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B Cinque

Publications and source records attributed to B Cinque.

17 recordsLinked to original sources
PubMed2006

Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell interaction.

In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and zeta potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm.

Animals↗
PubMed2006

Teratological risk evaluation and prevention of voluntary abortion.

AIM: Many women exposed to completely innocuous agents during pregnancy have a high perception of adverse effects to such an extent that they may interrupt their pregnancy. The objective of our study is to evaluate the importance of the perception of the risk level in making the decision to end the pregnancy and the relevance that a teratology consultation can have in preventing unmotivated terminations of pregnancy METHODS: We carried out a survey on 350 women in Rome who voluntarily interrupted their pregnancy to evaluate the prevalence due to presumed teratogen. Contemporarily we studied the pregnancy outcomes, the clinical, the psychological and the socio-economic factors of 142 women who contacted our Teratology Information Service (TIS) in the 1(st)trimester of pregnancy because suspected of teratogen exposure: 72 decided to terminate their pregnancy, whereas 70 were used as a control group. RESULTS: On 350 women who voluntarily interrupted their pregnancy, 4 cases (1.4%) reported exposure to a suspected teratogen, but our evaluation determined only 1 case. On 72 women decided to terminate their pregnancy and who contacted our TIS, after counselling 73% continued their pregnancy with respect to 97% of the control group. Those women who interrupted their pregnancy did so because of personal reasons independently to or the type of exposure or the risk attributed by us. CONCLUSIONS: From our data it appears that a percentage of voluntary abortions is related to suspected teratogen exposure and that TIS are effective in the prevention of this kind of voluntary abortions caused by groundless fears.

Abnormalities, Drug-Induced↗
PubMed2005

Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease.

BACKGROUND AND AIMS: Epithelium derived interleukin (IL)-15 signalling via IL-15Ralpha is critical for the development, activation, and survival of intraepithelial lymphocytes (IEL). We aimed to better understand the IL-15 driven effects on IEL underlying mucosal damage and lymphomagenesis in coeliac disease (CD). METHODS: Enterocytes, IEL, and lamina propria mononuclear cells (LPMC) were isolated from 46 patients with uncomplicated CD (25 untreated and 21 treated) and 22 controls. IL-15 and IL-15Ralpha expression were determined by immunoblotting. Secretion of IL-15, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), and granzyme B into cell culture supernatants was assessed by ELISA. The ability of IL-15 to regulate IEL proliferation, perforin/granzyme dependent cytotoxicity, and apoptosis was tested by adding different combinations of IL-15, IL-15 blocking antibody, or chloroquine to IEL cultured alone or with Caco-2 cells as target. IL-15 mucosal levels were also determined by ELISA in five patients with complicated CD (two ulcerative jejunoileites, one refractory sprue, and two enteropathy associated T cell lymphomas) tested for T cell receptor gamma chain clonality. RESULTS: IL-15 was overexpressed in untreated CD enterocytes and LPMC, and in the mucosa of complicated CD patients and uncomplicated untreated CD patients, where its levels correlated with the degree of mucosal damage. Enterocytes from untreated, but not treated, CD patients and controls secreted IL-15. Untreated CD IEL, characterised by higher IL-15Ralpha expression, showed increased proliferation, production of IFN-gamma and TNF-alpha, and perforin/granzyme dependent cytotoxicity, and a decreased propensity to apoptosis in response to IL-15. CONCLUSIONS: Our findings suggest that IL-15 plays a crucial role in the generation of epithelial damage in active CD. Its promotion of IEL survival in CD may predispose to the emergence of T cell clonal proliferations. Blocking IL-15, by suppressing uncontrolled IEL activation and survival, has the potential to provide new therapeutic tools to prevent tissue damage and lymphomagenesis in CD.

Adult↗
PubMed2004

Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease.

