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Biomedical subjects

P Stenberg

Publications and source records attributed to P Stenberg.

At least 73 records · Page 4Linked to original sources
PubMed1980

A specific, fluorescent activity staining procedure applied to plasma and red blood cells in congenital factor XIII deficiency.

The activity staining procedure introduced by Stenberg & Stenflo (1979) has been applied to studies on human blood transamidases (transglutaminases; endo-gamma-glutamine:epsilon-lysine transferases; e.g. factor XIII). The technique combines agarose gel electrophoresis with activity staining based on the transamidase catalysed incorporation of monodansylthiacadaverine (N-(5-amino-3-thiapentyl)-5-dimethylamino-1-naphtalenesulfonamide) into casein. The method permits detection of plasma factor XIII activity down to 1% of the normal adult standard. The technique was used on plasma from two patients with tentative congenital plasma factor XIII deficiency (based on clot solubility). No activity was found in platelet poor as well as in platelet rich plasma which confirmed the diagnosis. In the erythrocytes studied in genetic determinations of the plasma and red blood cell transamidases. Using immunoelectrophoresis, the plasma factor XIII b subunit was found to be 43% and 44% of the concentration in normal standard plasma.

Adolescent↗
PubMed1980

Tissue perfusion and distribution of cardiac output during ketamine anesthesia in normovolemic rats.

Based on previous clinical experience, an anesthetic technique for the rat, using ketamine, has been evaluated. The method comprised an i.v. bolus injection of 30 mg/kg for induction and an i.v. continuous infusion of 1.5 mg/kg/min for maintenance of anesthesia. Minor differences in ketamine metabolism between man and the rat are discussed. It appears that a higher ketamine concentration at the receptor site was required in the rat as compared to man. During ketamine anesthesia in the rat, fractional distribution of cardiac output and regional tissue perfusion were determined with the aid of the microsphere method. The study showed increased fractions to the heart, brain and tongue. The carcass fraction was elevated shortly after induction but reduced during steady-state anesthesia. Stomach, bowel and kidneys received reduced fractions early, but after these fractions returned to their initial levels. As a consequence of the increased cardiac output, regional tissue perfusion was increased in practically all organs.

Anesthesia, Intravenous↗
PubMed1980

Characteristics of the factor VIII protein and Factor XIII in various factor VIII concentrates.

The in vitro properties of 5 factor VIII preparations (AHF-Kabi, Hemofil Hyland, AHF-Profilate Abbott, Kryobulin Immuno and Factorate High Purity Armour) and an ordinary cryoprecipitate were studied with reference to factor VIII clotting activity (VIII:C), factor VIII clotting antigen (VIII:CAg), factor VIII related antigen (VIIIR:Ag) (EI, IRMA, CIE), ristocetin cofactor activity (VIIIR:RCF), fibrinogen and factor XIII. All the preparations with the exception of Factorate had higher levels of VIII:CAg than VIII:C indicating inactivation of the biological activity of VIII:C during the procedure. AHF-Kabi (fraction I-0) and the cryoprecipitate, the only preparations capable of normalising the defect in patients with von Willebrand's disease, showed the same level of VIIIR:Ag determined by EI and by IRMA, while all the other preparations (i.e. cryoprecipitates purified further in different ways) had considerably lower levels of VIIIR:Ag determined by IRMA than by EI. Based on these in vitro techniques it seems to be possible to predict which preparations can be used successfully in patients with von Willebrand's disease, while no such conclusions can be made from VIIIR:RCF determinations. EI yielded similar concentrations of factor XIII a subunit in all the preparations tested. 3 functional assays showed high factor XIII activities in AHF-Kabi but low or no activities in the others. Thus, considerable differences were found on the in vitro properties of the proteins in 5 factor VIII concentrates and a cryoprecipitate. The action of proteases and the techniques used in the purification procedure are probably of crucial importance for the properties of the various factors.

