Serum bile acid profile in women during pregnancy and childbed.

Oestrogens produce cholestasis by inhibition of bile acid (BA) transport as well as by inhibition of BA synthesis in the liver. The present work was done to clarify the relevance of altered serum BA profile in 28 healthy pregnant women from the 15th to the 40th weeks of pregnancy with increasing oestrogen serum concentrations in comparison to 6 to 8 weeks after delivery with normalized oestrogen status. For the first time 6 free and 10 taurine- and glycine-conjugated BAs were analysed during the normal pregnancy by HPLC with postcolumn derivatisation and fluorescence detection. The primary BAs cholic (CA) and chenodeoxycholic acid (CDCA) as well as their glycine (G-) and taurine (T-) conjugates amount to nearly 70 % of total BAs in serum and were not changed from the 15th to the 40th weeks of pregnancy, but free and G-CDCA increased significantly after delivery. Among the secondary BAs, which were produced in the intestine by bacteria due to dehydroxylation of the primary bile acids CA and CDCA, only taurine-conjugated deoxycholic acid (T-DCA) decreased significantly after delivery. The free BAs, produced by bacteria in the intestine due to deconjugation, were not changed during pregnancy but had doubled in childbed. Some BAs occurred seldom and in small amounts in the serum, but during pregnancy not more frequent than after delivery. Contrary to expectation the increasing oestrogen concentrations did neither enhance total serum bile acids nor change bile acid profile during pregnancy.

Perinatal morbidity in women with undiagnosed gestational diabetes in northern thuringia in Germany.

INTRODUCTION: Undiagnosed gestational diabetes mellitus (GDM) is associated with severe perinatal complications. PATIENTS AND METHODS: Out of 970 women, infant and maternal morbidity was assessed in 114 mother-children-pairs with an infant birth weight over the 90th percentile (Voigt et al., 1996). It was the aim of this retrospective study to assess the number of mothers with undiagnosed GDM, who have born a macrosomic child. RESULTS: The macrosomia rate in newborns was 12 % in this study excluding macrosomic infants of mothers with preexisting diabetes mellitus. Maternal data: Age 28.3 +/- 5.3 years, adipositas (body-mass-index > 30 kg/m) in 42.1 % vs. 30.4 % in the peer group (p < 0.02), increase in weight > 15 kg during pregnancy in 57.9 % of the mothers who have given birth to a macrosomic child vs. 30.9 % in the peer group (p < 0.0001), family history of diabetes mellitus (28.0 % vs. 11.3 % in the peer group, p = 0.006), preeclampsia in 8.8 % vs. 2.7 % in the peer group (p = 0.002), cervical insufficiency in 2.6 % vs. 0.4 % in the peer group (p = 0.02). After delivery HbA1c was elevated in 38.6 % of the women having born macrosomic infant (mean HbA1c: 5.0 % +/- 0.5). Infant data: neonatal jaundice 16.7 % vs. 4.5 % in the peer group, p < 0.0001. There were no statistically significant differences concerning perinatal condition and malformations. Neonatal hypoglycaemia occurred in 9.6 % of the macrosomic infants. Cord blood insulin levels were significantly elevated in comparison to the peer group of mothers without metabolic disorders and having born eutroph infants (8.4 mU/l [3.0 - 100.0] vs. 5.3 mU/l [3.0 - 30.7], p = 0.01). 11.4 % of all macrosomic infants had cord blood insulin levels above the normal range. CONCLUSION: More than one third of the mothers having born one or more macrosomic infants had an impairment of glucose metabolism immediately after birth. The elevated prevalence of preeclampsia in this group confirms the relationship of hypertension and impaired glucose metabolism during pregnancy. The detection of hyperinsulinaemia, postnatal hypoglycaemia, elevated prevalence of neonatal jaundice with need of further therapy and diabetic fetopathy in macrosomic infants of mothers, whose metabolism was not monitored during pregnancy, pinpoint the need for a diagnostic screening for GDM.

Peroxidative and glutathione status in uterus and placenta after normal and pathological pregnancy.