BACKGROUND AND AIMS: To verify whether targeting defective mucosal T cell death underlies the sustained therapeutic benefit of infliximab in Crohn's disease, we explored its in vivo proapoptotic effect after 10 weeks of treatment, and its in vitro killing activity on lamina propria T cells (LPT) and peripheral blood T cells (PBT), both isolated from Crohn's disease patients. METHODS: Endoscopic intestinal biopsies were collected from 10 Crohn's disease patients (six steroid refractory and four fistulising) before and after three consecutive infusions of infliximab, administered at week 0, 2, and 6 in a single intravenous dose (5 mg/kg), and from 10 subjects who proved to have functional diarrhoea. Apoptosis was determined in vivo by TUNEL assay, and in vitro by fluorescein isothiocyanate-annexin V/propidium iodide staining on LPT and PBT from Crohn's disease patients cultured with infliximab. The effect of the broad caspase inhibitor Z-VAD-FMK and the neutralising anti-Fas antibody ZB4 was tested in vitro on LPT and PBT treated with infliximab. Caspase-3 activity was determined by immunoblotting. RESULTS: In Crohn's disease patients, infliximab treatment induced a sustained LPT apoptosis, still evident four weeks after the last infusion. In vitro infliximab induced death of LPT from Crohn's disease patients occurred via apoptosis rather than necrosis. LPT showed a higher susceptibility to infliximab induced apoptosis than PBT in Crohn's disease patients. The signalling pathway underlying the restoration of infliximab induced LPT apoptosis occurred via the caspase pathway but not Fas-Fas ligand interaction in Crohn's disease. CONCLUSIONS: These findings demonstrate that apoptosis is the major mechanism by which infliximab exerts its killing activity on LPT in Crohn's disease. The sustained LPT proapoptotic action of infliximab, which extends far beyond its circulating half life, may be responsible for the sustained remission induced in Crohn's disease patients by infliximab retreatment.

Adult↗
PubMed2000

Hypothalamic-pituitary-adrenal axis sensitivity to opioids in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the influence of the opioid system on the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Academic research environment. PATIENT(S): Eight lean and 12 obese women with PCOS, and seven lean and 5 obese control subjects. INTERVENTION(S): Each patient received an i.v. bolus of naloxone at a dose of 125 microgram per kilogram of body weight; 48 hours later, each patient received 16 mg of loperamide p.o. MAIN OUTCOME MEASURE(S): Samples were collected for 2 hours for the naloxone test and for 3 hours for the loperamide test. Levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in all plasma samples. RESULT(S): The obese women with PCOS had a greater ACTH and cortisol response to opiate blockade than either the lean women with PCOS or the control subjects, but there was no difference between the lean or obese control subjects and the lean women with PCOS. There was no difference in the responsiveness of the hypothalamic-pituitary-adrenal axis to loperamide between the PCOS and control groups. CONCLUSION(S): The data indicate that the sensitivity of the hypothalamic-pituitary-adrenal axis to opioids cannot be altered in women with PCOS. However, abnormalities of the hypothalamic-pituitary-adrenal axis in women with PCOS could be central in origin, as suggested by the effects of naloxone administration, and probably are related to the anthropometric characteristics of these hyperandrogenic patients.

Adrenal Glands↗
PubMed2000

Erk-dependent cytosolic phospholipase A2 activity is induced by CD95 ligand cross-linking in the mouse derived Sertoli cell line TM4 and is required to trigger apoptosis in CD95 bearing cells.

In the present study we demonstrated that CD95L cross-linking generated reverse signalling in the mouse derived Sertoli cell line TM4. Treatment of TM4 cells with mAb anti-CD95L induced activation of the cytosolic phospholipase A2 (cPLA2). Cytosolic PLA2 activation was controlled by the MAPK pathway as indicated by the ability of the specific MEK inhibitor, PD098059, to abolish cPLA2 activation. In addition, Western blot experiments showed a rapid increase in phosphorylated Erk1/2 following CD95L cross-linking, while no effect on the phosphorylation of other MAPK, p38 or JNK, was observed. CD95L cross-linking by mAb increased the levels of soluble CD95L and apoptotic activity of TM4 cell supernatants, which was blocked by co-incubation with the PLA2 inhibitor, AACOCF3 or PD098059. Finally, pre-treatment of TM4 cells with AACOCF3 or PD098059 completely abolished TM4-induced apoptosis of Jurkat T cells, thus indicating that the Erk/cPLA2 pathway is required for CD95L-induced apoptosis.

Animals↗
PubMed1999

Effect of the lactic acid bacterium Streptococcus thermophilus on ceramide levels in human keratinocytes in vitro and stratum corneum in vivo.

The effects of Streptococcus thermophilus on ceramide levels either in vitro on cultured human keratinocytes or in vivo on stratum corneum, have been investigated. In vitro, Streptococcus thermophilus enhanced the levels of ceramides in keratinocytes in a time-dependent way. The presence of high levels of neutral, glutathione-sensitive, sphingomyelinase in Streptococcus thermophilus could be responsible for the observed ceramide increase. The application of a base cream containing sonicated Streptococcus thermophilus in the forearm skin of 17 healthy volunteers for 7 d also led to a significant and relevant increase of skin ceramide amounts, which could be due to the sphingomyelin hydrolysis through bacterial neutral sphingomyelinase. Indeed, similar results were obtained with a base cream containing purified bacterial neutral sphingomyelinase. In addition, the inhibition of bacterial neutral sphingomyelinase activity through glutathione blocked the skin ceramide increase observed after the treatment. The topical application of a sonicated Streptococcus thermophilus preparation, leading to increased stratum corneum ceramide levels, could thus result in the improvement of lipid barrier and a more effective resistance against xerosis.

