Superoxide Anion Production (superoxide + anion_production)

Distribution by Scientific Domains


Selected Abstracts


Characterization of bovine neutrophil ,2 -adrenergic receptor function

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010
T. P. LaBRANCHE
LaBranche, T. P., Ehrich, M. F., Eyre, P. Characterization of bovine neutrophil ,2 -adrenergic receptor function. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01143.x. This study compares bovine leukocyte ,-adrenergic receptor densities to that of the rat, demonstrates for the first time a functional ,2 -adrenergic receptor signaling pathway in steer neutrophils, and investigates the effect of an inflammatory stimulus on that signaling pathway. The ,1 -/,2 -adrenergic antagonist [3H]CGP-12177 demonstrated that rat lymphocyte specific binding-site density was highest, followed by steer and dairy cow lymphocytes, and lastly steer and dairy cow neutrophils. The ,2 -adrenergic agonist terbutaline stimulated steer neutrophil adenosine 3,5-cyclic monophosphate (cAMP) production, an effect increased by inclusion of ,1 × 10,8 m phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. Both terbutaline and the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) independently decreased steer neutrophil superoxide anion production in a concentration-dependent manner, with 1 × 10,4 m IBMX enhancing both the potency and efficacy of the terbutaline effect (up to 74% reduction in superoxide anion production). Superoxide anion production was also reduced by the synthetic cAMP analog 8-bromo-cAMP, which increased the potency of the IBMX effect on superoxide anion production. Taken together, these data demonstrate the presence of a ,2 -adrenergic receptor signaling pathway in bovine neutrophils much like that described in other animal species, as well as the potential for an inflammatory stimulus to alter its function. [source]


Metformin decreases platelet superoxide anion production in diabetic patients

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2002
P. Gargiulo
Abstract Background Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans. Methods We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O2,) elicited by collagen, was determined by lucigenin assay. Results Patients with diabetes had higher platelet O2, production than controls; no correlation was observed between blood glucose and platelet O2, production. Group A patients had platelet O2, production similar to that of healthy subjects but lower than Group B and Group C patients. Conclusion The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Potentiation of 3-hydroxyglutarate neurotoxicity following induction of astrocytic iNOS in neonatal rat hippocampal cultures

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2001
Stefan Kölker
Abstract Neuronal damage in glutaryl-CoA dehydrogenase deficiency (GDD) has previously been addressed to N- methyl- d -aspartate (NMDA) receptor-mediated neurotoxicity of the accumulating neurotoxic metabolite 3-hydroxyglutarate. However, acute encephalopathic crises in GDD patients are typically precipitated by febrile illness or even routine vaccinations, suggesting a potentiating role of inflammatory cytokines. In the present study we investigated the effect of interleukin-1, and interferon-, on 3-hydroxyglutarate toxicity in rat cortical astrocyte cultures and neonatal rat hippocampal cultures. A cotreatment of both culture systems with interleukin-1, and interferon-, induced the protein expression of astrocytic inducible nitric oxide synthase (iNOS), resulting in increased nitric oxide (NO) production. Cytokine pretreatment alone had no effect on cell viability but potentiated 3-hydroxyglutarate neurotoxicity. NOS inhibition by aminoguanidine and L-NAME prevented an iNOS-mediated potentiation of 3-hydroxyglutarate neurotoxicity but failed to protect neurons against 3-hydroxyglutarate alone. In contrast, superoxide dismutase/catalase as well as MK-801 prevented toxicity of 3-hydroxyglutarate alone as well as its potentiation by iNOS, supporting a central role of NMDA receptor stimulation with subsequently increased superoxide anion production. It is concluded that the potentiation of 3-hydroxyglutarate neurotoxicity is most probably due to an induction of astrocytic iNOS and concomitantly increased NO production, enabling enhanced peroxynitrite formation. Thus, we provide evidence for a neuroimmunological approach to the precipitation of acute encephalopathic crises in GDD by inflammatory cytokines. [source]