Antigens↗
PubMed1979

Specificity of guinea pig liver transglutaminase for amine substrates.

The amine specificity of guinea pig liver transglutaminase, a model enzyme for endo-gamma-glutamine:epsilon-lysin transferases, was explored with the aid of synthetic substrates of high apparent affinities. As exemplified by dansyl- (5-dimethylamino-1-naphthalenesulfonyl), (2,4-dinitrobenzenesulfonyl)-, and (2,4,6-triisopropylbenzenesulfonyl)-cadaverines--each of which showed affinities of approximately 4 x 10(7) M-1--the best amine substrates carried a large hydrophobic substituent attached to an alkylamine side chain of about 7.2 A in length. Altogether, our results point to the importance of a hydrophobic binding region in the enzyme from where the alkyl side chain reaches into a narrow crevice toward the active center and positions the primary amine of the substrate for attacking the carbonyl group of the acyl enzyme intermediate.

Amines↗
PubMed1979

Food-induced reduction in bioavailability of atenolol.

The influence of food intake on the bioavailability of the beta-adrenoceptor blocker atenolol was assessed by measurement of its single-dose kinetics in ten healthy volunteers, who took 100 mg both in the fasting state and together with a standardized breakfast. Food intake significantly shortened the time to reach peak concentration (2.7 h vs 1.5 h), but caused a significant reduction in AUC values, the mean decrease being 20%. The elimination half-life was unaffected. Atenolol, which is relatively hydrophilic, is incompletely absorbed in the fasting state, and escapes first-pass metabolism. The present findings indicate that food intake causes further impairment of its absorption, even though the absorption rate may initially be enhanced. This contrasts with previous observations on the more lipophilic beta-adrenoceptor blockers propranolol and metoprolol.

Adult↗
PubMed1979

Ketamine infusions: pharmacokinetics and clinical effects.

The clinical effects and pharmacokinetics of ketamine, administered as an i.v. infusion, were studied in 31 patients. Anaesthesia was induced with ketamine 2 mg kg-1 i.v. and maintained using an i.v. infusion of ketamine, supplemented by nitrous oxide. The plasma concentrations of ketamine, nor-ketamine and dehydro-nor-ketamine were analysed using gas-liquid chromatography. The average maintenance dose of ketamine was 41 +/- 21 microgram kg-1 min-1, but there was an obvious decrease in the dose required as anaesthesia progressed. This dose gave a stable plasma concentration of ketamine of 9.3 +/- 0.8 mumol litre-1. Patients recovered at 2.7 +/- 0.9 mumol litre-1. Plasma half-life of ketamine was 79 +/- 8 min. Maximum concentration of nor-ketamine was 4.7 +/- 2.4 mumol litre-1 and of dehydro-nor-ketamine 3.2 +/- 1.9 mumol litre-1. There were transient increases (15-30% of pre anaesthetic values) in arterial pressure, heart rate and cardiac output during operation. No post-operative respiratory depression was seen.

Adult↗
PubMed1979

Fatal iron intoxication with multiple coagulation defects and degradation of factor VIII and factor XIII.

A severe iron intoxication in a 15-year-old girl resulted in profound damage to vital organs and multiple clotting defects, but no haemorrhagic diathesis. Investigation revealed not only impaired synthesis of coagulation factors but also abnormal proteolysis by plasmin as well as by other proteolytic enzymes liberated from leucocytes and damaged tissue cells affecting especially factor VIII and factor XIII.

Adolescent↗
PubMed1979

A new gel for intracervical application of prostaglandin E2.

