Biomedical subjects

U Heinrich

Publications and source records attributed to U Heinrich.

At least 37 records · Page 2Linked to original sources

PubMed1998

Ligand blot analysis of insulin-like growth factor-binding proteins using biotinylated insulin-like growth factor-I.

A nonradioactive method for the detection of insulin-like growth factor-binding proteins (IGFBPs) was developed utilizing human recombinant insulin-like growth factor-I (IGF-I) biotinylated with N-hydroxysuccinimido-biotin. Human plasma samples were separated by 15% SDS polyacrylamide gel electrophoresis, and proteins were transferred to nitrocellulose by Western blotting. The nitrocellulose sheets were incubated overnight with IGF-I-biotin at 4 degrees C. The next day streptavidin-peroxidase was added for 1 h, and IGFBPs were visualized by an enhanced chemiluminescence system. Five characteristic bands with molecular weights of 41 and 39 (IGFBP-3), 34 (IGFBP-2), 30 (IGFBP-1) and 24 kD (IGFBP-4) were detected. Binding was specific for IGFs, since unlabeled IGF-I inhibited IGF-I-biotin binding. IGFBP ligand blots with biotinylated IGF-I and (125)I-IGF-I yielded comparable results. The suitability of the new assay for clinical purposes was demonstrated by several clinical examples. In summary, a rapid, reliable, nonradioactive assay for qualitative analysis of IGFBPs has been developed.

Adult↗

PubMed1998

North Baden venous lysis trial (NBVL): multicentre prospective randomized phlebographically controlled trial on the effect of ultra-high versus conventional doses of streptokinase in fresh leg-pelvis venous thromboses.

Since no previous randomized comparison has been carried out between ultra-high and conventional dosage streptokinase therapy of fresh venous thromboses, the NBVL trial was carried out as a prospective, randomized, multicentre, phlebographically monitored comparison of the results and adverse effects of these two fibrinolytic treatment options. Using the normal exclusion criteria, 156 patients with a leg-pelvis venous thrombosis presumed to be a maximum of 14 days old were treated with 1.5 million U streptokinase/h for 6h daily (n = 77, group A) or conventional dosage with 100,000 U streptokinase per hour (n = 79, group B). There were 15 patients (eight in group A, seven in group B) who had to stop therapy prematurely, and eight patients (five in group A, three in group B) could not be evaluated because of incorrect monitoring times. The phlebograms were evaluated using IFP-C scores. These showed a reduction in the IFP score from 4.55 to 2.2 in the 64 patients in group A after a mean of 2.7 +/- 0.6 therapy cycles with administration of 24.4 +/- 5.7 million U streptokinase, i.e. 47% of the baseline value. The 69 patients in group B had a reduction in score from 4.2 to 2.93 after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million units, i.e. a fall of 30% in the baseline values (p = 0.007). There were 132 out of 281 completely occluded venous segments in group A (47%) and 81 out of 279 segments in group B (29%) that showed complete patency. Eight out of 27 three-segment occlusions in group A and only one of 26 in group B showed complete patency. The IFP score improved by 55% in the 45 men in group A, compared with only 30% in the 47 men in group B (p = 0.002). When both dosages are combined, men showed a greater improvement in IFP score than women (42 versus 29%; p = 0.02). The IFP score improved more in the 20 patients aged more than 60 years in group A than in the 19 patients aged over 60 years of age in group B (61 versus 20%; p = 0.003). No other significant differences in effect were seen on analysis of sub-groups and individual factors (sex, age, presumed age of thrombus and side of thrombosis). In the 77 patients in group A, haemorrhagic complications were less frequent than in the 79 patients in group B (22.1 versus 36.7%; p = 0.054), especially concerning urogenital haemorrhage (6.5 versus 22.8%; p = 0.004). Women were affected more frequently by haemorrhagic complications than men (35.2 versus 26.5%), and the 19 patients aged more than 65 years old were affected more than the 137 younger patients (21.1 versus 13.9%). There were no deaths, and clinically insignificant pulmonary emboli occurred three times. Ultra-high dosage streptokinase shows better and more rapid thrombolytic treatment for popliteal-femoral-iliac venous thromboses and causes fewer haemorrhagic complications than conventional dosage streptokinase. The better effect of ultra-high dosage can be observed particularly for three-segment occlusion as well as in male patients. In older patients, accurate diagnosis is required because of the higher rate of haemorrhagic complications.

