Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 145 records · Page 8Linked to original sources

PubMed1997

The effect of neocortical lesions on the number of cells in neonatal or adult feline caudate nucleus: comparison to fetal lesions.

After a unilateral resection of the frontal cortex in fetal cats the volume of the caudate nucleus increases while the packing density of neuronal and glial cells does not change. In the present report we address the questions of whether a similar lesion sustained neonatally or a more extensive neodecortication sustained neonatally or in adulthood may have the same unusual effect. Stereological methods were used to determine bilaterally the volume of the caudate nucleus as well as to estimate the total number and packing density of neurons and glial cells in the caudate nucleus ipsilateral to the lesion. Comparisons between each of three experimental groups and intact animals were made at a time when all animals were young adults. In cats with a unilateral frontal cortical lesion performed between postnatal days 8 and 14, none of the measured parameters changed significantly compared to intact controls. In cats with removal of the entire left neocortex in adulthood, the ipsilateral caudate nucleus volume decreased by 18.1% and by 21.5% relative to intact and to neonatal hemidecorticated cats respectively (P < 0.05), with no change in the contralateral caudate. In the ipsilateral caudate the total number of neurons decreased by 21.8% (P < 0.05) compared to controls while the number of glial cells did not change significantly. In the same caudate the packing density of neurons did not change significantly (except for a 17.1% decrease, P < 0.05, relative to frontal-lesioned cats) while that of glial cells increased by 19.9% and by 24.7% compared to intact and neonatal neodecorticated cats respectively (P < 0.05). In adult cats in which a similar hemineodecortication was performed between postnatal days 8 and 13, the only significant changes were a 25.8% (P < 0.05) and a 30.6% (P < 0.05) decrease in neuron packing density compared to intact and frontal-lesioned cats, respectively. In summary, a restricted unilateral neocortical resection in neonatal cats did not induce any morphological changes in the caudate nucleus that we could detect with the methods employed. In contrast, an extensive neodecortication sustained in adulthood produced ipsilateral caudate shrinkage with substantial neuron loss and increase in packing density of glial cells, while a similar lesion but sustained neonatally only altered substantially the packing density of glial cells (decreased). Therefore, we concluded that (i) the caudate nucleus hypertrophy which we reported after a unilateral discrete cortical removal during the prenatal period is a unique phenomenon which is peculiar to the cat brain during the last third of gestation; (ii) the caudate nucleus changes seen in the cats with hemineodecortication in adulthood are degenerative in nature and closely resemble those which we reported for other subcortical nuclei following a similar lesion; and (iii) the animals with neonatal hemidecortication are relatively spared from these degenerative effects. Overall, these results indicate that, as for other structures, the morphological changes of the caudate nucleus following neocortical damage depend on the maturational state of the brain at the time of the injury and on the size of the lesion, and support the notion that the consequences of cerebral cortex lesions upon subcortical brain nuclei are of a different nature when sustained in prenatal as compared to postnatal cats.

Animals↗

PubMed1997

Glutathione S-transferase activity in epithelial ovarian cancer: association with response to chemotherapy and disease outcome.