Signal transduction and functional changes in neutrophils with aging

AGING CELL, Issue 4 2004
Tamas Fulop
Summary It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as a modulator of the adaptive immune response has become more widely recognized. One of the most important cell components of the innate response is neutrophils and it is therefore important to elucidate their function during aging. With aging there is an alteration of the receptor-driven functions of human neutrophils, such as superoxide anion production, chemotaxis and apoptosis. One of the alterations underlying these functional changes is a decrease in signalling elicited by specific receptors. Alterations were also found in the neutrophil membrane lipid rafts. These alterations in neutrophil functions and signal transduction that occur during aging might contribute to the significant increase in infections in old age. [source]


Probing structural requirements of fMLP receptor: On the size of the hydrophobic pocket corresponding to residue 2 of the tripeptide

JOURNAL OF PEPTIDE SCIENCE, Issue 2 2002
Susanna Spisani
Abstract The conformationally constrained f- L -Met-Acnc- L -Phe-OMe (n = 4,9,12) tripeptides, analogues of the chemoattractant f- L -Met- L -Leu- L -Phe-OH, were synthesized in solution by classical methods and fully characterized. These compounds and the published f- L -Met-Xxx- L -Phe-OMe (Xxx = Aib and Acnc where n = 3, 5,8) analogues were compared to determine the combined effect of backbone preferred conformation and side-chain bulkiness at position 2 on the relation of 3D-structure to biological activity. A conformational study of all the analogues was performed in solution by FT-IR absorption and 1H-NMR techniques. In parallel, each peptide was tested for its ability to induce chemotaxis, superoxide anion production and lysozyme secretion from human neutrophils. The biological and conformational data are discussed in relation to the proposed model of the chemotactic receptor on neutrophils, in particular of the hydrophobic pocket accommodating residue 2 of the tripeptide. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source]


Effects of areca nut extracts on the functions of human neutrophils in vitro

JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2000
Shan-Ling Hung
Aqueous extracts of ripe areca nut without husk (ripe ANE) and fresh and tender areca nut with husk (tender ANE) were examined for their effects on the defensive functions of human neutrophils. Exposure of peripheral blood neutrophils to ripe ANE and tender ANE inhibited their bactericidal activity against oral pathogens, including Actinobacillus actinomycetemcomitans and Streptococcus mutans, in a dose-dependent manner. At the concentrations tested, ripe and tender ANEs did not significantly affect the viability of neutrophils as verified by their ability to exclude trypan blue dye. However, both ANEs inhibited the production of bactericidal superoxide anion by neutrophils as measured by cytochrome c reduction. Moreover, the ripe ANE inhibited neutrophils more effectively than did tender ANE. Arecoline, a major alkaloid of areca nut, only exhibited an inhibitory effect on the functions of neutrophils when high concentrations were used. Therefore, arecoline could not be used to explain the inhibitory effects observed for ANEs. In conclusion, our results demonstrated that ripe and tender ANEs reduced the antibacterial activity and the superoxide anion production of neutrophils. This effect may contribute to a less efficient elimination of bacteria from the periodontal environment. Inhibition of the antimicrobial functions of neutrophils may alter the microbial ecology of the oral cavity, and this may be one possible mechanism by which areca nut compromises the oral health of users of areca nut products. [source]


Characterization of bovine neutrophil ,2 -adrenergic receptor function

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010
T. P. LaBRANCHE
LaBranche, T. P., Ehrich, M. F., Eyre, P. Characterization of bovine neutrophil ,2 -adrenergic receptor function. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01143.x. This study compares bovine leukocyte ,-adrenergic receptor densities to that of the rat, demonstrates for the first time a functional ,2 -adrenergic receptor signaling pathway in steer neutrophils, and investigates the effect of an inflammatory stimulus on that signaling pathway. The ,1 -/,2 -adrenergic antagonist [3H]CGP-12177 demonstrated that rat lymphocyte specific binding-site density was highest, followed by steer and dairy cow lymphocytes, and lastly steer and dairy cow neutrophils. The ,2 -adrenergic agonist terbutaline stimulated steer neutrophil adenosine 3,5-cyclic monophosphate (cAMP) production, an effect increased by inclusion of ,1 × 10,8 m phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. Both terbutaline and the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) independently decreased steer neutrophil superoxide anion production in a concentration-dependent manner, with 1 × 10,4 m IBMX enhancing both the potency and efficacy of the terbutaline effect (up to 74% reduction in superoxide anion production). Superoxide anion production was also reduced by the synthetic cAMP analog 8-bromo-cAMP, which increased the potency of the IBMX effect on superoxide anion production. Taken together, these data demonstrate the presence of a ,2 -adrenergic receptor signaling pathway in bovine neutrophils much like that described in other animal species, as well as the potential for an inflammatory stimulus to alter its function. [source]