Adult↗

PubMed1997

The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type.

Primary extranodal malignant non-Hodgkin's lymphoma arising from the mucosa-associated lymphoid tissue (MALT-type lymphoma) represents a subtype of B-cell lymphoid malignancies with distinct clinicopathological features and is often associated with a favorable prognosis. Unlike the situation in nodal non-Hodgkin's lymphoma of B-cell lineage, few data are still available concerning the chromosomal constitution of MALT-type lymphomas. Until now, cytogenetic data from 29 low-grade MALT lymphomas with karyotypic alterations have been reported from different institutions, and virtually no data were available for high-grade MALT-type lymphomas. We have analyzed the cytogenetics of 44 MALT lymphomas arising in the stomach, parotid gland, thyroid gland, lung, breast, and conjunctiva. Clonal chromosome aberrations have been detected in 13 of 20 (65%) low-grade and 20 of 24 (83%) high-grade tumors. More than half of the low-grade lymphomas with abnormal karyotypes (7 of 13 cases, 53%) displayed clonal t(11;18)(q21;q21), thus specifically associating this translocation with MALT-type lymphomas for the first time in a larger series. In contrast, t(11;18) was not found in a single case of 20 high-grade MALT-type lymphomas with abnormal karyotypes, nor were translocations t(14;18) or t(3;14), characterizing about 10-35% of primary nodal large cell lymphomas. Instead, these lymphomas were associated with t(8;14)(q24;q32) in three cases, frequent deletions in the long arm of chromosome 6, and partial or whole gains of chromosomes 3, 7, 17, 18, and 21.

Chromosome Aberrations↗

PubMed1997

FISH-deletion mapping defines a 270-kb short stature critical interval in the pseudoautosomal region PAR1 on human sex chromosomes.

Deletions of the pseudoautosomal region (PAR1) of the sex chromosomes have recently been discovered in individuals with short stature, and a minimal common deletion region of 700 kb within PAR1 has subsequently been defined. We have cloned this entire region, which is bounded by the Xp/Yp telomere, as an overlapping cosmid contig. In the present study, we have used fluorescence in situ hybridization (FISH) to study four patients with X-chromosomal rearrangements, two with normal height and two with short stature. Genotype-phenotype correlations have narrowed down the the critical "short stature interval" to a 270-kb region containing the gene with an important role in growth. A minimal tiling path of 6-8 cosmids bridging this interval is now available for interphase and metaphase FISH and provides a valuable tool for diagnostic investigations of patients with idiopathic short stature.

Adolescent↗

PubMed1997

Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome.

Growth retardation resulting in short stature is a major concern for parents and due to its great variety of causes, a complex diagnostic challenge for clinicians. A major locus involved in linear growth has been implicated within the pseudoautosomal region (PAR1) of the human sex chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and different rearrangements on Xp22 or Yp11.3. This deletion was not detected in any of the relatives with normal stature or in a further 30 individuals with rearrangements on Xp22 or Yp11.3 with normal height. We have isolated a homeobox-containing gene (SHOX) from this region, which has at least two alternatively spliced forms, encoding proteins with different patterns of expression. We also identified one functionally significant SHOX mutation by screening 91 individuals with idiopathic short stature. Our data suggest an involvement of SHOX in idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients.

Adolescent↗

PubMed1997

Evidence for antioxidant nutrients-induced pigmentation in skin: results of a clinical trial.

