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Biomedical subjects

H Fritz

Publications and source records attributed to H Fritz.

At least 127 records · Page 7Linked to original sources

Modulation of resynthesis of 1-alkyl-2-arachidonyl-glycero-3-phosphocholine and phosphatidylinositols for interception in vivo of free arachidonic acid, lyso-PAF, diacyl-glycerols, and phosphoinositides.

Thermal injury causes directly a liberation of inositolphosphates, diacylglycerols, free arachidonic acid, and lyso PAF from eukaryotic cells. From lyso PAF derivates PAF, from free arachidonic acid are derivating PG, LT, and TX. These "soluble mediators" are stimulating inflammatory cell populations in a feedback mechanism: the stimulus activates the inflammatory cells to produce the same soluble mediators (Fig.1). The arising soluble mediators are the take off for the inflammation cascade causing as later step the activation of kinin, clotting, and complement systems. The pure biochemical lesions at the onset results in the clinical manifestation of oedema, increased dermal temperature, and pains. The possibilities for prevention and allevation of early pain, due to the acute burn, lie in the inhibition of the spreading out of inflammatory mediators (Bauer 1987a) (Fig.2).

Animals↗

Evaluation of contrast dose reduction for excretory urography using computed radiography.

We prospectively investigated whether performing excretory urography by computed radiography (CR) - with CR's broader dynamic range and potential for post-processing - would permit lower contrast dose while maintaining usual image quality. The rationale for this experiment was to evaluate whether CR had potential in reducing the risks and costs associated with urography. Sixty sequential patients were randomly assigned to undergo computed urography with either our full (282 mg I/kg body weight) or half our usual dose (141 mg I/kg body weight) of intravenous 60% diatrizoate meglumine. Three blinded observers judged automatically post-processed full dose tomograms and KUBs as qualitatively superior to both automatically post-processed and individually, interactively post-processed half dose images. Thus, post-acquisition image manipulation could not fully compensate for diminished image quality due to contrast dose reduction.

Diatrizoate Meglumine↗

Susceptibility to beta-lactam antibiotics and gentamicin of gram-negative bacilli isolated from hospitalized patients: a Swedish multicenter study.

A total of 952 blood and 1543 urine isolates of gram-negative bacilli from hospitalized patients in 1986-1987 were consecutively collected by 10 Swedish laboratories and tested for susceptibility to 8 beta-lactam antibiotics and to gentamicin. The isolates were mostly Escherichia coli (58% and 44%, respectively) and Klebsiella sp. (17% and 18%). Resistance to ampicillin in blood and urine isolates was found in 35% and 45%, respectively, to piperacillin in 5% and 6%, to cephalothin in 26% and 34%, to cefuroxime in 12% and 22%, to cefotaxime in 3% and 5%, to ceftazidime in 1% and 1%, to imipenem in 0.5% and 0.1%, to aztreonam in 3% and 2%, and to gentamicin in 0.8% and 0%. Resistance of clinically important gram-negative bacilli to new beta-lactam antibiotics and to gentamicin is infrequent in Sweden.

Ampicillin↗

Intra-peritoneal aprotinin therapy for acute pancreatitis. Preliminary pharmacodynamic studies.

In acute pancreatitis a toxic exudate accumulates within the peritoneal cavity, which contains activated pancreatic proteinases. Peritoneal lavage removes the exudate effectively, washing it away with large volumes of saline solution, but is of unproven therapeutic value and may have deleterious effects. These may be avoided by combining lower volume peritoneal washouts with intra-peritoneal installation of a proteinase inhibitor, although therapeutic effectiveness may be compromised by systemic absorption depending on the inhibitor selected. This latter effect was studied in fifteen patients with acute pancreatitis, treated by simple peritoneal washout and bolus intra-peritoneal administration of aprotinin (Trasylol) solution.

Absorption↗

Human mucus proteinase inhibitor (human MPI). Human seminal inhibitor I (HUSI-I), antileukoprotease (ALP), secretory leukocyte protease inhibitor (SLPI).

