Erick Y. Hakanson

Pregnancy in the massively obese: Course, outcome, and obesity prognosis of the infant

The obstetric performance and pregnancy outcome in 208 massively obese patients who were delivered over an eight-year period were compared with those of nonobese control subjects. The incidence of obesity in their infants was also compared. No significant increase in the incidence of urinary tract infection, diabetes, breech presentation, cesarean section, forceps delivery, or maternal and infant morbidity was noted in the obese women. Significantly increased incidences of hypertensive disorders of pregnancy (p less than 0.01), gestational diabetes (p less than 0.01), inadequate weight gain (p less than 0.001), and wound or episiotomy infection (p less than 0.05) were observed in the study group. The mean birth weight of the infants of obese women was 209 grams greater than that of the control subjects. A significantly increased number of the obese patients were delivered of excessive-sized infants. Despite this, the incidence of obesity in infants of obese women was not significantly increased at birth or six months of age. By 12 months of age, however, these infants were significantly more obese than the control infants.

Adolescent pregnancy prevention services in high school clinics.

In 1973 the St. Paul Maternal and Infant Care (MIC) Project opened a health clinic in a local junior-senior high school. This article describes the evolution of the program and services offered and discusses the impact of its birth control activities on the adolescent population served. Wide use of services and high rates of contraceptive continuation led fertility rates to decline by 56% between 1973 and 1976 from 79 to 35 births per 1000. A retrospective review of the records of all students who received family planning services and prenatal care between 1973 and 1979 showed that 403 students had received initial family planning educational medical and counselling services in the 3 MIC school clinics. By the end of the 3rd year 92% of pregnant students had obtained prenatal services and the school dropout rate after delivery declined from 45% to 10%. The 12-month contraceptive continuation rate for 1973-76 calculated by the life-table method was 86.4 per 100 women and the continuation rate for the later years of the project increased to 92.8 per 100 women. Comparison of the high school clinic group with the overall MIC adolescent population served shows a higher proportion in the school group belonging to minority races and a lower proportion of never-pregnant contraceptors. Significantly fewer patients were lost to follow-up in the school group than in the overall MIC teen clinic group. Factors contributing to the effectiveness of the program in the schools included consistency of staff offering personalized services with guaranteed confidentiality accessibility of free services and provision of educational and social as well as medical services.

Pregnancy in the underweight woman. Course, outcome, and growth patterns of the infant.

The obstetric performance and pregnancy outcome of 354 underweight patients were compared with matched control subjects of normal weight. The growth patterns of their infants were also compared. The underweight women had significantly higher rates of cardiac/respiratory problems, anemia, PROM, and endometritis but were less prone to develop pre-eclampsia. Prematurity and low Apgar scores were significantly more frequent in the infants of underweight women. There was no difference in the frequency of IUGR and in perinatal mortality rates. The mean birth weight of the infants of underweight women was 231 grams less than that of infants of control subjects. Underweight women, particularly if they were anemic, had a higher incidence of low-birth-weight infants despite adequate weight gain. AGA infants of underweight women were more likely to be below the twenty-fifth percentile for weight correlated with length by 12 months of age.

17β-Hydroxysteroid and 20α-hydroxysteroid dehydrogenase activities of human placental microsomes: Kinetic evidence for two enzymes differing in substrate specificity☆

