A two-dimensional protein map of human amniotic fluid at 17 weeks' gestation

Using updated technical procedures (immobilized pH gradients for isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: IPG/SDS-PAGE) we provide a two-dimensional (2-D) map of amniotic fluid (AF) proteins. This map comprises over 800 silver-stained spots. Over 150 spots have been identified by matching on the net with human plasma and cerebrospinal fluid maps available from SWISS 2DPAGE database; several additional spots were assigned by immunoblotting and/or microanalytical techniques. This report details our investigation on AF proteins focusing on the 17th week of gestation, when AF is most commonly used for clinical evaluation of fetal disorders. As a whole, the map displays a number of potential markers for fetal development and for gestation abnormalities. The 2-D electrophoretic technique allows the monitoring of all these proteins at the same time along with additional spots that may prove of diagnostic significance.     

The simultaneous assay of progesterone, 17-hydroxyprogesterone, and deoxycorticosterone in human plasma by competitive protein binding

Testosterone oenanthate was administered intramuscularly in six infertile men with oligozoospermia and its effects on serum gonadotropins and some constituents in the seminal plasma were studied. One week after injection the mean serum FSH level was decreased to about 50%. Serum LH levels did not change. The mean ornithine decarboxylase activity in human semen was increased by 100% after the testosterone administration. The androgen dependent nature of ODC, fructose and sialic acid have been demonstrated.     

The relationship of corpus luteum volume to relaxin, estradiol, progesterone, 17-hydroxyprogesterone and human chorionic gonadotropin levels in early normal pregnancy

Current suture techniques limit the postoperative management for flexor tendons. A double loop locking suture (DOLLS) technique has been described that provides sufficient in vitro strength (average 4,400 g) for early active mobilization of the flexor tendon. This paper details four cases in which the flexor digitorum profundus (FDP) tendons were repaired using the DOLLS technique. Early active mobilization was initiated 3 to 7 days postoperatively. Results were classified according to Strickland's formula. Two patients achieved excellent results, one a good result, and one a fair result. One rupture of a flexor digitorum superficialis (FDS) tendon, which had been repaired with a modified Kessler technique, occurred. Although this FDS tendon ruptured, the FDP tendon, which had been repaired with the DOLLS technique, remained intact. With the use of a protective splint, early active mobilization of tendons repaired by the DOLLS technique appears to be an effective method for postoperative management.     

Serial measurement of arterial plasma progesterone levels throughout gestation and parturition in individual rats

Daily blood samples were taken from 6, chronically cannulated, fully conscious rats to measure plasma progesterone levels throughout gestation. Progesterone levels in individual rats fluctuated by up to 28 ng/ml per day, but tended to be consistently higher or lower than the group mean. The accuracy of predicting progesterone levels in individual rats from previous values was examined. Progesterone levels on day 7 of gestation were negatively correlated with foetal weights near term. There was little indication that high progesterone levels at any stage of gestation lead to increased foetal or placental weights. Progesterone levels on day 17 were positively correlated with the number of corpura lutea but there was little relationship between progesterone and either the number or total mass of the placentas. Serial blood samples taken from a second group of 6 rats at 2 hourly intervals showed that the time between the major fall in progesterone levels to below 12 ng/ml and the onset of parturition was relatively constant (varying by only 8 h) despite a 29 h range in the total length of gestation.     

Follicular fluid immunoreactive-inhibin concentrations in relation to follicular diameter and estradiol-17 beta, progesterone and testosterone concentrations in individual ovarian follicles in buffalo, Bubalus bubalis

BACKGROUND: Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation. METHODS: In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11]. RESULTS: During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS). CONCLUSIONS: Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.     

Relaxin levels in amniotic fluid, extraembryonic coelomic fluid and maternal serum in early human pregnancy

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid together with maternal serum were collected from 22 women between 8 and 11 weeks of pregnancy and analysed for relaxin by immunoassay. Relaxin levels in maternal serum (median 1085 pg/ml; range 390-1259 pg/ml) were substantially higher than those in extraembryonic coelomic fluid (median 57.5 pg/ml; range 17-145 pg/ml; P < 0.0001; Mann-Whitney U-test). In turn, the levels of relaxin in coelomic fluid were higher than those in amniotic fluid (median 10 pg/ml; range 10-37 pg/ml; P < 0.0001; Mann-Whitney U-test). A linear correlation was found between relaxin levels in maternal serum and coelomic fluid (r = 0.68; P = 0.001) but there was no relation between levels in the other fluid compartments.     

