293 results on '"LUCINI, V."'
Search Results
102. Correspondence and Short Communications Melatonin and Immunity
- Author
-
Fraschini, F., primary, Scaglione, F., additional, Franco, P., additional, Demartini, G., additional, Lucini, V., additional, and Stankov, B., additional
- Published
- 1990
- Full Text
- View/download PDF
103. Relation between Lymphocyte Subpopulations and Pineal Function in Patients with Early or Metastatic Cancer.
- Author
-
LISSONI, P., BARNI, S., TANCINI, G., CRISPINO, S., PAOLOROSSI, F., CATTANEO, G., LUCINI, V., MARIANI, M., ESPOSTI, D., ESPOSTI, G., and FRASCHINI, F.
- Published
- 1988
- Full Text
- View/download PDF
104. Photoperiodic and endocrine control of seasonal breeding in Grey partridge ( Perdix perdix).
- Author
-
Sharp, P. J., Massa, R., Bottoni, L., Lucini, V., Lea, R. W., Dunn, I. C., and Trocchi, V.
- Published
- 1986
- Full Text
- View/download PDF
105. Tricyclic Alkylamides as Melatonin Receptor Ligands with Antagonist or Inverse Agonist Activity
- Author
-
Lucini, V., Pannacci, M., Scaglione, F., Fraschini, F., Rivara, S., Mor, M., Bordi, F., Plazzi, P. V., Spadoni, G., Bedini, A., Piersanti, G., Diamantini, G., and Tarzia, G.
- Abstract
This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d]cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure−activity studies on MT
1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2-[125I]iodomelatonin displacement assay and intrinsic activity by the GTPγS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT2 affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d ) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative4b produced a noticeable reduction of GTPγS binding at MT2 receptor, thus being among the few inverse agonists described.- Published
- 2004
106. Three-Dimensional Quantitative Structure−Activity Relationship Studies on Selected MT<INF>1</INF> and MT<INF>2</INF> Melatonin Receptor Ligands: Requirements for Subtype Selectivity and Intrinsic Activity Modulation
- Author
-
Rivara, S., Mor, M., Silva, C., Zuliani, V., Vacondio, F., Spadoni, G., Bedini, A., Tarzia, G., Lucini, V., Pannacci, M., Fraschini, F., and Plazzi, P. V.
- Abstract
The three-dimensional quantitative structure−activity relationship comparative molecular field analysis (3D-QSAR CoMFA) approach was applied to some classes of melatonin (MLT) membrane receptor ligands, with the principal aim of exploring the correlation between their steric features and MT
2 -selective antagonism. Binding data obtained from cloned MT1 and MT2 receptor subtypes were used to develop 3D-QSAR models for agonists and for antagonists at the two receptor subtypes, looking for the structural requirements for receptor subtype selectivity. In particular, we superposed the compounds showing antagonist activity, or very low intrinsic activity at the GTPγS test, following the hypothesis that the occupation of an additional pocket positioned out of the plane of MLT is one of the major determinants for MT2 selectivity; the statistical models obtained confirmed this hypothesis. Structure−intrinsic activity relationship studies, applied to a set of compounds homogeneously tested, allowed the identification of the structural features whose modulation shifts the behavior from that of the agonist to that of the antagonist. The pocket out of the plane of MLT was identified as one of the key features for obtaining selective MT2 antagonists. The reliability of our statistical models was further confirmed by the correct prediction of the pharmacological behavior of some N-substituted melatonin derivatives, which were prepared and tested on cloned receptor subtypes.- Published
- 2003
107. 2-N-Acylaminoalkylindoles: Design and Quantitative Structure−Activity Relationship Studies Leading to MT<INF>2</INF>-Selective Melatonin Antagonists
- Author
-
Spadoni, G., Balsamini, C., Diamantini, G., Tontini, A., Tarzia, G., Mor, M., Rivara, S., Plazzi, P. V., Nonno, R., Lucini, V., Pannacci, M., Fraschini, F., and Stankov, B. M.