Respiratory burst activity of polymorphonuclear cells is dependent on the cell preparation technique

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2003
J. Zhao
Background: Controversial results have been reported regarding the effect of anaesthetics on superoxide anion production during the respiratory burst (RB) of polymorphonuclear cells (PMN). The differences could be caused by the cell preparation methods and the aim of this study was to compare two techniques. Methods: RB activity was measured in cell suspensions isolated with the single-step Ficoll procedure and in unfractionated whole blood. Two concentrations of propofol (therapeutic and 10-fold of this, 6 µg ml,1 or 60 µg ml,1) were investigated after cell preparation with both methods. RB was stimulated with Escherichia coli (E. coli), phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) and measured by means of fluorescence intensity in a flow cytometer. Results: The percentage of PMNs in whole blood which generate superoxide anions in response to fMLP was significantly lower (2.5 ± 0.7%; mean ± SEM) than that in Ficoll isolated cell suspensions (15.1 ± 1.7%). Incubation with propofol led to a concentration-related decrease of RB activity in Ficoll separated PMNs after both PMA and fMLP stimulation. No significant effect of propofol was observed on the RB in PMA stimulated whole blood samples. Conclusion: The results suggest that the influence of cell preparation methods should be considered when the in vitro effects of anaesthetics on PMN functions are studied with flow cytometric methods. [source]


Reduction of oxidative changes in human spermatozoa by exogenous gangliosides

ANDROLOGIA, Issue 1 2005
M. Gavella
Summary The effect of exogenous gangliosides, the sialic acid-containing glycosphingolipids, on oxidative changes in human spermatozoa was investigated. The incorporation of disialogangliosides or trisialogangliosides (GD1b and GT1b, respectively) into the iron/ascorbate promoter system for induction of lipid peroxidation decreased the release of malondialdehyde (MDA) from peroxidizing spermatozoa. The application of monosialogangliosides and disialogangliosides (GM1 and GD1a, respectively) did not have any effect under identical experimental conditions. GT1b, at a micromolar concentration, significantly inhibited the production of MDA, a breakdown product of lipid peroxide decomposition in spermatozoa of normozoospermic infertile men (P < 0.001; n = 51). An enhanced generation of MDA exhibited by the sperm population from the low-density Percoll fraction containing defective and/or immature spermatozoa was significantly reduced in the presence of GT1b. These results and the experiments on the influence of iron-chelating agent ethylenediamine tetraacetic acid (EDTA) as well as ferrous ion concentration itself on lipid peroxidation support the hypothesis that the protective effect of ganglioside against MDA generation could be the result of its chelating activity. Furthermore, superoxide anion release of phorbol myristate acetate-stimulated spermatozoa was significantly reduced in the presence of 50 and 100 ,mol l,1 GD1b (P < 0.05) and GT1b (P < 0.005). The inhibitory effect of 100 ,mol l,1 GT1b on spermatozoa from infertile normozoospermic men was statistically significant (P < 0.001; n = 21) and did not depend on the initial superoxide anion production. In conclusion, the protective action of GD1b and GT1b could be related to both scavenging of free radicals and metal-chelating properties, which might have relevance in the protection against oxidation-induced processes in human spermatozoa. [source]


Phagocytosis of heat-killed Staphylococcus aureus by eosinophils: comparison with neutrophils