BACKGROUND: Conflicting data have been reported about the association between glutathione S-transferase (GST), a family of proteins implicated in detoxification of cytotoxic drugs in human ovarian in vitro models, and response to chemotherapy and prognosis in ovarian cancer patients. The aim of this study was to analyze the possible clinical role of GST activity in a large series of primary ovarian cancer patients. PATIENTS AND METHODS: The study included a large series of primary untreated ovarian cancer patients who underwent cytoreductive surgery and chemotherapy and who were followed up in a single institution. GST activity levels were assessed in tumor extracts by using a biochemical assay. A cut-off of 250 units of enzymatic activity was chosen according to the receiver operating characteristics (ROC) curve. RESULTS: GST activity levels were distributed in an asymmetrical manner (median: 266 units; range: 4-918 units) and did not seem to be associated with stage, histopathological grading, ascites, or residual tumor after surgery. Higher GST activity levels were found in patients who responded to chemotherapy (median: 298 units, range: 50-691) than in those who responded only partially (median: 227 units, range: 19-747) or not at all to chemotherapy (median: 246 units, range: 4-811) (H = 7.02, P = 0.029). Moreover, the percentage of cases with > 250 units was significantly higher among complete responders (66%) than partial responders (37%) or non-responders (48%) (chi 2 = 7.32; P = 0.025). When multivariate analysis, including clinico-pathological parameters and GST activity status as predictors of response to chemotherapy, was carried out, residual tumor, stage and GST status retained independent predictive value. Patients with high GST activity had more favourable prognosis than those with low GST activity. The median PFS was 42 months for patients with high GST activity compared to 17 months for those with low GST activity (P = 0.037). The median overall survival was 72 months for high-GST-activity and 42 months for low-GST-activity patients (P = 0.043). Substantially similar results were obtained in the subgroup of stage II-III-IV ovarian cancer patients. Multivariate analysis including the clinico-pathological parameters and GST activity status was performed in stage III-IV ovarian cancer patients: Stage IV disease, residual tumor > 2 cm, the presence of ascites and low GST activity status retained independent negative prognostic roles. CONCLUSION: A direct association between high GST activity and a better clinical outcome in terms of response to chemotherapy and survival has been observed in a large series of primary untreated ovarian cancer patients. These results, which are contrary to the expectations raised by in vitro studies, emphasize the need for caution when translating in vitro-generated hypotheses to the clinical setting.

Antineoplastic Agents↗

PubMed1997

Synergistic antiproliferative activity of tamoxifen and docetaxel on three oestrogen receptor-negative cancer cell lines is mediated by the induction of apoptosis.

The taxanes are a promising family of anti-tumour drugs that block cell cycle replication by interfering with the microtubule network. The clinical use of these drugs involves some problems related to their low solubility and occurrence of resistance, which is mainly dependent on the multidrug-resistant (MDR) phenotype. To investigate the possible interaction between docetaxel and tamoxifen (TAM), three oestrogen receptor-negative cancer cell lines, MDR- MDA-MB 231, MDR + CEM-VBLr and MCF-7 ADRr, were used. In all three cell lines, the combination of docetaxel and TAM was more effective in terms of growth inhibition than single drug exposure. Isobolic analysis confirmed the presence of synergism in all cell lines when docetaxel was used at 0.2 microM and TAM at a dose equal to or higher than 1 microM. Flow cytometric DNA analysis performed on the three cell lines showed that TAM was able to increase the G2/M blocking activity of docetaxel. This blocking activity was followed by an increased flow cytometric DNA fragmentation suggestive of the presence of apoptosis, which was confirmed by DNA gel fragmentation and morphological analysis. While an antagonistic effect on P-glycoprotein (P-gp) activity may contribute to the synergistic effect of tamoxifen and docetaxel on CEM-VBLr and MCF-7 ADRr, other mechanisms must be involved, as the synergistic effect is also apparent with a P-gp-negative cell line.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

High-dose carboplatin, etoposide and melphalan (CEM) with peripheral blood progenitor cell support as late intensification for high-risk cancer: non-haematological, haematological toxicities and role of growth factor administration.

The present report describes the non-haematological toxicity and the influence of growth factor administration on haematological toxicity and haematopoietic recovery observed after high-dose carboplatin (1200 mg m(-2)), etoposide (900 mg m(-2)) and melphalan (100 mg m(-2)) (CEM) followed by peripheral blood progenitor cell transplantation (PBPCT) in 40 patients with high-risk cancer during their first-line treatment. PBPCs were collected during the previous outpatient induction chemotherapy programme by leukaphereses. CEM administration with PBPCT was associated with low non-haematological toxicity and the only significant toxicity consisted of a reversible grade III/IV increase in liver enzymes in 32% of the patients. Haematopoietic recovery was very fast in all patients and the administration of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) or granulocyte-macrophage colony-stimulating factor (GM-CSF) plus EPO after PBPCT significantly reduced haematological toxicity, abrogated antibiotic administration during neutropenia and significantly reduced hospital stay and patient's hospital charge compared with patients treated with PBPCT only. None of the patients died early of CEM plus PBPCT-related complications. Low non-haematological toxicity and accelerated haematopoietic recovery renders CEM with PBPC/growth factor support an acceptable therapeutic approach in an adjuvant or neoadjuvant setting.

