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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

At least 145 records · Page 8Linked to original sources
PubMed1997

Severe haemorrhagic diathesis in an adult patient with cystic fibrosis after long-term antibiotic treatment of pulmonary infection.

We describe the case of a 22 yr old male patient with cystic fibrosis, who, after long-term antibiotic treatment of pulmonary infection, developed a haemorrhagic diathesis with severe bleeding from the mucus membrane of the mouth, and haematuria. Rapid recovery was observed after infusion of vitamin K. During 8 months of follow-up, no evidence of recurrence of the clotting disturbances and anaemia were noted. The combination of impaired absorption of vitamin K due to underlying disease with the antibiotic-induced suppression of vitamin K synthesis by intestinal bacteria could be a possible explanation for this disorder.

Adult↗
PubMed1997

The newly synthetized pyridobenzoxazocynone inhibits HIV-1 reverse transcriptase activity.

We synthetized pyridobenzoxazocynone that differs in the enlarged eight-membered heterocyclic system from the basic structure of pyridobenzoxazepinones a known class of non-nucleoside HIV-1 reverse transcriptase inhibitors. Pyridobenzoxazocynone hydrochloride was found to inhibit HIV-1 reverse transcriptase activity. At concentration 0.35 microM the enzyme activity decreased by 64 +/- 14%. Higher concentrations of pyridobenzoxazocynone hydrochloride completely abolished the enzyme activity expressed as radioactivity of acid insoluble products. These results suggest that pyridobenzoxazocynones may represent a new class of HIV-1 reverse transcriptase inhibitors.

Gene Products, pol↗
PubMed1996

Effect of substance P and its precursor alpha-protachykinin on intracellular free calcium concentration in human polymorphonuclear leukocytes.

The increase in intracellular free calcium concentration is an important step in signal transduction leading to phagocyte activation. The undecapeptide substance P can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, phagocytosis, and respiratory burst. In this study we investigated the ability of low-concentration (that can occur in vivo) substance P (10(-7) M) and its precursor alpha-protachykinin (3 x 10(-7) M) to increase the intracellular free calcium concentration in human polymorphonuclear leukocytes. Cells isolated from ten healthy donors were incubated with substance P or alpha-protachykinin in 1 mM calcium medium for 5 min and the intracellular free calcium concentration was monitored using the fluorescent calcium indicator Fura-2am. Polymorphonuclear leukocytes from 40% of donors responded to both agonists. The substance P- and alpha-protachykinin-induced increase in intracellular free calcium concentration was 59 +/- 13 nM and 58 +/- 12 nM and the extracellular calcium influx contributed to 87 +/- 8% and 54 +/- 8% of the calcium response, respectively. alpha-Protachykinin released almost all the calcium from intracellular stores, while substance P mobilized only 24 +/- 5% of this calcium pool. Finally, cells that responded to a single challenge with substance P and alpha-protachykinin were able to increase their intracellular free calcium concentration in response to each of three consecutive stimulations with these agonists. This may be an additional mechanism by which substance P and its precursor modify the function of human polymorphonuclear leukocytes.

Calcium↗
PubMed1996

Comparison of PAF- and fMLP-induced [Ca2+]i transients in human polymorphonuclear leukocytes.

Changes of [Ca2+]i in human polymorphonuclear leukocytes (PMNL) were studied. PMNL suspension was activated three times every 5 min with 10(-7) M PAF and fMLP. Both PAF and fMLP, induced three consecutive [Ca2+]i transients in PMNL suspended in medium with 1 mM Ca2+. The first Ca2+ response was a result of Ca2+ release from internal stores and the extracellular Ca2+ influx, while the second and third responses were completely dependent on Ca2+ influx from extracellular space. The contribution of Ca2+ from intracellular stores to the first PAF-induced Ca2+ response was about 1.4-fold lower in comparison with the first fMLP induced Ca2+ response (27 +/- 1 vs 37 +/- 6% (p < 0.05). Previous addition of PAF enhanced 3-fold (p < 0.001) the PMNL response to fMLP while cells pretreated with fMLP failed to increase their [Ca2+]i after challenge with PAF. PMNL from 40% of donors did not respond to PAF in the presence of 100 nM Ca2+. However, the cells responding to PAF as the cells treated with fMLP or cyclopiazonic acid released almost the entire Ca2+ from intracellular stores after challenge. Subtraction of mean [Ca2+]i transients in the presence of 100 nM Ca2+ from that obtained in medium with 1 mM Ca2+ showed that, in PMNL stimulated with PAF in contrast to the cells treated with fMLP, the onset of Ca2+ influx from extracellular space precedes Ca2+ release from intracellular stores. These results suggest that PAF-induced Ca2+ influx from extracellular space is at least partly independent of Ca2+ release from intracellular stores.

