Sertraline versus desipramine in the treatment of premenstrual syndrome: an open-label trial.

BACKGROUND: Antidepressant medications have appeared to be effective treatments for premenstrual syndrome (PMS) in several small trials. This open-label study examined the efficacy of and tolerance for a new serotonergic antidepressant compared with a traditional tricyclic antidepressant in PMS treatment. METHOD: For two menstrual cycles in women meeting well-defined criteria for PMS, an open-label comparison of the serotonin selective sertraline (N = 17) and the noradrenergic desipramine (N = 15) was performed. Dose was flexible, with a mean dose in the second cycle of 87 mg/day for sertraline and 110 mg/day for desipramine. Outcome measures were the premenstrual daily symptom report (DSR) scores and the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Sertraline and desipramine reduced depressive symptoms as assessed by the HAM-D, both achieving similar reductions in the HAM-D scores. Reduction of total premenstrual symptoms as assessed by the DSR score was observably greater with sertraline, but the difference compared with desipramine was not statistically significant in this small sample. Subjects were more likely to perceive desipramine side effects as intolerable; 4 of the 15 desipramine-treated subjects discontinued compared with none in the sertraline group. Subjects who were previously treated in a PMS program without good therapeutic response were less likely to respond to either medication, suggesting a treatment-resistant group. CONCLUSION: Sertraline and possibly desipramine appear to be effective treatments for PMS. Sertraline was better tolerated, resulting in greater patient acceptance. A placebo-controlled trial in which subjects are randomly assigned to the medication is clearly needed to support or refute these preliminary findings.

Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.

The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) family. Very little is known about VLDLR localization and regulation. Immunohistochemical analysis of human placenta with a specific polyclonal antibody detected VLDLR in syncytiotrophoblast and intermediate trophoblast cells. VLDLR transcripts were also localized in these cells by in situ hybridization histochemistry. In addition, VLDLR messenger RNA (mRNA) was detected in villous core endothelial cells and cells appearing to be Hofbauer cells. Northern blot analysis of placenta revealed a 2.6-fold increase in VLDLR mRNA at term compared to that in the first trimester. The regulation of VLDLR expression was studied in JEG-3 and BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Treatment of these cells with 8-bromo-cAMP caused a profound suppression of VLDLR message, whereas LDLR transcripts were increased. Incubation of JEG-3 cells with 25-hydroxycholesterol did not lead to sterol negative feedback on VLDLR gene expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up-regulated VLDLR message in JEG-3 cells 2-fold, as did the fibrate hypolipidemic drug, clofibric acid. We conclude that 1) VLDLR is expressed in human placental trophoblast cells in a pattern consistent with a role in placental lipid transport; 2) VLDLR expression is high at term relative to that in the first trimester; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and up-regulation by insulin and fibrate hypolipidemic drugs.

Effect of follicular size on oocyte retrieval, fertilization, cleavage, and embryo quality in in vitro fertilization cycles: a 6-year data collection.

OBJECTIVE: To determine the effect of follicular size, including the size of the leading follicle, on oocyte retrieval, fertilization, cleavage, and embryo quality in IVF cycles based on a large data collection. DESIGN: Retrospective analysis of 1,109 IVF cycles between 1987 and 1993 at the Hospital of the University of Pennsylvania including 606 patients ranging in age from 23 to 49 years. RESULTS: Follicles with a volume < or = 1 mL show a significantly lower oocyte recovery rate than follicles with a volume of > 1 mL. The highest recovery rate (83.5%) was found in follicles with a volume of 3 to 4 mL. Above a follicular volume of 7 mL, the oocyte recovery drops below that observed for follicles between 1 and 7 mL. Fertilization and cleavage rates were also higher in oocytes obtained from follicles > 1 mL compared with follicles < or = 1 mL. Although fertilization rates were fairly stable above volumes of 1 mL, cleavage rates continued to rise to a peak percentage of 92% with volumes between 6 and 7 mL. Leading follicle size did not have an effect on fertilization and cleavage rates of cohort oocytes. Embryo quality was not influenced significantly by follicular volume. CONCLUSION: Based on this evaluation of a large number of follicles, follicular size is a useful indicator of oocyte recovery, fertilization, and cleavage in IVF cycles. For optimal results, the follicular fluid volume in gonadotropin- and hCG-stimulated cycles should be > 1 mL, which corresponds to a follicle diameter of > 12 mm, and not larger than 7 mL (24 mm). For timing of hCG administration, the number of adequate size follicles appears to be more important than the size of the leading follicle(s).

Neonatal depression after a protamine sulfate injection. A case report.

The intravenous administration of protamine sulfate in adults has been associated with acute hypotension, bradycardia and anaphylactoid reactions. However, no reports of its use in pregnancy have been available before. We describe a case of severe neonatal depression following maternal protamine sulfate injection immediately prior to delivery.

Longitudinal study of semen quality in Wisconsin men over one decade.

To determine whether there has been a time-related change in semen quality, we examined a Wisconsin population of men over a 10-year period. The semen quality of potential sperm donors was assessed between the years 1978 and 1987. The semen analyses included sperm concentration, motility, and morphology. No significant changes over time were observed for sperm concentration or motility. The percentage of morphologically abnormal sperm rose sharply between 1982 and 1983. This, however, coincided with a change in criteria used to identify abnormal sperm, and was, therefore, due to a procedural artifact. In summary, we found no evidence of a decline in semen quality in our Wisconsin population over a 10-year period.

Localization of human epidermal growth factor receptor in cervical intraepithelial neoplasias.

