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Biomedical subjects

P Entzian

Publications and source records attributed to P Entzian.

17 recordsLinked to original sources
PubMed1997

Antiinflammatory and antifibrotic properties of colchicine: implications for idiopathic pulmonary fibrosis.

The ancient drug colchicine has repeatedly been proposed as a novel drug for therapy of pulmonary fibrosis. The present study was undertaken to add to the knowledge on colchicine's antiinflammatory and antifibrotic properties and thus help determine its actual rank in the treatment of pulmonary fibrosis. In vitro cell culture experiments with stimulated and unstimulated normal donor peripheral blood mononuclear cells (PMNC) and a human lung fibroblast cell line (WI-38) were used to determine the effects of colchicine on PMNC cytokine release (interleukin-6 and tumor necrosis factor-alpha) as well as on fibroblast proliferation and collagen synthesis rates. Reverse transcriptase polymerase chain amplifications of alpha 1 (III) collagen were done to detect collagen messenger ribonucleic acid (mRNA) expression. Colchicine did not significantly modulate tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release of PMNC. Colchicine inhibited fibroblast proliferation and total collagen synthesis significantly at concentrations obtainable in serum in vivo. Transcription of the alpha 1 (III) collagen gene into mRNA continued under colchicine. We conclude that colchicine is a potent in vitro inhibitor of fibroblast functions in terms of proliferation and collagen synthesis. The mechanism of collagen inhibition is more likely an inhibition of cellular collagen secretion than a switch off of collagen mRNA transcription. On the other hand, although colchicine is known to inhibit many leukocyte functions, it is a poor inhibitor of cytokines known to be important for fibrogenesis (e.g. IL-6, TNF-alpha, IL-1, platelet-derived growth factor, and transforming growth factor-beta). This makes colchicine, at least from a theoretical standpoint and as concluded from in vitro studies, a preferable candidate for a combined therapeutic strategy.

Cells, Cultured↗
PubMed1997

Pentoxifylline in treatment of sarcoidosis.

The optimal therapy for sarcoidosis remains unclear. Most patients show a short-term response to corticosteroid therapy, but they have to face the risk of significant side effects. Because tumor necrosis factor alpha (TNF) plays a critical role in granuloma formation and sustenance as well as in the progression of sarcoidosis, we investigated pentoxifylline (POF), which exerts TNF-inhibitory activity, as a therapeutic agent in active pulmonary sarcoidosis. Twenty-three previously untreated patients with documented disease progression during the preceding 3 mo were treated with POF (25 mg/kg daily) and followed for 6 mo of therapy. Two patients were lost to follow-up, and three patients discontinued POF therapy because of gastrointestinal side effects; 18 patients were thus evaluated. Eleven patients improved, seven remained stable and, most importantly, none deteriorated. Lung function tests-DL(CO), Pa(O2) and Pa(O2)[exercise]-were significantly improved in the patient group as a whole and increased in a highly significant manner in those who improved. Three patients with corticosteroid-resistant disease progression were additionally treated with a combination of corticosteroids with POF. In all three patients the combination therapy resulted in an immediate complete decrease of disease activity, even after tapering prednisone to 7.5 mg daily or tapering off corticosteroids. These promising results suggest that POF may improve therapeutic regimens in pulmonary sarcoidosis either by sparing or replacing corticosteroids.

Adult↗
PubMed1997

[Pentoxifylline inhibits experimental bleomycin-induced fibrosing alveolitis].

Therapy of idiopathic pulmonary fibrosis (IPF) is directed at 1) inhibition of alveolitis and tissue damage, and 2) inhibition of matrix deposition. We and others have identified pentoxifylline (POF) as a promising drug in achieving these aims. For further clarification, we established a model of bleomycin-induced fibrosing alveolitis. Fisher 344 rats (n = 7 per group) were given bleomycin intratracheally once (0.7 U/100 g bw) and treated with POF (1.5 or 3 mg/kg bw per day i.p.), prednisolone (15 mg/kg bw i.m. per day), or sodium chloride solution (NaCL). The extent of inflammatory reactions was determined after 8 days by differentiation of cells of broncho-alveolar lavage (BAL) and by quantification of proliferating cells in lung interstitium subsequent to staining of the Ki-67 antigen. POF inhibited neutrophil alveolitis in BAL and reduced the amount of proliferating cells in the lungs significantly while prednisolone and NaCL did not. Both POF and prednisolone exerted a positive influence on postoperative weight loss as well as on lung weight increase subsequent to bleomycin instillation. The postoperative body weight loss and the lung weight increase after bleomycin instillation are most likely due to an inflammatory reaction subsequent to operation and bleomycin deposition. Tumor necrosis factor alpha (TNF-alpha) has been shown to be a key cytokine in bleomycin-induced fibrosing alveolitis as well as in IPF; it also exerts catabolizing effects. Since both POF and prednisolone are known to effectively inhibit proinflammatory cytokines and, among those, TNF-alpha, nonspecific antiinflammatory effects probably explain the benefits. Additionally, however, this study proved POF to be more effective in inhibition of BAL neutrophils and number of proliferating cells in lung interstitium. Further, it has been shown that POF, but not prednisolone, inhibits activation of neutrophil granulocytes and formation of reactive oxygen species. Thus we believe that the mechanism of action of xanthines might contribute to therapy of IPF. For further clarification, a prospective clinical study of POF in IPF therapy has been initiated.