Blood Coagulation Factors↗
PubMed1996

The effect of ozone exposure on allergen responsiveness in subjects with asthma or rhinitis.

The aim of this study was to determine whether ozone enhances bronchial responsiveness to allergens in subjects with allergic asthma, or facilitates a bronchial response in subjects with allergic rhinitis. Twenty-four subjects with mild stable allergic asthma, 12 subjects with allergic rhinitis without asthma, and 10 healthy subjects participated in the study. Subjects breathed 250 ppb ozone or filtered air (FA) for 3 h of intermittent exercise. Airway responsiveness to methacholine was determined 1 h before and after exposures, and allergen responsiveness 3 h after exposures. We determined the concentration of methacholine (PC20FEV1) and the dose of allergen (PD20FEV1) producing a 20% fall in FEV1. In the subjects with asthma, FEV1 decreased by 12.5 +/- 2.2% (mean +/- SEM; p = 0.0001), PC20FEV1 of methacholine by 0.91 +/- 0.19 doubling concentrations (p = 0.0001) and PD20FEV1 of allergen by 1.74 +/- 0.25 doubling doses (p < 0.0001) after ozone compared with FA. The changes in lung function, methacholine, and allergen responsiveness did not correlate with each other. In the subjects with rhinitis, mean FEV1 decreased by 7.8% and 1.3% when ozone or FA, respectively, were followed by allergen inhalation (p = 0.035). Therefore, our data suggest that short-term exposure to ozone can increase bronchial allergen responsiveness in subjects with mild allergic asthma or rhinitis.

Adult↗
PubMed1996

Increased content of hydrogen peroxide in the expired breath of cigarette smokers.

Cigarette smoking causes an influx of mononuclear phagocytes and polymorphonuclear leucocytes into the lower airways. These cells have altered oxygen metabolism and release more H2O2 than phagocytes from nonsmokers. In this study, we intended to determine whether asymptomatic cigarette smokers exhale more H2O2 than healthy nonsmokers. The content of H2O2 in the expired condensate of 27 nonsmokers and 33 cigarette smokers was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 level in the expired breath condensate of all cigarette smokers was about fivefold higher than that found in the whole nonsmoker group (0.24 +/- 0.32 versus 0.05 +/- 0.11 nM). However, only 16 smokers (49%) and 6 nonsmokers (22%) had detectable levels of H2O2 in expired breath that reached values 0.49 +/- 0.28 and 0.23 +/- 0.10 nM, respectively. Although the cigarette smoking status was similar for both male and female smokers, females expired 2.5 fold less H2O2 than males (0.15 +/- 0.24 (n = 21) versus 0.38 +/- 0.39 (n = 12) nM. No correlation was found between expired H2O2 levels and cigarette smoking status expressed as the daily cigarette consumption, cumulative cigarette consumption and urinary cotinine concentration. It is suggested that in some smokers, expressed H2O2 can be a noninvasive marker of oxidant overload in the lower airways related to cigarette smoking.

Adult↗
PubMed1996

Prevalence of respiratory symptoms, bronchial hyperresponsiveness and atopy among adults: west and east Germany.

The prevalence of respiratory symptoms, atopic sensitization and bronchial hyperresponsiveness was compared in a random sample of adults, 20-44 yrs of age, in two cities in West and East Germany, Hamburg and Erfurt, respectively. There were much higher levels of outdoor air pollution due to sulphur dioxide and suspended particulates in Erfurt, and major differences in living conditions during the last 40 yrs. Within the European Respiratory Health Survey, a short questionnaire was answered by 3,156 (80% response rate) subjects in Hamburg and 3,272 (74%) in Erfurt. A subset of responders to the short questionnaire completed a long questionnaire, spirometry, methacholine or bronchodilator test, skin test, and total and specific immunoglobulin E (IgE) measurements, with a total number of 1,159 participants in Hamburg and 731 in Erfurt. Six out of 8 questions on respiratory symptoms and diagnoses were answered in the affirmative more frequently in Hamburg than in Erfurt. In Hamburg, mean forced expiratory volume in one second (FEV1)% of predicted was 105 vs 107% in Erfurt (p < 0.0001), and bronchial hyperresponsiveness was more frequently observed in Hamburg than in Erfurt (25 vs 19%; p < 0.05). Atopic sensitization was more prevalent in Hamburg than in Erfurt regarding the results of skin tests against grass pollen (24 vs 19%; p < 0.05), birch pollen (19 vs 8%; p < 0.0005), cat (10 vs 2%; p < 0.0005), and Dermatophagoides pteronyssinus (14 vs 10%; p < 0.05). This was reflected by the prevalences of positive specific IgE values, which were higher in Hamburg than in Erfurt for grass (26 vs 20%; p < 0.05), birch (20 vs 10%; p < 0.0005) and cat (12 vs 8%; p < 0.05). In Hamburg, compared to Erfurt, there was: a lower mean number of siblings (p < 0.005); a higher degree of childhood and current exposure to environmental tobacco smoke (p < 0.005); and a higher frequency of fitted carpets and reported mould or mildew inside the house (p < 0.005). Therefore, these data may support the hypothesis that childhood factors and exposure to indoor allergens and irritants may have been more relevant for the development of asthma and atopy than the potential long-term exposure to high concentrations of sulphur dioxide and particulate matter.