- Abstract
Several indole analogues of melatonin (MLT) were obtained by moving the MLT side chain from C
3 to C2 of the indole ring. Binding and in vitro functional assays were performed on cloned human MT1 and MT2 receptors, stably transfected in NIH3T3 cells. Quantitative structure−activity relationship studies showed that 4-methoxy-2-(N-acylaminomethyl)indoles, with a benzyl group in position 1, were selective MT2 antagonists and, in particular, N-[(1-p-chlorobenzyl-4-methoxy-1H-indol-2-yl)methyl]propanamide (12 ) behaved as a pure antagonist at MT1 and MT2 receptors, with a 148-fold selectivity for MT2 . We present a topographical model that suggests a lipophilic group, located out of the plane of the indole ring of MLT, as the key feature of the MT2 selective antagonists.- Published
- 2001
108. IS THERE A RELATIONSHIP BETWEEN ANDROGEN METABOLISM, STEROID-DEPENDENT ENZYMES AND SOCIO-SEXUAL BEHAVIOR?
- Author
-
MILONE, MARIO, VARRIALE, BRUNO, CALIENDO, MARIA FILOMENA, Massa R., Lucini V., Dessì Fulgheri F., Lupo di Prisco C., Larsson K., Milone, Mario, Varriale, Bruno, Caliendo, MARIA FILOMENA, Massa, R., Lucini, V., Dessì Fulgheri, F., Lupo di Prisco, C., and Larsson, K.
- Subjects
ANDROGENS ,B-GLUCURONIDASE ,MOUSE - Published
- 1982
109. Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression
- Author
-
Bellodi, L., Erzegovesi, S., Bianchi, L., Lucini, V., Conca, R., and Lucca, A.
- Published
- 1997
- Full Text
- View/download PDF
110. The melatonin receptor in the human brain: cloning experiments and distribution studies
- Author
-
Mazzucchelli, C., Pannacci, M., Nonno, R., Lucini, V., Fraschini, F., and Stankov, B. M.
- Published
- 1996
- Full Text
- View/download PDF
111. Melatonin Receptor Ligands: Synthesis of New Melatonin Derivatives and Comprehensive Comparative Molecular Field Analysis (CoMFA) Study
- Author
-
Mor, M., Rivara, S., Silva, C., Bordi, F., Plazzi, P. V., Spadoni, G., Diamantini, G., Balsamini, C., Tarzia, G., Fraschini, F., Lucini, V., Nonno, R., and Stankov, B. M.
- Abstract
The CoMFA methodology was applied to melatonin receptor ligands in order to establish quantitative structure−affinity relationships. One hundred thirty-three compounds were considered: they were either collected from literature or newly synthesized in order to gain information about the less explored positions. To this end, various melatonin derivatives were prepared and their affinity for quail optic tecta melatonin receptor was tested. Compounds were aligned on the putative active conformation of melatonin proposed by our previously reported pharmacophore search, and their relative affinities were calculated from the displacement of 2-[125I]-iodomelatonin on different tissues expressing aMT receptors. Compounds were grouped into three sets according to their topology. Subset A: melatonin-like compounds; subset B: N-acyl-2-amino-8-methoxytetralins and related compounds; subset C: N-acyl-phenylalkylamines and related compounds. CoMFA models were derived for each set, using the steric, electrostatic, and lipophilic fields as structural descriptors; the PLS analyses were characterized by good statistical parameters, taking into account the heterogeneity of the binding data, obtained with different experimental protocols. From the CoMFA model for the melatonin-like compounds, besides the well-known positive effect of 2-substitution, a low steric tolerance for substituents in 1, 6, and 7, and a negative effect of electron-rich 4-substituents were observed; the information provided by the newly synthesized compounds was essential for these results. Moreover, a comprehensive model for the 133 compounds, accounting for a common alignment and a common mode of interaction at the melatonin receptor, was derived (Q2 = 0.769, R2 = 0.905). This model validates our previously reported pharmacophore search and offers a clear depiction of the structure−affinity relationships for the melatonin receptor ligands.