Adult↗

PubMed1997

Prognostic significance of ras/p21 alterations in human ovarian cancer.

Ras/p21 oncoprotein expression and K-ras mutations were analysed by Western blot and/or K-ras oligonucleotide hybridization in 78 primary ovarian cancers, 20 omental metastases, two low malignant potential tumours (LMP), nine benign ovarian tumours and 10 normal ovaries. A cut-off value of an integral of absorbance (i.a.) of 2.20, obtained by receiver operating characteristic (ROC) curve, was shown to be the best cut-off for defining p21 positivity. p21 levels were higher in malignant tumours than in benign tumours (median 2.10 i.a. vs median 1.22 i.a.; P = 0.014) and in omental metastases than in primary ovarian carcinomas (median 2.54 i.a. vs median 2.1 i.a.; P = 0.0089). p21 overexpression did not correlate with any of the clinicopathological parameters examined. Follow-up data were available for 63 patients. A significant relationship was shown between p21 positivity and a shorter overall survival (OS) (P < 0.03) and progression-free survival (PFS) (P < 0.03). In multivariate analysis only the presence of ascites, p21 levels and epidermal growth factor receptor status retained an independent prognostic role. K-ras gene mutations were frequently detected in benign and low malignant potential tumours (71.4%), which were mostly mucinous (P = 0.0152).

Animals↗

PubMed1997

Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis.

Several reports have evaluated the correlation between cathepsin-D and overall survival or disease-free survival in node-negative breast cancer patients. Because conflicting data have so far been reported, a meta-analysis was conducted to clarify this problem. Eleven studies were included in our meta-analysis (total of 2690 patients). A specific meta-analytical methodology for censored data was used, and disease-free survival was the primary end point. Patients with low cathepsin-D levels had a significantly better disease-free survival than patients with high cathepsin-D values (meta-analytical odds ratio from 0.59 to 0.60 over the interval from 1 to 7 years). A secondary meta-analysis conducted exclusively on the data from eight studies based on cytosol assay gave substantially similar results. One limitation of our study is that the cut-off values to define high and low cathepsin-D concentrations were not identical in the various studies included in our meta-analysis (range from 20 to 78 pmol mg(-1) protein), thus introducing a possible bias in the statistical analysis of the data. However, a simulation based on the well-accepted method of the so-called publication bias showed that more than 100 null studies would be required to lead our results to a statistical level of non-significance. Considering the results of our meta-analysis, we conclude that the data presently available confirm a statistically significant association between high cathepsin-D values and poor disease-free survival in node-negative breast cancer patients.

Breast Neoplasms↗

PubMed1997

Influence of chronic Naltrexone treatment on growth hormone and insulin secretion in obese subjects.

OBJECTIVE: Recent studies have demonstrated the restoration of a normal 24 h GH profile induced by a reduction of insulinaemia after weight loss, suggesting a reciprocal relationship between plasma insulin and GH concentrations. We aimed to clarify if an opiate-induced reduction in plasma insulin could affect GH secretion in obesity. DESIGN: We have studied the insulin response to an oral glucose tolerance test (OGTT) and the GH response to GHRH before and after prolonged treatment with Naltrexone (NTX). C-peptide, IGF-I, IGFBP-3 plasma levels and the IGF-I/IGFBP-3 molar ratio were also determined. SUBJECTS: Twelve obese women (aged 25-41 y; Body mass index (BMI): 31-39 kg/m2) and six lean normal women (aged 25-38; BMI: 19.8-23.1 kg/m2). MEASUREMENT: GH was determined by the IRMA method; insulin, C-peptide, IGF-I and IGFBP-3 were assayed by the RIA method. For molar comparison between IGF-I and IGFBP-3 we have considered 30.5 kDa the molar weight of IGFBP-3. Results are expressed as mean +/- s.e.m. RESULTS: We observed a significant decrease in basal concentration of both insulin (230.1 +/- 34.9 vs 133.2 +/- 16.9 pmol/L; P < 0.005) and C-peptide (3.7 +/- 0.3 vs 2.4 +/- 0.1 micrograms/L; P < 0.02). No modifications in the insulin secretory response to the OGTT were observed. A significant increase of the GHRH-induced GH peak response (7.7 +/- 1.4 vs 19.7 +/- 3.1 micrograms/L; P < 0.01) and GH-AUC (533 +/- 151 vs 1415 +/- 339 micrograms/L/120 min; P < 0.01) was found after NTX treatment. A negative correlation was found between basal insulin and GH peak values, both before (r = -0.641, P = 0.027) and after NTX (r = -0.714, P = 0.013). No modifications were found in IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio. Moreover, NTX affected neither the insulin response to OGTT or IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio in a group of six lean controls. Conversely, NTX significantly reduced the GH response to GHRH, when expressed as both peak and AUC values. CONCLUSIONS: The opiate antagonist significantly reduced basal insulin concentrations and augmented the GH response to GHRH in obese subjects. In the absence of modifications in IGF-I and IGFBP-3 plasma levels and their molar ratio, we propose that insulin may exert a negative feedback on GH secretion.