The aim of this study was to demonstrate that modification of the cellular redox-equilibrium occurs as a consequence of antioxidant nutrients intake (carotenoids, vitamine E and vitamine C) and that these nutrients play a role in the pigmentation of the skin without any UV exposure. We conducted a randomized, double-blind study in 20 healthy subjects to evaluate and to compare the efficacy of two mixtures of dietary antioxidants with regard to direct determination of melanin and carotenes by chromametry at selected skin sites and multiple reflection spectrometry from a 1 cm2 region of skin of different parts of the body. Efficacy was assessed by a significant improvement of these parameters, in comparison with measurements performed on the day of randomization, before dietary supplement intake. The formulations per capsule of study dietary supplements are: 13 mg of beta-carotene, 2 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B13/L2) or 3 mg of beta-carotene, 3 mg of lycopene, 5 mg of vitamine E and 30 mg of vitamine C (B3/L3). A 8-week B13/L2-supplementation lead to a detectable carotenodermia whereas the B3/L3-supplementation not. Signicative increase of melanin concentrations in skin were found after 4, 5, 6 and 8 weeks of dietary antioxidant intake in both groups (p < 0.05). These results are discussed with regard to the redox control theory of melanocytes which regulates the tyrosinase activity.

Adult↗

PubMed1997

Aerosolized surfactant inhibits acetylcholine-induced airway obstruction in rats.

Exogenous surfactant treatment inhibits antigen-induced airway obstruction in sensitized guinea-pigs. Aerosolized surfactant also improves respiratory function in asthmatic patients. The aim of the present study was to determine whether aerosolized surfactant inhibits nonallergic airway obstruction induced by acetylcholine. Anaesthetized Wistar rats were treated by aerosol with the beta2-adrenoceptor agonist terbutaline, surfactant (Alveofact), a surfactant-terbutaline combination, or vehicle (control). Animals were then challenged by aerosolized acetylcholine to elicit receptor-mediated airway obstruction. A second group of animals was challenged with intravenous acetylcholine. Respiratory function variables were measured by body plethysmography before and after treatment, and after the acetylcholine challenge. Baseline lung function values before and after treatment were similar in all groups. Acetylcholine challenge by aerosol increased lung resistance by 64% in control animals. Pretreatment with terbutaline and surfactant significantly limited the increase of lung resistance to +36 and +34%, respectively. Simultaneous aerosolization of surfactant and terbutaline also inhibited airway obstruction but their effects were not additive. By contrast, terbutaline treatment inhibited the effects of intravenous acetylcholine, but surfactant did not. In conclusion, we suggest that surfactant aerosol may prevent acetylcholine and other pharmacological agents from reaching the airway smooth muscle from the airway lumen but not via the bloodstream.

Acetylcholine↗

PubMed1997

Impaired postprandial regulation of insulin-like growth factor binding protein-1 in children with chronic renal failure.

Patients with chronic renal failure (CRF) have elevated plasma levels of insulin-like growth factor-1 (IGFBP-1). We sought to determine the dynamics of plasma IGFBP-1 in response to an endogenous insulin pulse during an oral glucose tolerance test (oGTT) in 12 prepubertal children with advanced CRF [glomerular filtration rate (GFR) 12.5 +/- 4 mL/min/1.73 m2] and in 9 age-, gender-, and body size-matched controls with normal renal function. Glucose and insulin responses to oGTT were significantly elevated in CRF (P < 0.01), indicating decreased sensitivity to the hypoglycemic action of insulin. Fasting plasma IGFBP-1 levels in CRF (235 +/- 40 ng/mL) were 2.5-fold increased compared with controls (94 +/- 11.6 ng/mL, P < 0.0001). In controls, plasma IGFBP-1 levels rapidly decreased with time by 52%, to a level of 45 +/- 6.7 ng/mL 180 min after the oral glucose load. In contrast, plasma IGFBP-1 levels in CRF patients slowly decreased with time by 25%, to a level of 176 +/- 28 ng/mL (P < 0.001 vs. controls) 180 min after the oral glucose load. For the group as a whole, the percent decrease in IGFBP-1 at 180 min was positively correlated with GFR (r = 0.85, P < 0.0001). Plasma GH concentrations were not statistically different at baseline, but showed a paradoxical increase in CRF patients thereafter. Plasma IGF-I concentrations at baseline were comparable in CRF patients and controls and similarly decreased by about 10% (P < 0.01) after the oral glucose load. In summary, our study shows that the decline of plasma IGFBP-1 in response to an oral glucose load is impaired in children with CRF despite increased insulin levels. This impaired postprandial decline of plasma IGFBP-1 might interfere with glucose homeostasis by blocking insulin-like activity of free IGFs in vivo and thereby contribute to glucose intolerance in uremia.

