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Biomedical subjects

H J Kruse

Publications and source records attributed to H J Kruse.

At least 37 records · Page 2Linked to original sources

Formation of biologically active autacoids is regulated by calcium influx in endothelial cells.

The blocker of receptor-mediated calcium entry SK&F 96365 was used to evaluate the contribution of calcium influx to the formation of biologically active endothelial prostanoids and endothelium-derived relaxing factor (EDRF). SK&F 96365 inhibited histamine-stimulated calcium entry into human umbilical vein endothelial cells but not its discharge from intracellular stores as determined spectrofluorometrically by changes of intracellular calcium concentration in fura-2-loaded cells. Concordantly, SK&F 96365 inhibited histamine-induced endothelial synthesis of 6-keto-prostaglandin F1 alpha and thromboxane B2 in a dose-dependent manner. To assess the functional significance of endothelial formation of prostacyclin and EDRF to platelets, the cAMP- and cGMP-dependent phosphorylation of two platelet proteins, rap1B and a 50-kD vasodilator-stimulated phosphoprotein (VASP), was analyzed in coincubation experiments of endothelial cells with platelets. Autacoids released by histamine-stimulated endothelial cells caused the phosphorylation of rap1B and VASP in platelets, which was only partly inhibited by either indomethacin or NG-monomethyl-L-arginine but was almost completely suppressed by SK&F 96365. The concomitant endothelial release of thromboxane A2 had no effect on protein kinase C- and calcium-dependent phosphorylation of platelet proteins. The results demonstrate that blockade of receptor-mediated calcium entry by SK&F 96365 markedly reduced the release of biologically active prostacyclin and EDRF from endothelial cells. Thus, calcium influx but not calcium release from intracellular stores plays a critical role in the receptor-stimulated formation and liberation of prostacyclin and EDRF in endothelial cells.

Animals↗

Role of L-type calcium channels on stimulated calcium influx and on proliferative activity of human coronary smooth muscle cells.

Dihydropyridine (DHP) calcium channel blockers are widely used in treatment of coronary artery disease. To evaluate the specific role of L-type calcium channels in the antianginal and possibly antiatherosclerotic properties of DHP inhibitors, we examined the effects of a 1,4-DHP agonist and antagonist on angiotensin II (ANG II)- and serum-stimulated calcium influx and proliferation of human coronary smooth muscle cells (cSMC). Fluorometry of fura-2 was used to measure changes in free cytosolic Ca2+ concentration ([Ca2+]i) in cSMC after short- and long-term pretreatment with the calcium agonist Bay K 8644 or the antagonist nitrendipine, respectively. Proliferative activity was quantified during exponential growth in serum-supplemented medium with or without both DHPs. Short- and long-term pretreatment with Bay K 8644 increased basal [Ca2+]i significantly in resting cells and augmented ANG II- and serum-induced sustained [Ca2+]i responses. Concordantly, proliferation rate was increased. In contrast, nitrendipine had no significant effect on basal or stimulated [Ca2+]i after short-term treatment, but decreased [Ca2+]i after 24-h incubation, attenuated the plateau phase of ANG II- and serum-evoked [Ca2+]i transients, and reduced proliferative activity of these cells. The results indicate that 1,4-DHPs modulate ANG II- and serum-induced Ca2+ influx in cSMC. Thus, L-type calcium channels may contribute to [Ca2+]i transients evoked by ANG II and serum. Moreover, the modulating effects of both DHPs on proliferative activity suggest involvement of DHP-sensitive calcium channels. Calcium influx through L-type channels may be one of the mechanisms that determine responsiveness to vasoconstrictors and proliferative activity of human cSMC.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Platelet activating factor enhances receptor-operated Ca(++)-influx and subsequent prostacyclin synthesis in human endothelial cells.

Platelet activating factor (PAF) primes vascular actions of mediators such as histamine and stimulates human umbilical vein endothelial cells (HUVECs) to produce prostacyclin (PGI2), which is important for the regulation of vascular tone, perfusion and hemostasis. We demonstrate that pretreatment of HUVECs with PAF enhances thrombin- or histamine-induced rises of cytosolic free Ca(++)-concentration and subsequent Ca(++)-dependent PGI2-synthesis. Inhibition of Ca(++)-influx and PGI2-formation by SKF96365 (blocker of receptor-operated Ca(++)-channels) in PAF-treated cells indicates that the enhancement of PGI2-synthesis by PAF is due to sensitization of Ca(++)-entry. This suggests cooperative effects of PAF on activation processes induced by thrombin or histamine in HUVECs.