Adult↗

PubMed1997

Generation of multinuclear tartrate-resistant acid phosphatase positive osteoclasts in liquid culture of purified human peripheral blood CD34+ progenitors.

Circulating CD34+ cells were isolated from leukapheresis products collected from patients with ovarian cancer. CD34 contaminating cells, identified immediately after immunoselection, ranged from 5% to 25% in five different experiments and were predominantly CD3+ T-lymphocytes (range 2-12%), CD3+/CD16+/CD56+ natural killer cells (range 2-11%) and rare mature CD15+/ CD11b+ granulocytes (range 1-2%). CD34+ cells were cultured in liquid medium in the presence of interleukin-3, granulocyte-macrophage colony stimulating factor. stem cell factor, granulocyte colony stimulating factor and a powerful proliferation with prevalent differentiation along the granulocytic/monocytic lineage was obtained. After 10 d of culture a small but consistent number of early multinucleated osteoclasts were identified with a frequency of one cell per 700 granulocytic/monocytic cells, as revealed by cytologic examination. This observation was confirmed by staining for tartrate-resistant acid phosphatase activity which revealed red multinucleated elements with a frequency comparable to that reported above. Conversely, no osteoclasts were observed in those cultures in which macrophage overgrowth was obtained by culturing CD34+ cells until day 35. These observations suggest that circulating progenitors have a multilineage potential in vitro and contribute to the clarification of osteoclast development in humans: additionally, they provide the basis for the future development of optimized osteoclast culture techniques in liquid medium and the basic culture system, to test the distinct activity of 1,25(OH)2D3. parathyroid hormone interleukin-11 and of other cytokines on osteoclast development in humans.

Acid Phosphatase↗

PubMed1997

Purified unfractionated G-CSF/chemotherapy mobilized CD34+ peripheral blood progenitors and not bone marrow CD34+ progenitors undergo selective erythroid differentiation in liquid culture in the presence of erythropoietin and stem cell factor.

A combination of erythropoietin (EPO) plus stem cell factor (SCF) drove purified unfractionated granulocyte colony stimulating factor (G-CSF)/chemotherapy mobilized peripheral blood CD34+ cells to selective erythroid differentiation in liquid culture with an average 28-fold increase in the total cell number after 21 d. From day 6 of culture cytologic and cytofluorimetric characterization revealed that cultured cells belonged to the erythroid lineage with a gradual wave of maturation along the erythroid pathway to terminal cells. A similar pattern of erythroid differentiation was observed when the same peripheral blood CD34+ cells were culture with EPO plus SCF in serum-free medium. This cytokine combination produced selective erythroid differentiation with the complete exhaustion of the clonogenic potential on day 21. In parallel experiments the same circulating CD34+ cells underwent granulocytic/ monocytic differentiation in liquid culture in response to granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and SCF, demonstrating that these CD34+ progenitors had intact pluripotent differentiating potential. Conversely, bone marrow CD34+ cells isolated from bone marrow allografts were unable to selectively differentiate along the erythroid pathway when they were exposed to EPO plus SCF combination. However, these cells maintained a greater number of colony forming cells on day 21 of culture compared to mobilized peripheral blood CD34+ cells. This model is a simple and reliable way to obtain selective erythroid differentiation of peripheral blood G-CSF/ chemotherapy mobilized CD34+ progenitor cells in liquid culture. The absence of cytokines such as GM-CSF and IL-3 in the culture medium permits studies on in vitro erythropoiesis without disturbance of prevalent myelopoiesis.

