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Biomedical subjects

A Mancini

Publications and source records attributed to A Mancini.

At least 55 records · Page 3Linked to original sources
PubMed2000

Inhibitory action on GHRH-induced GH secretion of chronic tamoxifen treatment in breast cancer.

OBJECTIVE: Previous in vitro and in vivo studies on animal models have demonstrated that tamoxifen (TAM) inhibits GH secretion. Studies in humans are conflicting. The aim of this study was to evaluate the effect of chronic TAM treatment on GH secretory dynamics in the presence of negligible endogenous oestrogens, in postmenopausal women with breast cancer. PATIENTS: Ten female patients were studied over a 6-12-month period after surgical therapy, before medical therapy, and during chronic treatment with TAM (20 mg/day p.o.). MEASUREMENTS: In all subjects we performed a standard GHRH-test (50 mg i.v. as a bolus) and compared the single time points, the peak response and the areas under the curves (AUC), before and during treatment. In basal samples, we evaluated the circulating levels of IGF-1, IGF-BP3 and their ratio, SHBG, FSH, LH, Oestradiol (E2) and PRL. GH was assayed by Immunoradiometric assay (IRMA). Insulin-like growth factor type I (IGF-I), Insulin-like growth factor-binding protein-3 (IGF-BP3), FSH, LH and PRL were measured by Radioimmunoassay (RIA). SHBG was measured by a noncompetitive liquid phase immunoradiometric assay, while E2 was measured directly in plasma by a liquid phase technique. RESULTS: TAM chronic treatment significantly reduced GH response to GHRH at single time point evaluations, GH peak response (mean decrease: 59.8 +/- 7.3%) and GH-AUC (mean decrease 53.8 +/- 8.9%). TAM also significantly reduced plasma IGF-1 levels. No significant variations were found in IGF-BP3 levels or in the IGF-1/IGF-BP3 ratio. A significant inverse correlation between SHBG and IGF-1 circulating levels was noticed during TAM treatment. CONCLUSIONS: Our data show that long-term tamoxifen treatment blocks the response of GH to exogenous GHRH and reduces IGF-1 levels, possibly by a central mechanism other than the demonstrated peripheral action. The results of this study, keeping in mind the demonstrated mitogenic role of IGF-1 in cancer proliferation, can contribute to clarify the mechanism by which TAM exerts its antiproliferative effect.

Aged↗
PubMed1999

FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation.

Hematopoietic cell growth, differentiation, and commitment to a restricted lineage are guided by a set of cytokines acting exclusively on cells expressing the corresponding cytokine receptor. The macrophage colony stimulating factor (M-CSF, also termed CSF-1) and its cognate receptor, the tyrosine kinase c-Fms, are essential for monocyte and macrophage development. The underlying molecular mechanism, however, is poorly understood. Here we identified a novel Fms-interacting protein (FMIP, MW 78 kDa) which binds transiently via its N-terminal 144 residues to the cytoplasmic domain of activated Fms-molecules. Binding of FMIP was paralleled by rapid tyrosine phosphorylation within the binding domain which drastically reduced its ability to associate with Fms. Binding was specific as evidenced by co-immunoprecipitation and association with recombinant GST-Fms fusion proteins. No binding was observed with the tyrosine phosphorylated cytoplasmic domains of c-Kit, TrkA, c-Met, and the insulin receptor. The role of FMIP in hematopoietic differentiation was studied in the bipotential myeloid progenitor cell line, FDC-P1Mac11. Overexpression of FMIP prevented M-CSF induced macrophage differentiation. Instead, cells differentiated into granulocytes. Our data suggest that the level of FMIP expression could form a threshold that decides about differentiation either into macrophages or into granulocytes.

Amino Acid Sequence↗
PubMed1999

Purification of ethanolaminephosphotransferase from bovine liver microsomes.

CDP-ethanolamine:diacylglycerol ethanolaminephosphotransferase (EC 2. 7.8.1) has been purified to electrophoretic homogeneity and in a catalytically active form from bovine liver microsomes. The purification method is based on the high hydrophobicity of the protein whose charged sites appear to be masked from the interaction with the chromatographic stationary phases when membranes are solubilized with an excess of non-ionic detergent. The isolated protein has a molecular mass of about 38 kDa, as estimated by SDS-PAGE mobility, and exhibits both ethanolaminephosphotransferase and cholinephosphotransferase activities. Evidence is given that both activities are Mn2+-dependent and that the same catalytic site is involved in cholinephosphotransferase and ethanolaminephosphotransferase reactions. Mg2+-dependent CDP-choline:diacylglycerol cholinephosphotransferase (EC 2.7.8.2) is completely inactivated during the solubilization and purification steps.

Animals↗
PubMed1999

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism.

