Bradykinin is not liberated by working skeletal muscle in diabetes type II.
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Adult↗
Biomedical subjects
E Fink
Publications and source records attributed to E Fink.
Kinins are not liberated by working skeletal muscle in the majority of patients with essential hypertension.
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Adult↗
Angiotensin converting enzyme in human seminal plasma is synthesized by the testis, epididymis and prostate.
The activity of angiotensin converting enzyme (ACE) was assessed in human body fluids (serum, seminal plasma, prostatic secretions), in tissue extracts of the testis, epididymis, prostate and skeletal muscle, in split ejaculates and in seminal plasma obtained from patients before and after vasectomy. To ensure the specificity of the results the dependence of ACE activity on specific inhibitors was evaluated. Enzyme activity found in tissues of the male genital tract was considerably higher than that in serum and other tissues. ACE in human seminal plasma is synthesized by the testis, epididymis and prostate in different amounts.
Epididymis↗
A tissue kallikrein in the synovial fluid of patients with rheumatoid arthritis.
Tissue kallikrein is an enzyme that forms the vasoactive peptide kallidin from an endogenous substrate L-kininogen. Tissue kallikrein has been identified in joint fluids and in inflammatory infiltrates within synovial membranes. It is suggested that tissue kallikrein and kinins have an important role in synovitis and joint damage. Immunoreactive tissue kallikrein and amidase activity were both measured in the synovial fluid of 24 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Active enzyme concentrations were higher in RA than in OA and correlated well with the lysosomal enzymes beta-glucuronidase and lactate dehydrogenase. Both total immunoreactive tissue kallikrein and the proenzyme values were similar in RA and OA. Tissue kallikrein was localised by immunocytochemistry to the polymorphonuclear leucocytes present in the synovial fluid and membranes of patients with RA.
Adult↗
Local generation of kinins in working skeletal muscle tissue in man.
The effect of standardized isometric forearm work on circulating and local kinin concentrations was investigated in 12 healthy volunteers using the forearm catheter technique. Radioimmunological kinin determination in arterial blood and in the venous effluent of forearm muscle tissue was performed using a modification of Shimamoto's technique of blood sampling and kinin extraction. Under basal conditions, there was no arterio-venous difference of kinins. Throughout the whole experiment, arterial--reflecting systemically circulating--kinins did not change. In muscle venous blood, immunoreactive kinins were not significantly elevated during work, whereas a marked increase was detected in the recovery period (5.0 +/- 0.6 vs. 10.2 +/- 2.0 pmol/l; p less than 0.01). The data demonstrate, that kinins are locally generated in calculated amounts (32.7 +/- 8.4 fmol/(100 g x min) that are known to be sufficient to induce local vasodilatory and metabolic effects at the site of muscle contraction, but below the threshold for systemic cardiovascular actions.
Adult↗
[Improved insulin action by ACE inhibition in type-2 diabetics].
The effect of the angiotensin converting enzyme inhibitor captopril (25 mg by mouth) on glucose metabolism of skeletal muscle and the whole organism was studied in nine normotensive type II (non-insulin dependent) diabetics using a combination of euglycaemic-hyperinsulinaemic glucose-clamp and forearm catheter techniques. The administration of captopril resulted in a significant rise of both the whole-body glucose elimination and utilization rate in the forearm musculature. At the same time the arterial kinin level rose, while the concentrations of insulin, free fatty acids and gluconeogenesis precursors, as well as the number and activity of insulin receptors (measured in an erythrocyte-binding study) remained unchanged. The data support the view that, in type II diabetics, ACE inhibition raises the insulin-stimulated glucose uptake of the whole organism, predominantly due to an increased glucose uptake by the skeletal musculature. The demonstration of an increased kinin level points to this effect possibly being caused by the reduced breakdown of locally liberated kinins.
Axilla↗
Local liberation of kinins by working skeletal muscle tissue in man.
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Adult↗
Pharmacokinetic studies with recombinant hirudin in dogs.
The knowledge of the pharmacokinetics of recombinant hirudin is essential for potential clinical use of this selective thrombin inhibitor. For detailed information about absorption, distribution and elimination, pharmacokinetic studies with recombinant hirudin were carried out in dogs. The plasma concentration time curve after intravenous injection could be best described by an open two-compartment model with first order kinetics. The subcutaneous application of recombinant hirudin produced anticoagulantly effective blood level for a prolonged period of time. Recombinant hirudin is distributed into the extracellular space. This is also found in nephrectomized dogs. Recombinant hirudin is eliminated through the kidneys by glomerular filtration in active form with a half-life of 72 minutes.
Animals↗
Toxicological studies with recombinant hirudin.
After daily administration of 1 mg/kg over a period of 4 weeks, hirudin did not influence growth and general behaviour of the animals. There was no indication of treatment-related effects on the liver and the kidneys, on number and function of thrombocytes, on number and differentiation of white cells or on the erythrocytic system. Haemorrhagic complications did not occur. Formation of antibodies was not detectable. Histopathological changes due to application of r-hirudin were not found. LD50 is greater than 50 mg/kg body weight for intravenous application.
Animals↗
On the genomic organization of the human pancreatic secretory trypsin inhibitor.
Oligonucleotide probes were synthesized according to the published cDNA sequence of human pancreatic secretory trypsin inhibitor (PSTI) and used for the screening of a cosmid library of human genomic DNA. One positive clone was isolated, and a subclone obtained after cleavage with a restriction endonucleae (BamHI) was sequenced. The subcloned fragment contained two exons separated by one intron and parts of the two other introns flanking the exons. The exons are encoding five amino acids of the signal peptide and the subsequent 42 N-terminal amino acids of the human PSTI. The available data allow the conclusion that the arrangement of exons and introns in the human PSTI gene is completely identical to that of the chicken ovomucoid and chicken ovoinhibitor genes.
