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Biomedical subjects

Antonio Lanzone

Publications and source records attributed to Antonio Lanzone.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of vascular endothelial growth factor synthesis and release by human luteal cells in vitro.

CONTEXT: Vascular endothelial growth factor (VEGF) is essential for normal luteal development and function, but little is still known about the regulation of its production by human midluteal phase luteal cells. OBJECTIVE: We investigated whether human chorionic gonadotropin (hCG) or local factors, including chemical hypoxia, IGF-I and IGF-II, prostaglandin (PG)E(2), and PGF(2alpha) prevail in modulating VEGF mRNA and protein production in human midluteal phase luteal cells. The effect of progesterone (P) on luteal VEGF mRNA expression and protein secretion was also evaluated. Finally, we investigated whether VEGF could directly affect luteal P secretion. INTERVENTIONS: In human midluteal phase luteal cells, VEGF mRNA expression was evaluated by semiquantitative RT-PCR, whereas VEGF and P release was evaluated by ELISA and RIA, respectively. RESULTS: hCG was unable to significantly affect luteal VEGF mRNA and protein synthesis, which in turn was significantly increased by both chemical hypoxia and IGFs. Conversely, VEGF mRNA and protein production was reduced by PGs and P. Finally, VEGF did not affect P luteal secretion. CONCLUSIONS: Our results suggest that local ovarian factors, rather than hCG, predominate in regulating VEGF mRNA and protein production by human midluteal phase luteal cells. For VEGF, a lack of a direct luteal steroidogenic effect was also demonstrated.

Cells, Cultured↗
PubMed2006

Plasma levels of neuropeptides in Alzheimer's disease.

BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.

Aged↗
PubMed2005

L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism.

CONTEXT: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. OBJECTIVE: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. DESIGN: This study was a randomized placebo, not double-blind, trial. SETTING: The study was performed in an academic research center. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. INTERVENTION(S): Patients underwent two hospitalizations before and after 8 wk of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. MAIN OUTCOME MEASURE(S): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. RESULTS: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P < 0.03). CONCLUSIONS: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.

Blood Glucose↗
PubMed2005

Effect of metformin on the growth hormone response to growth hormone-releasing hormone in obese women with polycystic ovary syndrome.

OBJECTIVE: Obese women with polycystic ovary syndrome (PCOS) show a marked growth hormone (GH) hyporesponsiveness to several stimuli. We aimed to evaluate the impact of insulin metabolism on the GH secretion impairment in these subjects in relation to food ingestion. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Nine obese women with PCOS. INTERVENTION(S): Metformin (1,500 mg/daily) was administered for three months. The study protocol, which was performed before and after therapy, included hormonal and lipid assays, oral glucose tolerance test (75 g), euglycemic hyperinsulinemic clamp, and growth hormone-releasing hormone (GHRH) test (50 microg/ev), both on fasting and after a standard meal. MAIN OUTCOME MEASURE(S): Growth hormone response to GHRH (expressed as the area under the curve) in different experimental conditions. RESULT(S): The preprandial GH response to GHRH was not modified by the therapy, whereas a significant increase (P<.05) occurred in the postprandial GH secretion, thus resembling the response of obese normal persons. This change was accompanied by a trend towards improvement, though not statistically significant, of all the evaluated glycoinsulinemic parameters. A significant reduction in cholesterol (P<.01) and androstenedione (P<.05) and an increase in sex hormone-binding globulin (P<.05) were also achieved. CONCLUSION(S): These data suggest that metformin is able to affect GH secretion in obese women with PCOS, even with minimal metabolic modifications.