17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages

OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture. STUDY DESIGN: Primary tissue culture of human term placental cells was performed. RESULTS: Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations. CONCLUSIONS: Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.     

Regulation of progesterone biosynthesis in the human placenta by estradiol 17 beta and progesterone

The information available concerning the effects of chemotherapy administered during pregnancy is limited and consists of case reports and small series. A registry has been established at the National Cancer Institute, but there are currently only several hundred cases of neonates exposed to chemotherapy registered. All clinicians who care for women receiving chemotherapy during pregnancy should report those experiences to the National Cancer Institute to increase the data base. When chemotherapy is used during the embryogenesis period in the first trimester there is an increased rate of spontaneous abortion and major birth defects. The most toxic chemotherapeutic agents administered during pregnancy are methotrexate and aminopterin and should be avoided when possible, particularly during the first trimester. Pregnancy-related physiologic changes should be kept in mind when dosing and administering cytotoxic chemotherapy. The risk of fetal malformation when chemotherapy is administered during the second and third trimesters is probably not greater than background rate, but there may be a greater risk of stillbirth, fetal growth restriction, premature birth, and maternal and fetal myelosuppression. Breastfeeding should be avoided in women receiving chemotherapy.     

Research on sexual orientation and human development: A commentary.

Over the last 25 yrs, dramatic advances have occurred in the understanding of the development of sexual orientation. Gay and lesbian interests and behavior appear to result from a complex interplay of genetic, prenatal, and environmental influences. Gender identity develops early, especially for males, and is difficult to change. Homosexuality is less likely to be characterized as pathological, although discrimination and hate crimes continue to affect many gay men and lesbians. The overall emotional well-being of gay men and lesbians, as well as children raised in gay and lesbian families, is as psychologically healthy as that of their heterosexual counterparts. Methodological difficulties in research remain with continued needs for more delineated definitions of sexual orientation and empirically derived databases of population statistics of gay men and lesbians. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Internal pH of human spermatozoa: effect of ions, human follicular fluid and progesterone

The internal pH (pHi) of human spermatozoa was measured by the fluorescent indicator 2,7-bicarboxyethyl-5,6-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and the distribution of the radioactive [14C]-methylamine under different external ionic conditions. The effect of the addition of progesterone and human follicular fluid (HFF) on the spermatozoa pHi was also analysed. The pHi values obtained were almost identical with the two probes used. In sodium (NaM) and potassium (KM) media, a linear relationship between the internal and external pH was observed. In NaM, the pHi values were approximately 0.4 pH unit less than the external pH. In KM, the pHi measured was higher than in NaM and only slightly inferior to the external pH (0.1-0.2 pH unit). Addition of 10 microM progesterone, oestradiol 17 beta or 20% HFF to spermatozoa incubated at pH 7.2 in NaM did not induce any rapid variation of the BCECF fluorescence or change in the accumulation of methylamine. A slight change in pH (approximately 0.5 units) occurred with progesterone after 15 min. As a control, addition of 10 mM of NH4Cl induced a rapid alkalinization (0.4 pH unit) of the cell interior while 10 mM lactate produced only a slight acidification (approximately 0.2 pH unit). Under the same conditions (NaM, pH 7.2), the pHi of the spermatozoa prepared by Percoll gradient was found more acidic by 0.2 pH unit than washed unfractionated spermatozoa. Progesterone, oestradiol 17 beta and HFF had no effect on the pHi of these spermatozoa. The results obtained in this study show that it is possible to measure accurately the internal pH of human spermatozoa. Internal pH was found to be dependent upon the pH of the external medium and a quasi-linear relationship exists between the internal and external pH, suggesting no specific pH regulatory mechanisms. Our data suggest instead that the protons, under our experimental conditions, are passively distributed. Progesterone, oestradiol 17 beta and HFF, known to promote both capacitation and the acrosome reaction, do not act through a rapid pHi change.     

