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Biomedical subjects

H Fritz

Publications and source records attributed to H Fritz.

At least 109 records · Page 6Linked to original sources
PubMed1991

Pharmacokinetics, effect on clotting tests and assessment of the immunogenic potential of hirudin after a single subcutaneous or intravenous bolus administration in man.

The pharmacokinetics and the anticoagulant effects of hirudin were investigated in 12 healthy volunteers after single subcutaneous or intravenous bolus administrations. Hirudin concentrations in citrated plasma and urine were determined with a radioimmunobioassay, which detects the inhibitor by its thrombin-binding capacity. Plasma profiles could be adequately described by the equation for an open two-compartment model (intravenous route) and by the Bateman equation (subcutaneous route), respectively. Within 24 h half of the administered hirudin dose was recovered in the urine in biologically active form. The prolongation of clotting times (activated partial thromboplastin and thrombin time) was dependent on the hirudin plasma concentration. All test subjects tolerated the hirudin injection without visible or measurable side effects. No hirudin-specific antibodies were found after single parenteral administrations.

Biological Assay↗
PubMed1991

Anti-neutrophil elastase defense of the normal human respiratory epithelial surface provided by the secretory leukoprotease inhibitor.

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease with a high capacity for inhibiting neutrophil elastase (NE), is produced by cells of mucosal surfaces including the human lung. The molar concentrations of SLPI in total respiratory tract epithelial lining fluid (ELF) were 56 +/- 10% that of alpha 1-antitrypsin, suggesting SLPI may be more important for the anti-NE protection of the pulmonary epithelial surface than previously thought. However, evaluation demonstrated that SLPI in respiratory ELF was only one-third functional. Studies aerosolizing recombinant SLPI (rSLPI) to sheep demonstrated that in the short term, neither aerosolization and alveolar deposition nor the lavage procedure inactivated the SLPI molecule. In vitro studies with rSLPI demonstrated that exposure to oxidants did not modify the form of the molecule, while exposure to oxidants and NE caused the molecule to be cleaved from 12 to 8 kD. Consistent with this, evaluation of SLPI in lavage fluid of individuals with cystic fibrosis (a condition with oxidants and NE on the respiratory epithelium) showed that the SLPI was degraded. However, evaluation of SLPI in normal ELF by molecular sieve analysis and Western analysis demonstrated an intact 12-kD molecule, suggesting that the partial inactivation of SLPI in normals in vivo is not because it is complexed to NE or exposed to oxidants + NE. Together, these observations demonstrate that SLPI is present in large amounts in respiratory ELF, but since the majority of the SLPI is inactive, it likely does not play a significant role in protecting the normal respiratory epithelium, except perhaps in the upper airways where the levels of SLPI are the highest.

Adult↗
PubMed1991

Detection of cathepsin B in tumor cytosol and urine of breast cancer patients.

In order to evaluate the role of cathepsin B (CB) as a proteinase involved in mammary tumor progression and its potential role as a tumor marker, we have measured the CB activity in cytosols of breast cancer tumor tissue using Z-Arg-Arg-AMC as the substrate and found a 23fold increase when compared to distantly located breast tissue from the same patient. In addition, urine of breast cancer patients under adjuvant chemotherapy was screened for CB immunoreactivity with a sandwich type enzyme immunoassay which revealed significant interindividual differences in concentrations with some urines containing immunoreactivity comparable to healthy controls. The urines were also investigated for CB activity but no differences between patients and controls were observed. However, urine contains thiol activatable proteinases causing substrate hydrolysis, which is to a varying extent inhibited by E-64 or Z-Phe-Phe-CHN2.

Adult↗
PubMed1990

Evaluation of the teratogenic potential of chemicals in the rat.

On the basis of the results of a variety of teratogenicity studies in Sprague-Dawley-derived albino rats, carried out over several years in our laboratory, an appraisal of the principal experimental procedures is set forth. Various categories of chemicals were used for the evaluation of dosage-related teratogenic potency. Salicylate, prednisolone, cyclophosphamide, 5-hydroxytryptamine (serotonin), glycinonitrile, and dimethylformamide have proven to be teratogenic under certain of the experimental conditions used. Particular differences in the embryotropic effects of acetylsalicylic acid were caused by qualitative and quantitative changes of the vehicle. Fetal morphological abnormalities, classified either as 'malformations' or as 'anomalies', may occur independently of overt maternal toxicity and/or embryotoxicity. Further, they may be closely correlated with general inhibitory effects on growth. Drugs may affect developing tissues and organs selectively due to their pharmacological activity and/or specific organ toxicity. The limitation of maternal treatment to a very short period of gestation may disclose a specific susceptibility of developmental stages of the embryo or fetus. Finally, the importance of data collected from a historical control population to the interpretation of teratogenicity data is emphasised.

Animals↗
PubMed1990

Effect of recombinant hirudin, a specific inhibitor of thrombin, on endotoxin-induced intravascular coagulation and acute lung injury in pigs.