In 10 women with disturbed pregnancies without hypertension, reduced (GSH) and oxidized glutathione (GSSG) as well as lipid peroxides as thiobarbituric acid reactive substances (TBARS) were determined in the placenta and in the uterine tissue after unexpected stress-induced Caesarian section (group II). Production of TBARS was also measured in vitro in the 9000 x g supernatant of both tissues. The results were compared with those from women after normal pregnancy and expected Caesarian section (group I). After normal pregnancy higher TBARS and lower GSH with higher GSSG/GSH ratio were found in the placenta in comparison to the uterine tissue, indicating an oxidant/antioxidant imbalance in the placenta. No statistically significant differences were shown between the parameters of groups I and II. The possible oxidant stress associated with disturbed pregnancy and subsequent unexpected Caesarian section in this study was insufficient to alter tissue levels of glutathione nor the peroxidative status of placenta and uterus.

[The concentration of oxacillin and ampicillin (Penstabil) in serum and mother's milk in puerperal mastitis]. / Untersuchungen zur Konzentration von Oxacillin und Ampicillin (Penstabil) in Serum und Muttermilch bei der Mastitis puerperalis.

In 23 women in childbed suffering from mastitis puerperalis the transport of oxacillin and ampicillin into the milk was investigated. Moreover the concentration of the antibiotics in the urine of babies nursed during therapy of their mothers with antibiotics was measured. After a regular taking (good compliance) the drug-concentrations in the serum and the milk of the mothers are higher than the minimal inhibiting concentrations necessary against the number of bacteria found in the milk. In the urine of suckling babies drug concentrations were differently high or undetectable as well. During the therapy of nursing mothers with antibiotics the milk should be misplaced.

[Placental passage of nalidixic acid (Negram) and pharmacokinetic studies in the newborn infant]. / Die Plazentapassage von Nalidixinsäure (Negram) und pharmakokinetische Untersuchungen bei Neugeborenen.

Nalidixic acid and hydroxynalidixic acid penetrate the placenta during labour. During the first 24 h of life the serum concentrations of nalidixic acid and nalidixic acid plus hydroxynalidixic acid decline slowly and show individual differences. The changed kinetic parameter in the newborn, especially the delayed elimination of nalidixic acid as well as nalidixic acid plus hydroxynalidixic acid lead to the consequence of recommendation of a very strong therapeutic indication in the peripartal period.

[The pharmacokinetics of ampicillin in pregnant women with H-gestosis in the last trimester of pregnancy]. / Untersuchungen zur Pharmakokinetik von Ampicillin bei Schwangeren mit einer H-Gestose im letzten Trimenon der Schwangerschaft.

In this paper pharmacokinetic data of ampicillin in 9 pregnant women with H-gestosis are compared with those from 8 healthy pregnant women in the last trimenon. 5 g Ampicillin were given as an i.v. bolus-injection. Ampicillin was determined in serum and urine by a polarographic method. Important kinetic data, such as concentration in serum, distribution into the peripheral compartment and t1/2 beta do not differ. The non-significantly changed central distribution volume (V1) as well as the reduced renal excretion in combination with normal serum creatinin values have to be considered in connection with the general constriction of blood vessels in pregnant women with H-gestosis. From the kinetic data one cannot derive any necessity for changing the mode of application or the dose of ampicillin in pregnant women with H-gestosis.

[Blood level kinetics of sodium noramidopyrine methanesulfonate (Analgin) in late pregnancy]. / Untersuchungen zur Blutspiegelkinetik von Noramidopyrinmethan-sulfonat-Natrium (Analgin) in der Spätschwangerschaft.

The pharmacokinetic parameters were investigated after a single application of 1,0 g of Analgin to women in labour in comparison with a nonpregnant control group. During the late stage of pregnancy the distribution volume is only slightly increasing. For Analgin a fundamental influence on the level of serum concentration could not be shown. The biological half-life of Analgin shows remarkable individual differences and does not differ significantly between the two investigated groups. Therefore, during pregnancy a change of the applied dose is not indicated.

[Studies on the kinetics of methaqualone during the late stage of pregnancy (author's transl)]. / Untersuchungen zur Kinetik von Methaqualon in der Spätschwangerschaft.

After oral administration of 0.4 g of methaqualone to pregnant and non-pregnant women, the authors stated that the half-life of this drug was significantly reduced during the last trimester of pregnancy. The two experimental groups showed no significant differences in the volume of distribution and the fictitious initial concentration. The commonly used therapeutical dosages are not likely to produce increased blood levels during normal pregnancy.

[Pharmacokinetics and electrolyte balance following administration of furosemide in pregnant women with E gestosis]. / Pharmakokinetik und Elektrolythaushalt nach Furosemidgabe bei Schwangeren mit E-Gestose.