Examination of 17 beta-estradiol and progesterone levels in peritoneal fluid and blood serum of women with endometriosis

Authors have presented and assessment of estradiol and progesterone levels in peritoneal fluid and blood serum in women with endometriosis. Peritoneal fluid was collected during laparoscopy performed in luteal phase of the cycle. In this cycle ovulation was controlled in all women. An ovulation was confirmed ultrasonographically and laparoscopically in 45% of women with endometriosis and in 80% of that without the illness. Progesterone concentration in peritoneal fluid in women with endometriosis was significantly lower to the control (p < 0.01).     

Immunohistochemical localization of estradiol and progesterone receptors in human uterus throughout pregnancy: expression in endometrial blood vessels

Although progesterone and estrogens are essential to maintain human pregnancy after implantation, the localization of their specific receptors in different uterine cell types during pregnancy has not been investigated. We studied uteri (n = 40) obtained during the first 3 months of pregnancy (n = 21) and in late pregnancy (n = 9) as well as from women 5-14 weeks pregnant (n = 10) who had received the antiprogestagen RU 38486 (Roussel-UCLAF) to induce cervical dilation. Frozen tissues were processed for indirect immunocytochemical staining with specific monoclonal antibodies against estrogen receptors (ER; Abbott Laboratories) and progesterone receptors (PR; Li 417). Specific staining for steroid receptors was only detected in the nucleus. In the endometrium, PR staining remained fairly constant throughout pregnancy, whereas ER staining was initially weak and then undetectable. PR was widely expressed in stromal cells and in spiral arterial wall cells, whereas ER was expressed in scattered stromal cells and arterial cells. Both PR and ER were absent from glandular epithelium, contrasting with the secretory activity during the first trimester. Spiral arteries of the endometrium and myometrial smooth muscle cells showed intense PR and moderate ER staining in early pregnancy. The progesterone antagonist RU 38486 (mifepristone), given in early pregnancy at a dose of 200 mg, caused a marked increase in ER staining and a smaller increase in PR staining in stromal cells, whereas the glandular epithelium remained negative for both ER and PR (except for one and two specimens, respectively). We conclude the following. 1) Stromal cells retain PR despite the high progesterone levels during pregnancy, in keeping with the role of progesterone in stromal decidualization. The absence of PR from the secretory glandular epithelium suggests a paracrine link between decidualized stromal cells and epithelial cells. 2) Significant PR down-regulation by progesterone during pregnancy occurs only in epithelial cells of the endometrium. 3) In contrast, the absence or low level of ER staining in the various cell types of the endometrium during gestation concurs with the known effect (down-regulation) of steroid hormones on ER mRNA or protein levels. The increase in ER in human decidua after RU 38486 treatment indicates that the main cause of the low ER levels is progesterone secretion. 4) The intense PR staining in smooth muscle cells of spiral arteries during early pregnancy suggests that progesterone is essential for modulating blood flow during pregnancy.     

Childhood sexual abuse, stigmatization, internalizing symptoms, and the development of sexual difficulties and dating aggression.

Potential pathways from childhood sexual abuse (CSA) to subsequent romantic intimacy problems were examined in a prospective longitudinal study of 160 ethnically diverse youth with confirmed CSA histories. Participants were interviewed at the time of abuse discovery, when they were 8-15 years of age, and again 1-6 years later. Stigmatization (abuse-specific shame and self-blame) and internalizing symptoms (posttraumatic stress and depressive symptoms), more than abuse severity, explained which youth with CSA histories experienced more sexual difficulties and dating aggression. Stigmatization was found to operate as a predictive mechanism for subsequent sexual difficulties. Internalizing symptoms were not predictive of romantic intimacy problems, although they did show correlational relations with sexual difficulties and dating aggression. Early interventions such as trauma-focused cognitive-behavioral therapy that target stigmatization may be important for preventing the development of sexual difficulties in CSA youth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): II. Effects of preoptic area lesions, castration, and testosterone.