APMIS, Issue 2 2009
YASUKO HATANO
Eosinophils are characterized by several functional properties, such as chemotaxis, adhesion, superoxide anion production, and degranulation. In this article, we have studied the role of bacterial ingestion by eosinophils in comparison with that by neutrophils. Eosinophils and neutrophils were purified by using the Percoll gradient method followed by selection with CD16-coated immunomagnetic beads and centrifugation through a Ficoll-Hypaque gradient combined with dextran sedimentation, respectively. Both cells were preincubated with anti-Fc,RIIa mAb (CD32 mAb), anti-Fc,RIIIb mAb (CD16 mAb), anti-CR3 (CD11b mAb), or anti-CR1 (CD35 mAb) before being examined for phagocytosis of opsonized heat-killed Staphylococcus aureus (S. aureus). Phagocytosis and production of hydrogen peroxide were simultaneously measured by flow cytometry using S. aureus labeled with propidium iodide and stained with 2,,7,-dichlorofluorescein diacetate. Eosinophils showed significantly lower activity than neutrophils in both phagocytosis and hydrogen peroxide production. Phagocytosis by both cells was decreased by heat-inactivated serum. Phagocytosis by neutrophils was significantly inhibited by CD16 mAb and CD32 mAb, whereas that by eosinophils was only inhibited by CD35 mAb. Whereas the mechanism of phagocytosis by neutrophils was mediated by CD16 and CD32, that of eosinophils was modulated by complement receptor 1 (CD35). [source]


Immune response, growth and survival of Labeo rohita fingerlings fed with levamisole supplemented diets for longer duration

AQUACULTURE NUTRITION, Issue 4 2009
C.K. MISRA
Abstract The study was to determine the effect of long-term administration of different dosages of levamisole on growth, immune response and disease resistance against Aeromonas hydrophila & Edwardsiella tarda in Labeo rohita fingerlings. Fish were fed with four different dosages of levamisole (0, 125, 250 and 500 mg kg,1 diet) for 56 days. Different serum biochemical and haematological parameters such as serum total protein content, albumin content, globulin content, albumin/globulin ratio, glucose content, leucocytes count; cellular immune parameters including superoxide anion production, phagocytic activities, lymphokine production index; humoural immune parameters including lysozyme, complement and serum bactericidal activities were evaluated after 14 days interval. After 56 days, fish were divided into two subgroups under each treatment group for challenge with pathogens A. hydrophila and E. tarda. The cumulative mortality (%) and agglutinating antibody titre was recorded on 28th day postchallenge. WBC count, phagocytic ratio, lymphokine production index, lysozyme activity and serum bactericidal activity were increased upon administration of levamisole dosages for long term. However, the growth performance and survival against pathogens was not significantly changed over 56 days administration of levamisole. But incorporation of moderate dosage of levamisole for 42 days results better immune response without effect on growth and survival of L. rohita fingerlings. [source]


Comparative study of the intracellular superoxide anion production in different penaeid species through the NBT-reduction assay

AQUACULTURE RESEARCH, Issue 7 2010
Cristhiane Guertler
Abstract The capacity of reactive oxygen intermediates production upon haemocyte stimulation is one of the most important immunoparameter utilized to assess the health status in cultivated shrimps. In the present study, we compared oxidative stress potential, by measuring the superoxide anion production in three penaeid shrimps: two wild Atlantic species, the pink shrimp Farfantepenaeus paulensis and the white shrimp Litopenaeus schmitti and one cultivated Pacific species, the white shrimp, Litopenaeus vannamei, through the nitro-blue-tetrazolium-reduction assay. We also proposed an optimized experimental protocol for this assay, that produces rapid and consistent results with low levels of basal superoxide anion (O2,) production by unstimulated haemocytes and high levels of this oxygen radical after cell stimulation. Among the different cell elicitors used (zymosan, laminarin, lipopolysaccharide and phorbol myristate acetate), laminarin (,-1,3-glucans , 2 mg mL,1) was the most potent cell activator for the haemocytes of all three penaeids and we recommend this immunostimulant to routinely evaluate shrimp respiratory burst. In general terms, the most elevated levels of O2, production, after cell stimulation with microbial components, were detected in L. schmitti. Interestingly, the stimulation profile of the haemocytes of L. vannamei was more similar to F. paulensis, than to L. schmitti, which is more phylogenetically related. [source]


Effects of dietary prebiotics on the growth, feed efficiency and non-specific immunity of juvenile red drum Sciaenops ocellatus fed soybean-based diets