6-Ketoprostaglandin F1 alpha↗

Potentiation of clobazam's anticonvulsant activity by etifoxine, a non-benzodiazepine tranquilizer, in mice. Comparison studies with sodium valproate.

The interaction of two tranquilizers, the 1,5-benzodiazepine clobazam (CBZ, Frisium) and the non-benzodiazepine etifoxin (Hoe-36,801) hydrochloride (EFX, 6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine HCl) was investigated for anticonvulsant activity in mice. Corresponding experiments were performed with the antiepileptic drug sodium valproate (VPA). Tonic-clonic (maximal) seizures were induced by maximal electroshock (MES; 12 mA, 200 ms) and clonic (threshold) seizures by pentetrazol (PTZ; 85 mg/kg s.c.). The addition of an anticonvulsant threshold dose of EFX (50 mg/kg p.o.) led to an increase of CBZ's potency against both MES- and PTZ-seizures by 410 or 450%, respectively. Under the same conditions, EFX enhanced the potency of VPA only by 20 or 80% and a threshold dose of VPA (100 mg/kg p.o.) enhanced the potency of CBZ by 110 or 0%, respectively. It is concluded that this potentiation of CBZ's anticonvulsant activity by EFX may be beneficially used in epileptic patients either to increase CBZ's antiepileptic effects or to reduce CBZ's therapeutic doses in order to prevent or delay the development of resistance.

Animals↗

Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam.

The anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (etifoxine), a non-benzodiazepine tranquilizer, was evaluated in mice in comparison to valproate, phenytoin and clobazam. Maximal seizures were induced by electroshock (MES) and the chemical convulsants pentetrazol (PTZ), picrotoxin (PTX), bicuculline (BIC), isoniazid (INH), nicotine (NIC) and strychnine (STR). Tonic extensor convulsions were prevented by etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (BIC), and greater than 800 mg/kg p.o. (STR). Clonic seizures were induced by threshold doses of PTZ, PTX and pilocarpine (PIL) and antagonized by etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence, etifoxine blocked both tonic and clonic seizures but was more potent against the tonic component. The anticonvulsant profile of etifoxine appeared similar to that of valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test) etifoxine was on an average 3.7, 12 and 14 times superior to valproate, respectively. It is concluded that etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type.

Animals↗

[Evaluation of foetal movement by antenatal cardiotocography (author's transl)].

The part played by cardiotocographically recordable foetal movements was studied. The totality of all cardiotocographically, that is objectively, foetal movements together with all movements perceived, subjectively, by the pregnant women concerned was used as reference value. - A HP-2100S computer was used in on-line evaluation. Those foetal movements perceived by the women concerned were fed into the computer by keyboard input. - Two thirds of all foetal movements were recorded both ways, at one and the same time. A total of 9.1 per cent was not confirmed by the probands, while 27.4 per cent were perceived only by the probands. A total of 72.6 per cent of all foetal movements was recorded by the cardiotocograph, while 80.9 per cent were perceived by the women involved. - Hence, there should be no clinical objection to non-stress testing, but the above data should be taken into account. - As soon as subjectively perceived foetal movements can be objectively marked, the question should be asked for possible superiority of such human perception over tocometry.

Computers↗

[Continuous cervix measurement (author's transl)].

A new technique has been devised for high-continuity recording of cervical dilatation during labour. The measuring principle is based on Hall's effect. The sensor is superior to conventional methods by its smaller dimensions and weight and the possibility of on-line processing. The new method is used in conjunction with cardiotocography to test the action of medicaments upon cervical behaviour and labour.

Cervix Uteri↗

[Normal standards for birth weight and birth length of newborns in the DDR].

Normal anthropometric standards of birth weight and birth length are presented for newborn boys and girls in the GDR between 28 and 44 weeks' gestational age. Newborns with uncertain duration of gestation, multiple births, malformations and stillbirths have been excluded. It is directed to necessity of regional standards.

Anthropology, Physical↗

[Immunochemical investigations on the protein of the "pregnancy zone". XI. Serum concentration of the pregnancy-associated alpha2-glycoprotein (Pregnancy Zone protein) in normal pregnancy (author's transl)].