- Published
- 1998
112. 2-[N-Acylamino(C<INF>1</INF>−C<INF>3</INF>)alkyl]indoles as MT<INF>1</INF> Melatonin Receptor Partial Agonists, Antagonists, and Putative Inverse Agonists
- Author
-
Spadoni, G., Balsamini, C., Bedini, A., Diamantini, G., Giacomo, B. Di, Tontini, A., Tarzia, G., Mor, M., Plazzi, P. V., Rivara, S., Nonno, R., Pannacci, M., Lucini, V., Fraschini, F., and Stankov, B. M.
- Abstract
The synthesis of several novel indole melatonin analogues substituted at the 2-position with acylaminomethyl (
8 − 11 ), acylaminoethyl (5a − k ), or acylaminopropyl (13 ) side chains is reported. On the basis of a novel in vitro functional assay (specific binding of [35S]GTPγS), which can discriminate agonist from partial agonist, antagonist, and inverse agonist ligands,5a ,g ,h ,j and13 were shown to be partial agonists,5d ,e and8 − 11 competitive antagonists, and5b ,c ,k putative inverse agonists. Binding and functional assays were performed on cloned human MT1 receptor. Structure−activity relationship considerations indicate that N-[1-aryl-2-(4-methoxy-1H-indol-2-yl)(C1 −C2 )alkyl]alkanamides represent a lead structure for this type of ligands.- Published
- 1998
113. 1-(2-Alkanamidoethyl)-6-methoxyindole Derivatives: A New Class of Potent Indole Melatonin Analogues
- Author
-
Tarzia, G., Diamantini, G., Giacomo, B. Di, Spadoni, G., Esposti, D., Nonno, R., Lucini, V., Pannacci, M., Fraschini, F., and Stankov, B. M.
- Abstract
A new series of indole melatonin analogues, bearing the amido ethyl side chain attached at the N-1 position of the indole nucleus, were synthesized and tested for their affinity for the melatonin receptor isolated from quail optic tecta in a series of in vitro ligand-binding experiments using 2-[125I]iodomelatonin as the labeled ligand. The biological activity was evaluated using two models: effects on the forskolin-stimulated cAMP accumulation in explants from quail optic tecta and evaluation of the GTPγS index derived from competition experiments performed in the absence or presence of GTPγS. Compounds
2a and2k −n , obtained by shifting the methoxy group and the ethylamido side chain from the C-5 and C-3 positions of melatonin to the C-6 and N-1 positions of the indole nucleus, exhibited an affinity similar to that of melatonin itself, as well as full agonist activity. Optimization of the C-2 substituent by introducing Br, phenyl, or COOCH3 (2b −d ) resulted in a significantly enhanced affinity (in the picomolar range) and improved agonist biological activity. Compounds lacking the methoxy group and bearing an N-alicyclic group (2h −j ) behaved as partial agonists or antagonists.- Published
- 1997
114. Conformationally Restrained Melatonin Analogues: Synthesis, Binding Affinity for the Melatonin Receptor, Evaluation of the Biological Activity, and Molecular Modeling Study
- Author
-
Spadoni, G., Balsamini, C., Diamantini, G., Giacomo, B. Di, Tarzia, G., Mor, M., Plazzi, P. V., Rivara, S., Lucini, V., Nonno, R., Pannacci, M., Fraschini, F., and Stankov, B. M.
