Treatment of severe psoriasis and psoriatic arthritis with leflunomide.
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Anti-Inflammatory Agents, Non-Steroidal↗
Biomedical subjects
I Beckmann
Publications and source records attributed to I Beckmann.
Release of tumor necrosis factor-alpha and prostanoids in whole blood cultures after in vivo exposure to low-dose aspirin.
BACKGROUND: The preventive effect of low-dose aspirin in cardiovascular disease is generally attributed to its antiplatelet action caused by differential inhibition of platelet cyclooxygenase-1. However, there is evidence that aspirin also affects release of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha). It is not known whether this is caused by direct action on the cytokine pathway or indirectly through cyclooxygenase inhibition and altered prostanoid synthesis, or both. METHODS: We assessed the capacity of lipopolysaccharide-activated leukocytes in whole blood cultures of eight healthy subjects following a single oral dose of 80 mg aspirin to release TNF-alpha, prostanoid E2 (PGE2) and prostanoid I2 (PGI2), and thromboxane A2 (TXA2). TNF-alpha and prostanoids were determined by enzyme-linked immunoassays. RESULTS: In seven subjects, TNF-alpha release in blood cultures decreased 24h after intake of aspirin. The effect of aspirin on prostanoid release was assessed in three individuals: PGE2 increased in all subjects, PGI2 increased in two and remained unchanged in one, and TXA2 was reduced in two and unchanged in one individual The presence of DFU, a specific inhibitor of cyclooxygenase 2, did not affect the reduction of TNF-alpha release by aspirin, but abolished prostanoid production in all three individuals. CONCLUSION: The capacity of activated leukocytes to release TNF-alpha is reduced by ingestion of low-dose aspirin, independent of changes in prostanoid biosynthesis.
Adult↗
Circulating bioactive tumor necrosis factor-alpha, tumor necrosis factor-alpha receptors, fibronectin, and tumor necrosis factor-alpha inducible cell adhesion molecule VCAM-1 in uncomplicated pregnancy.
OBJECTIVES: Our goal was to assess in a longitudinal study of uncomplicated pregnancy the course of maternal plasma concentrations of the bioactive cytokine tumor necrosis factor-alpha, the soluble tumor necrosis factor-alpha receptors sTNFRI and sTNFRII, the soluble cell adhesion molecule sVCAM-1, and circulating fibronectin. STUDY DESIGN: Blood was collected from 22 healthy pregnant women at 7 to 17, 18 to 22, 23 to 28, and 30 to 36 weeks' gestation and post partum. Plasma samples were measured by bioassay for bioactive tumor necrosis factor-alpha, by immunoassay for sTNFRI, sTNFRII, and VCAM-1, and by radial immunodiffusion for circulating fibronectin, and data were statistically analyzed. RESULTS: Plasma concentrations of all variables were significantly linked with gestational age. Levels of bioactive tumor necrosis factor-alpha and sTNFRII showed a parallel rise in the second trimester and a decrease thereafter. Values for sTNFRI and sTNFRII and for these receptors and VCAM-1 were correlated, a weak correlation between bioactive tumor necrosis factor-alpha and sTNFRII was observed, and no correlation between circulating fibronectin and other variables was apparent. CONCLUSIONS: All variables studied exhibited a characteristic pattern depending on gestational age, which supports the concept of a physiologic role of tumor necrosis factor-alpha in pregnancy.
Adolescent↗
Tumor necrosis factor-alpha in response to endotoxin administration in the pregnant guinea pig.
OBJECTIVE: Our purpose was to test the hypothesis that an intramuscular endotoxin challenge induces production of tumor necrosis factor-alpha in the pregnant guinea pig and to investigate some of the metabolic effects. STUDY DESIGN: Twelve randomly selected guinea pigs at 33 days' gestation with a sampling catheter in the carotid artery received an intramuscular injection of a solution of endotoxin isolated from Bacteroides fragilis (n = 6) or of solvent alone (n = 6). Plasma values of tumor necrosis factor-alpha, hematocrit, and 6-keto-prostaglandin F1 alpha were determined before and several hours after injection. RESULTS: Tumor necrosis factor-alpha was detected in five of six guinea pigs, but it could not be demonstrated in five of six placebo animals. The hematocrit was significantly decreased, and prostaglandin F1 alpha significantly increased 24 to 48 hours after endotoxin injection. CONCLUSION: In pregnant guinea pigs an intramuscular endotoxin challenge induces the release of tumor necrosis factor-alpha, followed by a reduced hematocrit and an increased prostacyclin concentration. These effects could be involved in the pathogenesis of endotoxin-induced fetal growth retardation.