Administration, Oral↗

PubMed1996

[Atresia of the aortic arch. A rare cause of asymmetrical arterial hypertension in adulthood].

HISTORY AND CLINICAL FINDINGS: A 58-year-old man, previously resident in Russia, was known since the age of 18 years to have arterial hypertension of unknown cause in only the right arm. A single syncope was the only previous symptom. On examination the pressure was 230/110 mmHg in the right arm, 150/100 mmHg in the left one. The pulse in the right arm and neck was strong and heaving, that in the left arm and the legs much more weakly palpable. INVESTIGATIONS: Electrocardiogram and echocardiogram showed left ventricular hypertrophy. The chest radiogram demonstrated rib notching. Digital subtraction angiography revealed aortic arch atresia just distal to the common carotid artery. No other cardiovascular abnormalities were found. TREATMENT: The patient declined operative treatment. Cautious antihypertensive drug treatment with Atenolol (25 mg daily) reduced the pressure in the right arm to 180/90 mmHg. CONCLUSION: This rare malformation of aortic arch atresia should be considered in the differential diagnosis of asymmetrical arterial hypertension in an adult.

Adrenergic beta-Antagonists↗

PubMed1996

Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

Conversion of testosterone (T) to dihydrotestosterone (DHT) in genital tissue is catalysed by the enzyme 5 alpha-reductase 2, which is encoded by the SRD5A2 gene. The potent androgen DHT is required for full masculinization of the external genitalia. Mutations of the SRD5A2 gene inhibit enzyme activity, diminish DHT formation, and hence cause masculinization defects of varying degree. The classical syndrome, formerly described as pseudovaginal perineoscrotal hypospadias, is characterized by a predominantly female phenotype at birth and significant virilization without gynecomastia at puberty. We investigated nine patients with steroid 5 alpha-reductase 2 deficiency (SRD). Phenotypes, which were classified according to the severity of the masculinization defect, varied between completely female (SRD type 5), predominantly female (SRD type 4), ambiguous (SRD type 3), predominantly male with micropenis and hypospadias (SRD type 2), and completely male without overt signs of undermasculinization (SRD type 1). T/DHT-ratios were highly increased ( > 50) in the classical syndrome (SRD type 5), but variable in the less severe affected patients (SRD types 1-4) (14-35). Mutations in the SRD5A2 gene had been characterized using PCR-SSCP analysis and direct DNA sequencing. A small deletion was encountered in two patients, while all other patients had single base mutations which result in amino acid substitutions. We conclude that phenotypes may vary widely in patients with SRD5A2 gene mutations spanning the whole range from completely female to normal male without distinctive clinical signs of the disease. Hence, steroid 5 alpha-reductase deficiency should be considered not only in sex reversed patients with female or ambiguous phenotypes, but also in those with mild symptoms of undermasculinization as encountered in patients with hypospadias and/or micropenis. A classification based on the severity of the masculinization defect may be used for correlation of phenotypes with enzyme activities and genotypes, and for comparisons of phenotypes between different patients as the basis for clinical decisions to be made in patients with pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1996

[Results of the North Baden Venous Lysis--NBVL--Study. Prospective phlebographically controlled randomized multicenter evaluation of ultra high versus conventional dose streptokinase in acute thrombosis of the leg and pelvic veins].