OBJECTIVE: To investigate the involvement of opioid tone, obesity, and hyperinsulinemia in GH secretion in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Catholic University of Sacred Heart School of Medicine in Rome, Italy. PATIENT(S): Twenty-two patients with PCOS and 14 healthy, normally ovulating volunteers, matched for age and body mass index. INTERVENTION(S): Patients underwent a GH-releasing hormone (GHRH) test and an oral glucose tolerance test before and after 4-5 weeks of treatment with 50 mg/d of naltrexone. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin, glucose, steroids, and gonadotropins, as well as the GH area under the curve (AUC-GH) and the insulin area under the curve (AUC-I), were measured before and after naltrexone treatment. RESULT(S): In patients with PCOS, the administration of naltrexone increased the GH response to the GHRH test without interfering with the insulin response to the oral glucose tolerance test. However, the GH response to the GHRH test was improved significantly only in lean patients with PCOS, whereas obese patients with PCOS did not show any improvement in GH secretion. In obese control subjects, the treatment reduced plasma basal insulin concentrations and increased the AUC-GH, whereas in lean control subjects, the treatment reduced the GHRH-induced response. In normoinsulinemic patients with PCOS, the GH response to the GHRH test increased significantly after treatment, whereas the AUC-I was not affected. In hyperinsulinemic patients with PCOS, treatment with naltrexone significantly reduced the AUC-I, whereas the AUC-GH increased only in lean hyperinsulinemic patients with PCOS. CONCLUSION(S): Naltrexone treatment improves GHRH-induced GH secretion in patients with PCOS. However, this GH response is heterogeneously represented in relation to both obesity and hyperinsulinism.

Adult↗
PubMed1999

Hypothalamic derangement in traumatized patients: growth hormone (GH) and prolactin response to thyrotrophin-releasing hormone and GH-releasing hormone.

OBJECTIVE: To study the impact of severe head injury on both basal pituitary hormone secretion and the response to exogenous synthetic hypothalamic releasing factors (TRH and GHRH) in order to evaluate sequential changes in the central control of hypophyseal secretion in the days following head injury. DESIGN: Prospective clinical study PATIENTS: 21 comatose male patients with head injuries, each intubated and ventilated, intensively monitored and having no previous endocrine problems. MEASUREMENTS: AND RESULTS The GH and PRL responses to TRH (200 microg iv), and the GH and PRL responses to GHRH (50 microg iv) were evaluated, respectively, on the days 1 and 16 and on days 2, 7and 15 after admission. Daily blood samples were also collected for GH, PRL, TSH, T3 and T4 evaluation. In the basal samples taken on days 2, 7 and 15, IGF-I and cortisol were also determined. Nitrogen balance was assessed daily. On the day 1, TRH increased GH levels from 9.8 +/- 2.2 to 22.4 +/- 6.5 mU/l but failed to induce GH release on day 16. The PRL response to TRH was normal. The GH peak response to GHRH was normal on the day 2 (35.7 +/- 13.9 mU/l), but was increased on days 7 and 15 (68.3 +/- 10.7 mU/l on day 7; 73.8 +/- 9.2 mU/l on day 15, P < 0.01 vs. day 2). We found a significant PRL response to GHRH during the whole period of observation. In the daily evaluation, nitrogen balance was negative in all patients from the day 1 to 5. On average, all patients reached a positive nitrogen balance on the day 8. Compared to the day 2, a statistical increase in IGF-I concentration was observed on days 7 and 15. CONCLUSIONS: The evaluation of pituitary dynamics in the acute phase of a severe injury demonstrates an alteration of GH and PRL secretion, which correlate with the aminergic and/or peptidergic derangements. Taken together, our data suggest augmented tone of both GHRH and somatostatin in the very acute phase, while an imbalance of releasing factors is hypothesized in the following days. The metabolic consequences of this neuroendocrine pattern could be advantageous in the rapid recovery from the cascade of events produced by the trauma, as documented by the increase in IGF-1 levels and the positive nitrogen balance.

Accidents, Traffic↗
PubMed1999

Plasma leptin levels after biliopancreatic diversion: dissociation with body mass index.

