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Biomedical subjects

N Surico

Publications and source records attributed to N Surico.

At least 19 recordsLinked to original sources

The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs.

Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of beta2-adrenergic receptors. Since nitric oxide is known to modulate or mediate beta2-adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of beta2-adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release.

Adrenergic beta-2 Receptor Antagonists↗

Human placental lactogen decreases regional blood flow in anesthetized pigs.

In 22 pigs anesthetized with sodium pentobarbitone, changes in blood flow caused by infusion of human placental lactogen into the left renal, external iliac, and anterior descending coronary arteries were assessed using electromagnetic flowmeters. In 17 pigs, infusion of human placental lactogen whilst keeping the heart rate and arterial pressure constant decreased coronary, renal and iliac flow. In 5 additional pigs, increasing the dose of human placental lactogen produced a dose-related decrease in regional blood flow. The mechanisms of the above response were studied in 15 of the 17 pigs by repeating the experiment of infusion. The human placental lactogen-induced decrease in regional blood flow was not affected by blockade of cholinergic receptors (5 pigs) or of alpha-adrenergic receptors (5 pigs), but it was abolished by blockade of beta2-adrenergic receptors (5 pigs). The present study showed that intra-arterial infusion of human placental lactogen primarily decreased coronary, renal and iliac blood flow. The mechanism of this response was shown to be due to the inhibition of a vasodilatory beta2-adrenergic receptor-mediated effect.

Adrenergic alpha-Antagonists↗

Ingenol derivatives inhibit proliferation and induce apoptosis in breast cancer cell lines.

We present an analysis of the antitumour effects of a library of ingenol derivatives synthesized in our laboratory and published elsewhere. Fluoro-ingenol (1), ingenol-20-deoxy-20-phtalimido (2), ingenol-3-benzoate-20-deoxy-20-benzamide (3), ingenol-3-benzoate (4), ingenol-3,5-dibenzoate (5), ingenol-3,20-dibenzoate (6), 20-deoxy-20-benylureidoingenol-3-benzoate (7), ingenol-20-deoxy-20-fluoro-3-benzoate (8), ingenol-20-deoxy-20-fluoro-3,5-dibenzoate (9), ingenol-20-phenylcarbamate (10), ingenol-20-benzoate (11), ingenol-3-benzoate-20-phenylcarbamate (12) were tested in vitro on two well characterized breast cancer cell (BCC) lines, namely T47D and MDA-MB-231, as representative of two opposite types of hormone-sensitiveness and differentiation stage. These experiments led us to identify ingenol-20-benzoate (11) as a promising antitumour compound characterized by a relevant inhibition of cell growth and apoptotic cell death involving a p53-mediated pathway.

Antineoplastic Agents↗

Exogenous prostaglandin E2 inhibits TPA induced matrix metalloproteinase-9 production in MCF-7 cells.

Elevated levels of prostaglandin E2 (PGE2) have been reported in many high metastatic human breast cancers, but no relationship between exogenous PGE2 activity, expression of matrix metalloproteinases (MMPs) and metastasis in human tumor cells has been reported. The poorly invasive human breast cancer cell line MCF-7 was cultured for 24h in the presence of both phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 50 nM) and PGE2 (1 microM) and the activity of MMP-9, one of the MMPs involved in metastasis, was measured, in growth medium by gelatin substrate zymography. TPA induced a strong production of MMP-9 while exogenous PGE2 had no effect on the basal MMP-9 level, but inhibited the TPA induced enzyme expression and matrigel invasiveness. We showed that MCF-7 cells expressed EP2, EP3 and EP4 receptors for PGE2 and that its action was probably mediated by EP4 receptor and adenylyl cyclase activation while cAMP dependent PKA was not involved in the process of inhibition of MMP-9 production. These findings suggest a possible inhibitory role for exogenous PGE2 in the metastatic process development.

Breast Neoplasms↗

Aggressive angiomyxoma of the vulva.

BACKGROUND: Aggressive angiomyxoma is a rare soft tissue tumour that carries a high risk of local relapse. It is a slowly growing and locally infiltrating tumour. CASE: We describe the case of an aggressive pelvic-perineal angiomyxoma arising in a 36-year-old woman. The patient had a mass that grew before, during and after her pregnancy. Transperineal surgery was performed. The resection margins were free of disease. CONCLUSION: Our case confirms what has previously been published concerning the possible hormone-dependence of this neoplasm. Given the positive estrogen and progesterone receptor status of this tumour, we will consider hormonal treatments in the case of a future relapse.