- Abstract
The design, synthesis, and biological profile of several indole melatonin analogues with a conformationally restricted C3 amidoethane side chain are presented. Examination of the accessible conformations of the melatonin side chain led us to explore some of its fully or partially restricted analogues,
2 −12 , the binding affinity values of which were utilized to gain further insight on the melatonin binding site. Two pharmacophoric models have been devised for melatonin and the active compounds by conformational analysis and superimposition performed using the DISCO program. In these models, the melatonin side chain can adopt a gauche/anti conformation out of the indole plane. Another contribution of this study regards the observation of a possible binding point interaction around the C2 position of the indole, as suggested by the remarkably increased binding affinity observed in the C2-substituted analogues6 and9 and especially in the more rigid analogue5 . The biological activity and the efficacy of the new compounds were tested by measuring the inhibition of the forskolin-stimulated cAMP accumulation and the GTPγS index. Both analyses demonstrated that all of the compounds were full agonists with the exception of4 and9 , which showed a slight reduction in efficacy and would seem to be partial agonists.- Published
- 1997
115. Predictive value of tryptophan/large neutral amino acids ratio to antidepressant response
- Author
-
Lucini, V., Lucca, A., Catalano, M., and Smeraldi, E.
- Published
- 1996
- Full Text
- View/download PDF
116. Effect of photoperiod and gonadectomy on testosterone metabolism in vitroby the prostate of the golden hamster
- Author
-
Lucini, V., Bottoni, L., and Massa, R.
- Abstract
Testosterone metabolism was studied in vitroin the prostate of intact and castrated golden hamsters maintained either in short days (8 h light: 16 h darkness, 8L : 16D) or in long days (14L : 10D). Testosterone was found to be converted into 17β-hydroxy-5α-androstan-3-one (5α-DHT), 5α-androstane-3α, 17β-diol, 5α-androstane-3, 17-dione and androstenedione. The mean conversion of testosterone to 5α-DHT was higher in prostates from animals maintained in long days than in short days (P< 0·0025) while that to androstenedione was higher in short days (P<0·0005); no significant changes in the formation of the other three metabolites were noted. Castration of animals maintained in short days resulted in a significant (P<0·05) decrease in the mean conversion to all four metabolites. In contrast, castration of animals kept in a long-day regime caused a significant (P<0·01) decrease in the mean formation of 5α-DHT but a significant (P<0·05) increase in the mean formation of 5α-androstane-3α, 17β-diol.
- Published
- 1983
- Full Text
- View/download PDF
117. Simultaneous inhibition of glioma angiogenesis, cell proliferation, and invasion by a naturally occurring fragment of human metalloproteinase-2
- Author
-
Bello, L., CARLO GIORGIO GIUSSANI, Pluderi, M., Tomei, G., Villani, R. M., Nikas, D., Carroll, R. S., Machluf, M., Zhang, J., Black, P. M., Lucini, V., Carrabba, G., Bikfalvi, A., Bello, L, Lucini, V, Carrabba, G, Giussani, C, Machluf, M, Pluderi, M, Nikas, D, Zhang, J, Tomei, G, Villani, R, Carroll, R, Bikfalvi, A, and Black, P
- Subjects
Adult ,Male ,Mice, Nude ,Apoptosis ,Brain Neoplasm ,Mice ,Peptide Fragment ,Cell Movement ,Cell Adhesion ,Animals ,Humans ,Neoplasm Invasiveness ,Receptors, Vitronectin ,Vitronectin ,Aged ,Neoplasm Invasivene ,Neovascularization, Pathologic ,Animal ,Brain Neoplasms ,Apoptosi ,Glioma ,Middle Aged ,Xenograft Model Antitumor Assays ,Peptide Fragments ,Culture Media ,Matrix Metalloproteinase 2 ,Female ,Fibroblast Growth Factor 2 ,Endothelium, Vascular ,Cell Division ,Human - Abstract
Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. This study demonstrates that a fragment derived from the autocatalytic digestion of matrix metalloproteinase (MMP)-2, called PEX, acts simultaneously as an inhibitor of glioma angiogenesis, cell proliferation, and migration. PEX is detected in the cultured medium of various human glioma, endothelial, breast, and prostate carcinoma cell lines. PEX is purified from the medium of glioma cell lines by chromatography, where PEX is constitutively expressed as a free and a TIMP-2-bound form. In human glioma tissue, PEX expression correlates with histological subtype and grade and with alpha v beta 3 integrin expression to which it is bound. Systemic administration of PEX to s.c. and intracranial human glioma xenografts results in a 99% suppression of tumor growth with no signs of toxicity. Thus, PEX is a very promising candidate for the treatment of human malignant gliomas.