Adolescent↗
PubMed2004

Assessment of insulin sensitivity from measurements in the fasting state and during an oral glucose tolerance test in polycystic ovary syndrome and menopausal patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) and menopausal subjects are characterized by an increased cardiovascular and type 2 diabetes mellitus risk, at least partially related to insulin disturbances. The evaluation of insulin resistance in these patients could be useful as primary prevention. The aim of the study was to verify the validity of several indexes of insulin sensitivity in PCOS and menopausal subjects by comparing the data obtained by these indexes to those of euglycemic-hyperinsulinemic clamp studies. METHODS: One hundred PCOS and 110 menopausal subjects were analyzed; all subjects underwent an oral glucose tolerance test (75 g) and euglycemic-hyperinsulinemic clamp study. Seven PCOS patients and 13 menopausal subjects had impaired glucose tolerance or type 2 diabetes mellitus and were excluded from the study. After analysis of correlation coefficients between the evaluated indexes and the clamp studies, the sensitivity and specificity of different cut-off values for each parameter were analyzed by receiver operating characteristic (ROC) curves. RESULTS: The best correlation coefficients with clamp studies were obtained with the Avignon insulin sensitivity index (SiM) (R(s) = 0.7812) in PCOS patients and the Matsuda and De Fronzo index (R(s) = 0.6178) in menopausal patients. The best predictive index of insulin resistance in PCOS was a Avignon insulin sensitivity basal index (SibB) value of 62 or less (78% sensitivity, 95% specificity) and an insulin area under the curve (AUC) of 7,000 microIU/ml or more (>/=50,225 pmol/liter) x 120 min (83% sensitivity, 90% specificity). In the menopausal population, the best predictive performance was obtained by an insulin AUC of 10,000 microIU/ml or more (>/=71,750 pmol/liter) x 240 min (70% sensitivity, 88% specificity). CONCLUSIONS: The presence of high correlation coefficients does not necessarily mean that the indexes of insulin resistance have an optimal predictive performance; this is probably due to the presence of many borderline values. The simple evaluation of insulin AUC seems to effectively replace the euglycemic-hyperinsulinemic clamp in routine clinical practice, allowing results superimposable to those obtained by minimal model analysis.

Adolescent↗
PubMed2004

Effects of nicotine on human luteal cells in vitro: a possible role on reproductive outcome for smoking women.

We investigated the effect of nicotine and its methylated metabolite, N-methyl-nicotine (M-nicotine), on human luteal cells by measuring release of progesterone and prostaglandins (PGs) from cultured cells and by testing gene expression of vascular endothelial growth factor (VEGF), an angiogenic factor strictly involved in luteal pathophysiology. Primary cultures of human luteal cells were treated for 24 h with nicotine and M-nicotine (from 10(-6) to 10(-11) M) either alone or combined with hCG (25 ng/ml); progesterone and PGs were assayed in the culture medium. In another group of experiments, luteal cells were treated for 24 h with nicotine and M-nicotine (10(-7) M) to perform reverse transcriptase-polymerase chain reaction on VEGF mRNA. Nicotine and M-nicotine negatively affected basal luteal steroidogenesis at all tested concentrations, but neither was able to affect hCG-induced progesterone release. Both substances were able to significantly increase PGF2alpha release from luteal cells, with a dose-related efficacy for M-nicotine. On the contrary, PGE2 release was significantly inhibited by both nicotine and its metabolite. Finally, nicotine was able to increase VEGF mRNA expression significantly, whereas M-nicotine was not. In conclusion, nicotine and M-nicotine can induce a sort of luteal insufficiency by inhibiting progesterone release, probably through modulation of the PG system.

Adult↗
PubMed2004

Effects of insulin-like growth factor I and II on prostaglandin synthesis and plasminogen activator activity in human umbilical vein endothelial cells.

IGFs seem to contribute to the endothelial dysfunction observed in some vascular diseases. Because locally increased IGFs levels were detected in the preeclamptic fetoplacental unit, we hypothesized their involvement in the dysregulation of fibrinolysis and vascular tone typically observed in the fetoplacental compartment in this pregnancy disease. Therefore, in human umbilical vein endothelial cells (HUVECs), the potential effect of IGFs on the synthesis of plasminogen activators (PAs), PA inibitor-1 (PAI-1), and vasodilator and vasoconstrictor prostaglandins (PGs) was investigated. Moreover, in HUVECs treated with IGFs, the expression of cyclooxygenase (COX)-2, the rate-limiting enzyme in PG synthesis, was evaluated.HUVECs were treated for 24 h with IGFs (1-100 ng/ml) or IL-1beta (0.1 ng/ml). PA, PAI-1, and COX-2 mRNA was determined by RT-PCR and PG release and PA activity by RIA and colorimetric assay, respectively.We demonstrated an inhibition of urokinase-type PA activity and a 50% reduction of urokinase-type PA mRNA in HUVECs treated with IGFs. No effect was seen on PAI-1. Finally, both IGFs significantly decreased all PGs tested and COX-2 mRNA, whereas, as expected, IL-1beta had an opposite effect. In conclusion, our results suggest for IGFs a potential involvement in the endothelial dysfunction observed in preeclamptic fetoplacental unit.

