Ochratoxin A induced TNFα release from the isolated and blood- free perfused rat liver.

Ochratoxin A (OTA) a naturally occuring mycotoxin is nephrotoxic, hepatotoxic, teratogenic, embryotoxic, genotoxic, cancerogenic and immunosuppressive. Focussing on the immunemodulating effects, we found that OTA induces cytokine release from the isolated and bloodfree perfused rat liver. In the present study, we have characterized the liberation of tumor necrosis factor alpha (TNFα) by OTA and we described interactions with various mycotoxins andE.coli lipopolysaccharide (LPS).

[Clenbuterol and fenoterol--animal experiment comparison of 2 tocolytic agents (with special reference to cardiovascular side effects)]. / Clenbuterol und Fenoterol--Tierexperimenteller Vergleich zweier Tokolytika (mit besonderer Berücksichtigung der kardiovaskulären Nebenwirkungen).

During animal experiments two substances, which are used for tocolysis (Fenoterol and Clenbuterol) have been compared regarding their tocolytic efficiency (determinations of myometrial cyclic AMP after long term treatment of the pregnant rat), their effects upon myocardial high energy phosphates (determinations of maternal myocardial high energy phosphates as well as of maternal and fetal myocardial cyclic AMP after long term treatment of the pregnant rat) and upon the hemodynamic situation (acute experiments with thoracotomized dogs). While significant hemodynamic derangements could be stated when using Fenoterol, no significant evidence for such alterations could be found during Clenbuterol administration during acute experiments. Determinations of myocardial high energy phosphates however reflected an augmented myocardial workload, both after Fenoterol and Clenbuterol administration. As by means of myometrial cyclic AMP determinations Clenbuterol proved to be at least as efficient as Fenoterol, concerning the tocolytic effect, Clenbuterol can be recommended as an oral tocolytic because of its pharmaco-cinetic advantages and the encouraging results from our hemodynamic investigations. According to results from chronical experiments an additional cardioprotection by means of magnesium substitution and eventually beta 1-blockade is still recommended.

[The effect of the beta 1-blocker metoprolol on cyclic 3',5'-adenosine monophosphate in various tissues during long-term tocolysis with fenoterol. Animal experiments on the question of the interactive effects of the principal and adverse effects of beta 2-mimetics with special regard to fetal cardioprotection]. / Zum Einfluss des beta 1-Blockers Metoprolol auf das zyklische 3',5'-Adenosinmonophosphat in verschiedenen Gewebsarten unter Langzeittokolyse mit Fenoterol. Tierexperimentelle Untersuchungen zur Frage interaktiver Effekte bei Haupt- und Nebenwirkungen von beta 2-Mimetika unter besonderer Berücksichtigung der fetalen Kardioprotektion.

Using pregnant Wistar rats a comparative study was carried out, which was aimed to investigate the effect of long-term tocolysis (second half of gestation) with fenoterol alone as well as in combination with the cardioselective beta-blocker metoprolol (Beloc) upon the level of beta-adrenoceptor stimulation in maternal pulmonal, myocardial and myometrial tissue and in the myocardium of the fetuses. Radioimmunologic assessment of cyclic AMP tissue concentrations was used to obtain a parameter for beta-adrenoceptor stimulation. During treatment with fenoterol alone a significant rise of cyclic-AMP could be observed in all tissues, fetal myocardium showing the most pronounced rise. When combining fenoterol and metoprolol no derangement of the desired therapeutical beta 2-effect upon myometrium and lung could be found. Cyclic-AMP concentration in the maternal myocardium, however, was reduced significantly after combination therapy as compared to the monotherapy group, stressing the cardioprotective effect of metoprolol during beta 2-mimetic therapy, which yet has been demonstrated by means of other experimental models. As a similar tendency could be found in fetal myocardium, the conclusion may be drawn that combining metoprolol with fenoterol exerts also a fetal cardioprotection during beta 2-mimetic therapy of pregnant individuals. Furthermore possible effects of this combined therapy upon fetal beta-adrenergic reactions in general are discussed in this study.