We hypothesized that thrombin activation may play a prominent role in endotoxin-induced secondary organ failure, such as acute lung injury. To test this hypothesis, we administered a thrombin-specific inhibitor, recombinant hirudin, in endotoxemic pigs. The pigs were anesthetized, mechanically ventilated, and prepared with Swan-Ganz and extravascular lung water (EVLW) catheters. A total of 18 randomly selected animals received a pretreatment of 1,000 U/kg of hirudin, followed by a continuous infusion over 6 h of 500 U/kg/h given simultaneously with the infusion of 10 micrograms/kg/h of Salmonella abortus equi endotoxin. Another 18 animals received a continuous infusion over 6 h of endotoxin but did not receive hirudin. All animals were fluid resuscitated with 17 ml/kg/h of saline for the duration of the experiment. Data are expressed as the mean (95% confidence interval). Hirudin reduced the endotoxin-induced consumption of plasma fibrinogen from -110 (-138 to -82) mg/100 ml to -39 (-67 to -12) mg/100 ml (p = 0.0001) and endotoxin-induced increases in the soluble fibrin in plasma from 434 (369 to 499) ng/ml to 236 (171 to 300) ng/ml (p = 0.0002). These data suggest an effective inhibition of the endotoxin-generated thrombin by hirudin. Furthermore, hirudin significantly reduced endotoxin-induced increases in pulmonary vascular resistance from 32 (27 to 37) kdyn x s x cm-5 x kg to 20 (15 to 25) kdyn x s x cm-5 x kg (p = 0.0015) and increases in EVLW from 15.4 (13.2 to 17.6) ml/kg to 12.2 (10.0 to 14.4) ml/kg (p = 0.0299).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

A new, highly sensitive enzymic assay for human tryptase and its use for identification of tryptase inhibitors.

A chromogenic two-stage assay for human tryptase, a specific marker of mast cell activation, was developed based on the tryptase-induced conversion of prothrombin to thrombin. This assay proved to be more sensitive and reliable than measurements of amidolytic activity of tryptase with small synthetic substrates such as Bz-Arg-Nan and was suitable to detect tryptase activity in human body fluids. In addition, the assay was useful for studies of natural and recombinant inhibitors of tryptase.

Biotransformation↗
PubMed1990

Human leukocyte elastase inhibitors: designed variants of human pancreatic secretory trypsin inhibitor (hPSTI).

Variants of human secretory trypsin inhibitor were constructed with the aim of producing inhibitors specific for human leukocyte elastase. Models of the hPSTI/HLE and hPSTI/chymotrypsin complexes were generated by computer aided protein design and used to plan better HLE inhibitors. This resulted in the production of the strongest and most specific inhibitors of HLE known.

Animals↗
PubMed1989

The hypotensive response to des-Arg9-bradykinin increases during E. coli septicemia in the pig.

The sensitivity to des-Arg9-bradykinin of the cardiovascular system was largely increased in piglets with E. coli bacteremia. However, the sensitivity to bradykinin was unchanged under the same condition. These findings indicate the appearance of the kinin B1-receptor in the systemic circulation of the pig during septicemia. Bradykinin induced responses suggest a stable effect mediated by the classical B2-receptor.

Animals↗
PubMed1989

[Angular measurements of the hindfoot in CT].

The absence of soft tissue superimposition on bone makes CT greatly superior to conventional radiographs, even using special views, for demonstrating the hind foot. Views derived from both methods are compared. Semicoronary and transverse planes have been defined in relation to specific points in the tarsus. In the semicoronary plane, the calcaneus-valgus angle varies from +10 degrees (valgus) to -10 degrees (varus) and the sustentaculum angle varies from 18 to 28 degrees. In the transverse plane, the plantar talocalcaneal angle is 60 degrees to 70 degrees and the calcaneal-cuboidal angle is 20 degrees to 35 degrees. These values are based on measurements of 62 normal feet. They are valuable for judging quantitatively posttraumatic deformities, displacement of fragments and operative results.

Adolescent↗
PubMed1989

[Pathologic changes in the hindfoot angle following fracture of the calcaneus].

Forty fractured calcanei (13 without and 27 with involvement of the joint) were examined by CT and the angle of the hind foot measured. Following a typical compression fracture there is a negative calcaneus-valgus angle, i.e. varus deformity of the tuberosity fragment. The sustentaculum angle is increased. There are changes in the talo-calcaneal and calcaneo-cuboidal angles. The length ratio of calcaneus to talus is reduced. Reproducible measurements make it possible to compare the results of operative correction and of changes in shape following conservative treatment, e.g. during weight-bearing.

Adult↗
PubMed1989

Inhibition of proteinases with recombinant eglin C during experimental Escherichia coli septicemia in the pig.

Administration of the proteinase inhibitor eglin C reduces the symptoms of capillary leakage in a porcine model of septic shock. This was assessed by measurements of blood pressure, plasma protein concentration, hematocrit, and duration of urine production. Eglin C plasma levels around 1.2 microM resulted from a dose of 1.9 mg.kg-1.h-1 for 4 h and were therapeutically effective. A higher dose of eglin C (7.7 mg.kg-1.h-1 for 4 h) induced levels of approximately 5.6 microM in plasma and was not superior. This observation indicates that lysosomal proteases from neutrophils or degranulation of mast cells play a crucial role in the increase of capillary permeability during septicemia.

Animals↗