Abstract During storage at 4 °C, the 17β-hydroxysteroid dehydrogenase activity of human placental microsomes with estradiol-17β was more stable than that with testosterone. In order to evaluate the basis for this difference, kinetics with C18-, C19-, and C21-steroids as substrates and/or inhibitors was studied in conjunction with an analysis of the effects of detergents. Both 17β-hydroxysteroid dehydrogenase (17β-HSD) and 20α-hydroxysteroid dehydrogenase (20α-HSD) activities were detected. At pH 9.0, apparent Michaelis constants were 0.8, 1.3, and 2.3 μ m for estradiol-17β, testosterone, and 20α-dihydroprogesterone, respectively. 17β-HSD activity with testosterone was inhibited by estradiol-17β,5α-dihydrotestosterone, 5β-dihydrotestosterone, 20α-dihydroprogesterone, and progesterone. In each case 90 to 100% inhibition was observed at 50 to 200 μ m steroid. Activity with 20α-dihydroprogesterone was similarly sensitive to inhibition by C19-steroids. By contrast, 25 to 45% of the activity with estradiol-17β was not inhibited by high concentrations of C19- or C21-steroids and differed from the 17β-HSD activity with testosterone and the major fraction of that with estradiol-17β by being insensitive to solubilization by detergent. These results are consistent with an association of two dehydrogenase activities with human placental microsomes. One recognizes C18-, C19-, and C21-steroids as substrates with comparable affinities. The second appears to be highly specific for estradiol-17β. The former activity may account for most if not all of the oxidation-reduction at C-17 of C19-steroids and at C-20 of C21-compounds at physiological concentrations by term placental tissue.

Modification of the kinetic properties of 5-ene, 3β-hydroxysteroid dehydrogenase of human placental microsomes by hydrogen peroxide and 2-mercaptoethanol

The kinetic properties of 5-ene,3β-hydroxysteroid dehydrogenase of human placental microsomes were modified by H2O2 and 2-mercaptoethanol. With microsomes prepared in the presence of 2-mercaptoethanol the KM values were 0.035 μM for pregnenolone and 1.9 μM for NAD+. When the microsomes were treated with H2O2 the values were 1.20μM for pregnenolone and 30.0 μM for NAD+. The H2O2 effect was reversed by 2-mercaptoethanol. Identical effects were seen with detergent-solubilized enzyme. With H2O2-treated enzyme progesterone, androstenedione and 20α-hydroxyprogesterone were non-competitive inhibitors with KI values of 5.5, 0.83 and 4.1 μM respectively. The results indicate that the enzyme can exist in at least two kinetically different forms and that the km values for NAD+ and pregnenolone in vivo may be significantly lower than previously thought.

Inhibition of human placental 17β-hydroxysteroid dehydrogenase by steroids and nonsteroidal alcohols: Aspects of inhibitor structure and binding specificity

Abstract Inhibition of human placental 17β-hydroxysteroid dehydrogenase by C 18 and C 19 steroids and nonsteroidal alcohols was assayed at pH 9.0 with 17β-estradiol 3-methyl ether and NAD + as reactants. The nonstaroidal alcohols tested were poor inhibitors. Cyclopentanol and cyclohexanol had K i values greater than 5 m m . Nonaromatic C 18 and C 19 steroids with oxygen functions at both positions 3 and 17 gave no detectable inhibition or had K i , values greater than or equal to 160 μ m . 3μ-Hydroxy-5,16-androstadiene, 5-androsten-3β-ol, 1,3,5(10)-estratrien-3-ol, and 1,3,5(10),16-estratetraen-3-ol, steroids lacking a C(17) oxygen function, had K i values of 1.8, 6.0, 0.04, and 0.17 μ m , respectively, demonstrating that both C 18 and C 19 steroids can bind at the steroid site. Binding specificity is narrowed and binding affinity for nonaromatic steroids weakened by oxygen functions at C(17) or both C(3) and C(17). The structural implications of the specificity data for steroid recognition and complex formation and in vivo control of enzyme activity are discussed.

Inhibition of 17β-hydroxysteroid dehydrogenase (17β-HSD) activities of human placenta by steroids and non-steroidal hormone agonists and antagonists

Various naturally occurring steroids, synthetic steroid derivatives and non-steroidal hormone agonists and antagonists were assayed as inhibitors of human placental 17β-HSD activities. Microsomal 17β-HSD was inhibited by C18 -,C19- and C21-steroids. Soluble 17β-HSD was highly specific for C18-steroids. In contrast to the soluble activity, the microsomal enzyme also had a strong affinity for ethinylestradiol (KI=0.3 μM) and danazol (KI=0.6 μM); anabolic steroids and norethisterone were weaker inhibitors. Of the non-steroids tested only diethylstilbestrol and o-demethyl CI-680 were inhibitors and they showed a greater affinity for soluble 17β-HSD. KI-values for estradiol-17β, (0.8 μM), progesterone (27.0 μM) and 20α-dihydroprogesterone (1.5 μM) were comparable to reported tissue levels of these compounds, consistent with a possible competition in vivo among naturally occurring C18-, C19-, and C21-steroids for the active site of microsomal 17β-HSD.

