plateletcrit were measured in 1033 F2 animals on 240 days from a White Duroc × Erhualian intercross resource population. A total of 183 informative microsatellites distributed across 19 pig chromosomes (SSC) were genotyped across the entire resource population. Thirty-three QTL were identified for the examined traits, including eight genome-wide significant QTL for white blood cells and differential leucocyte counts on SSC2, 7, 8, 12 and 15 and six significant QTL for platelet-related traits on SSC2, 8, 13 and X. Erhualian or White Duroc alleles were not systematically associated with increased phenotypic values. These results not only confirmed many QTL identified previously in the mouse and swine, but also revealed a number of novel QTL for the traits recorded. Moreover, it is the first time that QTL for platelet-related traits in pigs have been reported. [source] Haematological response and growth performance of Nile tilapia (Oreochromis niloticus L.) fed diets containing folic acidAQUACULTURE RESEARCH, Issue 8 2009Margarida Maria Barros Abstract Haematological response and growth performance over 150 days, and resistance to a low-temperature stress of Nile tilapia fed diets with increasing folic acid (FA) levels were evaluated. The experiment was conducted in a completely randomized design with eight FA levels (0.0, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0 and 6.0 mg kg,1 feed) supplemented in purified diets (32.0% CP and 13 398 kj DE kg,1). One hundred and ninety-two fingerlings were randomly assigned to 32 net cages distributed in eight 1000 L aquaria with a physical and biological filter and a temperature control system (26.0 ± 1.0 °C). For cold-induced stress, fish were transferred to 24 30 L-aquaria with individual biofilters and aeration. The water temperature was gradually reduced until it reached 13 °C. Haematological parameters evaluated before and after cold stress were total erythrocytes and leucocytes count, differential leucocyte, haemoglobin, haematocrit, total plasmatic protein and haematometric indices. Growth performance parameters were mean weight gain, feed conversion ratio and survival. Dietary FA supplementation did not influence erythropoiesis under normal temperature conditions; cold stress impaired erythropoiesis, causing hypochromic microcytic anaemia and leucopoiesis, and also neutrophilia. Growth performance is influenced by folate and supplementation between 0.5 and 1.0 mg FA kg,1 diet, which makes up for nutritional demands, guaranteeing production and health under appropriate temperature conditions. [source] Effects of sulfamerazine on selected haematological and immunological parameters in rainbow trout (Onchorhynchus mykiss, Walbaum, 1792)AQUACULTURE RESEARCH, Issue 4 2009Naim Saglam Abstract In the present study, effects of sulfamerazine on some haematological and immunological parameters of rainbow trout (Oncorhynchus mykiss) were examined. Four groups of rainbow trout were fed experimental diets containing either no sulfamerazine (control) or supplemented with sulfamerazine at 100 mg kg,1 (Exp-A), 200 mg kg,1 (Exp-B) or 400 mg kg,1 (Exp-C) for 21 days. Blood samples were taken for the haematological and immunological parameters from fish on the third, seventh, 14th and 21st days of feeding. Haematological parameters [haematocrit, leucocrit, numbers of erythrocytes (RBC) and leucocytes (WBC), haemoglobin (Hb), mean corpuscular volume (MCV), mean haemoglobin concentration (MHC) and mean corpuscular haemoglobin concentration (MCHC)] and immunological parameters [phagocytic ratio (PR) and index (PI), glass-adherent NBT-positive cell activation, total plasma protein and total immunoglobulin (Ig)] were evaluated during the experimental trial. It has been observed that MCV (P<0.05), PR and PI (P>0.05) were increased and haematocrit and leucocrit value, numbers of erythrocytes and leucocyte, haemoglobin, MHC and MCHC values and total plasma protein and total Ig levels were decreased in rainbow trout after application of three different doses of sulfamerazine. [source] Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007Masako Shimada Summary Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large-scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3 -169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0·0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD. [source] Low-dose cyclophosphamide conditioning for haematopoietic cell transplantation from HLA-matched related donors in patients with