[Magnesium aspartate as a cardioprotective agent and adjuvant in tocolysis with betamimetics. Animal experiments on the kinetics and calcium antagonist action of orally administered magnesium aspartate with special reference to simultaneous vitamin B administration]. / Magnesiumaspartat als Kardioprotektivum und Adjuvans bei Tokolyse mit Betamimetika. Tierexperimentelle Untersuchungen zu Kinetik und kalzium-antagonistischer Wirksamkeit oral applizierten Magnesiumaspartats unter besonderer Berücksichtigung von synchroner Vitamin B6-Gabe.

With pregnant Wistar-rats, suffering from alimentary magnesium deficiency, absorption and distributing of Mg28 has been studied, the latter having been applied as aspartate and as chloride, with and without simultaneous substitution of vitamin B6. Absorption and tissue pooling were found to be augmented when using the aspartate and even more when adding vitamin B6. These differences were significant in the blood as well as in fetal and myocardial tissue. Correlation between blood-Mg28 und Mg28-activities in various tissues shows, that blood magnesium levels indicate a magnesium deficiency at least in the tissues of interest: fetus, myocardium, uterus and placenta. Nevertheless blood magnesium levels fail to reflect an additional tissue pooling, that exerts a beneficial action in the respect of cardio protection and of saving beta-mimetic tocolytics. When measuring magnesium and calcium excretion during chronic experiments with and without oral magnesium aspartate substitution, it could be demonstrated, that the amount of substituted magnesium has been pooled almost totally. Oral magnesium substitution furthermore reduces intestinal calcium absorption. Investigation on calcium uptake into the maternal myocardium revealed, that oral magnesium aspartate substitution significantly diminishes myocardial calcium uptake, the latter among others being responsible for cardiac hazards during tocolysis with beta-mimetic substances, while the pharmacologic calcium-antagonist Verapamil failed to do so.

[The cardiac hazard of tocolysis and antagonizing possibilities. II. Communication: protection of the myocardium by means of substitution of magnesium]. / Das kardiale Risiko bei Tokolyse und Möglichkeiten zu dessen Antagonisierung. II. Mitteilung: Kardioprotektion durch Magnesiumsubstitution.

In a comparative study the value of the substitution of magnesium for the evaluation of cardiac side-effects of tocolysis has been assessed with regard to haemodynamic as well as to metabolic and morphologic alterations. Haemodynamic studies at the thoracotomized dog using the technique described in the first publication showed significantly less severe haemodynamic alterations in a group with normal magnesium blood levels than in the second group with reduced magnesium blood levels. Significant differences could be found at systolic blood pressure, cardiac output, velocity and acceleration of pressure rising, total peripherial resistance, myocardial contraction status and myocardial oxygen consumption. Likewise, a beneficial tendency could be found at the parameters: heart rate, Bretschneiders index of inotropy, pulmonal arterial pressure and coronary reserve. During chronic experiments at the rat, the addition of magnesiumaspartate led to a significantly improved preservation of high-energy phosphates in the myocardium with a concomitant reduction of lactic acid output. Also the increase of body weight was significantly higher when substituting magnesium. Microscopic examination showed no irritations of myocardial structure within the magnesium-substituted group, whereas lymphocytic infiltrations and a slight fibrosis of the endocardium could be seen at the animals having received only Fenoterol. Together, these findings lead to the conclusion, that the substitution of magnesium can act prophylactically against cardiac alterations, induced by Fenoterol. Consequently, magnesium deficiency, which frequently accompanies pregnancy, should be balanced before starting a tocolytic therapy.

[The cardiac hazard of tocolysis and antagonising possibilities. I. The haemodynamic situation of the patient during tocolysis/Protection of the myocardium by means of cardioselective beta-blockade. Experimental results (author's transl)]. / Das kardiale Risiko bei Tokolyse und Möglich-keiten zu dessen Antagonisierung. I. Mitteilung: Zur hämodynamischen Situation der tokolysierten Patientin/Kardioprotektion durch Kardioselektive beta-blocker. Tierexperimentelle Ergebnisse.

