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Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 235 records · Page 13Linked to original sources

In vitro human growth hormone increases human chorionic gonadotropin and progesterone secretion by human placenta at term: evidence of a modulatory role by opioids.

We examined the in vitro effect of human growth hormone (hGH) on hormone placental production and the modulation by opioids of this function. Small placental fragments from 12 term placentas were incubated at 37 degrees C in a 95% air and 5% CO2 atmosphere for 4 h with various concentrations of hGH (1-1000 ng/ml) or naloxone (3-500 ng/ml). Both hGH and naloxone increased the concentrations of human chorionic gonadotropin (hCG) and progesterone in the media. The effect of the hGH was dose-dependent and statistically significant at 10 ng/ml, while naloxone was able to increase hCG and progesterone production only at the highest doses (250-500 ng/ml). The concomitant treatment with ineffective doses of naloxone and hGH was able to enhance hCG and progesterone secretion reaching levels similar to those obtained with the highest doses of hGH alone. High naloxone concentrations significantly decreased both hCG and progesterone secretion induced by high doses of hGH. This study confirms the relevance of growth hormone in sustaining placental endocrine activities and indicates an effect of opioids in modulating these functions.

Chorionic Gonadotropin↗

Effect of corticotropin-releasing factor on the pituitary-ovary axis in human luteal phase.

In order to test the possible negative effect of corticotropin-releasing factor (CRF) on the pituitary-gonadal axis, two gonadotropin-releasing hormone (GnRH) tests, on two consecutive days, were performed in five normally cycling women in the midluteal phase of the menstrual cycle. The first GnRH test was performed after 2 h during which time basal blood samples were collected every 10 min. On the second day, the GnRH test was repeated after a 2-h CRF infusion which was continued throughout the GnRH test. Our results demonstrate that while CRF increases cortisol levels it affects neither the basal nor the GnRH-stimulated gonadotropin levels. Similarly, both basal and luteinizing hormone (LH)-stimulated progesterone concentrations were not modified by the CRF infusion thereby also excluding a possible direct effect of the peptide on corpus luteum steroidogenesis.

Adult↗

Growth retardation in pregnancy: experimental model in the rabbit employing electrically induced thermal placental injury.

Intrauterine growth retardation involves haemodynamic modifications in the uterus and placenta. In order to study intrauterine growth retardation we obtained an electrically induced thermal placental injury in a rabbit experimental model. The effects on weight of fetuses, placentas and single organs were recorded and statistically analysed. Fetal growth retardation was recorded in 71% of fetuses exposed to 15 mA direct current per 40 seconds, and resulted in only 7.9% of normal fetuses. The data presented in this study have shown a retardation of fetal growth particularly evident in the liver weight with a relative sparing of brain development. Kidney and heart do not present a statistically significant reduction in growth. This growth retardation model is simple and readily reproducible.

Animals↗

Effect of synthetic and naturally occurring chalcones on ovarian cancer cell growth: structure-activity relationships.

This study was carried out to determine the effect of 15 different natural and synthetic chalcones on the proliferation of both established and primary ovarian cancer cells expressing type II oestrogen binding sites (type II EBS). The binding affinity of chalcones for type II EBS was also tested. At concentrations from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related variation in IC50 (concentration resulting in a 50% inhibition of cell growth) and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type II EBS), it appeared that the presence of an alpha-beta double bond, the hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were important to both the antiproliferative and binding activity. Structure-related variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for chalcone antiproliferative activity. Our data indicate that chalcones could be considered as potential new anticancer drugs.

Binding Sites↗

Polycystic ovary disease. A risk factor for gestational diabetes?

We investigated the impact of pregestationally elevated insulin plasma levels on glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve patients with PCOD who became pregnant within six months following evaluation of their metabolic status were the study subjects. Four were obese and six (two obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT). They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12 normal patients and 10 consecutive patients with gestational diabetes; all were at the same gestational age. Plasma levels of insulin and glucose were determined in the samples collected for a period of four hours after glucose load (100 g). All PCOD patients significantly increased their insulin secretion in pregnancy. The hyperinsulinemic PCOD patients developed gestational diabetes (two patients) and impaired gestational glucose tolerance (three patients). The area under the insulin curve was greater in PCOD patients than in control and gestational diabetes patients (P < .01). In spite of their large increase in insulin secretion observed during pregnancy, patients with PCOD may develop a derangement of glycemic control, probably related to their pregestational insulinemic status.