118. Suppression of malignant glioma recurrence in a newly developed animal model by endogenous inhibitors
- Author
-
Bello, L., Giussani, C., Carrabba, G., Mauro Pluderi, Lucini, V., Pannacci, M., Caronzolo, D., Tomei, G., Villani, R., Scaglione, F., Carroll, R. S., Bikfalvi, A., Bello, L, Giussani, C, Carrabba, G, Pluderi, M, Lucini, V, Pannacci, M, Caronzolo, D, Tomei, G, Villani, R, Scaglione, F, Carroll, R, and Bikfalvi, A
- Subjects
Male ,Time Factors ,Time Factor ,Animal ,Mice, Nude ,Glioma ,Recombinant Protein ,Platelet Factor 4 ,Immunohistochemistry ,Recombinant Proteins ,Protein Structure, Tertiary ,Neoplasm Metastasi ,Disease Models, Animal ,Mice ,Recurrence ,Tumor Cells, Cultured ,Animals ,Humans ,Matrix Metalloproteinase 2 ,Neoplasm Metastasis ,Cell Division ,Neoplasm Transplantation ,Human - Abstract
Glioma recurrences develop at the borders of the surgical cavity and are the main cause of their poor prognosis. There are no therapeutic advances to reduce the incidence of recurrence or animal models that closely mimic the clinical scenario to evaluate novel therapeutics. This work investigates the efficacy of endogenous inhibitors, in preventing the recurrence of human malignant gliomas, in a newly developed animal model of glioma surgical resection. We developed a nude mice model in which human glioma xenografts were microsurgically removed. After surgery, small islets of tumor cells persisted in the normal brain parenchyma, grew, and formed a recurrence. As inhibitors we used PEX and a fragment of platelet factor 4 (PF-4/CTF), which were administered systemically on a daily basis or in metronomic combination with chemotherapy for 120 days. Treatment was started 1 or 15 days after tumor removal. PEX or PF-4/CTF produced a significant improvement in survival, and delayed the appearance of glioma recurrence. Survival of animals that received daily PEX or PF-4/CTF was similar to that of animals that received metronomic PEX or PF-4/CTF and chemotherapy, respectively. The effect of treatment was dependent on the time at which the treatment was initiated. The highest level of inhibition was observed when the treatment was administered 1 day after surgical resection and when PEX was used as the inhibitor (120 days versus 35 days of the control). Tumors treated with PEX or PF-4/CTF were small and well delineated, with few vessels. Postsurgical administration of PEX or PF-4/CTF significantly reduces the incidence human malignant glioma recurrences for a long period of time.