Maternal intravenous ethanol in the prevention of respiratory distress syndrome.

The occurrence of respiratory distress syndrome (RDS) was studied in 68 premature neonates whose mothers were treated with at least one six-hour course of intravenous ethyl alcohol within 48 hours before delivery. At the gestational interval of 28 to 32 weeks, significant differences were observed in the incidence of RDS (p = less than 0.05), in severe RDS (p = less than 0.005), and in the mortality rate from RDS ( = less than 0.05), when compared to premature neonates not treated with alcohol and delivered during the same time interval. Several high-risk factors were found unevenly distributed between treated and control groups of patients, and their relevance to RDS was discussed. Premature rupture of membranes of more than 24 hours did not protect infants from RDS in the patients studied. Explanations for possible mechanisms of action are discussed.

A simple method for detecting steroid aggregation and estimating solubility in aqueous solutions.

Abstract Steroids are generally sparingly soluble in water. Thus, for in vitro studies of steroid metabolism or enzymology it is common practice to solubilize steroids by the addition of a small amount (2–10%, v/v) of an organic cosolvent. Methanol, ethanol, and 1,2-propanediol, singly or in combination, have been widely used (1). Effects of organic solvents on the kinetic parameters, Km and Vmax, of steroid-metabolizing enzymes with various substrates have been demonstrated (2,3), and the results are consistent with the conclusion that organic solvent influences on catalytic activity reflect, in part, effects on the aggregation state and solubility of steroid substrates. Light-scattering measurements have been applied extensively in studies of macromolecular structure (4) and micelle formation by a large variety of amphiphilic substances [reviewed in Ref. (5)]. Jones and Gordon (6) used a commercial instrument, designed specifically for light-scattering measurements, to characterize micelle formation in aqueous solutions by Δ5-3-ketosteroids containing various substituents at the 17β position. They showed that turbidity versus concentration plots were of the form seen in studies of micelle formation (5) and that steroids can exist in solution in monomeric or micellar forms, their aggregation state being a function of the polarity of the steroid solute and the composition of the solvent. To estimate solubility quantitatively 3H- or 14C-labeled steroids have been used in conjunction with centrifugation (3), dialysis (7), or filtration (8). These techniques allow for accurate estimates of solubility, but one may encounter problems due to nonspecific absorption on membranes or the unavailability of the labeled steroid of interest. We have observed that steroid aggregation and solubility can be estimated easily and with high sensitivity with a commercially available fluorometer. In this report the method is described and examples demonstrating the reproducibility and sensitivity of the technique are presented.

Microsomal 17β-hydroxysteroid dehydrogenase of guinea pig liver: Detergent solubilization and a comparison of kinetic and stability properties of bound and solubilized forms

Abstract Microsomal 17β-hydroxy steroid dehydrogenase of guinea pig liver, solubilized in Triton X-100, was obtained in phospholipid-free form and physical parameters were estimated by agarose gel chromtography and density gradient centrifugation. The values for the sedimentation constant, s20,w = 5.2 s, partial specific volume, v = 0.78 ml/g , and Stokes radius, a = 66 A, indicated a molecular weight of 176,000 for the solubilized enzyme and were consistent with the presence of a significant amount of bound detergent. Triton X-100 was an inhibitor competitive with testosterone with a K1 of 0.11%. With solubilization the apparent km for testosterone was increased from 2.2 μM to 7.3 μM and the apparent KM for NAD+ reduced from 164 to 100 μM. The susceptibility to urea or trypsin inactivation was increased after solubilization. Enzymatic activity was stable for at least 48 h in 1% (v/v) Triton X-100 but was lost within 24 h in deoxycholate. The results show that phospholipids are not absolutely required for activity but the changes in kinetic and stability properties with solubilization are consistent with a role for membrane components or bound detergent in affecting the structure and catalytic properties of the enzyme.