Animals↗
PubMed1996

Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines.

Several cytokines exhibit a high degree of temporal regulation as well as somnogenic potency (e.g., interleukin-1 [IL-1], tumor necrosis factor-alpha [TNF-alpha]). Seeking the underlying cause of obstructive sleep apnea syndrome (OSAS), we investigated whether circadian rhythms of cytokine release were altered in 10 patients with OSAS. Ten healthy volunteers served as the control population. Seven of the 10 OSAS patients were reexamined after 3 mo of therapy with nasal continuous positive airway pressure (nCPAP) mask ventilation. Circadian cytokine release (IL-1, IL-6, gamma-interferon [gamma-IFN], TNF-alpha) was investigated ex vivo by short-term culture of blood samples. The circadian rhythm of TNF-alpha release was significantly disturbed in OSAS patients: nocturnal physiologic peaks in this cytokine had almost disappeared and an additional daytime peak had developed. Circadian variations in IL-1, IL-6, and gamma-IFN, and in the immunoregulatory hormones melatonin and cortisol, did not differ from those in the controls. Because TNF-alpha is a known modulator of sleep, and nCPAP therapy did not normalize TNF rhythms, we assume that TNF-alpha could well play a pathophysiologic role in OSAS. Further studies should be directed at whether a physiopathologic and/or pathogenic link exists between TNF-alpha and OSAS.

Adult↗
PubMed1995

Common CFTR mutations are not likely to predispose to chronic bronchitis in northern Germany.

The frequency of six common mutations in the cystic fibrosis transmembrane conductance regulator gene was studied in 100 patients hospitalized with chronic bronchitis. Only one patient with chronic bronchitis and diffuse bronchiectasis was heterozygous for the common delta F508 mutation. R553X, G542X, G551D, N1303K and 621 + 1G-->T were not detected. This result is not significantly different from the frequency of cystic fibrosis carriers in Northern Europe. Predisposition of heterozygotes for chronic bronchitis is therefore unlikely.

Aged↗
PubMed1995

Frequency of common cystic fibrosis gene mutations in chronic bronchitis patients.

It has been suggested that the delta F508 deletion, the most common mutation in the cystic fibrosis (CF) gene, might be linked to chronic bronchial hypersecretion. We investigated whether such an association could be found in chronic bronchitis, since chronic bronchial hypersecretion is an important and specific element of chronic bronchitis. We screened 100 patients hospitalized for chronic bronchitis with six of the most frequently occurring CF gene mutations: delta F508, R553X, G542X, G551D, N1303K, and 621-1G-->T. Only one patient affected by chronic bronchitis and diffuse bronchiectasis was heterozygous for the deletion delta F508; no other mutations were found. This is not significantly different from the expected frequency of CF carriers in northern Europe, which is 1 in 25. Thus, no association between the most commonly occurring cystic fibrosis genes and chronic bronchitis is likely to exist and routine screening of patients without further signs of cystic fibrosis would seem to be of no benefit in northern Europe.

Aged↗
PubMed1992

A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction.

A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure. Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand. This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably. Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful' disease. On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again. This result fits well into the general observation of stress-induced down-regulation of immune responses.

Aged↗
PubMed1990

Determination of serum concentrations of type III procollagen peptide in mechanically ventilated patients. Pronounced augmented concentrations in the adult respiratory distress syndrome.