Human mucous secretions contain a proteinase inhibitor which is produced locally and inhibits, besides trypsin and chymotrypsin, granulocytic elastase and cathepsin G as well as mast cell chymase and tryptase. The various inhibitors isolated from different sources (bronchial mucus, parotid secretion, seminal plasma, cervical mucus, etc.) and named accordingly (bronchial mucus inhibitor, BMI; human seminal inhibitor I, HUSI-I; cervical mucus inhibitors, CUSI; antileukoprotease, ALP; secretory leukocyte protease inhibitor, SLPI) proved to be identical or derived from a mature inhibitory protein encoded by a single gene of the human genom. Therefore, this inhibitor should be named mucus proteinase inhibitor, MPI. Such a neutral terminus would help to avoid misleading interpretations of already published data and also of the biological role of this inhibitory protein because the MPI may serve several and different physiological functions.

Humans↗

Lithium and the developing rat kidney in transplacental target organ toxicity.

Pregnant female albino rats were treated orally with lithium carbonate dissolved in distilled water. Treatment at 100 mg/kg day 16 until day 20 of gestation caused marked maternal toxicity including polyuria. For the progeny increased rates of prenatal and postnatal mortality were noted. In part of the progeny sacrificed near term by Caesarean section, the visceral examination of the fetuses revealed an enlargement of the renal pelves in association with rudimentary or missing papillae. The renal anomalies are interpreted as being consistent with a developmental retardation due to specific lithium activity. After birth, i.e. after termination of maternal treatment, slight to moderate structural changes of the kidney were apparently compensated. 60 mg/kg through days 16-20 of pregnancy caused moderate maternal toxicity including polyuria. The offspring showed a postnatal development near the normal range, however, and no renal anomalies were recorded. In the view of the nephrotrophic property of lithium as known for the adult rat, the results indicate that possible transplacental effects on the fetal kidney as a target organ should be also considered.

Animals↗

Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration.

The pharmacokinetics (half-life time of absorption and elimination, total clearance, distribution volume etc.), effects on hemostasis (clotting times, blood cell counts) and renal excretion of hirudin were investigated on healthy volunteers after single subcutaneous (600, 800 or 1000 antithrombin units (AT-U)/kg; n = 3 per each dose) or intravenous (1000 AT-U/kg; n = 3) injections. Hirudin concentrations in citrated plasma and urine were determined by means of a radioimmunobioassay, whereby the inhibitor is detected by its thrombin binding capacity. Plasma profiles were adequately described by the Bateman equation (subcutaneous injection) and by an open two-compartment model (intravenous injection), respectively. Within 24 h about half of the applied hirudin dose was renally excreted in active form. The prolongation of clotting times (thrombin time, partial thromboplastin time (PTT), Quick) was dependent on the hirudin plasma level. The PTT proved to be the most reliable test for representation of the actual inhibitor plasma concentrations. Generally, the blood cell counts were unchanged by the hirudin administration. All test subjects tolerated the hirudin injection without visible or measurable side effects.

Adult↗

[Possibilities of biochemical differentiation of reactive effusions of the knee joint].

1. Differentiation of reaction effusions: Posttraumatic reaction effusions (fresh meniscus or capsular ligament lesion) displayed a greatly enhanced alkaline phosphatase activity, whereas postoperative reaction effusions that were poor and rich in cells had a comparatively high C3c value relative to the total amount of protein. In punctates from patients with patellar chondropathy and primary synovial reaction (no trauma, no postoperative condition) the lowest parameter values of of the entire study were seen. 2. Decision help with regard to therapy: Via determination of the sensitive inflammation parameter PMN elastase (E-a1PI) it is possible to initiate cartilage-protective therapy directly in case of a cartilage lesion of mild inflammatory character (E-a1PI 300-500 ng/ml), whereas in case of severe inflammation (E-a1PI 500-1000 ng/ml) anti-inflammatory drugs should be employed in the first instance. 3. Therapy control: In the follow-up control of reaction effusions the comparison of concentrations of biochemical parameters before and after intra-articular application of drugs offers a possibility of therapy control. Since with increasing inflammatory nature and disturbance of the blood-synovia barrier the concentration of the measured biochemical parameters (with the exception of glucose) increased in the synovial fluid, successful treatment should result in an absence of such an increase in concentration (or, if at all, in an only slight measure).