119. Long-term inhibition of glioma growth by systemic administration of human PEX
- Author
-
Pluderi, M., Lucini, V., Caronzolo, D., Pannacci, M., Costa, F., Giorgio Carrabba, Giussani, C., Grosso, S., Colleoni, F., Scaglione, F., Villani, R., Bikfalvi, A., Bello, L., Pluderi, M, Lucini, V, Caronzolo, D, Pannacci, M, Costa, F, Carrabba, G, Giussani, C, Grosso, S, Colleoni, F, Scaglione, F, Villani, R, Bikfalvi, A, and Bello, L
- Subjects
Male ,Time Factors ,Time Factor ,Blotting, Western ,Mice, Nude ,Angiogenesis Inhibitors ,Apoptosis ,Polymerase Chain Reaction ,Mice ,Peptide Fragment ,Tumor Cells, Cultured ,Animals ,Humans ,Endothelial Cell ,Animal ,Apoptosi ,Endothelial Cells ,Glioma ,Recombinant Protein ,Peptide Fragments ,Recombinant Proteins ,Disease Models, Animal ,Matrix Metalloproteinase 2 ,Cell Division ,Neoplasm Transplantation ,Angiogenesis Inhibitor ,Human - Abstract
The growth of gliomas depends on the balance of factors stimulating or inhibiting angiogenesis, tumor cell invasion and proliferation. The administration of endogenous inhibitors to experimental human gliomas in animal models resulted in a significant inhibition of tumor growth. It is becoming apparent that resistance can develop over time to many types of endogenous inhibitors and seems to be influenced by the tumor type and system of delivery.We recently isolated a potent endogenous inhibitor, called human PEX, from human glioma cells in culture. Human PEX is a potent inhibitor of angiogenesis, tumor and endothelial cell proliferation and migration. In this paper, we investigated the ability of human PEX to sustain inhibition of glioma growth for a prolonged period of time. We initially developed a recombinant form of the inhibitor and showed that this form had similar in vitro and in vivo activities to the natural one. Human PEX was then administered to nude mice intracranial human glioma model, in combination with metronomic chemotherapy, for a period of 185 days, starting 15 days after tumor cells implantation.Our data showed that the systemic administration of human PEX mantained a very prolonged inhibition of glioma growth (50% survival of animals treated with 2 mg/kg/days was 160 days vs 24 days of the control) and had a synergistic effect with low dose chemotherapy. Histological analysis of tumors, showed that treatment with PEX was associated with a decrease of vascularity, cell proliferation, and increase in apoptosis.These data indicate that human PEX controls tumor growth by separate mechanisms. In addition, treatment with PEX produced well delineated tumors, indicating the persistence of a direct anti-invasive effect of the molecule even after a prolonged period of treatment.
120. Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in vivo
- Author
-
Giussani, C., Carrabba, G., Mauro Pluderi, Lucini, V., Pannacci, M., Caronzolo, D., Costa, F., Minotti, M., Tomei, G., Villani, R., Bikfalvi, A., and Bello, L.
121. Local intracerebral delivery of endogenous inhibitors by osmotic minipumps effectively suppresses glioma growth in Vivo (Cancer Research (2003) (2499-2505))
- Author
-
CARLO GIORGIO GIUSSANI, Carrabba, G., Pluderi, M., Lucini, V., Pannacci, M., Caronzolo, D., Costa, F., Minotti, M., Tomei, G., Villani, R., Carroll, R. S., Bikfalvi, A., and Bello, L.
122. N-acyl-5- and -2,5-substituted tryptamines: Synthesis, activity and affinity for human mt(1) and MT2 melatonin receptors
- Author
-
Spadoni, G., Balsamini, C., Annalida Bedini, Carey, A., Diamantini, G., Di Giacomo, B., Tontini, A., Tarzia, G., Nonno, R., Lucini, V., Pannacci, M., Michaylov Stankov, B., and Fraschini, F.
123. Abnormal 24hour urinary excretory pattern of 6-sulphatoxymelatonin in both phases of cluster headache
- Author
-
Leone, M., Lucini, V., Damico, D., Licia Grazzi, Moschiano, F., and Fraschini, F.
124. Effect of photoperiod and gonadectomy on testosterone metabolism in vitro by the prostate of the golden hamster
- Author
-
Lucini, V., primary, Bottoni, L., additional, and Massa, R., additional
- Published
- 1983
- Full Text
- View/download PDF
125. Generation of Diffraction-Limited Parametric Superfluorescence in LBO.
- Author
-
Di Traponi, P. and Lucini, V.
- Published
- 1996
- Full Text
- View/download PDF
126. ChemInform Abstract: Conformationally Restrained Melatonin Analogues: Synthesis, Binding Affinity for the Melatonin Receptor, Evaluation of the Biological Activity, and Molecular Modeling Study.