Analysis of Variance↗

Hysteroscopically detected asymptomatic müllerian anomalies. Prevalence and reproductive implications.

OBJECTIVE: To assess the prevalence of uterine anomalies and relative reproductive function in 322 women with abnormal uterine bleeding (AUB) evaluated by diagnostic hysteroscopy. STUDY DESIGN: Uterine contours were classified as septate/bicornuate, arcuate or normal on the basis of hysteroscopy. A complete medical history was obtained from all the subjects; it included a questionnaire on menstrual characteristics, reproductive history and pregnancy outcome. Cumulative birth rates, frequency of spontaneous abortion, preterm delivery, malpresentation and mode of delivery in patients with normal and abnormal uteri were compared using life table analysis, the log-rank test and chi 2 analysis. RESULTS: Arcuate, septate/bicornuate and unicornuate uteri were observed in 6.5%, 3.7% and 0.3% of women, respectively. Although 24-month pregnancy rates and monthly fecundability rates were similar in women with and without müllerian anomalies, the 36-month cumulative live birth rate was significantly lower in women with a septate/bicornuate uterus. Overall, women with uterine malformations showed a significantly higher miscarriage rate (P < .05) and a significantly lower term delivery rate (P < .05) than women with a normal-shaped uterus. CONCLUSION: Diagnostic hysteroscopy in women with AUB detected a 10% prevalence of uterine anomalies, which were associated with a significantly higher incidence of spontaneous abortion and lower cumulative live birth rates.

Case-Control Studies↗

Maternal ultrasound bone density in normal pregnancy.

OBJECTIVES: The aim of the study was to investigate the effect of pregnancy on maternal bone mineral density by an ultrasound device. STUDY METHODS: Two hundred and thirty consecutive healthy pregnant women were evaluated by ultrasound densitometry during the 1st (n=45), the 2nd (n=56) and the 3rd (n=129) trimester of pregnancy, measuring the velocity (SoS) and frequency attenuation (BUA) of an ultrasound wave as it passes through the os calcis. Speed of sound (SoS) and Broadband Ultrasound Attenuation (BUA) values are combined in order to express a relational variable (Stiffness), indicator of bone quality. RESULTS: Statistically significant reductions in SoS, BUD and Stiffness values were observed during the 3rd trimester vs the 1st and the 2nd trimesters. Negative statistically significant relations were found between the gestational age and ultrasound densitometry parameters. CONCLUSION: A linear reduction of ultrasound bone density was observed throughout pregnancy, reaching a statistical significance in the 3rd trimester, when the greatest calcium transfer from the mother to the fetus occurs.

Bone Density↗

Autologous stem cell transplantation: release of early and late acting growth factors relates with hematopoietic ablation and recovery.

We have monitored the serum concentrations of hematopoietic growth factors (HGFs; ie, stem cell factor [SCF], leukemia inhibitory factor [LIF], interleukin-3 [IL-3], IL-6, IL-8, and granulocyte colony-stimulating factor [G-CSF]) in 15 lymphoma/leukemia and 6 ovarian cancer patients undergoing autologous bone marrow (BM) or peripheral blood (PB) stem cell transplantation (SCT). Thus, the analysis was performed during and after high-dose chemotherapy (from day -6 to day -1), at the time of SCT (day 0), and thereafter (through day +17). Despite the heterogeneity of these patients and their conditioning regimens, a consistent kinetic pattern was observed for all analyzed cytokines. Particularly, (1) SCF serum concentration did not significantly fluctuate. (2) High levels of LIF (approximately 250 to 450 pg/mL) before chemotherapy rapidly declined to markedly lower concentrations (approximately 10 ng/mL) starting from day -1 through day +17; (3) conversely, IL-3 level was low before treatment, sharply increased during chemotherapy, and rapidly returned to base-line level after SCT. Hypothetically, the sharp LIF decrease and IL-3 increase during chemotherapy may underlie the induction of stem cell cycling and differentiation caused by hematopoietic ablation. Furthermore, (4) IL-6 concentration was low before and immediately after chemotherapy, but increased starting from day +5, peaked at day +6 through 9 and then declined to baseline level from day +10 onward; (5) a strictly similar pattern was consistently observed for both G-CSF and IL-8 levels, in agreement with our previous studies. It is relevant that peak IL-6, G-CSF, and IL-8 concentrations were directly correlated to peak neutrophil numbers in the recovery phase, thus suggesting an important role for these cytokines in granulocyte rescue; in line with this interpretation, hematologic patients undergoing PBSCT (10 of 15) exhibited higher peaks of IL-6, G-CSF, and IL-8 and a more pronounced increase of neutrophil/platelet number than did hematologic cases undergoing BMSCT (5 of 15). Altogether, these studies indicate a coordinate pattern of cytokine release during hematopoietic ablation/recovery after chemotherapy and autologous SCT, the fluctuations of LIF and IL-3 levels during chemotherapy are seemingly related to stem cell recruitment, whereas the post-SCT increase of IL-6, G-CSF, and IL-8 may underlie the neutrophil recovery.