Animals↗
Detection of Bacteroides fragilis endotoxin in amniotic fluid by counterimmunoelectrophoresis.
The ability of counter immunoelectrophoresis (CIE) to detect Bacteroides fragilis endotoxin in amniotic fluid in small concentrations was evaluated. A method was developed which, in combination with ultrafiltration, permits detection of B. fragilis endotoxin in amniotic fluid in a concentration of 40 ng/ml or more. The sensitivity threshold was reduced to 2 ng/ml by using a highly reactive IgG-fraction isolated from rabbit anti-B. fragilis IPL E 323 antiserum.
Amniotic Fluid↗
Bioactive tumour necrosis factor alpha in pre-eclamptic patients with and without the HELLP syndrome.
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Adolescent↗
A comparison between two methods for measuring tumor necrosis factor in biological fluids.
The current study was undertaken to compare two methods for the efficiency of measuring tumor necrosis factor (TNF-alpha) in biological fluids, which is species undependent, reliable, sensitive, simple and not expensive. We have compared the MTT tetrazolium cytotoxic assay [1,2] and the 3H-thymidine (3H-TdR) incorporation cytostatic assay for measuring the anti-tumor activity of human recombinant TNF-alpha, of human colonic tissue and of supernatants of in vitro stimulated human and rat peritoneal macrophages. Two target cell-lines, namely murine myelomonocytic leukaemia WEHI-164- and L-929-transformed murine fibroblast cell-lines, were used in the MTT assay. The L-929 line was also used in the 3H-TdR assay. WEHI-164 was more sensitive than the L-929 cell-line in the MTT cytotoxic assay. Furthermore, the MTT assay was more sensitive to TNF-alpha than the 3H-TdR assay. Both methods can be used for the detection of anti-tumor activity in biological fluids but the MTT cytotoxic method has the advantage of being more sensitive and more simple.
Animals↗
Endotoxin-induced fetal growth retardation in the pregnant guinea pig.
OBJECTIVES: Our purpose was to test the hypothesis that bacterial endotoxin may reduce fetal growth and to assess some of the pathophysiologic mechanisms of such an effect. STUDY DESIGN: Two randomly selected groups of nine guinea pigs at 30 days' gestation were treated with a solution of endotoxin isolated from Bacteroides fragilis or with solvent alone. Antibody titers, glucose, triglycerides, and 6-keto-prostaglandin F1 alpha were determined in maternal or fetal blood samples. Fetal weight was determined at 61 days' gestation. RESULTS: Endotoxin-treated guinea pigs showed positive antiendotoxin antibody titers, reduced weight gain, and significantly higher serum levels of triglycerides and 6-keto-prostaglandin F1 alpha, but not of glucose, than did sham-treated controls. Fetuses of endotoxin-treated animals had significantly lower birth weights and serum glucose concentrations and significantly higher triglyceride levels than did control fetuses. CONCLUSIONS: Bacteroides fragilis endotoxin causes fetal growth retardation in the pregnant guinea pig, which may be due to alterations in carbohydrate and fat metabolism mediated by cytokine action.
6-Ketoprostaglandin F1 alpha↗
Activity of human peritoneal macrophages against a human tumor: role of tumor necrosis factor-alpha, PGE2 and nitrite, in vitro studies.