Adult↗

Angiomyofibroblastoma of the vulva: report of a case.

A case of solitary angiomyofibroblastoma of the vulva in a 16-year-old woman was examined by histology and immunohistochemistry. Microscopic examination of the tumor revealed typical features of a mesenchymal neoplasm, composed of bundle spindle cells with low cellular density, rich in collagen fibers and thin-walled blood vessels. Immunohistochemistry revealed immunoreactivity for progesterone receptor, CD34, desmin and vimentin, tumor cells expressing positivity, but not for estrogen receptors. The stains for the muscle-specific actin and S-100 were negative. These results were mostly consistent with those of previous reports and suggest that the tumors cells were derived from primitive mesenchymal cells which occur normally in this region and show the potential for diverse lines of myoid differentiation.

Adolescent↗

Insulin modulates PC-1 processing and recruitment in cultured human cells.

We evaluated whether insulin signaling modulates plasma cell glycoprotein (PC-1) plasma membrane recruitment, posttranslational processing, and gene expression in human cultured cell lines. Insulin induced a fourfold increase (P < 0.01) of membrane PC-1 expression by rapid and sensitive mechanism(s). This effect was reduced (P < 0.05-0.01) by inhibition of phosphatidylinositol 3-kinase (200 nmol/l wortmannin) and S6 kinase (50 nmol/l rapamycin) activities and intracellular trafficking (50 micromol/l monensin) and was not accompanied by PC-1 gene expression changes. Moreover, at Western blot, insulin elicited the appearance, in both plasma membrane and cytosol, of a PC-1-related 146-kDa band (in addition to bands of 163, 117, 106, and 97 kDa observed also in absence of insulin) that was sensitive to endoglycosidase H. Finally, inhibition of PC-1 translocation to plasma membrane, by wortmannin pretreatment, increases insulin-stimulated receptor autophosphorylation. Our data indicate that insulin stimulates PC-1 posttranslational processing and translocation to the plasma membrane, which in turn impairs insulin receptor signaling. Bidirectional cross talk between insulin and PC-1, therefore, takes place, which may be part of the hormone self-desensitization mechanism.

Androstadienes↗

The role of activation of the renin-angiotensin system on the reflex regional vasoconstriction caused by distension of the uterus in anaesthetized pigs.

Distension of the uterus in anaesthetized pigs has been shown to cause a reflex regional vasoconstriction and an increase in plasma renin activity (PRA) through efferent sympathetic mechanisms which respectively involved alpha- and beta-adrenergic receptors. The present study was undertaken to determine the possible contribution of the activation of the renin-angiotensin system (RAS) to the observed regional vasoconstrictive responses to uterus distension. In pigs anaesthetized with alpha-chloralose, blood flow in the left circumflex or anterior descending coronary, superior mesenteric, left renal and left external iliac arteries was assessed using electromagnetic flowmeters. Distension of the uterus for periods of 30 min was performed by injecting 20 ml of warm Ringer solution into balloons positioned within the viscus before and after blockade of angiotensin II receptors with losartan. Changes in heart rate and renal blood flows were respectively prevented by atrial pacing and injection of phentolamine into the renal arteries. Changes in baroreceptors activity and in regional perfusion pressure were minimized by section of cervical vagus nerves and denervation of carotid sinuses and by an aortic constriction. PRA was assessed during the last minute of distension by radioimmunoassay of angiotensin 1. Before blockade of angiotensin II receptors, in six pigs, distension of the uterus decreased coronary blood flow by 19%, and in other six pigs, decreased mesenteric and iliac blood flows by 13.1% and 29.4% in the absence of changes in arterial perfusion pressure. After losartan, these decreases were significantly reduced to 11.7%, 8.2% and 18%. These results showed that the activation of the RAS significantly contributed to the alpha-adrenergic receptor-mediated regional vasoconstrictive responses reflexly elicited by distension of the uterus.

Anesthesia↗

The effect of progesterone on coronary blood flow in anaesthesized pigs.