Cells, Cultured↗
PubMed2004

Endothelial function in post-menopausal women: effect of folic acid supplementation.

BACKGROUND: Higher than normal homocysteine levels are associated with an increased incidence of adverse cardiovascular events in post-menopausal women, perhaps via hyperhomocysteinaemia-induced vascular endothelial damage. Because folic acid supplementation reduces homocysteine levels, we attempted to evaluate whether folic acid supplementation may affect endothelial function in post-menopausal women. METHODS: Brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerin-induced dilatation (endothelium-independent) before and after a methionine load were analysed in 15 healthy post-menopausal women. Plasma levels of folate, homocysteine, glucose, insulin and lipids were measured, as was blood pressure. All studies were repeated after 1 month supplementation with 7.5 mg/day of folic acid. RESULTS: After folate, endothelial function rose 37% over pre-folic acid supplementation value (P < 0.001), and flow-mediated dilation before folic acid was reduced by 62% subsequent to methionine loading (P < 0.0001); this reduction was still present after folic acid, but was only 19% (P < 0.001). Nitroglycerin-induced dilatation did not change in response to methionine loading before or after folic acid supplementation. Among the other cardiovascular risk factors studied, only high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol showed significant changes after folic acid supplementation, with a 6% increase (P < 0.03) and a 9% decrease (P < 0.03) respectively. CONCLUSIONS: Although preliminary, these results indicate that folic acid supplementation may improve endothelial function and lipid profile in post-menopausal women, thus contributing to reduce their cardiovascular risk.

Brachial Artery↗
PubMed2004

Use of naltrexone in postmenopausal women with exaggerated insulin secretion: a pilot study.

OBJECTIVE: To determine the effect of naltrexone (an opiate receptor blocker) on insulin metabolism in postmenopausal women with different insulinemic patterns. DESIGN: Randomized placebo-controlled study. SETTING: Academic research environment. PATIENT(S): Forty-one healthy normoinsulinemic or hyperinsulinemic postmenopausal women. INTERVENTION(S): Oral glucose tolerance test (OGTT) before and after 5 weeks of the opioid antagonist (naltrexone, 50 mg/d orally) or the placebo administration; euglycemic-hyperinsulinemic glucose clamp. MAIN OUTCOME MEASURE(S): Glucose, insulin, and C-peptide plasma levels assessed in fasting condition and during the OGTT. Insulin sensitivity was calculated as total body glucose utilization. RESULT(S): Naltrexone reduced fasting and stimulated insulin response to the glucose load while inducing a significant improvement of the hepatic extraction, only in the hyperinsulinemic patients. No differences were found in the C-peptide pancreatic secretion and in the peripheral insulin sensitivity. No net change in the glycoinsulinemic metabolism was observed in normoinsulinemic patients or in placebo-controlled normoinsulinemic and hyperinsulinemic subjects. CONCLUSION(S): Similar to that reported in premenopausal women, endogenous opioid peptides are involved in the modulation of glycoinsulinemic metabolism in postmenopause. Through a prevalent action on liver insulin metabolism, without any clear improvement of insulin resistance and pancreatic beta-cell function, the chronic administration of naltrexone appears to reduce the hyperinsulinemia in those women with an exaggerated insulin response to the OGTT.

Blood Glucose↗
PubMed2004

Endometrial evaluation in superovulation programs: relationship with successful outcome.

