Apocynin and 1400 W prevents airway hyperresponsiveness during allergic reactions in mice

1. The contribution of reactive nitrogen species to the development of airway hyperresponsiveness in a mouse model of allergic inflammation was investigated by the use of selective inhibitors of nitric oxide and superoxide formation. 2. Sensitized mice, repeatedly challenged with ovalbumin showed a significant (P<0.001, n=9) increase in airway responsiveness measured using whole body plethysmography. This hyperresponsiveness was accompanied by an influx of eosinophils into the airway lumen and increased levels of ovalbumin-specific serum IgE. 3. Treatment of mice with the iNOS inhibitor 1400 W or the NADPH-oxidase inhibitor apocynin did not significantly alter cellular influx into the airway lumen nor serum ovalbumin specific IgE. In contrast, apocynin as well as 1400 W inhibited ovalbumin-induced airway hyperresponsiveness (P<0.001 and P<0.05 respectively, n=9). Furthermore, the airways of allergen challenged animals showed clear 3-nitrotyrosine staining, which was mainly located in eosinophils. Remarkably, treatment with apocynin or 1400 W did not alter 3-nitrotyrosine staining. 4. These data suggest that the development of airway hyperresponsiveness during the airway inflammation upon ovalbumin challenge is dependent on the release of both superoxide and nitric oxide and is therefore likely to be dependent on reactive nitrogen species. This mechanism, however, is not reflected by 3-nitrotyrosine formation in the airways.     

Decipinin A and decipienolides A and B: new bioactive metabolites from the coprophilous fungus Podospora decipiens

Decipinin A (1), a new compound with antifungal and antibacterial activity, has been isolated from liquid cultures of the coprophilous fungus Podospora decipiens (JS 270). Two new tetracyclic sesquiterpene lactones, decipienolides A (2) and B (3), were also obtained from this isolate as an inseparable mixture of epimers that showed antibacterial activity. The structures of 1-3 were elucidated by analysis of 1D and 2D NMR data, aided by chemical shift comparisons to related compounds.     

Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer

Although recombinant human interleukin-3 (rhIL-3) shortens both the duration of chemotherapy-induced neutropenia and thrombocytopenia, its effect on nadir counts is limited. Concurrent administration of rhIL-3 and chemotherapy may enhance this effect. However, simultaneous administration of other hematopoietic growth factors and chemotherapy has resulted in enhanced myelosuppression. We investigated whether concomitant administration of rhIL-3 and chemotherapy would result in enhanced myelosuppression. Twelve patients with relapsed small cell lung cancer received vincristine, ifosfamide, mesna, and carboplatin on day 1 every four weeks. RhIL-3 was administered subcutaneously on days 1-14 during cycle 1 at doses of 4 (three patients) or 8 micrograms/kg/day (nine patients). During cycle 2 patients received only chemotherapy. No significant difference in leukocyte (1.4 +/- 1.0 vs. 0.9 +/- 0.4 x 10(9)/l (mean +/- SD), neutrophil (0.5 +/- 0.6 vs. 0.2 +/- 0.2 x 10(9)/l), and platelet (64 +/- 60 vs. 38 +/- 58 x 10(9)/l) nadir counts were demonstrated. The hemoglobin nadir level was significantly higher during cycle 1 (6.5 +/- 1.1 vs. 5.5 +/- 0.9 mmol/l, P = 0.05). Both leukocyte and platelet recovery were significantly enhanced in the rhIL-3 cycle. There was no significant difference in chemotherapy postponement or platelet transfusions. As a result of severe headaches, rhIL-3 administration was discontinued in one patient at 8 micrograms. RhIL-3 during this chemotherapy regimen for relapsed small cell lung cancer did not enhance myelotoxicity but did improve bone marrow recovery. This observation may increase the application of rhIL-3, for instance in combination with other hematopoietic growth factors.     