Human obesity is associated with increased leptin levels, related to body composition and fat mass (FM). Insulin has been suggested to be a regulator of in vivo leptin secretion. To further investigate the relationships between insulin and leptin levels in human obesity, we have studied 10 obese females, aged 26-57 yr [body mass index (BMI), 42.9+/-6.3], successfully treated by biliopancreatic (BPD) diversion, in an early postoperative period (2 months after surgery, post-BPD I; BMI, 37.2+/-7.5) and a late postoperative period (16-24 months after surgery; BMI, 27.6+/-3.96). Fourteen normal female subjects (18-59 yr; BMI, 27.9+/-1.4 kg/m2) were studied as controls. In pre-BPD obese subjects, leptin levels were higher than those in controls (60.5+/-18.8 vs. 28.7+/-4.8 ng/mL; P<0.001). BMI and insulin levels were also significantly greater (P<0.0001 and P<0.03, respectively). After surgery, the three parameters considered significantly decreased (P = 0.0007 for BMI, P<0.0001 for leptin, and P = 0.038 for insulin, using Friedman's test for repeated data). Concerning the correlation between leptin and FM in our patients, control subjects and pre-BPD subjects confirmed the correlation found in the general population (r = 0.78; P<0.01). On the contrary, post-BPD patients at 2 months lay outside the general correlation between FM and leptin; in fact, patients with low leptin levels still had a high FM. Moreover, in the post-BPD patients there was no longer a significant correlation between FM and leptin. Concerning the correlation between insulin and leptin levels, a significant correlation was present in control subjects and pre-BPD patients (r = 0.46; P<0.05). Using correlation analysis for repeated measures in surgically treated obese patients, a significant correlation within the subjects was present (r = 0.91; P<0.0001). After operation, BMI and leptin levels had a different pattern of decrease; leptin decreased rapidly, without correlation with BMI, indicating that body composition is not the only factor regulating leptin levels. The consistent correlation with insulin levels suggests an important interaction between these two hormones in post-BPD obese subjects.

Adult↗
PubMed1999

Reactive oxygen species in male infertility. Review of literature and personal observations.

Reactive oxygen species, highly reactive molecules derived from the metabolism of oxygen, play an important role in the metabolism of spermatozoa, related to the hyperactivated motility and acrosome reaction. Various studies have demonstrated that these molecules, because of their reactivity, can induce peroxidative damage on the cell, especially on the lipid membranes. The spermatozoa, owing to their structure, appear to be very sensitive to the oxidative insult. Various experimental data sustain the hypothesis that, when produced in high amounts, reactive oxygen species can induce sperm damage and become potentially responsible for some forms of unexplained infertility. The cells possess various mechanisms of defense against the oxidative insult, mainly due to antioxidant molecules. An antioxidant treatment can produce an improvement in seminal parameters and sperm function in vitro, and represents a possible form of care for selected forms of infertility.

Fertilization↗
PubMed1999

Establishment and growth regulation of a novel ovarian cancer cell line from a poorly-differentiated adenocarcinoma: proposal for a new treatment.

A continuously growing cultured cell line has been obtained in vitro, starting from a specimen of ascites fluid obtained from a patient with ovarian cancer, in whom a poorly-differentiated adenocarcinoma was diagnosed. This cell line, named OC-A1, is routinely grown in standard, serum-supplemented culture medium and has been fully stabilized to long-term growth and characterized for both cultural and genetic parameters. OC-A1 cells express a set of characteristics, as determined in vitro which, when compared with the in vivo primary tumor, confirm the high malignity of this cancer. In addition, karyotype analysis showed a translocation of chromosome 8 which is correlated with the amplification of c-myc oncogene. However, the expression of this oncogene was found to be significantly inhibited by a new regulatory activity, recently found to be present in a liposarcoma cell line. Conditioned medium from these cells was indeed able to inhibit the growth of OC-A1 cells, arresting their cell cycle in the G1 phase and inducing them to apoptosis. Finally, the cell programmed death appeared to be related to the expression of antioncogene p53.

Adenocarcinoma↗
PubMed1999

Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver.

Aim of the study was to evaluate treatment efficacy and safety of a scaled-up version of our porcine hepatocytes based BAL system in pigs with complete liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by termino-lateral porta-caval shunts and sutures around the bile duct, the common hepatic and gastroduodenal arteries and their accessory branches. The hepato-duodenal ligament was completely transected. Four experimental groups were studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was connected to a centrifugal plasma-separator with a bottle representing the bioreactor volume, the third control group (LIS Empty-BAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-BAL, n = 8) was connected for a maximum period of 24 hours to our scaled-up BAL seeded with around 14 billion viable primary porcine hepatocytes. BAL treatment significantly prolonged life in large animals (approximately 35 kg) with complete LIS (Controls, mean +/- SEM: 33.1 +/- 3 h, Cell-BAL: 51.1 +/- 3.4 h; p = 0.001; longest survivor 63 h). In addition, blood ammonia and total bilirubin levels decreased significantly, indicating metabolic activity of porcine hepatocytes in the bioreactor. No significant differences were noticed among the three control groups, indicating that there was no device effect and that the plasmapheresis procedure was well tolerated. No important adverse effects were observed.

Animals↗
PubMed1998

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion.