Adult↗
PubMed1999

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.

OBJECTIVE: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. DESIGN: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. METHODS: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. RESULTS: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

Administration, Cutaneous↗
PubMed1998

A novel mechanism of CD4 down-modulation induced by monosialoganglioside GM3. Involvement of serine phosphorylation and protein kinase c delta translocation.

In this report the molecular mechanism(s) involved in the rapid and selective endocytosis of cell surface glycoprotein CD4 induced by exogenous monosialoganglioside GM3 in human peripheral blood lymphocytes have been investigated. Inhibition of the GM3-induced CD4 down-modulation was observed in the presence of specific protein kinase C (PKC) inhibitors. Scanning confocal microscopy revealed the translocation and clustering on the cell surface of PKC isozymes delta and theta (more evidently than alpha and beta) after GM3 treatment, suggesting the involvement of these isozymes in the ganglioside-induced CD4 down-modulation. Exogenous GM3 induced phosphorylation of CD4 molecule, which then dissociated from p56(lck), as early as after 5 min. Moreover, addition of GM3 resulted in a rapid (1 min) cytosolic phospholipase A2 activation with consequent arachidonic acid release, whereas no phosphatidylinositol-phospholipase C activity was observed. Both PKC translocation and CD4 down-modulation were blocked by the trifluoromethylketone analog of arachidonic acid, a selective inhibitor of cytosolic phospholipase A2 and by mitogen-activated protein kinase inhibitor PD98059. Taken together, these findings strongly suggest that GM3 may trigger a novel mechanism of modulation of the CD4 surface expression through the activation of enzyme(s) involved in the regulation of cellular functions.

Arachidonic Acids↗
PubMed1989

Usefulness of a hysteroscopic follow-up on patients with breast cancer in pre- and post-menopausal age.

Over the last years, the high incidence of multiple primary neoplasms has been of great interest. The association between carcinoma of the breast and endometrium has been particularly emphasized; it is based on similar epidemiological factors and common hormondependence in the two tumours. Following these assumptions, the Authors present the preliminary results of hysteroscopic and histological studies including 45 patients, 24 in pre-menopausal and 21 in post-menopausal age, who have undergone a mastectomy or quadrantectomy for breast cancer in the past 5 years. They were compared with respective control groups. In pre-menopausal women, there was a higher incidence of activated and irregular endometrium, precancerous lesions (such as glandular-cystic hyperplasia) and one case of adenocarcinoma of the endometrium in a completely asymptomatic woman. On the contrary, endometrial atrophy turned out to be the most frequent hysteroscopic and histological report in post-menopausal women. This supports the hypothesis of two different types of breast cancer that occur in pre- and post-menopausal age and it suggests the utility of a hysteroscopic follow-up, only in pre-menopausal women.

Adult↗
PubMed1986

Labor in humans: 1. Progesterone, 20 alpha-dihydro-progesterone, estrone and 17 beta-estradiol in near placental and most distant human amnion and chorion laeve in various stages of labor at term.

In some species the onset of labor is regulated by changes in the estrogen/progesterone ratio. The same change in fetal membranes has been suggested to be one of the triggering mechanisms of labor in humans. In order to examine if a gradient in steroid concentration existed in fetal membranes and if changes in concentrations could be observed with the onset and advancing labor, the concentration of progesterone (P), 20 alpha-dihydro-progesterone (20 alpha-OHP), estrone (E1) and 17 beta-estradiol (E2) were determined by specific radioimmunoassay in the near placental and most distant regions of human amnion and chorion laeve obtained at term, before, at the onset and in advanced labor. Both estrogen and progestin concentrations in the chorion were higher than in the amnion. No gradient in the concentration of steroids was found. No statistically significant differences in estrogen and progestin levels were associated with the onset of labor.

20-alpha-Dihydroprogesterone↗
PubMed1985

Corpus luteum function during the early puerperium.