- Author
-
SPADONI, G., BALSAMINI, C., DIAMANTINI, G., DI GIACOMO, B., TARZIA, G., MOR, M., PLAZZI, P. V., RIVARA, S., LUCINI, V., NONNO, R., PANNACCI, M., FRASCHINI, F., and STANKOV, B. M.
- Published
- 1997
- Full Text
- View/download PDF
127. Neutral Amino Acid Availability in Two Major Psychiatric Disorders
- Author
-
Lucca, A., Lucini, V., Catalano, M., and Smeraldi, E.
- Published
- 1995
- Full Text
- View/download PDF
128. Serine and glycine metabolism in schizophrenic patients
- Author
-
Lucca, A., Cortinovis, S., and Lucini, V.
- Published
- 1993
- Full Text
- View/download PDF
129. 2-[^1^2^5I]Iodomelatonin binding sites in the bovine hippocampus are not sensitive to guanine nucleotides
- Author
-
Nonno, R., Lucini, V., Stankov, B., and Fraschini, F.
- Published
- 1995
- Full Text
- View/download PDF
130. Plasma Tryptophan Levels and Plasma Tryptophan/Neutral Amino Acids Ratio in Patients With Mood Disorder, Patients With Obsessive-Compulsive Disorder, and Normal Subjects
- Author
-
Lucca, A., Lucini, V., Piatti, E., and Ronchi, P.
- Published
- 1992
- Full Text
- View/download PDF
131. Identification and functional significance of nicotinic cholinergic receptors in the rat pineal gland
- Author
-
Stankov, B., Cimino, M., Marini, P., and Lucini, V.
- Published
- 1993
- Full Text
- View/download PDF
132. Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models
- Author
-
Sergio M. Gaini, Carlo Giussani, Lorenzo Bello, Giorgio Carrabba, Yvan Torrente, Valeria Lucini, Francesco Acerbi, Marzia Belicchi, Andreas Bikfalvi, Federica Pisati, Nereo Bresolin, C. Marchesi, Martin Hagedorn, Sophie Javerzat, M. Gavina, Pisati, F, Belicchi, M, Acerbi, F, Marchesi, C, Giussani, C, Gavina, M, Javerzat, S, Hagedorn, M, Carrabba, G, Lucini, V, Gaini, S, Bresolin, N, Bello, L, Bikfalvi, A, and Torrente, Y
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Human Skin-Derived Stem Cell ,Brain tumor ,Mice, Nude ,Mice, Transgenic ,Cell Growth Processes ,Chick Embryo ,Biology ,Chorioallantoic Membrane ,Transforming Growth Factor beta1 ,Mice ,chemistry.chemical_compound ,Cell Line, Tumor ,Brain Tumor ,Glioma ,medicine ,Animals ,Humans ,Autologous transplantation ,Neoplasm Invasiveness ,Skin ,Neovascularization, Pathologic ,Brain Neoplasms ,Stem Cells ,Mesenchymal stem cell ,medicine.disease ,Xenograft Model Antitumor Assays ,Neural stem cell ,Vascular endothelial growth factor ,medicine.anatomical_structure ,Oncology ,chemistry ,Pericyte ,Stem cell ,Glioblastoma ,Stem Cell Transplantation - Abstract
Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-β1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation. [Cancer Res 2007;67(7):3054–63]
- Published
- 2007
133. Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression
- Author
-
Valentina Lucini, Laura Bellodi, Adelio Lucca, Laura Bianchi, Stefano Erzegovesi, Roberta Conca, Bellodi, Laura, Erzegovesi, S, Bianchi, L, Lucini, V, Conca, R, and Lucca, A.