7 mongrel dogs underwent general anaesthesia and thoracotomy. For the assessment of the haemodynamic situation the following parameters were measured: Left ventricular and aortic pressure, coronary flow, oxygen-saturation in the coronary sinus, pulmonal arterial pressure, central venous pressure, heart rate. From these measurements cardiac output volume and myocardial oxygen consumption could be calculated. Using an ultrasound transit-time method regional myocardial function could be assessed. After the establishment of these measurements Fenoterol has been given in an increasing dosage up to the upper therapeutical range. Then additionally the cardioselective beta-antagonist Metoprolol was administered stepwise up to a total dose of 1.2 mg/kg body weight. The measurements proved evidence, that a relatively small dose of 0,2-0,4 mg Metoprolol/kg body weight is sufficient to compensate the haemodynamic situation impaired by Fenoterol, esp. the rise in myocardial oxygen consumption.

[Effect of the combination of the beta-1-blocker metoprolol with the tocolytic fenoterol on uteroplacental hemodynamics and fetal cardiovascular sensitivity with particular consideration of intrauterine fetal malnutrition. Results of animal experiments]. / Zur Auswirkung der Kombination des beta 1-Blockers Metoprolol mit dem Tokolytikum Fenoterol auf die uteroplazentare Hämodynamik und die fetale kardiovaskuläre Reagibilität unter besonderer Berücksichtigung der fetalen intrauterinen Mangelversorgung. Tierexperimentelle Ergebnisse.

7 merino sheep in an advanced state of pregnancy received oxytocin for labour induction under the conditions of control, monotherapy with the beta 2-adrenergic tocolytic fenoterol, combination of the latter with the beta 1-blocking substance metoprolol (Beloc). Likewise, the effect of labour induction was investigated when putting an artificial stenosis around the a. uterina during simultaneous application of fenoterol alone and combined with metoprolol. The following parameters were measured: aortic pressure and heart rate both in dam and fetus, maternal left ventricular pressure rising velocity, intrauterine pressure, uterine blood flow, uterine vascular resistance and regional myometrial contraction patterns by means of an ultrasonic transit time method. Measurement of maternal cardiovascular parameters once more showed, that maternal cardiovascular derangements could excellently be antagonised by metoprolol. Intrauterine pressure measurements as well as regional myometrial contraction patterns proved evidence, that there is no counteraction between the beta 2-mimetic substance and the beta 1-blocking agent concerning the tocolytic effect. When artificially stenosing the a. uterina, a rise in uterine contraction status could be observed; this hypoxic augmentation of myometrial tone could almost completely be reverted when combining fenoterol and metoprolol. Finally, no difference could be observed in the reaction of fetal cardiovascular parameters to reduced uterine blood flow before and after application of the beta 1-blocking substance metoprolol.

[Optimation of postoperative prophylaxis of thrombosis in gynaecology (author's transl)]. / Optimierung der postoperativen Thromboseprophylaxe in der Gynäkologie. Ein Vergleich von Heparin, Dihydroergotamin, ihrer Kombination und Azetylsalizylsäure.

The prophylactic effect of heparin dihydroergotamine, the combination of these two (Heparin-Dihydergot) and acetylsalicylic-acid in the prevention of deep vein thrombosis was investigated in a prospective randomized clinical trial involving 454 patients. Evidence of thrombosis was detected by the 125I-fibrinogen-uptake-test in 22 out of 75 patients (29.3%) in the control group. The application of 2 x 0.5 mgDHE or 2 x 5000 IU of heparin reduced the incidence of deep vein thrombosis to 7%, which is statistically significant. After simultaneous prophylaxis with both drugs the incidence dropped to 2%. The combined use of DHE and heparin may be considered the best prophylactic regimen available for lowering postoperative DVT. After application of 3 x 0.5 g of ASS frequency of DVT decreased only to 15.3% and shows poor prophylactic efficacy.

[Quantitative assessment of drug-induced prophylaxis of postoperative thromboembolism. Comparison of frequencies of deep vein thrombosis and pulmonary embolism using acetylsalicylic-acid, dextran, dihydroergotamine, low-dose heparin and the fixed combination of heparin and dihydroergotamine (author's transl)]. / Quantitative Bewertung der postoperativen Thromboembolieprophylaxe. Vergleichende Untersuchungen über Thrombose- und Emboliehäufigkeiten unter Acetylsalicylsäure, Dextran, Dihydroergotamin, Heparin sowie der fixen Kombination von Heparin und Dihydroergotamin.