Progesterone and 17 beta-estradiol peripheral plasma levels have been determined during labor and after 1, 3, 6, 12, 24, 48, 72, 96, 120 and 144 h from delivery in a group of 7 women, whose corpus luteum had been removed at delivery and in a corresponding control group with intact corpus luteum. In both groups the results indicate a progressive fall of progesterone and 17 beta-estradiol, that is evident until 144 h for progesterone and 72 h from 17 beta-estradiol. The analysis of the two groups with the Student's t test has shown significantly lower levels in the group of women, whose corpus luteum had been removed, at the 6th h (p less than 0.01), 12th h (p less than 0.02) and 24th h (p less than 0.05) for progesterone and at 3rd h (p less than 0.01) and 6th (p less than 0.01) for 17 beta-estradiol. The significant difference for progesterone appearing later than for 17 beta-estradiol could be due to the fact that progesterone is also dismissed by the adipose tissue, where it is stored. A further statistical elaboration of the results, carried out by calculating the regression line and the transfer function, confirmed the different pattern in time of progesterone and 17 beta-estradiol plasma levels after delivery in the two groups of patients considered.

Adult↗
PubMedDate not supplied

Effect of Bifidobacterium infantis on Interferon- gamma- induced keratinocyte apoptosis: a potential therapeutic approach to skin immune abnormalities.

Current management of atopic dermatitis is mainly directed to the reduction of cutaneous inflammation. Since patients with atopic dermatitis show abnormalities in immunoregulation, a therapy aimed to adjust their immune function could represent an alternative approach, particularly in the severe form of the disease. Indeed, T-lymphocytes constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated T-cell induced keratinocyte apoptosis appears to be an important pathogenetic factor of the eczematous disease. In recent years, attention has been focused on the interaction between host and probiotics which may have anti-inflammatory properties and immunomodulatory activities. The aim of the present work is to investigate the effect of a selected probiotic extract, the Bifidobacterium infantis extract, on a human keratinocyte cell line (HaCaT) abnormal apoptosis induced by activated-T-lymphocyte. An in vitro model of atopic dermatitis was used to assess the ability of the probiotic extract to protect HaCaT from apoptosis induced by soluble factors (IFN-gamma and CD95 ligand) released by human T-lymphocytes in vitro activated with anti-CD3/CD28 mAbs or Phytohemoagglutinin. Evidence is given that the bacterial extract treatment was able to totally prevent T lymphocyte-induced HaCaT cell apoptosis in vitro. The mechanism underlying this inhibitory effect has been suggested to depend on the ability of the bacterial extract to significantly reduce anti-CD3/CD28 mAbs and mitogen-induced T-cell proliferation, IFN-gamma generation and CD95 ligand release. These preliminary results may represent an experimental basis for a potential therapeutic approach mainly targeting the skin disorders-associated immune abnormalities.

Apoptosis↗
PubMedDate not supplied

Endoscopy of the uterus and its congenital malformations.

Laparoscopy and hysteroscopy are two endoscopic procedures with which the outer surface of the uterus, its cavity can be studied with a detailed analysis of the endometrium and ostia. The stages of the study are described and uterine congenital malformations are described in relation to the reproductive performance of women.

Female↗
PubMedDate not supplied

Effects of interferon-beta on steroid receptors, prostaglandins and enzymatic activities in human endometrial cancer.

Steroid receptors, prostaglandin output and enzymatic activities were determined in explants derived from human endometrium exposed to natural interferon-beta (IFN-beta). Receptors and cell metabolism were evaluated before culturing the tissue fragments and after a 3-day treatment with varying concentrations of IFN-beta. Total steroid receptor levels were unchanged when explants were set up, but there was a redistribution of both estrogen and progesterone receptors (ER and PR). A decrease in cytoplasmic receptors corresponded to an increase in receptor molecules within the nucleus. Treatment with low concentrations of IFN-beta caused a significant enhancement (p < 0.05) of ER and PR in neoplastic endometrium. In basal conditions the ratio between prostaglandin F2 alpha (Pgf2 alpha) and prostaglandin E2 (PgE2) was higher in normal than in neoplastic endometrium. The addition of low concentrations of IFN-beta to the culture medium determined a significant increase (p < 0.02) in PgF2 alpha and a parallel increase in the above ratio in neoplastic tissue, while no variation was found in normal endometrium. Analysis of the results concerning the variations in hormone-related enzymatic activities due to IFN-B revealed a significant increase (p < 0.05) in 17 beta-hydroxy-steroid-dehydrogenase (17 beta-HSD) activity. The data presented here indicate that treatment with IFN-beta modifies those biological characteristics of neoplastic cells which are involved in hormone-responsiveness.

17-Hydroxysteroid Dehydrogenases↗