Adolescent↗

Effect of recombinant human interferon-alpha/2b on epidermal-growth-factor-, estrogen- and progesterone-receptor expression in primary cervical cancer.

The effects of a short period of in vivo systemic rh-IFN-alpha/2b treatment on epidermal-growth-factor(EGFR)-, estrogen(ER)- and progesterone(PR)-receptor content in 11 primary human cervical tumors was investigated by the radioreceptorial technique. EGFR levels were found to be significantly higher in cervical tumors after rh-IFN-alpha/2b treatment with respect to basal levels. In 2 cases, immunohistochemical and cytofluorimetric analysis showed that rh-IFN-alpha/2b treatment induces an increase in EGFR immunoreactivity and in the fraction of EGFR-positive cells. No difference in ER and PR levels in cervical tumors before and after rh-IFN-alpha/2b treatment was observed. Our results suggest that rh-IFN-alpha/2b up-regulates EGFR in primary human cervical tumors in vivo.

Aged↗

Interleukin-6 serum levels in patients with gynecological tumors.

Serum levels of IL-6 were evaluated in a large group of patients with benign or malignant gynecological tumors. The results obtained were correlated with the patients' clinicopathological features and follow-up data. Using a highly sensitive immunoenzymatic method for the evaluation of serum IL-6 levels, we observed that > 95% of normal healthy women exhibited values within the range of 1.9-6 pg/ml. Using a cut-off of 6 pg/ml, elevated levels of serum IL-6 were found in 53% of 45 patients with primary epithelial ovarian cancer and less frequently in patients with endometrial and cervical cancer (37% and 10% respectively). Elevated levels of IL-6 were occasionally seen in patients with benign disease. IL-6 serum levels appeared to be less sensitive than CA 125 in ovarian cancer diagnosis. In cancer patients, increased IL-6 serum levels were related to the presence of the tumor since all post-operative patients exhibited a marked decrease. In patients with advanced ovarian cancer post-operative levels of IL-6 correlated with residual disease. Very high levels of IL-6 were observed in the ascitic fluid of 9 ovarian cancer patients, but IL-6 mRNA was not detected in tumor cells. This suggests that the increased production of IL-6 observed in ovarian cancer is reactive. Higher levels of IL-6 were found in patients unresponsive to chemotherapy, as compared with responsive ones. Univariate analysis of survival data suggests that increased IL-6 serum levels correlate with negative prognosis.

Adult↗

Quercetin enhances transforming growth factor beta 1 secretion by human ovarian cancer cells.

Our study demonstrates that quercetin (Q)-induced growth-inhibitory activity in ovarian cancer cells may be mediated by modulation of transforming growth factor beta 1 (TGF beta 1) production. We used the OVCA 433 cell line which is very sensitive to the anti-proliferative effect of Q and expresses high-affinity, low-capacity TGF beta 1 receptors. Conditioned medium (CM) from Q-treated cells is able to displace 125I-TGF beta 1 from binding to its receptor; moreover Q (10 microM) increases TGF beta 1 activity in CM in a time-dependent fashion starting after 4 hr and reaching a maximum by 24 hr of Q treatment. Q-induced growth inhibition is reversed by a neutralizing anti-TGF beta 1 MAb both in OVCA 433 and in a clonogenic assay of cells from a primary ovarian tumor. Q-induced increase of TGF beta 1 activity in CM is specific since other anti-proliferative compounds, such as Dexamethasone, which is as active on the cell cycle as Q, had no effect on TGF beta 1 secretion. Northern-blot analysis of TGF beta 1 mRNA levels at various times of Q (10 microM) exposure revealed that there was no increase, suggesting that regulation of TGF beta 1 occurs at posttranscriptional levels.

Cell Division↗

Significance of epidermal growth factor receptor expression in primary human endometrial cancer.