Fanconi anaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005J. Zanis-Neto Summary Allogeneic haematopoietic cell transplantation (HCT) is effective therapy for Fanconi anaemia (FA). FA patients do not tolerate conditioning with 200 mg/kg of cyclophosphamide (Cy), typically used in aplastic anaemia. We previously published results of studies in which Cy doses were gradually reduced from 200 to 100 mg/kg. Here we update results of the initial studies and report data on 30 new patients conditioned with Cy either at 80 mg/kg (n = 7) or at 60 mg/kg (n = 23), given over 4 days before HCT from human leucocyte antigen-matched related donors. Methotrexate and cyclosporine were given for graft- versus -host disease (GVHD) prophylaxis. All seven patients given Cy at 80 mg/kg and 21 of 23 given Cy at 60 mg/kg had sustained engraftment, while two patients, both with clonal cytogenetics abnormalities, experienced graft failure. Grades 2,3 acute GVHD rates were 57% and 14% for patients given the higher and lower Cy doses, respectively (P = 0·001). Four patients given Cy at 80 mg/kg and 22 given Cy at 60 mg/kg were alive at a median of 47 (44,58) months and 16 (3,52) months, respectively. Cy at 60 mg/kg has acceptable toxicities, low rates of GVHD, and is sufficient for engraftment of related grafts in most FA patients. [source] Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Nicolaus Kröger Summary A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32,63). No primary graft failure occurred. The median time until leucocyte (>1·0 × 109/l) and platelet (>20 × 109/l) engraftment was 16 (range, 11,26) and 23 d (range, 9,139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft- versus -host disease (GvHD) grades II,IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0,32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow-up of 22 months (range, 4,59), the 3-year estimated overall and disease-free survival was 84% (95% CI: 67,100%). [source] Retroviral transduction of acute myeloid leukaemia-derived dendritic cells with OX40 ligand augments their antigen presenting activityBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2004Soshi Yanagita Summary Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms -like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF- ,. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8·5,27·2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)- , producing CD4+ T cells and in production of IFN- ,. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells. [source] Effects of warm-up on exercise capacity, platelet activation and platelet,leucocyte aggregation in patients with claudication ,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2005S. Pasupathy Background: The effects of exercise and warm-up were investigated in patients with claudication. Methods: This case,control crossover study involved two treadmill exercise tests, one preceded by a warm-up. Exercise continued until maximal leg pain (patients with claudication) or exhaustion (controls). Blood was taken before, and 5 and 60 min after exercise for flow cytometric analysis of platelet activation and platelet,leucocyte aggregation. Results: Both cohorts (eight patients with claudication of median age 63 years and eight healthy controls of median age 63·5 years) demonstrated improvement in exercise capacity after warm-up (13·1 per cent, P = 0·012 and 15·6 per cent, P = 0·008 respectively). Platelet activation increased after exercise in patients with claudication (fibrinogen binding: 1·11 per cent before exercise versus 2·63 per cent after exercise, P = 0·008; P-selectin: 0·68 versus 1·11 per cent, P = 0·028). Neither agonist stimulation nor warm-up altered this trend. Platelet,leucocyte (PLA) and platelet,neutrophil (PNA) aggregation were similarly increased immediately after exercise in patients with claudication (PLA: 7·6 versus 13·0 per cent, P = 0·004; PNA: 6·8 versus 10·2 per cent, P = 0·012). These remained high 60 min after exercise only in patients with claudication, but recovered to baseline levels when preceded by warm-up. Warm-up significantly desensitized PNA after stimulation with 10 µmol/l adenosine 5,-diphosphate at all time points. Conclusion: Warm-up increased the exercise capacity of patients with claudication. Exercise induced a thromboinflammatory response, with PLA and PNA persistently increased after 60 min in patients with claudication, an effect diminished after warm-up. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||||||||