In pregnant women with E-gestosis distribution and elimination of furosemid are significantly different to a non-pregnant control group. Furosemid guarantees a rapid and safe excretion of edemas. The efficiency of furosemid concerning electrolyte excretion is stronger in pregnant women with E-gestosis than in nonpregnant women. Therefore furosemide should be administered to pregnant women under intensive electrolyte control only.

[The pharmacokinetics of pethidin (Dolcontral) of parturient and their new-borns (author's transl)]. / Pharmakokinetik von Pethidin (Dolcontral) bei Kreissenden und ihren Neugeborenen.

The pharmacokinetic parameters were investigated after a single i.v. application of 50 mg of pethidine (Dolcontral) to women in labour and nonpregnant women. In comparison with the control group (4,2 h) the women in labour had a prolonged biological half life (7,5 h). Furthermore, there was a distinction of distribution parameters. The relation between the average concentration of pethidine in newborn and maternal serum was 0,72. The concentration of pethidine in newborn serum was stated always not as high as the corresponding maternal serum level. There was a significant correlation (r = 0,88) between maternal and fetal pethidine concentration. The half life of pethidine was found to be prolonged (17,2 h) in newborns within two days after birth. The distribution volume and the plasma distribution coefficient were repeatedly enhanced.

[Mass spectrometric determination of pethidine in biological samples (author's transl)]. / Massenspektrometrische Bestimmung von Pethidin in biologischen Proben.

A mass spectrometric method for the determination of pethidine in nanogram range is described. This method excels by its high sensitivity and specificity, which ensures the reliable quantitative determination of the pharmacon also in complex media. Pethidine is extracted with ether from the respective sample together with its (D5) derivative (which is added as an internal standard) and directly (or after gas-chromatographic separation from other components) determined by mass spectrometry. The pethidine concentration is calculated from the ratio of the sums of the molecular ion intensities M+-pethidine/M+-(D5)-pethidine, which are obtained from the chromatographic column by repetitive scanning during the elution of pethidine and its (D5) derivative, respectively.

[Studies on the kinetics of methaqualone in the course of labour (author's transl)]. / Untersuchungen zur Kinetik von Methaqualon sub partu.

A 0,4 g (1598,06 mumol) dose of methaqualone was administered orally to 19 parturient at the beginning of the first stage of delivery. In comparison with former results, got from a control-group of nonpregnant and pregnant women in the last third of pregnancy, it was found a significantly prolonged biological half-life and a decrease of the fictitious initial concentration.

[The effect of propranolol (Obsidan) as well as propranolol and fenoterol (Partusisten) on the motility of the smooth uterus musculature in vitro]. / Die Wirkung von Propranolol (Obsidan) sowie von Propranolol und Fenoterol (Partusisten) auf die Motalität der glatten Uterusmuskulatur in vitro.

Propranolol (1; Obsidan) relaxes in vitro stripes of smooth muscles of non-pregnant rat's uterus in a concentration dependent manner. In contrast, on uterine muscle stripes of pregnant rats 1 causes small contractions. In an combination of 1 and fenoterol (2; Partusisten) (20:1) 1 prevents the relaxing effect of 2, reported to be an inhibitor of uterine muscle activity. This antagonism is most distinct on stripes of pregnant rat's uterus.

[The pharmacokinetics of cephalothin following single and repeated administration in man]. / Zur Pharmakokinetik von Cefalotin nach einmaliger und wiederholter Applikation beim Menschen.

The repeated administration of substances, which are mainly excreted by tubular secretion, can cause an increase of its own elimination. Because cephalothin is tubularly transported, it was of interest to prove, whether or not the repeated administration of therapeutic doses for 5 d produces an increases of renal elimination. Pharmacokinetic parameters show only small differences between the single and repeated dosing, caused by changes of volume of distribution. No stimulation of the carrier transport system was found. On the contrary, the renal elimination was reduced slightly after therapy for 5 d. Our results show that the present dosage recommendations are valid also for repeated administrations.

[The effect of intrahepatic cholestasis in pregnancy on various forms of cytochrome P-450-dependent biotransformation reactions]. / Der Einfluss der intrahepatischen Schwangerschaftscholestase auf verschiedene Cytochrom P-450-abhängige Biotransformations-reaktionen.