BACKGROUND: Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a 'paradoxical' increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS: Ten obese female subjects, aged 23-54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a significant reduction in body weight (mean body mass index (BMI) 25.78 +/- 1.01 kg/m2 vs 44.68 +/- 1.73 kg/m2). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46 +/- 1.12 kg/m2). MEASUREMENTS: We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 microg/kg i.v., at 13.00 h) before and after a standard meal. RESULTS: In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06 +/- 4.56 vs 3.24 +/- 0.68 microg/L). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12 +/- 4.99 microg/L, P < 0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION: The surgical procedure restores a normal GH response to GHRH in the fasting state, but the 'paradoxical' GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD subjects suggests a role for metabolic fuels in the regulation of somatostatin (SRIF) secretion.

Adult↗
PubMed1998

Provocative hypothalamopituitary axis tests in severe head injury: correlations with severity and prognosis.

OBJECTIVE: To evaluate the effect of severe head injury on both the secretion of basal pituitary hormones and the response to exogenous synthetic hypothalamic releasing factors administration. DESIGN: Prospective, clinical study. SETTING: General intensive care unit in a university teaching hospital, Italy. PATIENTS: Comatose, head-injured patients (n = 22), all intubated and mechanically ventilated, invasively monitored without previous endocrinologic problems and substitutive therapies. INTERVENTIONS: Routine neuroemergency procedures; administration of exogenous, synthetic hypothalamic releasing hormones. MEASUREMENTS AND MAIN RESULTS: Determinations of basal concentrations of growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine, and thyroxine were performed daily in the first week and on days 15 and 16 after the trauma. Plasma insulin-like growth factor-I and cortisol were also determined on days 2, 7, and 15. We carried out a thyrotropin-releasing hormone (TRH) test for the evaluation of the PRL, TSH, and GH responses on days 1 and 16 after the trauma and a growth hormone-releasing hormone (GHRH) test for the evaluation of GH and PRL responses on days 2, 7, and 15 after the trauma. Outcome was evaluated at 6 mos with the GOS. Triiodothyronine showed low values, even if in the normal range; thyroxine remained in the normal range. Significant increases in insulin-like growth factor-I concentrations were observed on both days 7 and 15 compared with day 2 (p = .024 and p = .034, respectively). The GH response to GHRH was significantly greater on days 7 and 15 than in the very acute phase (p< .01 comparing days 7 and 15 vs. day 2). We found a higher GH response to GHRH on day 7 in group 1 vs. group 2 (as both peak and area under the curve, p = .018 and p = .015, respectively). No difference in GH response was detected on days 2 and 15. A "paradoxical" response of GH to TRH was observed on the day after the head trauma (basal vs. peak, p = .002) but not on day 16. The GH peak response to TRH was greater on day 1 in those patients with an unfavorable course (group 1 vs. group 2, p < .05). The TSH response to TRH was not significantly correlated to the severity of trauma, but it was significantly (p < .04) higher in group 1 than in group 2. Finally, a "paradoxical" PRL response to GHRH administration was present on day 2 (basal vs. peak, p=.0003), day 7 (basal vs. peak, p = .01), and on day 15 after the trauma (basal vs. peak, p = .04). CONCLUSIONS: Some of the responses to provocative tests have been identified as "paradoxical" and seem to have a great importance in the definition of prognosis in severe head-injured patients, specifically the GH response to TRH and the PRL response to GHRH that are significantly correlated with outcome.

Adolescent↗
PubMed1998

Issues related to caring for infants to adults on an integrated epilepsy unit.

We integrated the care of patients of all ages (ranging thus far from 4 weeks to 73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining to admission and discharge criteria, unit policies and procedures and an interdisciplinary quality assurance plan were examined in relation to the impact of combining both pediatric and adult patients. Clinical considerations included the diversified abilities needed to care for pediatric and adult patients both in relation to the technical skills as well as psychosocial skills required. The advantages of integrating patients of all ages on one unit include having a staff highly trained in assessment and intervention skills for a particular disorder. The psychosocial issues that arise in these patients, regardless of age, tend to encompass the entire family; therefore a holistic approach is appropriate for both children and adults. An autonomous nursing practice was established with the development of critical pathways and patient care protocols. Our experience suggests that integrated specialized units can enhance the care of patients with intractable seizures.

Adolescent↗
PubMed1998

Echobiometry of the ocular layers at the posterior pole.

The thickness of the retina, choroid and sclera in relation to macular oedema (ME) can be measured using A scan echography. Ninety diabetic patients (180 eyes) divided into two groups with and without ME, respectively, were studied compared to a third group of 73 healthy controls (146 eyes). Statistical analysis of results showed good specificity (80%) and reasonable sensitivity (70%) of the echographic method in showing the presence of ME confirmed by fluorescein angiography.

Adult↗