Human peritoneal macrophages collected from renal patients on continuous ambulatory peritoneal dialysis (CAPD) during inflammation-free periods were induced to express antitumor activity in vitro when cultured in the presence of bacterial lipopolysaccharide (LPS) and even more activity when they were kept in the presence of LPS + IND (indomethacin). The antitumor activity was expressed against a human tumor-cell line, RC43, either in a cell-to-cell contact set-up between the macrophages and the RC43 target cells or when the tumor cells were exposed to supernatants of the cultured macrophages. The antitumor activity of macrophages was correlated to a marked increase in production of tumor necrosis factor-alpha (TNF alpha), not correlated to an increase in nitrite production and inversely correlated to the production of PGE2. The RC43 tumor cells were susceptible to recombinant human TNF alpha, recombinant human IL-1 beta, sodium nitrite and the leukotriene LTB4. The results obtained suggest that activated human macrophages might represent a useful tool for cancer immunotherapy.
Animals↗
The effects of deoxycholate and sodium dodecyl sulphate on the serological reactivity of antigens isolated from six Bacteroides reference strains.
The detergents sodium dodecyl sulphate (SDS) and sodium deoxycholate (NaD) are frequently used as solvents for macromolecular polysaccharide complexes in immunochemical and serological techniques. The influence of the disaggregating surfactants on the serological reactivity of endotoxins isolated from six serotype specific reference strains of the Bacteroides fragilis group was investigated by comparing haemagglutinating and precipitating reactivities of antigen solutions in phosphate buffered saline (PBS), NaD and SDS. All antigens were phenol/water extracted endotoxins. Solutions of antigens isolated from serotypes A, B, C and D in PBS exhibited mainly serotype specificity and a few well known low-titer cross reactions; solutions in NaD showed additional cross reactivity, which was enhanced by solubilization of the antigens in SDS. In immunoelectrophoresis endotoxins isolated from serotypes A and C and dissolved in NaD or SDS showed additional precipitation lines compared to solutions of the same antigens in PBS. These changes in the serological reactivity are of relevance for investigations where the serological specificity of antigens is in question.
Antigens, Bacterial↗
Uterine artery estrogen receptors in the nonpregnant and pregnant guinea pig.
Uterine artery, heart, and aorta or carotid specimens of nonpregnant, midpregnant, and term pregnant guinea pigs were examined for estrogen receptors by immunocytochemical methods. Estrogen receptors were found in the nuclei of cells in the endothelial, muscle, and adventitia layers of the uterine artery wall. The concentration of estrogen receptors was slightly higher in nonpregnant and term pregnant animals than in midpregnancy. No estrogen receptors were found in the heart, aorta, or carotid specimens of all animals. These results confirm the uterine artery as a target organ of estrogen action that would eventually lead to arterial functional adaptation in different biologic periods.
Animals↗
Immune response to endotoxin isolated from Bacteroides fragilis in the pregnant guinea pig.
The humoral immune response to endotoxin isolated from Bacteroides fragilis was analyzed in the pregnant guinea pig by means of passive hemagglutination, passive hemolysis, a modified Coombs test, and by crossed immunoelectrophoresis. Pregnant animals were immunized with endotoxin on day 30 of gestation, and antibodies were determined on day 61 in maternal and fetal sera, and in amniotic fluid. The IgG and IgM responses in maternal sera were of the same magnitude as in sera of nonpregnant animals. Fetal sera contained IgG and sometimes IgM, and a higher percentage of incomplete antibodies against endotoxin than maternal sera. Low-titer anti-endotoxin antibodies, partially sensitive to dithiothreitol, were found in amniotic fluid. A statistically significant reduction in the growth of fetuses from endotoxin-immunized females was observed.
Amniotic Fluid↗
Detection of 2-keto-3-deoxyoctonate in endotoxins isolated from six reference strains of the Bacteroides fragilis group.
1. Endotoxins isolated from six serotype specific reference strains of the Bacteroides fragilis group were dephosphorylated by treatment with aqueous 50% hydrofluoric acid. 2. Mild acidic hydrolysis of the dephosphorylated endotoxins released 2-keto-3-deoxyaldonic acid, the presence of which was demonstrated by the colorimetric thiobarbituric acid assay (TBA). 3. Thin layer chromatography of the dephosphorylated lipopolysaccharide of B. fragilis IPL E 323 (serotype E2), after acidic hydrolysis, revealed a TBA-positive substance with the same Rf-value as authentical 2-keto-3-deoxyoctolusonic acid (KDO). 4. Quantification of 2-keto-3-deoxyoctonate-in the lipopolysaccharide of B. fragilis IPL E 323 by means of the TBA resulted in a KDO content of 15 nM mg-1 lipopolysaccharide.