AQUACULTURE RESEARCH, Issue 3 2010
J Alejandro Buentello
Abstract Previous work has demonstrated several benefits of dietary prebiotics for fish. Here, we report the effects of added dietary fructooligosaccharide (FOS), mannanoligosaccharide (MOS), transgalactooligosaccharide (TOS) and GroBiotic® -A (GBA) on the weight gain, feed efficiency and non-specific immunity of juvenile red drum fed soybean meal (SBM)-based diets, in brackish water at 25 ± 1 °C. Test diets incorporated FOS, MOS, TOS or GBA at 10 g kg,1 in place of cellulose in a basal diet with 40% crude protein, half from SBM and half from fishmeal. After a 4-week feeding period, experimental fish were challenged by exposure to Amyloodinium ocellatum, after which growth and survival were monitored for 2 more weeks. Feed efficiency, serum lysozyme and intracellular superoxide anion production were significantly (P<0.05) enhanced by prebiotic supplementation. Likewise, survival after A. ocellatum exposure was significantly higher for fish fed GBA, MOS and TOS (87%, 84% and 78%) versus 58% for fish fed either the FOS or the basal diet. Taken together, these results indicate that inclusion of several prebiotics at 10 g kg,1 of the diet is adequate to improve the feed efficiency of red drum as well as to enhance disease protection. [source]


Dose-dependent influences of dietary ,-1,3-glucan on innate immunity and disease resistance of hybrid striped bass Morone chrysops×Morone saxatilis

AQUACULTURE RESEARCH, Issue 14 2009
Peng Li
Abstract To investigate potential use of dietary ,-1,3-glucan for health management of hybrid striped bass, juvenile fish were fed diets supplemented with yeast glucan (MacroGuard®) at 0.05%, 0.1% or 0.2% of diet for 4 weeks, followed by immune response assays and a bath challenge with Streptococcus iniae. Dietary glucan significantly (P<0.05) enhanced neutrophil oxidative radical production, and fish fed 0.1% glucan had a significant (P<0.05) reduction in mortality (10%) after bacterial challenge compared with fish fed the control diet (46.7%). However, accumulative mortality of fish fed 0.2% glucan was not significantly different from that of fish fed the control diet. To further elucidate this observation, macrophages from sub-adult hybrid striped bass were isolated and cultured in L-15 medium with 10% foetal calf serum and penicillin/streptomycin supplemented with 0.2, 0.5, 1, 2, 5, 20 and 100 ,g soluble glucan (MacroGuard®) mL,1 for 24 and 48 h. Intracellular superoxide anion production was significantly (P<0.001) increased by 0.5 ,g glucan mL,1, but significantly (P<0.001) suppressed by doses >5 ,g glucan mL,1. It is concluded that dietary yeast glucan has potential for use in diet formulations of hybrid striped bass to limit the adverse effects of S. iniae, but dosage should be an important consideration in administration. [source]


High glucose levels enhance platelet activation: involvement of multiple mechanisms

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2006
Dzana Sudic
Summary Diabetes mellitus (DM) and hyperglycaemia are associated with platelet activation. The present study was designed to investigate how high glucose levels influence platelet function. Fasting human blood was incubated with different concentrations of d -glucose (5, 15 and 30 mmol/l) and other sugars without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30 mmol/l l -glucose, sucrose and galactose. Hyperglycaemia also increased TRAP-induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not counteract the enhancement of platelet P-selectin expression, but abolished the enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia. Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the hyperglycaemic enhancement of platelet P-selectin expression, but did not counteract the enhancement of TRAP-induced platelet fibrinogen binding. Hyperglycaemia did not alter platelet intracellular calcium responses to agonist stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3) kinase, or nitric oxide synthase, or the addition of insulin did not influence the effect of hyperglycaemia. In conclusion, high glucose levels enhanced platelet reactivity to agonist stimulation through elevated osmolality. This occurred via superoxide anion production, which enhanced platelet P-selectin expression (secretion), and PKC signalling, which enhanced TRAP-induced fibrinogen binding (aggregablity). [source]


Macrophage Stimulating Protein (MSP) evokes superoxide anion production by human macrophages of different origin