Type III procollagen peptide (PCP) is a byproduct of type III collagen synthesis and a potential marker of collagen secretion. In chronic diffuse interstitial lung diseases, elevated PCP concentrations have been found in serum as well as in bronchoalveolar lavage fluid. It has been proposed that PCP is a marker of early, active stages of fibrosis. As severe fibrosis is a frequent complication in adult respiratory distress syndrome (ARDS), we investigated PCP in patients with ARDS and compared the results with those from patients requiring mechanical ventilation because of heart failure and after neurosurgical and surgical interventions, and those from spontaneously breathing patients, including healthy volunteers and patients with pneumonia, liver cirrhosis, and renal failure. PCP concentrations in patients with ARDS were extremely elevated compared with those in control subjects (p less than 0.001) and correlated positively with FiO2 (r = 0.71, p less than 0.01). These results support the pathophysiologic concept of early fibrogenesis in ARDS. As preventing pulmonary fibrosis in ARDS is essential in improving survival rate, we believe PCP can be a valuable diagnostic tool in ARDS.

Adult↗
PubMed1990

[Interstitial lung fibrosis in rheumatoid arthritis--comparison of lung function and bronchoalveolar lavage].

In fibrosing alveolitides that are associated with rheumatoid arthritides, the BAL fluid reveals a characteristic cell pattern. These cellular changes occur at an earlier date than do the radiological signs of pulmonary fibrosis. Together with a measurement of the CO diffusion capacity, BAL is a suitable monitoring parameter for fibrosing alveolitides in rheumatoid arthritis.

Aged↗
PubMed1988

Increased release of free oxygen radicals by phagocytosing and nonphagocytosing cells from patients with active pulmonary sarcoidosis as revealed by luminol-dependent chemiluminescence.

Oxidative metabolism in phagocytes such as granulocytes, monocytes, and alveolar macrophages is becoming of increasing interest in efforts to determine the pathogenetic mechanisms in diseases related to tissue damage, e.g., sarcoidosis. The release of free oxygen radicals is dependent on the activation of the oxidative metabolism and can be measured by means of chemiluminescence. Basic luminol-dependent chemiluminescence released by monocytes and alveolar macrophages from 12 patients with untreated pulmonary sarcoidosis stage II was increased (p less than 0.01) compared with 12 control subjects. A less distinct difference could be observed in the chemiluminescence response of granulocytes (P less than 0.05). After stimulation with zymosan, alveolar macrophages and monocytes (P less than 0.01) as well as granulocytes (P less than 0.05) had an enhanced luminol-dependent chemiluminescence compared with the control group. Emission of chemiluminescence by alveolar macrophages was considerably lower than that of granulocytes and monocytes. No significant correlation could be demonstrated between chemiluminescence response of granulocytes and monocytes and cellular markers of sarcoidotic activity such as lymphocytosis in bronchoalveolar lavage and T-helper/T-suppressor ratio in the lavage fluid. In contrast to that, a significant correlation (P less than 0.01) could be observed both between nonstimulated chemiluminescence and stimulated chemiluminescence and lymphocytosis and T-helper/T-suppressor ratio in bronchoalveolar lavage. Enhanced chemiluminescence may indicate inflammatory activation in pulmonary sarcoidosis.

Adult↗
PubMed1987

Heart failure and airway obstruction.

We investigated 60 patients with severe left-sided heart failure before and after cardiac recompensation. We observed that the cardiac insufficiency had a marked effect on dynamic ventilatory parameters. The "effort independent part" of the flow-volume curve was changed significantly by means of cardiac therapy.

Airway Obstruction↗
PubMed1987

Modulation of oxygen-free radicals from human leukocytes during halothane- and enflurane- induced general anesthesia.

Oxidative metabolism correlates with the release of microbiocidal oxygen-free radicals, measured as luminol-dependent chemiluminescence. The effect of general anesthesia on the oxidative metabolism of human leukocytes was investigated. Sixteen patients undergoing a halothane-induced general anesthesia and 14 patients receiving an enflurane-induced general anesthesia participated in the study. Halothane-induced anesthesia was accompanied both by a suppression of basic chemiluminescence and by a decrease in chemiluminescence during the phagocytosis of zymosan A. This was monitored 15 min, 30 min and 60 min after starting general anesthesia and compared to the level of chemiluminescence before starting general anesthesia. Ninety minutes after finishing general anesthesia, a significant recovery of chemiluminescence was seen to exceed the level before general anesthesia. Comparable findings were observed with enflurane-induced general anesthesia, suggesting a decreased release of oxygen-free radicals during general anesthesia, and afterwards an increase exceeding the initial level.

Adolescent↗