BACKGROUND AND AIM: The Nordbaden Multicentre Study on lysis of venous thrombosis was prompted by a lack of randomized studies comparing ultra-high and conventional-dose streptokinase therapy in fresh iliac and leg vein thrombosis. The aim was to compare prospectively the phlebographically monitored results of three courses of ultra-high dosed with those of a 5-day course of conventionally dosed streptokinase treatment and to record any side-effects of fibrinolysis. PATIENTS AND METHOD: 77 patients were randomized to ultra-high-dose streptokinase (group A), and 79 to conventionally-dosed streptokinase (group B) therapy. In 13 patients of group A and 10 of group B, no monitoring phlebography was possible--in 15 patients (9.6%) who broke off treatment prematurely, and in 8 (5.1%) who failed to keep their phlebography appointment. RESULTS: Detailed analysis of the phlebographic findings (main target criterion) on the basis of the IFP score revealed a decrease in the score from 4.55 to 2.41 (47%) for the 64 group A patients after a mean of 2.7 +/- 0.6 courses of treatment with administration of 24 +/- 5.7 million IU streptokinase, and from 4.2 to 2.93 (30%) for the 69 group B patients after a mean of 3.7 +/- 1.2 days of treatment with administration of 8.6 +/- 3.3 million IU (p = 0.007). Of the 281 totally occluded vein segments in group A, 132 (47%) were rendered fully patent, while this was true of 81 (29%) of the 279 total occlusions in group B. Of the 21 incomplete occlusions in each group, 10 in group A and 16 in group B became fully patent. Analysis of subgroups and individual factors showed that the re-establishment of patency in the 45 men in group A was better (55%) than in the 47 group B men (30%); while the women showed no inter-group difference there was an overall difference vis-a-vis the men (p = 0.02). In group A, patients aged over 60 showed better results (61%) than those of the same age in group B (20%) (p = 0.003). The presumably older thrombi were just as readily lysable as fresher ones. Among the 77 group A patients, side-effects occurred significantly less frequently than among the 79 group B patients. For the most part, side-effects were haemorrhage overall (22.1% vs. 35.7%) and urogenital bleeding in particular (6.5% vs. 22.8%); there were no deaths. Women bled somewhat more often than men (35.2% vs. 26.5%), and bleeding was more commonly in patients older than 65 years. CONCLUSIONS: 1. Ultra-high-dose streptokinase treatment of deep venous thrombosis (iliac, femoral, popliteal veins) is more effective (at least in males) and produces less bleeding than conventional doses. 2. Presumably older thromboses (8 to 14 days) are no less responsive to ultra-high dose streptokinase. 3. In view of the higher risk of bleeding in over-65-year-olds, the indication for fibrinolytic therapy must be considered with care.

Adult↗

PubMed1996

Embryotoxicity study of monomeric 4,4'-methylenediphenyl diisocyanate (MDI) aerosol after inhalation exposure in Wistar rats.

One of the uses of MDI is as an alternative to formaldehyde in the manufacture of furniture, its main route of exposure to humans being by inhalation. There have been no previous studies on the potential prenatal toxic effects of this compound. To close this gap in information, gravid Wistar rats, Crl:(WI)BR, were exposed by whole-body inhalation to clean air (control) and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per day from Days 6 to 15 post conception (p.c.). Rats were killed on Day 20 p.c. and the following results were obtained: Treatment caused a dose-dependent decrease in food consumption in all substance-treated groups during exposure, returning to normal values after cessation of treatment. The lung weights in the high-dose group were significantly increased compared to the sham-treated control animals. Treatment did not influence any other material and/or fetal parameters investigated (maternal weight gain, number of corpora lutea, implantation sites, pre- and postimplantation loss, fetal and placental weights, gross and visceral anomalies, degree of ossification), although a slight but significant increase in litters with fetuses displaying asymmetric sternebra(e) was observed after treatment with the highest dose of 9 mg/m3. Although the relevance of an increase of this minor anomaly in doses which cause toxic effects in dams (reduced food consumption, increased lung weights) is limited and the number observed is within the limits of biological variability, a substance-induced effect in the high-dose group cannot be excluded with certainty. Consequently, a no embryotoxic effect level of 3 mg/m3 was determined.