Base Sequence↗
Kallikrein (kininogenase) in the mouse nephron: effect of dietary potassium.
Kininogenase activity of kallikrein was measured in microdissected mouse nephron segments using kininogen from dog plasma and a radioimmunoassay for bradykinin. When single nephron segments were examined, results showed a large scatter. This was found to be due to heterogeneity of distal convoluted tubules (DCT) from different nephrons, since replicate measurements in pools of DCT structures did not show this degree of variation. Nearly 20% of activity was accessible to extracellular substrate when freshly dissected segments were incubated in isoosmotic media. Freezing and thawing which markedly releases activity of intracellular enzymes, did not significantly elevate kininogenase activity. On the other hand deoxycholate and trypsin treatment increased tubular kininogenase activity in an additive fashion. A detailed analysis of microdissected tubule fragments revealed that kallikrein is concentrated in late distal convoluted tubule before entering a branching point (connecting tubule). In contrast initial portions of distal convoluted tubules and cortical collecting tubules contained only little kallikrein activity. Potassium rich diet increased basal and total activity 5-fold, when compared to a potassium poor diet.
Animals↗
Effect of aprotinin and C1-esterase inhibitor on activation of the plasma kallikrein-kinin system in vivo.
Infusion of dextran sulfate in pigs rapidly activates the intrinsic cascade of the coagulation system including plasma prokallikrein and leads to release of kinin by limited proteolysis of kininogen. In this model, strong suppression of the DXS-induced activation of the plasma kallikrein-kinin system is seen at plasma aprotinin levels above 400 KIU/ml and C1INH levels above 4 U/ml.
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↗
Quantitative enzyme-linked immunosorbent assay (ELISA) for hirudin.
A competitive ELISA assay has been developed that permits reproducible quantitation of the anticoagulant hirudin in buffer and urine. Coupling of peroxidase and hirudin was performed with the heterobifunctional reagent N-succinimidyl-3-(2-pyridyldithio)-propionate. In both solvents the lower limit of sensitivity was 8 ng hirudin/ml (0.08 AT-U) while the upper limit was 7.7 micrograms/ml (78.45 AT-U).
Animals↗
The tissue kallikrein-kinin system in human seminal plasma--biochemical and functional aspects.
At least three species of tissue kallikrein-like antigens are present in human seminal plasma which differ in their molecular masses and enzymatic activities. At least one of these species is a genuine tissue kallikrein as judged by the criteria of molecular mass, immunoreactivity, inhibition by aprotinin and non-inhibition by soybean trypsin inhibitor, and the ability to release kallidin from kininogen. The prostatic gland was identified as the origin of the seminal fluid tissue kallikrein first by indirect studies and then by demonstrating the presence of immunoreactive tissue kallikrein both in prostatic tissue and secretion.
Humans↗
Cost effectiveness of alcoholism treatment in partial hospital versus inpatient settings after brief inpatient treatment: 12-month outcomes.
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Adult↗
The primary structure of bdellin B-3 from the leech Hirudo medicinalis. Bdellin B-3 is a compact proteinase inhibitor of a "non-classical" Kazal type. It is present in the leech in a high molecular mass form.
A proteinase inhibitor was isolated from extracts of the leech Hirudo medicinalis by gel filtration and anion exchange chromatography. This inhibitor is similar to the bdellins in that it blocks the activity of trypsin, plasmin and sperm acrosin but has a molecular mass, as estimated by SDS polyacrylamide electrophoresis, of about 20 kDa, whereas the bdellins have molecular masses in the range 5-6 kDa. It is therefore designated as high-molecular mass bdellin B-3 (HMB). The amino-acid sequence of the inhibitor was elucidated as far as position 56. This revealed that the molecule consists of a bdellin B-3 moiety, corresponding to the N-terminal 46 residues, which is then extended at the C-terminus by a polypeptide chain of the composition Asx15, Glx25, Gly6, Val, His26-27 and Lys4. It has been formerly concluded from a partial amino-acid sequence that bdellin B-3 is a Kazal-type inhibitor. However, the complete sequence of bdellin B-3, represented by the N-terminal 46 residues of HMB, discloses that bdellin B-3 is a non-classical Kazal-type inhibitor when the number of amino-acid residues between half-cystines are considered. Presuming that formation of disulfide bridges principally follows the same pattern as in classical Kazal-type inhibitors the bdellin B-3 molecule was modeled based on the known three-dimensional structure of the third ovomucoid domains. This showed that a compact arrangement of the peptide chain of bdellin B-3 is conceivable.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Inhibition of mast cell chymase by eglin c and antileukoprotease (HUSI-I). Indications for potential biological functions of these inhibitors.
Recombinant eglin c (originally isolated from the medical leech) and antileukoprotease (HUSI-I from human seminal plasma) were examined for their ability to inhibit the mastcell protease chymase. Both inhibitors react rapidly with the enzyme: when about equimolar concentrations (in the range of 10(-8) M) of chymase and HUSI-I or eglin c were incubated the complex formation was apparently at equilibrium after 1 or 5 min respectively. When a constant amount of chymase (approximately 3 X 10(-8) M) was incubated with increasing concentrations of inhibitor a concentration of HUSI-I of 7 X 10(-7) M was necessary to cause 50% inhibition of the initial enzyme activity, whereas 8 X 10(-8) M eglin c was sufficient. The dissociation constant of the chymase-eglin c complex was calculated to be 4.4 X 10(-8) M. These results are discussed with respect to the possible in vivo function of antileukoprotease as an inhibitor of mast cell chymase.
Animals↗