Adult↗
PubMed1996

[Bronchial asthma--a cost of illness analysis].

We performed an economic evaluation of the costs of asthma in Germany. Estimates of direct medical expenditures and indirect costs were derived from official health statistics of 1992. Adding up direct and indirect costs, the total sum is approximately 2.66 billions ECU which is equivalent to 5.13 billions DM or 3.11 billions US-$, respectively, for a total population of 80.3 millions. Direct costs make up 61.5% of this sum and comprise of outpatient medical care, drugs, hospital treatment, rehabilitation and compensation for occupational asthma as well as sickness benefits. Indirect costs of 38.5% are caused by payments for days off work, premature retirement and premature death due to asthma. Based on these figures, we speculate that an optimised treatment according to published recommendations should be accompanied by a reduction of the high amount of indirect costs.

Asthma↗
PubMed1996

Changes of serum concentration of lipid peroxidation products in patients with pneumonia.

During lower respiratory tract infection, massive influx and activation of phagocytes is observed. Reactive oxygen species (ROS) released by macrophages and polymorphonuclear neutrophils (PMNs) kill microorganisms and cause damage to host tissues. One feature of this damage may be enhanced lipid peroxidation. Therefore, the aim of this study was to estimate the serum concentration of lipid peroxidation products in combination with clinical and biochemical indicators of inflammation in 32 patients with pneumonia. Serum concentration of lipid peroxides (CLP) and malondialdehyde (CMDA) was measured at Day 1, 4, 10 and 14 of observation, whilst chest radiography and routine blood analysis were performed at Day 1 and 14 during a 2 week treatment of lower airway infection. The CLP decreased during treatment (p < 0.05) from 0.059 +/- 0.024 to 0.043 +/- 0.017 (A532 nm) and the CMDA (p < 0.05) from 3.5 +/- 1.4 to 2.8 +/- 1.3 nmol.mL-1. A negative correlation between CLP and radiological regression (r = 0.49) and a drop in white blood cell count (WBC) (r = 0.39) was observed during the treatment. A positive correlation between CMDA and serum trypsin inhibitory capacity (STIC) (r = 0.47) and erythrocyte sedimentation rate (ESR) (r = 0.43) was found. Our data indicate that an enhanced process of lipid peroxidation occurs during pneumonia and that serum concentration of lipid peroxides returns to normal values quicker than the concentration of malondialdehyde during recovery. The use of antioxidants is suggested as an adjuvant treatment in patients with pneumonia.

Adult↗
PubMed1995

Metopon and two unique derivatives: affinity and selectivity for the multiple opioid receptors.

5 beta-Methyl-7,8-dihydromorphinone (metopon), an isomer [6aS-(6a alpha,9a alpha, 10 beta)13aS]-1,10-methano-4-hydroxy-11-methyl- 6,6a,8,9,10,11,12,13-octahydro-[1]-benzopyrano[4,3,e]isoquinoline- 7-(9aH)-one (compound 1) derived from a photochemical rearrangement of 5 beta-methylmorphinone, and [6aS-(6a alpha,9a alpha,10 beta)13aS]-1,10-methano-4-hydroxy-11-methyl- 6,6a,8,9, 10,11,12,13-octahydro-[1]-benzopyrano[4,3,e]-14 beta- (p-nitrocinnamoylamino) isoquinoline-7-(9aH)-one (compound 2) were characterized for opioid receptor affinity, selectivity and analgesic properties. In competition binding assays using bovine striatal membranes, the three compounds inhibited the binding of 0.25 nM [3H][D-Ala2,(Me)-Phe4,Gly(ol)5]enkephalin (DAMGO), a mu-selective peptide, with IC50 values less than 5 nM. All three compounds exhibited lower affinity for delta- and kappa-opioid receptors. In the mouse 55 degrees C warm-water tail-flick assay, both metopon and compound 1 displayed antinociception that lasted for 60 min after i.c.v. injection. Morphine sulfate, metopon and compound 1 produced 50% antinociception with i.c.v. doses of 0.83, 2.0 and 4.0 nmol, respectively. The mu-selective, irreversible opioid receptor antagonist beta-funaltrexamine blocked antinociception induced by metopon and compound 1, while delta- and kappa-opioid receptor selective antagonists did not effect antinociception. These findings demonstrate metopon and its isomer bound with high affinity to the mu-opioid receptor and produced antinociception through this receptor.