A quantitative study of the pregnancy zone proteins was made in the sera of 383 healthy pregnant women by means of radial immunodiffusion according to Mancini and co-workers. The serum levels related to a pregnancy serum standard were measured from the 6th to 44th week of pregnancy. The serum concentration of the protein showed a considerable individual variation. The mean concentration began to rise in gestational weeks 8 to 24. Until the week 32 a rather stable average level was reached. Before delivery a slight decrease was observed. Women with over term pregnancies showed particular high mean concentrations. The differences of serum levels were statistically significant until the gestational week 14.

Animals↗

[Intrauterine extra-amnial administration of prostaglandin F 2 alpha for the induction of abortion in primigravidae and problem cases].

With 529 patients (4 groups) abortion was induced through intermittend extraamniotic application of PGF2alpha. In 97,9 per cent, the hourly instillation of PGF2alpha led to the desired success: 25 (4,7 per cent) complete abortions, 416 (78,6 per cent) incomplete abortions, 77 (14,6 per cent) "missed" abortions with opening of the cervix. In groups I to III (primigravidae betw-en the 6th and 12th weeks of pregnancy), in the mean PGF2alpha dosages there were no significant differences between 6,84 and 6,27 mg. The mean abortion time was between 8 hr 32 min and 7 hr 43 min. In group IV ("problem cases" in the first and second trimester of pregnancy), the mean PGF2alpha dosage was 10,68 mg. The mean abortion time 12 hr 04 min. The total complication rate was at 2,2 per cent.

Abortion, Induced↗

[Induction of labor by prostaglandin F 2 alpha in the treatment of hydatidiform mole].

Labour was induced by intravenous infusion of prostaglandin F2alpha (PGF2alpha) in 12 patients with hydatidiform mole. After a mean infusion time of 15 h 51 min and a mean dosage of 25,1 mg PGF2alpha, the infusion of 5 to 40 mug PGF2alpha/min led to 1 to 3 cm dilatation of the cervix. In this way, it was possible to perform a mild evacuation of the molar tissue with vacuum curette or fixation forceps and curette. Under continued PG-infusion the uterus was contracted in the time of evacuation of hydatidiform mole. At present the preoperative dilatation of the cervix by means of PG-induced labour and vacuum curettage is the method of choice in the management of hydatidiform mole because of its effectiveness and few undesirable side effects.

Adolescent↗

[Production of obstetrical reports using a computer].

A rational method of production of medical reports in obstetrics is reported. The basis of this method is the approved computer guided system (DOKUMEDA) in clinics of radiology. Advantages and disadvantages of using are discussed.

Adult↗

[Results of standard-value determinations in newborn infants in the German Democratic Republic. II. Head circumference, biparietal and fronto-occipital diameter].

Using the measurements taken from 6645 male and 6381 female newborns from the GDR-population the normal values from head circumference, fronto-occipital and biparietal diameter are reported. The results were given in relation to duration of pregnancy (31. to 44. week of pregnancy) expressed in percentile tables. Head circumference and fronto-occipital diameter were larger in males than in females. The head circumference values are compared directly and in their relation to birth weight and length with the data reported by other authors.

Cephalometry↗

[Results of a standard value determination concerning newborn infants in the German Democratic Republic. III. Morphologic assessment of maturity].

A simple technique for estimating of maturity in 15589 newborns without technical expense were performed in connection with the examination of birthweight, length, head circumference and head diameters at a gestational age of 31st to 44th week in 21 women's clinics in the GDR. The estimation of maturity is based on the gradual assessment of 8 external physical characteristics. The coefficients of correlation is not differed between characteristics of maturity, measures of newborns and duration of pregnancy. It is not possible to make an accurate statement of duration of pregnancy by this score of maturity than by measures of the newborns.

Anthropometry↗

[Body measurements and morphological signs of maturity in newborn infants after hyperemesis gravidarum].

Birth weights from 128 males and 139 females born between the 39th and 42nd week of pregnancy whose mothers suffered from hyperemesis gravidarum were compared with normal groups of newborns. In the hyperemesis group, the females were on an average 97 g (p less than 0,05) and the males 61 g (p greater than 0,05) heavier than in the control groups. Birth lengths and cephalic measures differed not in both groups. The morphological maturity score was decreased in the hyperemesis groups.

Anthropometry↗