Antigens, CD34↗

PubMed1997

Autologous stem cell transplantation: evaluation of erythropoietic reconstitution by highly fluorescent reticulocyte counts, erythropoietin, soluble transferrin receptors, ferritin, TIBC and iron dosages.

The plasma concentrations of erythropoietin (Ep), soluble transferrin receptors (sTfRs), iron, total iron binding capacity (TIBC) and ferritin were monitored in five leukaemia patients undergoing autologous bone marrow stem cell transplantation (BMSCT) and in 10 lymphoma and 21 ovarian cancer patients undergoing autologous peripheral blood SCT (PBSCT); 9/21 ovarian cancer patients received recombinant human G-CSF and Ep and six recombinant human GM-CSF and Ep following SCT. All parameters were evaluated in relation to the kinetics of erythroid reconstitution as evaluated by haemoglobin (Hb) and reticulocyte levels [including the fraction of immature reticulocytes, also called highly fluorescent reticulocytes (HFR)]. Leukaemia patients undergoing BMSCT showed only a delayed (occurring at days 35-50 after SCT) and partial RBC, neutrophil and platelet recovery, whereas all patients undergoing PBSCT exhibited a rapid (occurring at days 10-15 after SCT) and sustained haemopoietic recovery. The various levels of erythroid rescue observed among these patients markedly influenced the kinetics of the different parameters investigated: (i) in leukaemia BMSCT patients sTfRs declined following SCT and remained at low levels thereafter, whereas Ep, iron. TIBC and ferritin showed a progressive and significant increase; (ii) in the different groups of patients undergoing PBSCT: (a) sTfR levels first declined following SCT and then returned to pre-therapy values at days 12-16, this response preceded erythropoietic recovery; (b) Ep, total iron, TIBC and ferritin showed an initial increase in the first days following SCT and then returned to pre-therapy values. Altogether, these observations indicate that: (i) both sTfR levels and reticulocyte counts are predictive parameters of erythropoietic recovery; (ii) coordinated changes of biochemical parameters underlying iron metabolism (iron, TIBC and ferritin) accompany erythroid rescue following SCT.

Adolescent↗

PubMed1997

The cellular activity of different sized follicles in cycles treated with gonadotrophin-releasing hormone analogue.

The activity of granulosa cells derived from different sized follicles surrounding oocytes of apparently comparable maturity was evaluated in hyperstimulated ovaries. Granulosa cells were obtained from women undergoing gamete intra-Fallopian transfer procedures who had been treated with gonadotrophin-releasing hormone analogue and gonadotrophins. Only follicles with oocytes of apparently comparable maturity were considered. Granulosa cells from large and small follicles (> or = 18 and < 15 mm diameter respectively) collected from each patient were cultured separately for up to 48 h in the presence or absence of follicle-stimulating hormone (FSH: 50 ng/ml) or insulin (at varying doses, 0.005-25 mg/ml). We found that aromatase activity was elicited by FSH plus insulin, but not by FSH alone, in granulosa cells from both large and small follicles. Progesterone production was maximal in granulosa cells from large follicles, and in these cells was insensitive to further stimuli, in contrast with those collected from small follicles. Prostaglandin oestradiol was secreted in large amounts by granulosa cells from large follicles. Cyclic adenosine monophosphate (cAMP) concentration did not differ between cells from large and small follicles. Our data demonstrate that there are significant differences in granulosa cells derived from different sized follicles with oocytes of apparently comparable maturity.

Adult↗

PubMed1997

Further evidence of increased aromatase activity in granulosa luteal cells from polycystic ovary.