Acute-Phase Proteins↗

Influence of chain shortening on the inhibitor properties of hirudin and eglin c.

To find out minimal sizes of the proteinase inhibitor proteins hirudin and eglin necessary for their biological activity the inhibitors were incubated with exopeptidases. From the incubation mixtures shortened derivatives were isolated and characterized. Eglin c can be N-terminally shortened by up to 6 amino-acid residues without any loss of affinity towards chymotrypsin. The complex of thrombin with hirudin lacking 3 C-terminal amino-acid residues showed a 15-20-fold increased Ki value as found previously for desulfato-hirudin and desulfato-hirudin shortened by 2 amino-acid residues. Obviously, the C-terminal part of the hirudin molecule has a positive influence on its affinity to thrombin.

Amino Acids↗

Evaluation of the kinin-induced pathomechanisms in the development of ARDS by kallikrein inhibition in vivo.

Our findings indicate that the kallikrein-kinin system might participate in the development of acute respiratory failure. They were assessed by measurements of plasma kininogen levels, blood pressure recordings and lung morphology. Aprotinin plasma concentrations ranging from 4 to 7 KIU/ml proved sufficient to inhibit effectively the hemodynamic and morphologic effects caused by tissue kallikrein infusion.

Animals↗

[Captopril in hypertensive patients with type II diabetes mellitus].

Since the angiotensin converting enzyme (ACE) is identical with kininase II, the reduction of its activity by an ACE-inhibitor such as captopril will not only decrease the concentration of angiotensin II but also elevate the levels of kinins. Although the slight increase of the latter will not contribute to the antihypertensive action of ACE-inhibitors, we are sure today that it exhibits local metabolic effects in cardiac and skeletal muscle tissue. These endogenous kinins have been shown to improve the utilisation of glucose in the human forearm, the whole organism and the isolated perfused rat heart and seem to exhibit their effects via prostaglandins. A cross-over plot of the glycolytic intermediates at the height of phosphofructokinase induced by bradykinin in rat heart and the activation of the purified enzyme from rabbit heart by PGE2 point to an enhanced glycolytic rate as their mode of action. From these findings similar effects under ACE-inhibitors can be assumed. This was investigated in ten non-insulin-dependent diabetics, whose glucose disposal rate was measured by the glucose clamp technique. After 25 mg of captopril their peripheral insulin resistance was significantly improved, which was found to be due to an accelerated rate of glucose uptake into their forearm muscle tissue. To evaluate the clinical relevance of these data, 15 mildly hypertensive, overweight type II-diabetic patients (mean age: 53 years; seven women) were hospitalized. After a seven-day wash-out period, the patients were given 25 mg of captopril twice daily for seven days. During the treatment, systemic kinin concentrations significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus.

We have isolated cDNA clones for the human antileukoprotease HUSI-I, an elastase inhibitor, from a library, containing cDNA inserts made from human cervix uterus. A library of 10 000 recombinants was screened using a mixture of 16 different oligodeoxyribonucleotides which correspond to amino acids 79-84 and one 20mer oligodeoxyribonucleotide corresponding to amino acids 19-26. Two overlapping cDNA clones, containing the entire coding sequence and part of the 5'- and 3'-untranslated region, were isolated. DNA sequence data showed that our clone corresponds with the available protein sequence data. For expression, the cDNA fragment was inserted in a derivative of plasmid pPLc236 and expressed under the control of lambda PL promoter. Expression of antileukoprotease was proven by Western blot analysis and inhibition of chymotrypsin.

Amino Acid Sequence↗