It is well known that an adequate endometrial receptivity is required for successful implantation in both natural and assisted reproductive cycles. In particular, a brief "implantation window", during which endometrium undergoes anatomical and molecular changes necessary for embryo implantation, has been observed. The hormonal treatment applied to induce ovulation seems to be able to modify the normal development of the prenidatory endometrium, with possible negative effect on the implantation rate. For this reason, several attempts have been made to identify specific markers of endometrial receptivity, useful for predicting implantation outcome in clinical practice. Even if different histological, immunohistochemical, and ultrasonographic parameters are studied, none unfortunately has been univocally shown to be predictive of pregnancy outcome. Therefore, the evaluation of endometrial receptivity remains a challenge in clinical practice.

Endometrium↗
PubMed2003

The effects of nitric oxide on prostanoid production and release by human umbilical vein endothelial cells.

Human umbilical vein endothelial cells (HUVEC) express and synthesize both constitutive and inducible nitric oxide synthase (NOS) and cyclo-oxygenase (COX) enzymes, and have been extensively used as an in vitro model to investigate the role of these enzymes in the patho-physiology of placenta-fetal circulation. In this study we investigated the role of NO in regulating prostanoid production and release from HUVEC. Both untreated and IL-1beta-treated HUVEC were exposed to various NOS inhibitors and NO donors in short-term (1 or 3 hours) experiments, and the effects on prostanoid production were evaluated through the measurement of prostaglandins (PG) I2, E2 and F2alpha released in the incubation medium. We found that the inhibition of inducible NOS but not endothelial NOS antagonizes the IL-1beta-induced increase in PGI2 release. However, NOS inhibitors do not modify baseline PGI2 production. Pharmacological levels of NO, obtained with various NO donors, inhibit basal and IL-1beta-stimulated PG release.

Cells, Cultured↗
PubMed2003

In vitro regulation of beta1 and beta3 integrin subunits in endometrial epithelial cells from normal endometrium.

OBJECTIVE: To evaluate the effect of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) on integrin expression. DESIGN Cultures of endometrial epithelial cells from normal endometrium. SETTING: All endometrial specimens were obtained from the Obstetrics and gynecology Department of the Catholic University, Rome, Italy. PATIENTS: Four patients were normal menstrual cycles undergoing operative laparoscopy for non-endometrial problems. INTERVENTION: Endometrial samples were collected by uterine courettings. MAIN OUTCOME MEASURE: Immunocytochemistry for beta1 and beta3 integrin subunits. RESULTS: PGE2 clearly enhances both beta1 and beta3 integrin subunit expression. IL-1beta seem to slightly increase only beta3 subunit expression. CONCLUSIONS: In light of the critical role played by eicosanoids in endometrial differentiation, we suggest that PGE2 is also involved in local paracrine regulation of integrin expression.

Cells, Cultured↗
PubMed2003

Interleukin-1 beta stimulates progesterone production by in vitro human luteal cells: evidence of a mediatory role of prostaglandins.

We have investigated whether IL-1 beta, a cytokine with an important role in ovarian physiology, is also involved in progesterone (P) synthesis in human luteal cells, and whether this effect is mediated via the cyclooxygenase (COX) pathway. Human luteal cells were cultured for 24 h in the presence of IL-1 beta (0.01-10 ng/ml), given alone or in combination with human chorionic gonadotropin (100 ng/ml), indomethacin (1 micro g/ml), or P (100 ng/ml). We observed a significant increase in prostaglandin (PG)release after IL-1 beta treatment; the cytokine was more effective on PGE(2) than PGF(2 alpha) release. The effect of IL-1 beta was abolished by human chorionic gonadotropin, which had no action on basal PG levels when given alone; in contrast, P reduced basal, but not IL-1 beta-stimulated, PG production. Treatment with the human IL-1 receptor antagonist was associated with a decrease in both basal and IL-1 beta-stimulated PG production. Moreover, IL-1 beta induced a concentration-dependent increase in P production and release, an effect counteracted by the COX inhibitor indomethacin. In conclusion, our data show the ability of IL-1 beta to influence P secretion via the COX pathway, thereby suggesting a possible luteotropic role in human ovary based on an autocrine-paracrine mechanism.