Administration, Inhalation↗

PubMed1996

The carcinogenic potency of carbon particles with and without PAH after repeated intratracheal administration in the rat.

The role of carcinogenic PAH in soot- and carbon black-related lung tumour induction in rats was investigated after intratracheal administration of carbon blacks (CB) and two types of diesel soot (DS), either as original or as toluene extracted particles. The total particle dose per animal was 15 mg subdivided into 16-17 weekly applications. There was one vehicle control and two groups were treated with a total dose of either 30 or 15 mg pure BaP as positive control. The main tumour results were: (a) original DS induced a higher tumour rate than extracted DS; (b) the carcinogenic potency of extracted CB probably depends on the size of the primary carbon particles and on the specific surface area of the particles; (c) extracted DS covered with 11 micrograms BaP per mg carbon particles caused a lower lung tumour rate than original DS containing only 0.9 ng BaP per mg, but a variety of other PAH and NO2-PAH; (d) a total dose of 15 mg pure BaP caused a lung tumour rate very similar to that of 30 mg extracted DS, 15 mg original DS or 15 mg Printex 90T CB extracted or covered with approximately 29.5 micrograms BaP per mg CB.

Animals↗

PubMed1996

32P-postlabeling of a DNA adduct derived from 4,4'-methylenedianiline, in the olfactory epithelium of rats exposed by inhalation to 4,4'-methylenediphenyl diisocyanate.

Tissues obtained from female Wistar rats exposed to a 0.9 microm aerosol of 4,4'-methylenediphenyl diisocyanate (MDI) for 17 h per day, 5 days per week, for one year, at levels of 0, 0.3, 0.7 and 2.0 mg/m(3), were analyzed for DNA adducts. A 32P-postlabeling method was used to detect (i), adducts formed by the reaction of the isocyanate group(s) of MDI with DNA; and a 32P-postlabeling method was adapted to detect (ii), a DNA adduct formed by 4,4'- methylenedianiline (MDA), a hydrolysis/decarboxylation product of MDIV. In the lung, neither isocyanate adducts nor the arylamine adduct were detectable. The same negative result was seen in the liver, the bladder, the kidney, the respiratory epithelium and in peripheral lymphocytes. In the olfactory epithelium, on the other hand, the arylamine-derived DNA adduct was detected, at the very low levels of 5,9 and 10 adduct-nucleotides per 10(10) nucleotides, for the three dose groups, respectively. The adduct co-chromatographed with the one formed in the liver of rats after oral gavage of MDA. The results are discussed in terms of the importance of genotoxic versus nongenotoxic aspects of carcinogenesis.

Administration, Inhalation↗

PubMed1996

Growth hormone as a new treatment modality for short children with chronic renal failure. The German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Recombinant human growth hormone (rhGH) has become a new treatment modality for short children with chronic renal failure (CRF) and after renal transplantation. The rationale for high-dose rhGH treatment is the insensitivity of the uremic organism to GH. As the insensitivity to GH is expressed more in end-stage renal failure than in earlier stages of CRF, patients on dialysis respond less to rhGH. In transplanted children, rhGH can counterbalance the growth-depressing effects of corticosteroids. In prepubertal children, rhGH improves the height standard deviation score by a mean of +2 within 5 years. The effect of rhGH treatment on final height remains to be studied.

Child↗

PubMed1995

Hemoglobin adducts and urine metabolites of 4,4'-methylenedianiline after 4,4'-methylenediphenyl diisocyanate exposure of rats.