The elimination of caffeine from plasma and the excretion of the main metabolites of metamizol (noramidopyrinemethanesulphonate sodium) into the urine were determined in healthy pregnant women (weeks 30-38 of pregnancy) and in patients with intrahepatic cholestasis in pregnancy (weeks 28-39 of pregnancy). From the elimination velocity of these model substances conclusions concerning the activity of 3-methylcholanthrene (caffeine elimination) and phenobarbital inducible isoenzymes (metamizol elimination) of cytochrome P-450 are drawn. Patients with intrahepatic cholestasis in pregnancy (t1/2 = 15.8 +/- 1.8 h) eliminate caffeine more slowly than healthy pregnant women (t1/2 = 11.0 +/- 0.8 h) at this stage of pregnancy. The excretion of the metabolites of metamizol is only in tendency diminished in patients with intrahepatic cholestasis. The influence of the intrahepatic cholestasis on the cytochrome P-450 isoenzymes investigated differs in degree.

[Comparison of the pharmacokinetics of iron in pregnant and nonpregnant women after oral administration of Vitaferro]. / Vergleichende Untersuchungen zur Pharmakokinetik von Eisen bei schwangeren und nichtschwangeren Frauen nach Gabe von Vitaferro.

In this paper we represent results concerning pharmacokinetics and bioavailability of iron after the oral application of Vitaferro to women in the second half of pregnancy suffering or not from anaemia in comparison to nonpregnant women. The significance of different parameters used to proof an iron deficiency is discussed. In all pregnant probands the bioavailability of Vitaferro is about twice as high as in nonpregnant women. Also the parameters of elimination refer to an enhanced retention of iron during pregnancy. We conclude from our investigations that an iron deficiency may be diagnosed well by the determination of haemoglobin values, iron concentration in serum, binding capacity and resorption of iron. During pregnancy the preparation Vitaferro is well resorbed and does not cause incompatibilities. Thus it is suitable for the treatment of anaemia during pregnancy.

[The pharmacokinetics of magnesium sulfate in pregnant women with threatened abortion and fetal retardation]. / Untersuchungen zur Pharmakokinetik von Magnesiumsulfat bei Schwangeren mit drohender Frühgeburt und fetaler Retardierung.

A contribution concerning distribution and elimination of magnesium sulphate in pregnant women with preterm labour and fetal retardation is given. From the kinetic parameters calculated a dosage regimen is recommended. To describe the physiologic magnesium level in plasma by a two-compartment model a kind of "continuous infusion" was assumed.

[On the kinetics of pethidine in the late state of pregnancy (author's transl)]. / Zur Kinetik von Pethidin in der Spätschwangerschaft.

The kinetic of pethidine (Dolcontral) during late pregnancy was investigated by means of an open two-compartment-model. The results were compared with a control group of nonpregnant women. Some pharmakokinetic parameters were found changed during gravidity, especially the distribution (V1, Vdss, Cpo, delta'), the elimination half-life and the biological half-life (t 1/2; ke1, t 1/2; beta). There was no significant difference in urin excretion of pethidin and norpethidin between both groups.

[The pharmacokinetics of cephalothin during the late stage of pregnancy and in the course of labour (author's transl)]. / Pharmakokinetik von Cefalotin in der Spätschwangerschaft und unter der Geburt.

Using an open one- and two-compartment model, the authors studied the kinetics of cephalothin during pregnancy and in the course of labour as well as in a group of non-pregnant women. They found that the parenteral application of cephalothin leads to therapeutic levels in the serum, tissues and urine also during pregnancy and in the course of labour. The bearing of pregnancy and labour on the kinetics of cephalothin is but insignificant; consequently, no modification of the pharmacotherapy will be necessary.

[Studies on the kinetics of nitrofurantoin (Nifurantin) in normal pregnancy, gestoses, pyelonephritis and labor (author's transl)]. / Untersuchungen zur Kinetik von Nitrofurantoin (Nifurantin) in der normalen Schwangerschaft, bei Gestosen, Pyelonephritis und unter der Geburt.

After oral administration of 300 mg of nitrofurantoin (Nifurantin) to various groups of pregnants, to women in labour and nonpregnant women the blood level and renal excretion of nitrofurantoin were investigated. We stated that gravidity, pyelonephritis and EPH-gestosis did not alter neither the renal excretion nor the blood level. In contrast to this during labour the renal elimination of nitrofurantoin was diminished and the blood concentration was enhanced. The biotransformation of nitrofurantoin seems not to be changed by pregnancy.