We studied effects of lesions to the medial preoptic area (POA), castration, and testosterone replacement on instrumental and unconditioned sexual behavior in male rats. We achieved instrumental measures of sexual motivation by training males to work for an estrous female, presented in an operant chamber under a second-order schedule of reinforcement. POA lesions abolished mounts, intromissions, and ejaculation but did not disrupt instrumental responses, investigation of the female, or abortive mounting attempts. Castration abolished attempts to copulate and also caused a marked decrease in instrumental responses. Testosterone resulted in the prompt reinstatement of instrumental responses and more gradual recovery of unconditioned sexual behavior. We discuss these results in terms of the motivational and performance effects of these neuroendocrine manipulations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The predictive value of serum progesterone and 17-OH progesterone levels on in vitro fertilization outcome

PURPOSE: In order to identify parameters which predict prognosis for success with in vitro fertilization, 17-hydroxyprogesterone and progesterone levels were evaluated in 254 patients undergoing 296 in vitro fertilization cycles. Selected response and outcome data were recorded. RESULTS: Patients with intermediate values of serum progesterone (0.7-0.8 ng/ml) at the time of human chorionic gonadotropin administration achieved significantly higher pregnancy rates than patients with lower (< 0.7 ng/ml) or higher (> 0.8 ng/ml) levels. The clinical pregnancy rates were 46%, 31%, and 27% respectively (P = 0.02). There was no change in 17-hydroxyprogesterone concentration which predicted a higher pregnancy rate. CONCLUSION: Excellent clinical pregnancy rates were noted in cycles with a progesterone level of 0.7-0.8 ng/ml, as well as good results in cycles above 0.8 ng/ml. There is therefore no reason to administer human chorionic gonadotropin at a smaller follicle size to prevent a rise in serum progesterone.     

Comparison of the effects of stanozolol, oxymetholone, and testosterone cypionate on the sexual behavior of castrated male rats.

In 3 experiments, adult male Long-Evans rats were castrated and treated daily with an anabolic-androgenic steroid (AAS) compound (either stanozolol, oxymetholone, or testosterone cypionate) for 6 weeks. Subjects were assigned to 5 groups that received injections of a high, medium, or low dose of the AAS, testosterone propionate, or the oil vehicle. Stanozolol failed to maintain ejaculation at any dose tested. Although some subjects receiving the low dose of oxymetholone ejaculated, oxymetholone generally failed to stimulate ejaculation above the levels of the oil group. Testosterone cypionate sustained ejaculation at all doses tested. The relative potency of the medium dose of each AAS in the sex accessory tissues was (from most potent to least potent): testosterone cypionate?>?stanozolol?=?oxymetholone?=?oil. Thus, these 3 AAS compounds produced a range of behavioral and endocrine responses in castrated male rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of progesterone, testosterone and their 5 alpha-reduced metabolites on GFAP gene expression in type 1 astrocytes

Astrocytes possess steroid receptors as well as several enzymes typical of steroid target cells, such as 5 alpha-reductase, which converts testosterone (T) and progesterone (P) into their respective 5 alpha-reduced metabolites, and the 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). Because of this, it was deemed of interest to analyze whether the original hormones P and T, and their 5 alpha-reduced metabolites dihydrotestosterone (DHT), 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol), dihydroprogesterone (DHP) and 5 alpha-pregnan-3 alpha-ol-20-one (THP), might exert some effects on the expression of the most typical astrocytic marker, i.e. the glial fibrillary acidic protein (GFAP). Cultures of rat type 1 astrocytes were exposed to the various steroids for 2, 6, and 24 h, and the variations of GFAP mRNA were measured by Northern blot analysis. A significant elevation of GFAP mRNA levels was observed after exposure to either P or DHP; the effect of DHP appeared more promptly (at 2 h) than that of P (at 6 h). This result suggests that the effect of P might be linked to its conversion into DHP; this hypothesis has been confirmed by showing that the addition of finasteride (a specific blocker of the 5 alpha-reductase) is able to completely abolish the effect of P. After exposure to DHP or THP, a decrease of GFAP gene expression was observed at later intervals (24 h). In the case of androgens, T and 3 alpha-diol did not change GFAP expression at any time of exposure, while DHT produced a significant decrease of GFAP mRNA only after 24 h of exposure. Taken together, the data indicate that the 5 alpha-reduced metabolites of P and T may modulate the expression of GFAP in type 1 rat astrocytes.