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2001
Sandra Brunelleschi
Macrophage Stimulating Protein (MSP), a serum factor related to Hepatocyte Growth Factor, was originally discovered to stimulate chemotaxis of murine resident peritoneal macrophages. MSP is the ligand for Ron, a member of the Met subfamily of tyrosine kinase receptors. The effects of MSP on human macrophages and the role played in human pathophysiology have long been elusive. We show here that human recombinant MSP (hrMSP) evokes a dose-dependent superoxide anion production in human alveolar and peritoneal macrophages as well as in monocyte-derived macrophages, but not in circulating human monocytes. Consistently, the mature Ron protein is expressed by the MSP responsive cells but not by the unresponsive monocytes. The respiratory burst evoked by hrMSP is quantitatively higher than the one induced by N-formylmethionyl-leucyl-phenylalanine and similar to phorbol myristate acetate-evoked one. To investigate the mechanisms involved in NADPH oxidase activation, leading to superoxide anion production, different signal transduction inhibitors were used. By using the non selective tyrosine kinase inhibitor genistein, the selective c-Src inhibitor PP1, the tyrosine phosphatase inhibitor sodium orthovanadate, the phosphatidylinositol 3-kinase inhibitor wortmannin, the p38 inhibitor SB203580, the MEK inhibitor PD098059, we demonstrate that hrMSP-evoked superoxide production is mediated by tyrosine kinase activity, requires the activation of Src but not of PI 3-kinase. We also show that MAP kinase and p38 signalling pathways are involved. These results clearly indicate that hrMSP induces the respiratory burst in human macrophages but not in monocytes, suggesting for the MSP/Ron complex a role of activator as well as of possible marker for human mature macrophages. British Journal of Pharmacology (2001) 134, 1285,1295; doi:10.1038/sj.bjp.0704356 [source]


Macrophage Colony-stimulating Factor (M-CSF) Prevents Infectious Death Induced by Chemotherapy in Mice, While Granulocyte-CSF Does Not

CANCER SCIENCE, Issue 4 2002
Takao Hidaka
To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not unproved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group (P<0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) (P<0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy. [source]


Bioactive fMLF-OMe analogs containing a N -terminal oximic or formylhydrazonic moiety

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2000
I. Torrini
Abstract: In order to obtain chemotactic peptides with selective bioactivity, a new type of structural modification was introduced at the N -terminal position of HCO-Nle-Leu-Phe-OMe. Two groups of analogs have been synthesized both containing a N -terminal residue of the X=C(R)-CO-type replacing the native HCO-NH-CH(R)-CO-. In particular, the A group of pseudopeptides (2a - d) possesses a N -terminal oximic fragment (X=HO-N) and the B group (3a - d) a formylhydrazone fragment (X=HCO-NH-N). These new ligands have been examined for their capacity to induce chemotaxis and other cellular responses such as superoxide anion production and lysozyme release; although significantly active as chemoattractants they have been found to be practically devoid of secretagog activity, thus exhibiting selective behavior. The adopted chemical modification seems extensible in designing a new class of pseudopeptides (hydrazonopeptides) structurally related to both hydrazinopeptides and peptides containing ,,,-unsaturated residues. [source]


The effect of ascorbate on minor recurrent aphthous stomatitis

ACTA PAEDIATRICA, Issue 3 2010
K Yasui
Abstract Aim:, Minor recurrent aphthous stomatitis (MRAS) is a common, painful and inflammatory ailment of the oral cavity with juvenile onset and unknown aetiology. The purpose of this study was to evaluate the potential of ascorbate (vitamin C) to reduce the frequency of MRAS and severity of pain. Patients and methods:, Sixteen MRAS patients (9 boys and 7 girls: mean age, 12.0 ± 2.4 years old) were assigned to take an oral dosage of 2000 mg/m2/day ascorbate. Subjects:, Their baseline frequency of outbreaks and the level of pains were compared during the treatment; in addition, a crossover clinical trial was performed. Polymorphonuclear leucocytes play a role in the pathogenesis, and then superoxide anion production was evaluated in prior to ascorbate treatment. Results:, The data indicated a statistically significant 50% reduction in oral ulcer outbreaks and a decline of pain level. Neutrophils were primed for superoxide anion production in the patients with MRAS. Conclusion:, Ascorbate may modulate the generation of reactive oxygen species and augment neutrophil apoptosis, which could prevent neutrophil-mediated inflammation. Ascorbate seems to be effective, but the findings of our study were preliminary and it should be re-evaluated with a larger randomized controlled clinical trials. [source]