Analgesics, Opioid↗
PubMed1995

Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes.

In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized. The BAL fluid of nine patients with histologically proven isolated pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.

Adult↗
PubMed1995

Short term effect of methotrexate in severe steroid-dependent asthma.

The steroid-sparing capacity of methotrexate in asthmatics is still being debated. The present study was undertaken to evaluate the effect of low-dose methotrexate on steroid consumption in patients with severe asthma, who require very high doses of systemic corticosteroids. We conducted a randomized, double-blind, parallel clinical trial in 24 patients with long-standing asthma. After a 3-week run-in period, patients received a 16-week course of either 15 mg of oral methotrexate weekly or matched placebo in addition to their previous asthma therapy. The daily steroid dose (at run-in 30 +/- 14 mg/day in the methotrexate group; 25 +/- 9 mg/day in the placebo group (NS)) decreased by 24% in the methotrexate group (p < 0.01) and by 5% in the placebo group (NS) during weeks 9-16 of the treatment period when compared with run-in values. However, there was no difference in steroid consumption between the two groups at any time. We conclude that in patients with severe asthma who require very high doses of systemic corticosteroids, short-term treatment with methotrexate allows only a marginal steroid reduction. Our study does not support the use of methotrexate as a steroid-sparing agent in asthmatics.

Administration, Oral↗
PubMed1995

Effect of cytochalasin B on intracellular free calcium concentration in human polymorphonuclear leukocytes after repeated stimulation with n-formyl-methionyl-leucyl-phenylalanine.

Cytochalasin B can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, lysosomal enzyme release, and reactive oxygen species generation. In this study we investigated the effect of cytochalasin B on the increase in intracellular free calcium concentration after three consecutive additions of 10(-7) M N-formyl-methionyl-leucyl-phenylalanine. The interval between stimulations was 5 min. Intracellular free calcium concentration was monitored using the fluorescent calcium indicator FURA-2AM. Cytochalasin B (3.3 micrograms/ml) added 60 s before the cell stimulation enhanced all three polymorphonuclear leukocyte calcium responses by increasing the N-formyl-methionyl-leucyl-phenylalanine-induced calcium influx from the extracellular space. Cytochalasin B increased the peak intracellular free calcium concentration and elevated the plateau phase level, but had no influence on its shape. In addition, pretreatment with cytochalasin B of polymorphonuclear leukocytes suspended in low calcium medium restored their capacity to respond to a third stimulation with N-formyl-methionyl-leucyl-phenylalanine. Finally, in resting cells cytochalasin B caused a moderate increase in intracellular free calcium concentration which was independent of extracellular calcium.

Adult↗
PubMed1995

Ambroxol inhibits doxorubicin-induced lipid peroxidation in heart of mice.

A single intravenous injection of doxorubicin (DOX, 30 mg/kg body weight) caused a significant rise in the content of lipid peroxidation products in hearts of mice. The concentration of conjugated dienes (CD) and malondialdehyde (MDA) found 24 h after injection of DOX increased about 1.8- and 2.4-fold and reached values of 11.31 +/- 2.24 A233/g and 3.72 +/- 0.40 mumol/g, respectively. The same dose of 4'-epi-doxorubicin (EPI), a less cardiotoxic epimer of DOX, increased only the heart level of MDA. Both antracyclines were not able to induce increased formation of CD in murine liver and lungs. Ambroxol, an expectorant drug which possesses the ability to scavenge hydroxyl radicals, injected intravenously (70 mg/kg) 30 min prior to DOX, completely abolished the rise in heart content of CD and MDA. The heart levels of CD and MDA in animals treated with ambroxol and DOX were 3 and 2.7 times lower than those observed in mice treated with water and DOX, respectively. Ambroxol had no effect on DOX- and EPI-induced formation of MDA in the lungs. Our results indicate that (1) DOX is a more powerful inductor lipid peroxidation in the heart than EPI; and (2) ambroxol may be useful in preventing lipid peroxidation in the heart caused by DOX.

Ambroxol↗