The present study was designed to investigate the effect of progesterone on the coronary circulation and to determine the mechanisms involved. In pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous infusion of progesterone at constant heart rate and arterial blood pressure were assessed using an electromagnetic flowmeter. In 14 pigs, infusion of 1 mg h(-1) of progesterone caused an increase in coronary blood flow without affecting left ventricular dP/dtmax (rate of change of left ventricular systolic pressure) and filling pressures of the heart. In a further four pigs, this vasodilatory coronary effect was enhanced by graded increases in the dose of the hormone of between 1, 2 and 3 mg h(-1). The mechanisms of the above response were studied in the 14 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the coronary vasodilatation caused by progesterone. In the remaining eight pigs, this response was abolished by intracoronary injection of N(omega)-nitro-L-arginine methyl ester (L-NAME) even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L-NAME with continuous intravenous infusion of papaverine. The present study showed that intravenous infusion of progesterone primarily caused coronary vasodilatation. The mechanism of this response was shown to involve the endothelial release of nitric oxide.

Animals↗

Human anti-CD38 autoantibodies raise intracellular calcium and stimulate insulin release in human pancreatic islets.

CD38 is involved in transmembrane signaling in many cell types; anti-CD38 autoantibodies have been described in diabetic patients. We tested whether human anti-CD38 antibodies possess signaling properties by measuring their ability to raise intracellular calcium ([Ca2+]i) using the fluo-3-acetoxymethyl ester method in a human-derived T-cell line (Jurkat T-cells, expressing high levels of surface CD38) and in dispersed human islet cells from normal donors. In Jurkat T-cells, 11 of 19 anti-CD38-positive sera raised [Ca2+]i (by > or =20% of baseline), whereas no [Ca2+]i-mobilizing activity was found in 27 anti-CD38-negative sera (chi2 = 20.5, P < 0.0001). In dispersed human islet cells, 5 of 11 anti-CD38-positive sera (and none of three anti-CD38-negative sera) raised [Ca2+]i significantly. When preincubated with Staphylococcus aureus protein A to remove IgG, anti-CD38-positive sera showed a 70 +/- 5% reduction in [Ca2+]i-mobilizing activity. Preincubation with CD38-transfected NIH-3T3 fibroblasts, but not with mock-transfected NIH-3T3 cells, abolished [Ca2+]i mobilization. In blocking experiments, preincubation with nonagonistic anti-CD38 monoclonal antibodies also prevented [Ca2+]i mobilization. In cultured human islets, anti-CD38-positive sera exhibiting [Ca2+]i-mobilizing activity in Jurkat T-cells (n = 6) significantly stimulated insulin release at 3.3 mmol/l glucose (median [interquartile range] 738 microU/ml [234], P = 0.0001 vs. 320 [52] microU/ml of control), whereas 6 anti-CD38-positive sera without [Ca2+]i-mobilizing activity and 10 anti-CD38-negative did not. In further incubations, the five anti-CD38-positive sera displaying [Ca2+]i-mobilizing activity in dispersed islet cells significantly stimulated insulin release at both 3.3 mmol/l glucose (2.2 +/- 0.3% of insulin islet content, P < 0.002 vs. 1.2 +/- 0.1% of control) and 16.7 mmol/l glucose (3.7 +/- 0.3 vs. 2.3 +/- 0.3%, P < 0.002). We conclude that human anti-CD38 autoantibodies with agonistic properties on the CD38 effector system occur in nature; in human islets, their [Ca2+]i-mobilizing activity is coupled with the ability to stimulate insulin release.

3T3 Cells↗

[New techniques in childbirth assistance. Experience and results of theoretical and practical training].

In 1995, the Course on Integrated Obstetrical and Gynaecological Techniques was added to the training program of the Obstetrics and Gynaecology Clinic and to the Midwife Diploma School, at the Faculty of Medicine of the A. Avogadro University of East Piemonte. This addition was due to the demand to create a service to train young medical doctors and student midwives on the basis of the requirements of the World Health Organisation, concerning a more natural way of giving birth. In this paper the results obtained after a four years practical application of these clinical techniques are presented. The factors considered were the type of assistance offered in correlation with different outcomes for both mother and child. The study demonstrates a general improvement in the quality of assistance and a decrease of costs for the National Health Service. The data have been compared with those of the neighbour Hospital Division, where deliveries are assisted with traditional techniques.