2136 patients in general surgery, gynaecology and urology were investigated by the 125I-fibrinogen-uptake-test for detection of postoperative deep vein thrombosis (DVT). They received at random one of low-dose heparin, dihydroergotamine, the fixed combination of both drugs (Heparin-Dihydergot), low molecular weight dextran and acetylsalicylic-acid (ASS). When DVT was detected repeated lung perfusion scintigraphies were carried out for diagnosis of embolic pulmonary perfusion defects. Results demonstrate the outstanding effect of Heparin-Dihydergot, which is not only 2-3 times better than the anti-thrombotic standard low-dose heparin but also eliminates almost completely the risk of postoperative embolism. The preventive efficacy of ASS and dextran must be considered to be poor and not comparable to that obtained when using heparin, dihydroergotamine or the combination. Now Heparin-Dihydergot is the new standard with which all prophylactic procedures should be compared.

[Breech presentation and its significance (author's transl)]. / Die Beckenendlage und ihre Behandlung

From 1959 to 1975, 1060 (3.6%) breech presentations were found among 29,463 infants. The breech deliveries from May 1, 1959 to December 31, 1965 were compared with those from January 1, 1966 to December 31, 1975. Among the 3.6% breech deliveries there were 47% male and 53% female. There were more primigravida breech deliveries in both groups. The mean age of the mothers was 25.4 years for primigravidas and 29.4 years for multiparas. There was a maternal mortality of 0.2% (2 cases) in breech delivery. 29% of the breech deliveries were premature deliveries. There was a strickingly high incidence of frank and full breech deliveries among all patients. Knee presentations were rare. Delivery was primarily accomplished with the Bracht manoeuver in over 80% of the cases. Complete breech extractions decreased and the incidence of Caesarean Sections rose from 6% in the first group to 21% in the second group of patients. During the past 3 years the Caesarean Section rate was approximately 30%. Perinatal complications in the breech deliveries compare well to those reported in the literature. Of 750 mature infants (70.8%), 12 died (1.6%). Discounting children with congenital malformations and intrauterine stillbirth there remained 5 deaths from breech deliveries (0.7%). Of 1032 breech deliveries with a birth weight of 1000 grams or over, 74 infants (over all perinatal mortality 7.2%) died. 110 infants of all breech deliveries had a birth weight of less than 2500 grams (prematurity rate 29.2%). Of 102 cases of perinatal mortality in breech deliveries including those below 1000 grams 90 (88.2%) were premature. Of those 90 premature deaths, 28 infants were less than 1000 grams. 25 infants showed fetal congenital abnormalities. The corrected perinatal mortality of the premature deliveries was therefore 11.9%. The rate of birth trauma was 6.3% in the first group and 2.7% in the second group.

[The influence of pregnancy on the venous return from the lower extremities (author's transl)]. / Einfluss der Gravidität auf die venöse Drainagefunktion der unteren Extremitäten

Determination of intravenous pressure in the lower extremities revealed in 77 pregnant women a marked insufficiency of the venous drainage. In the last third of pregnancy the capacity of the venous drainage is reduced by approximately 30 per cent. Determination two to five days post partum showed a significant improvement but not yet complete normalization. The causes of the insufficiency of the venous drainage are hormonal influences, dilating the vessels, which are still active post partum. The insufficient venous return is a major factor in the genesis of varicosity during pregnancy. The disturbance of venous return by the large uterus will result in an increase of static venous pressure on the average of 10 mm Hg. In the upright position this is a qualitatively as well as quantitatively individually variable phenomenon. There ist no relation between the increase in static venous pressure and the occurrence of varicosity.

Improved fibrin plate method for fibrinolytic activity measurements: use of bentonite precipitation and agar solidification.

A modification of the fibrin plate method to assure sterility and fibrin stability is described. Bovine fibrinogen is precipitated with bentonite to remove the plasminogen and agar is added to assure stability. Storage of the plates up to 7-10 days has resulted in no bacterial growth. This rapid, sensitive method is useful in the isolation of plasminogen or its activators by chromatographic separation.