Cells, Cultured↗
PubMed2002

N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (PCOS). DESIGN: Prospective data analysis. SETTING: Volunteer women in an academic research environment. PATIENT(S): Six lean and 31 obese subjects, aged 19-33 years. INTERVENTION(S): Patients were treated for 5-6 weeks with NAC at a dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively obese subjects. Six of 31 obese patients with PCOS were treated with placebo and served as controls. MAIN OUTCOME MEASURE(S): Before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (OGTT) was performed. RESULT(S): Fasting glucose, fasting insulin, and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC after OGTT was significantly reduced, and the peripheral insulin sensitivity increased after NAC administration, whereas the hepatic insulin extraction was unaffected. The NAC treatment induced a significant fall in T levels and in free androgen index values (P<.05). In analyzing patients according to their insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects. CONCLUSION(S): NAC may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.

Acetylcysteine↗
PubMed2002

Naloxone decreases insulin secretion in hyperinsulinemic postmenopausal women and may positively affect hormone replacement therapy.

OBJECTIVE: To evaluate the influence of the opioid system on glyco-regulation in postmenopausal women before and after hormone replacement therapy (HRT). DESIGN: Prospective nonrandomized clinical study. SETTING: Academic research environment. PATIENT(S): Twenty-one healthy normo- or hyperinsulinemic postmenopausal women. INTERVENTION(S): Oral glucose tolerance test (OGTT) (saline study), OGTT with IV injection of naloxone (naloxone study), and hyperinsulinemic euglycemic clamp performed before treatment, after 12 weeks of estrogen replacement therapy (ERT), and after 12 additional weeks of estro-progestin combined therapy (i.e., HRT). MAIN OUTCOME MEASURE(S): Glucose, insulin, and c-peptide plasma levels assessed in fasting condition and during the two OGTTs (area under the curve [AUC]). Evaluation of fractional hepatic insulin extraction (FHIE) and peripheral sensitivity to insulin. RESULT(S): At baseline, there is a greater increase of the FHIE and a more significant reduction of the insulin AUC in the hyperinsulinemic patients during the naloxone study compared with the saline study. In these women, ERT enhanced the c-peptide AUC and improved the FHIE; naloxone infusion mainly increased these two parameters. HRT did not induce any further change. CONCLUSION(S): Endogenous opioid peptides are involved in the modulation of carbohydrate metabolism in menopause in hyperinsulinemic patients more than in other patients. The favorable changes of the glyco-insulinemic metabolism induced by HRT may be partially due to the induction of the opioidergic activity.

Area Under Curve↗
PubMed2002

Effect of the opioid blockade on the feeding-induced growth hormone response to growth hormone-releasing hormone in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the effect of naloxone, an opioid receptor antagonist, on the release of growth hormone (GH) induced by the growth hormone-releasing hormone (GHRH) in normal-weight and obese women with PCOS in relation to feeding. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Seventeen women with PCOS (10 who were normal weight and 7 who were obese) and 14 control women (7 who were normal weight and 7 who were obese). INTERVENTION(S): A GHRH test (50 microg i.v.) and, on a different day, a GHRH test during a naloxone infusion (1.6 mg/h) during fasting. The same tests were repeated after a standard meal. MAIN OUTCOME MEASURE(S): GH response to GHRH (expressed as the area under the curve [AUC]) in different experimental conditions. RESULT(S): All normal-weight women showed a significantly higher AUC-GH compared with obese women in the fasting state. Normal-weight controls had a decrease in GH response to GHRH after feeding, and naloxone did not reverse the decrease. In obese controls, feeding increased the GH response but naloxone induced a decrease in the AUC. In fasting, normal-weight women with PCOS, naloxone significantly decreased the AUC-GH; in these patients, food intake induced an inhibition of GH response to GHRH, reversed by naloxone infusion. In obese PCOS patients, GH levels did not increase significantly after GHRH stimulation, either in the fasting state or after a meal, and naloxone did not affect these responses. CONCLUSION(S): Factors other than obesity and insulin may be involved in disruption of GH secretion in women with PCOS.

Adult↗