Delivery, Obstetric↗

Multiple small intestinal stromal tumours in a patient with previously unrecognised neurofibromatosis type 1: immunohistochemical and ultrastructural evaluation.

Neurofibromatosis type 1 could be associated with multiple gastrointestinal stromal tumours, although their presence is not considered among the major diagnostic criteria. We present here a case of a 50-year-old female complaining of abdominal pain, with about 100 small intestinal stromal tumours. This finding prompted us to suspect a neurofibromatosis which was clinically confirmed afterwards. Light microscopy examination revealed a low-grade stromal tumour with skeinoid fibres. Mixed neural-interstitial cells of Cajal origin or, alternatively, neural differentiation of interstitial cells of Cajal are discussed on the basis of immunophenotype (CD117+, CD34+) and ultrastructure. A 2-year follow-up did not indicate an aggressive course in the case of this neoplasm.

Antigens, CD34↗

Functional topography of discrete domains of human CD38.

In addition to its catalytic activities as ecto-NAD+ glycohydrolase (NADase), CD38 displays the ability to transduce signals of biological relevance. Indeed, ligation of CD38 on peripheral blood mononuclear cells (PBMC) by agonistic monoclonal antibodies (mAbs) is followed by the transcription and secretion of a vast array of regulatory cytokines. The present work addresses the issue of whether the signals leading to calcium (Ca2+) mobilization, lymphocyte proliferation and release of cytokines is dependent on the epitopes recognized by the individual mAbs. Competition binding analysis identifies two families of mAbs, namely IB4, IB6 and AT2 on one side and OKT10, SUN-4B7 and AT1 on the other. Each mAb family binds epitopes that are completely or partially common. However, the functional activities of the CD38 molecule can not be simply attributed to the epitopes engaged: for instance, IB4 and OKT10 mAbs, which bind different epitopes, perform as agonistic mAbs in inducing PBMC proliferation and interferon (IFN)-gamma secretion. SUN-4B7 yields intermediate effects, whereas IB6, AT1 and AT2 mAbs are totally ineffective. The effects mediated by IB4 and OKT10 mAbs are apparent in 80% of the healthy individuals studied, whereas the effects of SUN-4B7 mAb operate only in 25% of the donors. Interleukin (IL)-6 secretion was observed in all individuals analyzed, irrespective of the epitopes triggered and of mAbs used to ligate the CD38 molecule. In addition, IB4 is the only mAb able to induce significant intracellular Ca2+ fluxes.

ADP-ribosyl Cyclase↗

Hormonal modulation of GM-CSF receptor alpha-chain in in vitro models of endometrial cancer.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that stimulates the proliferation and differentiation of bone marrow progenitors. Moreover, the presence and activity of GM-CSF and its receptor (GM-CSF-r) has been documented on tissues and cell lines of a non-hemopoietic origin. In this paper we studied the expression and putative role of GM-CSF and GM-CSF-r in endometrial cancer. The modulation of GM-CSF-r alpha-chain upon progesterone treatment suggests a role for GM-CSF and its receptor in the pathogenesis and development of endometrial cancer.

Dose-Response Relationship, Drug↗

Uterine malformations and pregnancy losses: is cervical cerclage effective?

For many years, we and others have reported the efficacy of cervical cerclage in the prevention of miscarriage in patients with uterine malformations. In this paper the experience of 275 cases collected between 1978 and 1998 is reported. Our data indicate that cervical cerclage is effective in preventing miscarriages, prevalently in those pregnancies bearing uterine malformations with simultaneous cervical incompetence.

Abortion, Spontaneous↗

Retinoids in breast cancer prevention and treatment. A review of the literature.

During the last three decades, research focused on cancer treatment has led to the development of many cytotoxic agents. Despite the fact that these efforts have significantly improved the prognosis of certain malignancies such as some lymphomas, leukemias and testicular carcinomas, other tumors such as ovarian, lung and metastatic breast cancer are still associated with a poor prognosis. An innovative approach has recently emerged, thanks to a better understanding of tumor cell biology and many efforts are aimed at finding compounds capable of restoring a more differentiated phenotype to tumor cells, thereby reducing the tumor's aggressiveness and ultimately reverting it to its normal counterpart [1, 2]. Retinoids are the prototype of this new therapeutical approach called "differentiation therapy".

Animals↗