This study evaluated the effect of atamestane (a competitive inhibitor of P-450 aromatase) on granulosa luteal cells from polycystic and normal ovaries. Treatment with atamestane (10 micromol/l) determined a strong inhibition of basal aromatase activity in both types of cells; however, its effect was markedly more pronounced in granulosa cells from normal ovary than in granulosa cells from polycystic ovaries (PCO; P < 0.01). Concomitant treatment with insulin (25 microg/ml) and increasing doses of atamestane (0.01-10 micromol/l) caused a dose-dependent inhibition of insulin-stimulated aromatase activity, but again with marked differences between the two types of cells. In granulosa cells from PCO, the minimal effective dose of atamestane was 1 micromol/l and it had an EC50 of 2.23 +/- 0.4 micromol/l and a maximal inhibitory effect of 75%; in granulosa cells from normal ovary, the minimal effective dose of atamestane was 0.01 micromol/l, the EC50 was 0.4 +/- 0.07 micromol/l, and the maximal inhibitory effect was 94%. Significant differences were observed between the different cells at all the studied dose points. Reversibility studies showed that resumption of aromatase activity in granulosa cells from PCO is basally greater and more inducible with insulin treatment. This study provides further evidence of an increased in-vitro function of the aromatase complex in granulosa cells from PCO, that could be induced by an altered cellular autoregulation.

Adult↗

PubMed1997

Heterogeneity in beta cell activity, hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome.

The aim of this study was to evaluate the impact of reduced peripheral insulin sensitivity, beta cell hypersecretion and reduced hepatic insulin clearance in the hyper-insulinaemia of lean and obese PCOS patients. A total of 35 women with polycystic ovary syndrome (PCOS) and 10 lean normo-ovulatory controls underwent an oral glucose tolerance test and an euglycaemic-hyper-insulinaemic clamp study. PCOS patients were classified into four groups according to their BMI and insulin secretion (normo-lean; normo-obese; hyper-lean; hyper-obese), and results were compared between groups and with the controls. All the PCOS groups showed significantly higher insulin secretion than controls; there were no differences in insulin response to glucose load between lean and obese normo- and hyper-insulinaemic patients. Secretion of c-peptide was greater in PCOS groups than controls. All the hyper-insulinaemic PCOS patients had lower values of hepatic insulin clearance, independent of BMI, when compared either with controls (P < 0.001) or with PCOS normo-insulinaemic women (P < 0.01). Normo- and hyper-insulinaemic obese patients had similar total body glucose utilization (M value), which was lower than in lean PCOS subjects and controls. Our results suggest that evaluation of insulin resistance alone does not fully characterize the PCOS population; differences in liver metabolism of insulin are present in obese insulin resistant subjects and in lean patients with normal insulin sensitivity when divided into normo- and hyper-insulinaemic subgroups. Insulin resistance and hyper-insulinaemia may represent two distinct features of the insulin disorder in PCOS: the former appear to reflect the presence of obesity, while the latter may be a primary feature of PCOS.

Adolescent↗

PubMed1997

Postoperative adhesion formation and reproductive outcome using Interceed after ovarian surgery: a randomized trial in the rabbit model.

The efficacy of an oxidized regenerated cellulose barrier (Interceed) in reducing postoperative adhesion formation and improving reproductive outcome after ovarian surgery was evaluated in a prospective randomized trial. Twenty-nine New Zealand White female rabbits were submitted to a mid-line laparotomy and a standardized surgical incision was made on both ovaries. At random, one ovary was entirely wrapped in a sheet of Interceed, whereas the contralateral ovary was left uncovered. Four weeks following surgery, the rabbits were mated with a male of proven fertility. Two weeks later, a second-look laparotomy was performed by a blinded observer who evaluated the incidence and score of adhesions, the number of corpora lutea in each ovary, the number of embryos in the ipsilateral uterine horn and also calculated the nidation index for each side. Adhesions were observed in 66% of Interceed-covered and in 97% of control ovaries (P < 0.0001). The adhesion score on the Interceed side was significantly lower than on the control side. The nidation index for the Interceed side was significantly higher than for the control side. The authors conclude that, in the rabbit model, Interceed significantly reduces the incidence and score of postoperative ovarian adhesions and significantly improves reproductive outcome.

Animals↗

PubMed1997

Heparin and low-dose aspirin restore placental human chorionic gonadotrophin secretion abolished by antiphospholipid antibody-containing sera.