Radioreceptorial assessment of EGFR expression was prospectively performed on 60 primary human endometrial tumors. Of these, 26 were EGFR-positive while 13 expressed high EGFR levels. High EGFR levels correlated well with poor histopathological grading. No correlation with histopathological type, stage, myometrial invasion, lymph-node involvement or steroid hormone receptor status was observed. Disease-free survival rate was significantly shorter in the cases with high than in the cases with low EGFR levels. These results suggest a potential role of EGFR expression assessment in prognostic characterization of endometrial cancer patients.

Adult↗

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma antigen (SCC) in patients with cervical cancer.

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma (SCC) serum levels were assayed in a group of 63 primary cervical cancer patients. IAP serum levels were significantly higher in cancer patients (median, 630 micrograms/ml; range, 290-1150) than in controls (median, 290 micrograms/ml; range, 135-775) (P < 0.01). The percentage of IAP-positive (> 613 micrograms/ml) cases was 50.7%. SCC serum levels were found to be above 2.5 ng/ml in 73% of cervical cancer patients, and in 6% of controls. A statistically significant correlation was observed between IAP and SCC levels in cancer patients (r = 0.35, P < 0.004). When IAP and SCC were considered together the overall sensitivity was 87.3% and an improvement of both predictive value of negative test and accuracy without any significant reduction of predictive value of positive test was found. IAP status correlated with metastatic lymph node involvement. A statistically significant association between a shorter survival and high serum LAP levels was observed. The 24-month overall survival (OS) was 92% for IAP- cases with respect to 65% for IAP+ cases (P = 0.036). In the univariate analysis, advanced stage of disease, clinical parametrial involvement, and lymph node involvement were also associated with poor survival. In the multivariate analysis IAP status showed a statistically significant association with poor survival (P = 0.049), together with lymph node involvement (P = 0.007) and advanced stage of disease (P = 0.008).

Adult↗

Combined use of CA 125 and CA 15-3 in patients with endometrial carcinoma.

Serum levels of CA 125 and CA 15-3 were measured in 148 patients with primary endometrial carcinoma. CA 125-positive levels were found in 33 and 22% of the cases using a cutoff of 35 and 65 U/ml, respectively. Thirty-five (24%) and 12 (8%) patients had CA 15-3 levels higher than 30 and 50 U/ml, respectively. Among 144 patients with clinical stage I-II, 17 (12%) had extrauterine disease. CA 125 (> 65 U/ml) and CA 15-3 titers (> 30 U/ml) were found in 59 and 47% of occult stage III with respect to 16 and 18% in stage I-II of disease, respectively (P = 0.0001 and P = 0.01). The combined use of CA 125 and CA 15-3 resulted in a reduction of false-positive results of CA 125 with an acceptable sensitivity of 41%. Low-risk patients (G1 and M0-M1 tumors) showed a CA 125 positivity (> 35 U/ml) of 10% with respect to 37% of high-risk patients (G2-G3 and M2 tumors) (P = 0.0026). CA 125 positivity (> 65 U/ml) was 22% in patients without metastatic lymph node involvement, compared to 58% of cases with histologically positive lymph nodes (P = 0.022). A similar trend, although not statistically significant, was found for CA 15-3. A good correlation was found between CA 125 and CA 15-3 serum levels and clinical course of disease during chemotherapy. A statistically significant relationship was demonstrated between CA 125 (> 65 U/ml) (P = 0.0027) and CA 15-3 positivity (CA 15-3 > 30 and 50 U/ml) (P = 0.0004 and P = 0.00025) and a shorter survival. Our data show that CA 125 and CA 15-3 may be used as predictors of extrauterine spread and in monitoring of chemotherapy response in endometrial cancer. Moreover, the presence of elevated levels of these antigens may identify a subset of patients with a particularly poor prognosis.

Aged↗

Menstrual and hormone patterns in women treated with high-dose cisplatin and bleomycin.