The involvement of iron and lipid peroxidation in the pathogenesis of HCB induced porphyria

Hexachlorobenzene (HCB) induces a porphyria characterized by a diminished activity of the enzyme uroporphyrinogen decarboxylase (URO-D), presumably due to inactivation by reactive metabolites of HCB. We studied the effect of iron on HCB porphyria in female rats, to determine whether the iron dependent process of lipid peroxidation was involved in the pathogenesis of porphyria. We showed that malondialdehyde formation is increased in rat liver tissue of porphyric rats and that high molecular weight proteins due to cross-linking are formed. We also showed that the induction of porphyria by HCB is dependent on the presence of iron. Our findings suggest that lipid peroxidation is involved in the toxicity of HCB and that the aggravating effects of iron on HCB are mediated by lipid peroxidation.     

Placental abruption and subchorionic hemorrhage in the first half of pregnancy: US appearance and clinical outcome

In 30 pregnant patients who experienced vaginal bleeding between 10 and 20 weeks gestation, subchorionic hematomas were demonstrated on ultrasound examination. In 18 patients (60%), the margin of the placenta was separated from the uterine wall. In 15 patients the outcome was favorable (full-term delivery of normal infant) and in 15 patients the outcome was unfavorable (seven preterm births, four stillbirths, three spontaneous abortions, one therapeutic abortion). The major prognostic factor related to pregnancy outcome was the volume of the hematoma and, to a lesser extent, the relative volume of the hematoma (volume of hematoma divided by volume of gestational sac). For a volume less than 60 ml, the outcome tended to be favorable, and for a relative volume less than 0.4, the outcome tended to be favorable.     

Detection of multivessel disease after myocardial infarction using intravenous stress digital subtraction angiography

Forty-six patients with prior myocardial infarction underwent stress intravenous digital subtraction angiography (DSA) and coronary angiography. The left ventricular ejection fraction (EF) and wall-motion responses to exercise were correlated with the coronary anatomy. Twenty-five patients with single vessel disease showed essentially no change in left ventricular EF with exercise (a decrease from 66% to 64%), but those with multivessel disease (21 patients) had a significant decrease in left ventricular EF (from 59% to 48%) (P = .0001). A decrease in left ventricular EF had a sensitivity of 95% and specificity of 60% for the detection of multivessel disease, whereas an increase in wall-motion abnormality had a sensitivity and specificity of 72% and 71%, respectively. After myocardial infarction, a fall in left ventricular EF with stress intravenous DSA is highly sensitive for the detection of multivessel disease, but there are a number of false-positive results, resulting in only moderate specificity. A new wall motion abnormality has only a moderate sensitivity and specificity.     

Antibody response to phenolic glycolipid I in inbred mice immunized with Mycobacterium leprae.

The level of circulating antibody to phenolic glycolipid I of Mycobacterium leprae was determined in 18 inbred strains of mice after immunization with M. leprae organisms. By using a solid-phase radioimmunoassay with phenolic glycolipid I as test antigen, a continuous distribution of antibody levels ranging from high to low was observed. The level was found to be controlled by multiple genes, including both H-2 complex- and Igh allotype complex-linked genes. Low antibody response to phenolic glycolipid I was shown to be inherited as a dominant trait in three combinations of high X low responder F1 progeny.     

HLA-DRβIII and HLA-DP induce comparable proliferation in primary mixed lymphocyte culture

To study the stimulatory capacity of HLA-DRβIII in the mixed lymphocyte culture (MLC) assay, an MLC matrix between 13 Dw 18 homozygous typing cells (HTCs) was analysed. Six of these HTCs were positive for the HLA-DRβIII allele LB-Ql as defined by T cell clones. Seven HTCs were positive for LB-Q4. The MLC responses between Dw18 HTCs, matched for LB-Q, were significantly lower than the responses between the mismatched combinations. Considering the fact that HLA-DP can induce proliferation in MLC, we then analysed the DP matched and mismatched combinations separately. The influence of HLA-DRβIII mismatches was in our experiments comparable to the influence of mismatches for HLA-DP. Surprisingly, 15 out of 22 DRβIII and DP matched combinations still showed positive MLC reactions.