This study was conducted to determine whether drugs used for conventional treatments of pregnant women with antiphosholipid syndrome might be able to restore the gonadotrophin-releasing hormone (GnRH)-induced secretion of placental human chorionic gonadotrophin (HCG) in vitro. We tested this hypothesis using a modified enzyme-linked immunosorbent assay (ELISA) and an in-vitro placental culture system. Pharmacological dose of low molecular weight heparin (20 IU/ml) significantly (P < 0.02) reduced the antiphospholipid antibody (aPL) binding in the ELISA and was able to restore GnRH-induced HCG secretion (P < 0.05) in presence of aPL-containing sera. Low-dose aspirin (0.03 M) did not modify aPL binding in the ELISA, but partially restored HCG secretion (P < 0.05). These observations may help to explain the role of these treatments in antiphospholipid syndrome.

Anti-Inflammatory Agents↗

PubMed1997

Postoperative GnRH analog treatment for the prevention of recurrences of uterine myomas after myomectomy. A pilot study.

Sixty-five patients with uterine myomas were studied after surgery to investigate the effect of periodic GnRH analog treatment on the prevention of recurrences. A group of patients was treated by leuprolide acetate depot 3 months a year for 3 years. At the end of treatment, these patients showed a significantly reduced uterine volume and myoma recurrence rate as compared to untreated patients. A role of GnRH analogs in the clinical prevention of myoma recurrence could be suggested.

Adult↗

PubMed1997

The impact of insulin secretion on the ovarian response to exogenous gonadotropins in polycystic ovary syndrome.

The aim of the study was to evaluate the influence of insulin level on the ovarian response to FSH when inducing ovulation in patients affected by polycystic ovarian syndrome (PCOS). To evaluate the presence of hyperinsulinemia, 34 patients affected by PCOS were studied by an oral glucose tolerance test, then patients were stimulated for 52 cycles using FSH to induce ovulation. The ovarian response to therapy was evaluated by ultrasounds and as estradiol (E2) and androstenedione (A) plasma level determinations. On the basis of the insulinemic response to the glucose challenge, 20 patients were considered to be hyperinsulinemic and 14 normoinsulinemic. The hormonal features of each group were similar. The ovulation rate was similar in hyperinsulinemic and normoinsulinemic subjects, whereas the incidence of ovarian hyperstimulation was significantly higher in the hyperinsulinemic group. The increase in ovarian dimensions observed in hyperinsulinemic subjects after gonadotropin stimulation was more marked than that observed in normoinsulinemic ones. This was caused by the development of a larger number of immature follicles. E2 levels gradually increased after gonadotropin stimulation in both groups of subjects; however, higher levels were observed in hyperinsulinemic patients. During stimulation, the higher E2/A ratio suggests the presence of a greater aromatization activity in hyper-insulinemic patients. In conclusion, the present study suggests that, in PCOS, the insulinemic pattern may influence the ovarian response to gonadotropin administration; thus, hyperinsulinemic subjects may be at greater risk of ovarian hyperstimulation syndrome than normoinsulinemic subjects.

Adult↗

PubMed1997

Influence of chronic naltrexone treatment on growth hormone secretion in normal subjects.

OBJECTIVE: To verify if a chronic opioid blockade could affect the GH/IGF-I axis. DESIGN: We have investigated the effects of naltrexone (NTX) treatment on GH response to GHRH in normal women. METHODS: GHRH test (50 micrograms i.v.) performed in seven normal female volunteers (age 25-38 years, with a body mass index ranging from 19.8 to 23.1 kg/m2) before and after 4-weeks NTX treatment (50 mg p.o. daily). RESULTS: Basal GH, IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3) plasma levels and the IGF-I/IGFBP-3 molar ratio remained unaffected by NTX. NTX significantly reduced the GH peak values (15.52 +/- 3.59 vs 4.78 +/- 0.49 micrograms/l; P < 0.01), and GH area under curve (918.93 +/- 253.96 vs 401.09 +/- 79.63 micrograms/l; P < 0.01). CONCLUSIONS: This finding suggests that the long-term opioid receptor blockade has an inhibitory role on GHRH-induced GH secretion. A central influence on neurotransmitter control of GH might be hypothesised. The inhibition of stimulated GH release, without interference with the basal level, could indicate an enhanced somatostatin secretion and/or activity. Opioids could be involved only in the regulation of GH dynamics and not in basal secretion. Nevertheless, a direct involvement of opioids at the pituitary level, which could be modified by NTX, cannot be excluded.

Adult↗