Bacteroides fragilis↗
Mycobacterium scrofulaceum, serovar Cole.
Cole strains of Mycobacterium, originally introduced as M. scrofulaceum serovar No. 44 and later rejected as belonging to M. avium were re-investigated and compared with well-documented strains of M. scrofulaceum. Our data show that the Cole serovar belongs to M. scrofulaceum and should be re-introduced as serovar No. 44 of M. scrofulaceum.
Agglutination Tests↗
Immunochemical investigations of antigens isolated from Bacteroides ovatus strain ATCC 8483.
A saline extract (SE) and a phenol/water extract (WL) were prepared from Bacteroides ovatus strain ATCC 8483. A fraction CS was isolated from the culture supernatant. WL was further split by ultracentrifugation into lipopolysaccharide (LPS) and supernatant (L1). Fractions SE, WL, LPS and L1 reacted serologically with homologous antiserum but did not cross-react with antisera against heterologous Bacteroides serotypes. Fraction CS was inactive in haemagglutination, haemagglutination inhibition and immunoelectrophoresis tests. SE, WL, LPS and L1 proved to be serologically heterogeneous. A distinct serological specificity for SE was demonstrated. The serological reactivity in SE and WL was not altered after treatment with proteolytic enzymes yet completely destroyed in WL and partially in SE by sodium metaperiodate. SE, WL, LPS and L1 contained the sugar components rhamnose, fucose, ribose, mannose, galactose, glucose and glucosamine in different molar ratios for each fraction. Galactosamine was found in WL and LPS, uronic acid in WL and L1. Two unidentified aminohexoses were detected in WL, one of which was also detectable in L1 and SE. 2-Keto-3-deoxyaldonic acid was demonstrated in LPS and L1 after strong acid hydrolysis.
Antigens, Bacterial↗
Immunochemical and biological studies of antigens isolated from a strain of Bacteroides fragilis.
Phenol/water-extracted lipopolysaccharide and a fraction of HM, extracted with acetate buffer pH 2.0, from Bacteroides fragilis strain 62/73 are antigenically different as shown by immunodiffusion, passive haemagglutination, haemagglutination inhibition and preliminary chemical investigations. Biological activity, assessed with the local Shwartzmann reaction, was demonstrated for the lipopolysaccharide whereas antigen HM was almost inactive in this test. HM is immunogenic in rabbits. Antibodies against HM were detected in seven out of ten sera of healthy humans.
Animals↗
[The antibacterial activity of a gel for burns and wounds containing tyrothricin, fomocaine, diphenhydramine and 8-hydroxyquinoline (author's transl)].
The antibacterial activity of a new jelly for burns and wounds with the components tyrothricin, 8-hydroxyquinoline, fomocaine and diphenhydramine (Herit) is described. The biological availability of tyrothricin and 8-hydroxyquinoline from the gel is in accordance with minimum inhibitor concentrations (MIC). Against strains of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans the jelly was most effective.
Anti-Bacterial Agents↗
[Serological reactivity of healthy and ill people in relation to antigens from Bacteroides-serotypes (author's transl)].
We investigated sera of healthy and ill people with different diagnoses to their reactivity against antigens isolated from six serotypes A--E2 (subspecies) of Bacteroides fragilis in indirect hemagglutination tests. These investigations were conducted partly in Poland and partly in the Netherlands. - In many cases antibodies towards several serotypes of Bacteroides fragilis were present in the healthy. In the Netherlands we found antibodies towards serotypes C and E2; in Poland serotypes D and E1 seem to be predominant in the healthy, whereas some reactivity towards other serotypes also could be observed (see table 1). - Hemagglutinationtiters in sera of the ill were frequently increased. In these sera we found also reactivity towards serotypes which are absent or rare in the healthy (see tables 2, 4 and 5). Sera of patients with carcinoma or sarcoma displayed high titers and especially reactivity towards those serotypes which are absent or rare in the healthy (see tables 3, 4 and 5).
Abortion, Septic↗