Menstrual and hormone patterns were investigated in 10 fertile women (median age 37, range 25-43 years) with locally advanced cervical cancer treated with neoadjuvant chemotherapy (CT). CT consisted of two cycles of high-dose cisplatin (CDDP, 40 mg/m2, Days 1 to 4) and bleomycin (B, 15 mg/m2, Days 1 and 8) separated by an interval of 21 days. Menstrual patterns before and during CT were recorded. FSH, LH, estradiol, and progesterone were assayed on the day that treatment was begun, after 2 and 4 days of CDDP administration, and weekly between and after the two cycles. Hormone assays during the first week of CT showed no significant change in hormone levels. After the first course of CT, five patients showed hypergonadotrophic amenorrhea and five patients maintained menses, two showing ovulatory and three showing follicular phase hormone patterns. After the second course of CT, one more patient become amenorrheic, and endocrine follow-up showed that two patients maintained hypergonadotrophic amenorrhea, four with hypergonadotrophic amenorrhea had a return of hormone levels to the follicular range of 7-9 weeks after, three maintained follicular phase hormone patterns until operation, and one ovulated. Gonadal dysfunction should be included among the side effects of high-dose CDDP and B regimens.

Adult↗

Laparoscopy versus laparotomy for ovarian conservative surgery: a randomized trial in the rabbit model.

OBJECTIVE: Our purpose was to compare postoperative adhesion formation and reproductive outcome after the same ovarian surgical procedure performed by laparoscopy or laparotomy by means of microsurgical techniques. STUDY DESIGN: Twenty-eight New Zealand White female rabbits were randomly assigned to laparotomy or laparoscopy for the same standardized surgical procedure: both ovaries were grasped with atraumatic forceps and longitudinally incised on the antimesenteric side from the cortex to the hilum with a microelectrode delivering a tissue power density of 66,666 W/cm. The rabbits were then mated, and 2 weeks later a second-look laparotomy was performed by a blinded observer for the evaluation of postoperative adhesions, number of corpora lutea in each ovary, number of embryos in the ipsilateral uterine horn, and nidation index for each side. RESULTS: At second look no statistically significant differences were found in postoperative adhesion formation, number of corpora lutea, number of embryos, and nidation index between the laparoscopy and the laparotomy groups. CONCLUSION: Laparoscopy or laparotomy for ovarian conservative surgery do not appear significantly different in postoperative adhesion formation and reproductive outcome in the rabbit model.

Animals↗

Growth hormone induction of rat granulosa cell tissue-plasminogen activator expression and progesterone synthesis.

The plasminogen activator (PA) system is present in the ovary and appears to be involved both in follicular growth and ovulation. Similarly, the growth hormone (GH) has been demonstrated to positively affect some ovarian activities. Interestingly, GH appears not only as a mediator of gonadotropin effects, but also as having an independent action of its own on the ovary. In the present study we wanted to investigate if GH could affect ovarian plasminogen activator (PA) activity and steroidogenesis. Granulosa cells from immature rats, injected with pregnant mare serum gonadotropin (PMSG) for inducing follicular growth, were cultured for 24 h with increasing concentrations of GH. A significant dose-dependent increase in tPA activity was observed in the GH-treated cells. This effect was exerted at the mRNA level and the use of cycloheximide, a protein synthesis inhibitor, suggested that GH did not require any other intermediary protein for inducing tPA-mRNA. Furthermore, cAMP levels were not affected by GH treatment. Finally, GH was found to increase progesterone (P) synthesis by granulosa cells. The correlation between the PA system and ovulation and the importance of a normal steroidogenesis for the ovarian physiology claim for a key role of GH in the ovarian activities.

Animals↗

Effect of gonadotropins, insulin and IGF I on granulosa luteal cells from polycystic ovaries.

The aim of this work is to evaluate the gonadotropin and growth factor effects in vitro on steroidal response in human granulosa luteal cells from polycystic ovaries compared with normal granulosa luteal cells in humans. The granulosa cells from polycystic (polycystic ovarian granulosa cells, POGC) and normo-ovulating women (normal cells, NC) were collected in the preovulatory phase after oocyte retrieval during the GIFT program. The cells were cultured serum-free for 24, 48 and 96 h. Estradiol and progesterone production was determined with or without HCG (1-200 ng/ml), FSH (10-300 ng/ml), insulin (1-50 micrograms/ml) and IGF I (1-50 ng/ml) addition. All treatments significantly induced a 2-3 fold estradiol increase at the 48-h and 96-h time points in POGC. The progesterone production was unaffected by HCG, FSH, insulin and IGF I addition, respectively, in POGC, whereas the NC were responsive at the 48-h and 96-h time points. FSH did not stimulate progesterone production in granulosa cells either from polycystic or normovulating subjects. Our findings indicate that POGC are hypersensitive to all substances in terms of estradiol production, whereas they show a reduced capacity of progesterone production with some treatments.

Adult↗