A new gel-formulation for intracervical application of prostaglandin E2 (PGE2) has been prepared. As a vehicle for the gel a cross-link starch polymer is used. PGE2 substance is added to the starch polymer and after homogenization and lyophilization a PGE2 powder is obtained. The powder can be stored at room temperature for more than four months without inactivation of the prostaglandin. Before clinical application a few ml of saline is added to the powder giving, within 30 seconds, an easily-handled ready to use PGE2-gel. Chemical analysis by spectrophotometric technique reveals that the amount of unchanged PGE2 is the same in the new gel-formulation as in a conventional cellulose gel. In a randomized double-blind study the new PGE2-gel was intracervically applied to twenty nulliparae before abortion by dilatation and evacuation (D & E). Ten women were given a gel containing 0.25 mg PGE2 (PGE2-gel) and ten a gel without PGE2 (placebo gel). It was found that the PGE2-gel, in contrast to the placebo gel, produced a rapid ripening of the cervix facilitating the subsequent D & E. No adverse systemic or local reactions were found during or after the treatment.

Abortion, Induced↗
PubMed1978

Effects of apomorphine and apomorphine-L-dopa-carbidopa on alcohol post-intoxication symptoms.

In a randomised double-blind clinical trial on 58 gamma-alcoholics, the effect of apomorphine given orally in individual subemetic doses was compared with apomorphine-L-dopa-carbidopa and with placebo. No positive effects of treatment with apomorphine, or with the combination apomorphine-L-dopa-carbidopa, on alcohol consumption or post-intoxication symptoms could be demonstrated. In the group which received the combination apomorphine-L-dopa-carbidopa, the post-intoxication symptoms lasted significantly longer than in the other two groups.

Adult↗
PubMed1975

Fibrin-stabilizing factor inhibitors. 12. 5-Dibenzylaminopentylamine and related compounds, a new type of FSF inhibitors.

A series of omegadibenzylaminoalkylamines and related compounds have been prepared and tested as inhibitors of fibrin cross-linking. This structural type was chosen in an attempt to develop noncompetitive inhibitors of fibrinoligase. By the combination of the dibenzylamino moiety at one end and the primary amino group at the other end of a polymethylene chain, the same compound could function both as a pseudo donor substrate and as a noncompetitive alkylating inhibitor. Some of the compounds, notably 74-79, are among the most active fibrinoligase inhibitors described. However, the data indicate that the compounds probably function only as pseudo donor inhibitors.

Benzyl Compounds↗
PubMed1975

Transamidase kinetics. Amide formation in the enzymic reactions of thiol esters with amines.

1. Beta-Phenylpropionylthiocholine and N-(5-aminopentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylcadaverine) serve as a pair of water-soluble (pH7.5) model substrates for transamidating enzymes. Amide formation could be followed directly through fluorescence measurements by monitoring the continuous extraction of the water-soluble coupling product, N-(beta-phenylpropionyl)dansylcadaverine, into n-heptane. By this procedure, the steady-state kinetics of glutamine-lysine endo-gamma-glutamyltransferase from human plasma (fibrinoligase, thrombin- and Ca2+-activated blood coagulation Factor XII) and from guinea-pig liver (liver transglutaminase) were investigated at 25 degrees C. 2. With beta-phenylpropionylthiocholine as the varied substrate, Lineweaver-Burk plots with various concentrations of dansylcadaverine intercept on the horizontal axis, suggesting that formation of the acyl-enzyme is rate limiting. 3. On the basis of functional normality of active sites, kcat. values of 1.8 s(-1) and 0.9 s(-1) were obtained for the plasma and liver gamma-glutamyltransferase respectively. The two enzymes show identical affinities for the first substrate, beta-phenylpropionylthiocholine, with Ka 4 times 10(-4) M. 4. Utilization of the second substrate, dansylcadaverine, appears to be an order of magnitude more efficient with the liver enzyme. 5. N-(5-Amino-3-thiapentyl)-5-dimethylaminonaphthalene-1-sulphonamide (dansylthiacadaverine) could be used instead of dansylcadaverine in the fluorescent kinetic system. 6. Competitive inhibition by a non-fluorescent amine substrate histamine was also evaluated.

Amides↗