Assessment of endothelial dysfunction: the role of symmetrical dimethylarginine and proinflammatory markers in chronic kidney disease and renal transplant recipients.

OBJECTIVES: The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙-) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. MATERIALS AND METHODS: We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). RESULTS: Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙- to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙- had better screening performance than SDMA alone. CONCLUSIONS: Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.

Assessment of inflammation based on the release of oxygen radicals by granulocytes in chronic uncontrolled asthma / Avaliação da inflamação com base na liberação de radicais oxidantes por granulócitos na asma crônica não-controlada

Objetivo: Avaliar a liberação espontânea de ânion superóxidopor granulócitos de sangue periférico de pacientescomasma crônica não-controlada antes e após corticoterapia e de indivíduos sadios. Métodos: Foram estudados 32 pacientes entre 6 e 18 anos (média 12,04 anos) e 29 indivíduos sadios como grupo decomparação.Os pacientes oramagrupados de acordocomo volumeexpiratório forçado no primeiro segundo: grupo I, volume expiratórioforçado no primeiro segundo entre 60 e 80%, 19 pacientes; e grupo II, volume expiratório forçado no primeiro segundo = 60%, 13 pacientes. A liberação espontânea de superóxido por granulócitos, medida por espectrofotometria utilizando superóxido dismutase, foi avaliada nos pacientes antes e após o tratamento com prednisona por via oral e beclometasona, budesonida ou fluticasona administradas por via inalatória. Na análise estatística foramutilizados os testes de análise de variância, Tukey e de Wilcoxon.Resultados: Comparando-se a liberação de ânion superóxido por granulócitos dos pacientes asmáticos e indivíduos sadios observamosque a liberação foi maior nos asmáticos não-controladosdo grupo II (p < 0,05). Avaliando-se a liberação de superóxido pelas células dos pacientes antes e após a terapiacomcorticosteroideuma diminuição significativa foi observada apenas no grupo I. Conclusão: O impacto dos glicocorticoides sobre a modulação da inflamação ocorreu nos indivíduos asmáticos não-controlados com volume expiratório forçado no primeiro segundo entre 60 e 80%.Naqueles com volume expiratório forçado no primeiro segundo = 60não foi observada essa modulação, havendo necessidade de mais estudos para avaliar o impacto de tal achado nos pacientes asmáticos.

Objective: To evaluate spontaneous release of superoxide anion by peripheral blood granulocytes of atopic patients with uncontrolled asthma undergoing glucocorticoid therapy and of healthy subjects. Methods: We studied 32 patients, aged 6 to 18 (mean 12.04), and 29 healthy subjects as a comparative group. Patients weregrouped according to the forced expiratory vital capacity in the firstsecond. Group I, forced expiratory vital capacity in the first second of between60and80%,had 19 patients, and group II, forced expiratoryvital capacity in the first second=60%,had 13 patients. Spontaneous superoxide release by granulocytes was measured by aspectrophotometer method based on superoxide dismutase, before and after oral prednisone and beclomethasone, budesonide or fluticasone inhaled therapy. Statistical analyses were performed using ANOVA, Wilcoxon and Tukey tests. Results: Comparing the superoxide anion release bygranulocytes of asthmatic patients and healthy subjects,weobserved a higher release by cells of the uncontrolled patient group II (p < 0.05). Evaluating the superoxide release by cells of asthmatic patients before and after steroid therapy, a significant decrease was found only in patient group I.Conclusion: The impact of corticosteroids on inflammatorymodulation occurred in the uncontrolled asthmatics with forced expiratory vital capacity in the first second between 60 and 80%. In those with forced expiratory vital capacity in the first second of = 60%, this findingwas not observed. Further studies are necessary to evaluate the effect of this finding on asthmatic patients.

Assessment of inflammation based on the release of oxygen radicals by granulocytes in chronic uncontrolled asthma.

OBJECTIVE: To evaluate spontaneous release of superoxide anion by peripheral blood granulocytes of atopic patients with uncontrolled asthma undergoing glucocorticoid therapy and of healthy subjects. METHODS: We studied 32 patients, aged 6 to 18 (mean 12.04), and 29 healthy subjects as a comparative group. Patients were grouped according to the forced expiratory vital capacity in the first second. Group I, forced expiratory vital capacity in the first second of between 60 and 80%, had 19 patients, and group II, forced expiratory vital capacity in the first second = 60%, had 13 patients. Spontaneous superoxide release by granulocytes was measured by a spectrophotometer method based on superoxide dismutase, before and after oral prednisone and beclomethasone, budesonide or fluticasone inhaled therapy. Statistical analyses were performed using ANOVA, Wilcoxon and Tukey tests. RESULTS: Comparing the superoxide anion release by granulocytes of asthmatic patients and healthy subjects, we observed a higher release by cells of the uncontrolled patient group II (p < 0.05). Evaluating the superoxide release by cells of asthmatic patients before and after steroid therapy, a significant decrease was found only in patient group I. CONCLUSION: The impact of corticosteroids on inflammatory modulation occurred in the uncontrolled asthmatics with forced expiratory vital capacity in the first second between 60 and 80%. In those with forced expiratory vital capacity in the first second of = 60%, this finding was not observed. Further studies are necessary to evaluate the effect of this finding on asthmatic patients.

Harvesting the noncirculating pool of polymorphonuclear leukocytes in rats by hetastarch exchange transfusion (HET): yield and functional assessment.

Isolation of polymorphonuclear leukocytes (PMN) provides an opportunity to study PMN activity in vitro and to label PMN for study of in vivo kinetics. However, simple phlebotomy (SP) of a small animal frequently yields too few PMN for in vitro handling, while PMN harvested from an induced-peritonitis may not accurately reflect PMN in a less stimulated state. We report a novel method of harvesting PMN from the circulation of rats, using hetastarch exchange transfusion (HET), which is both time and animal sparing. HET harvested 8-fold more PMN than SP. In vitro cell function was examined with assays of adherence, chemotaxis, bacterial killing, and superoxide generation. No significant (p less than 0.05) difference was found between PMN obtained by HET and pooled-PMN obtained by SP. In vivo function was examined following labeling with indium111-oxine. The kinetics pattern described suggested normal migratory activity when compared to previous reports. The data demonstrate that rats possess a relatively large, noncirculating pool of PMN which is readily accessible by HET.