Immunohistochemical staining of epidermal growth factor receptor (EGF-R) with a monoclonal antibody was performed in 43 biopsies of cervical tissue. The distribution of the receptors in normal cervical tissue differs from that of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix. Whereas the staining reaction in normal squamous epithelium was confined to the basal and deep parabasal cell layer, in all cervical intraepithelial neoplasias, with or without human papilloma virus association, a homogeneous EGF-R staining reaction could be observed throughout the entire lesion. This means that the dysplasia cells of a CIN I-III, like the tumor cells of a squamous cell carcinoma, have a raised EGF-R content, which in the normal squamous epithelium is usually only found in the basal and deep parabasal cells that are capable of dividing. No EGF-R staining reaction could be detected in the higher, differentiated cell layers of the normal squamous epithelium of the cervix.

Estrogen increases precursor for pregnenolone synthesis with temperature-sensitive occupancy of P-450scc in mitochondria of rabbit corpus luteum.

To examine the mechanism of estrogen's direct stimulation of steroidogenesis in the rabbit corpus luteum, we tested the hypothesis that the effect of estrogen on progestin production occurs at the site of processing of the precursor for pregnenolone (i.e. cholesterol) in the mitochondrion. For this purpose, we manipulated a model of estrogen stimulation by 1) removing sc estradiol-filled polydimethylsiloxane capsules from superovulated rabbits on day 9 of pseudopregnancy or 2) leaving the capsules in place to preserve a chronic estrogen stimulus. In the estrogen-deprived rabbits, the serum progesterone level fell precipitously in vivo within 24 h, but in rabbits with chronic estrogen stimulation, serum progesterone levels remained high. Our results show that the loss in progestin production caused by estrogen deprivation could not be attributed to loss of the mitochondrial cytochrome P-450 side-chain cleavage enzyme (P-450scc), a common rate-limiting step in progestin synthesis in many steroidogenic tissues. In addition, we confirmed that there was no loss in the catalytic activity of this enzyme. Treatment with aminoglutethimide in vivo followed by electron paramagnetic resonance spectroscopic analysis of mitochondria (prepared in aminoglutethimide-free buffers) showed that incubation of isolated mitochondria at 37 C and pH 6.2 caused an increased high spin state (g = 8.2 signal) and a concomitant decreased low spin state. This shift from low to high spin states, which is indicative of cholesterol-P-450scc complex formation, occurred in the luteal mitochondria from both estrogen-deprived and estrogen-stimulated rabbits. In further studies to localize estrogen's regulatory point, we determined that the initial (first minute) rate of production of pregnenolone (per mg protein or per U P-450scc) from endogenous precursor proceeded equally fast in mitochondria from estrogen-deprived and those from estrogen-stimulated rabbits. However, the rapid pregnenolone production in the estrogen-deprived group lasted for a shorter time and, after 30 min, yielded less pregnenolone per mg protein or per U P-450scc than did mitochondria from estrogen-stimulated rabbits. Addition of 25-hydroxycholesterol did not increase the initial rate of pregnenolone formation, indicating that precursor availability is not limiting during the initial period. In aggregate, these observations suggest that the effect of estrogen on progestin production in the rabbit corpus luteum is not regulation of the movement of cholesterol to the catalytic site on the inner mitochondrial membrane, even though this is a step in the regulation of protein hormone-stimulated steroidogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholesterol metabolism in estrogen-sensitive progestin synthesis by rabbit corpus luteum.

To learn whether either reduced de novo cholesterol synthesis and/or altered cholesteryl ester metabolism is responsible for the deficient progestin production induced by estrogen withdrawal from pseudopregnant rabbits, we measured the luteal activity of three enzymes: 1) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (the rate-limiting step in de novo cholesterol synthesis), 2) cholesteryl ester hydrolase, and 3) acyl coenzyme A:cholesterol acyltransferase (ACAT) in estrogen-stimulated and estrogen-deprived rabbits. The only change in the activity of these enzymes and of the enzyme NADPH-cytochrome c reductase (a microsomal marker enzyme) after estrogen capsule removal for 12 or 24 h was a 30% decrease in HMG-CoA reductase activity after 24 h. The decrease in HMG-CoA reductase activity was not accompanied by a detectable change in either the content or localization of cellular free cholesterol. Previous data from our laboratory have demonstrated that 24 h of estrogen deprivation has no effect on inner mitochondrial membrane P-450 side-chain cleavage activity (a rate-limiting step in the conversion of cholesterol to steroid hormones). These data, and our earlier finding that estrogen deprivation leads to accumulation of cholesteryl ester in the luteal cells, indicate that estrogen maintains rabbit luteal progestin production by stimulating the transfer of cytoplasmic cholesterol to the active site of P-450 side-chain cleavage on the inner mitochondrial membrane.

Isoenzymes of cAMP-dependent protein kinase in developing rat liver and in malignant hepatic tissues.

Total R proteins and total cAMP-dependent protein kinase activity during rat liver development reach highest values per unit DNA when the organ has attained full metabolic competence. The parallel changes indicate coordinate synthesis of R and C subunits during hepatic development. In contrast to total R2 . C2, protein kinase activation and endogenous cAMP levels were highest around birth. Immunotitration with anti-RI and anti-RII in the presence of protein-A-Sepharose of extracts obtained from various developmental stages and from hepatomas suggested a relation of both protein kinase I and II to the terminal differentiation of the organ rather than to cellular proliferation rates. The type-II enzyme appears to be subject to additional regulations connected with neonatal adaptation phenomena. A non-enzymic analysis of the protein kinase activation status is described. It is based on the determination of the ratio of amounts: R . cAMP/total R, which showed a linear correlation with the conventional protein kinase activity ratio (-cAMP/+cAMP).