4,4'-Methylenediphenyl diisocyanate (MDI) is a very important component in the production of polyurethane. In a long-term experiment, designed to determine the carcinogenic and toxic effects of MDI, rats were exposed chronically for 3 and 12 months, to 0.0 (control), 0.26, 0.70 and 2.06 mg MDI/m3 as aerosols. Hemoglobin adducts and urine metabolites of MDI were determined at the different doses in order to develop methods to biomonitor workers exposed to MDI and to assess a risk resulting from such exposure. Hemoglobin adducts and urine metabolites of 4,4'-methylenedianiline (MDA) were found in all rats, including controls. MDA and N-acetyl-MDA (AcMDA) were quantified by GC-MS after derivatization with heptafluorobutyric anhydride. The dose-response relationships for hemoglobin adducts and urine metabolites were non-linear over this dose range. In urine, free AcMDA and MDA were found after base extraction. The amount of MDA present in urine and to a lesser extent the AcMDA found in urine correlate well with the corresponding amount determined as hemoglobin adducts for all dose groups. In order to release MDA from possible conjugates of MDA and AcMDA, urine was treated under strong acidic conditions. Following this procedure higher MDA levels were found than the sum of MDA and AcMDA from mild base hydrolysis. Similar results were obtained with the rats exposed for 3 and 12 months, indicating that a steady state had been reached by 3 months. In order to perform further investigations of the bronchoalveolar lavage fluid one group of animals was given a 1 week recovery period before sacrifice. Hemoglobin adducts from these animals showed a decrease of approximately 40% for all dose groups. According to the lifetime of rat erythrocytes the levels of hemoglobin adducts should have decreased by only 22%. This suggests that the erythrocytes with modified hemoglobin have a shorter lifespan. In order to exclude the possibility that hemoglobin adducts may have resulted from ingestion of hydrolyzed MDI via licking of the fur, a single dose experiment with rats exposed through the nose only or with the whole body was carried out. The only difference observed between these two exposure regimes was that the hemoglobin adduct levels of AcMDA after nose only exposure were significantly higher than after total body exposure. The presence of AcMDA in urine and as a hemoglobin adduct indicates that MDA was bioavailable after MDI exposure. The presence of MDA may contribute significantly to the carciongenic potential of MDI, since MDA has been shown to be carcinogenic in animals.

Acetanilides↗

PubMed1995

Phagocytosis and chemotaxis of rat alveolar macrophages after a combined or separate exposure to ozone and carbon black.

Male Wistar rats were treated by ozone or carbon black (CB) alone as well as in combination. Intratracheal instillation with various amounts of CB was followed either by an acute 7-day or subchronic 2-month ozone exposure (0.5 ppm). Two functional parameters were investigated in alveolar macrophages from bronchoalveolar lavagates, the phagocytotic capacity and the chemotactic migration capability. In the phagocytosis assay, the percentage of phagocytizing macrophages decreased significantly in the CB-exposed groups whereas the ozone groups remained close to or at the control level after 7 days and 2 months of exposure, respectively. The number of ingested particles per macrophage and the formation of superoxide anion radicals were not changed after a 7-day exposure to ozone compared to the control group but were increased after a 2-month ozone exposure. However, a reduction was found in the CB groups. A stimulating effect of ozone was observed in the combined groups. Chemotactic migration was generally retarded in the CB-treated groups. From the results it can be concluded that ozone is able to stimulate the phagocytotic and chemotactic activity of alveolar macrophages whereas CB impairs these functions.

Administration, Inhalation↗

PubMed1995

Urinary metabolite profile of PAH as a potential mirror of the genetic disposition for cancer.

Polycyclic aromatic compounds such as polycyclic aromatic hydrocarbons or aromatic amines presently are considerably underestimated with regard to the formation of environmentally caused cancer diseases. The individual urinary metabolite profile raising from the PAH inhaled is invariant. This holds for tar-pitch aerosol exposed Wistar rats as well as for PAH-exposed workers. Significant individual differences of the urinary metabolite profile can be observed in different individuals. The differences reflect the different individual enzyme equipment. There is an individual correlation between the PAH-masses inhaled and the masses of their metabolites excreted in the urine; e.g. the excretion of phenanthrene varies from 5% to 20% for different coke workers. The PAH metabolite profile analysis appears to be a suitable tool to estimate the individual cancer.risk at PAH-exposed working places since the PAH-induced malign transformation is caused by specific PAH metabolites.

Animals↗