- Subjects
Adult ,Male ,Obsessive-Compulsive Disorder ,medicine.medical_specialty ,Fluvoxamine ,behavioral disciplines and activities ,chemistry.chemical_compound ,Internal medicine ,mental disorders ,medicine ,Humans ,Neurotransmitter ,Psychiatry ,Biological Psychiatry ,Depression (differential diagnoses) ,Retrospective Studies ,chemistry.chemical_classification ,Depressive Disorder ,Tryptophan ,Middle Aged ,medicine.disease ,humanities ,Amino acid ,Psychiatry and Mental health ,Endocrinology ,chemistry ,Major depressive disorder ,Female ,Serotonin ,Psychology ,Selective Serotonin Reuptake Inhibitors ,Anxiety disorder ,medicine.drug - Abstract
We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients. (C) 1997 Elsevier Science Ireland Ltd. Z8 0 ZR 0 ZS 0 ZB 8
- Published
- 1997
134. 2-Bromomelatonin: Synthesis and characterization of a potent melatonin agonist
- Author
-
B. M. Stankov, E. Duranti, Gilberto Spadoni, S. Capsoni, Valeria Lucini, Gabriele Biella, Franco Fraschini, Andrea Duranti, Duranti, E, Stankov, B, Spadoni, G, Lucini, V, Capsoni, Simona, Biella, G, and Fraschini, F.
- Subjects
Male ,Agonist ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,medicine.drug_class ,Receptors, Melatonin ,Socio-culturale ,Hamster ,In Vitro Techniques ,Biology ,Mass Spectrometry ,General Biochemistry, Genetics and Molecular Biology ,gamma-Aminobutyric acid ,Melatonin ,Structure-Activity Relationship ,chemistry.chemical_compound ,In vivo ,Cricetinae ,Internal medicine ,medicine ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,Receptor ,gamma-Aminobutyric Acid ,Bromosuccinimide ,Cerebral Cortex ,Neurons ,Mesocricetus ,Biological activity ,Organ Size ,General Medicine ,Receptors, Neurotransmitter ,Endocrinology ,chemistry ,Chromatography, Thin Layer ,Rabbits ,Acetamide ,medicine.drug - Abstract
A practical synthesis of N-[2-(2-bromo-5-methoxy-1H-indol-3-yl)ethyl]- acetamide (2-bromomelatonin) was achieved by direct bromination of melatonin with N-bromosuccinimide (NBS) in anhydrous acetic acid at room temperature under nitrogen, followed by flash-chromatography. 1H-NMR and mass spectra showed the bromine to be incorporated at the C-2 position of the indole moiety. Tests performed in vitro with isolated melatonin receptors from rabbit parietal cortex demonstrated that the relative binding affinity of 2-bromomelatonin was about ten times higher than that of melatonin and close to that of 2-iodomelatonin. 2-Bromomelatonin behaved as a potent agonist in the physiological studies. It showed enhanced activity in inhibiting the spontaneous firing activity of cortical neurons and similarly to melatonin and 2-iodomelatonin potentiated significantly the inhibitory effect of GABA. 2-Bromomelatonin was also an extremely effective agonist in the tests performed in vivo in the Syrian hamster gonadal regression model.
- Published
- 1992
135. Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma
- Author
-
Marilou Pannacci, Svetlana Shinkaruk, Xavier Canron, Silvia Grosso, Francesco Costa, Federica Colleoni, Gérard Déléris, Carlo Giussani, Dario Caronzolo, Giorgio Carrabba, Francesco Acerbi, Andreas Bikfalvi, Lorenzo Bello, Valeria Lucini, Mauro Pluderi, Giustino Tomei, Bello, L, Lucini, V, Costa, F, Pluderi, M, Giussani, C, Acerbi, F, Carrabba, G, Pannacci, M, Caronzolo, D, Grosso, S, Shinkaruk, S, Colleoni, F, Canron, X, Tomei, G, Deleris, G, and Bikfalvi, A
- Subjects
Male ,Cancer Research ,Time Factors ,Angiogenesis ,Combinatorial administration ,Apoptosis ,Endothelial Growth Factors ,Platelet Factor 4 ,Neovascularization ,chemistry.chemical_compound ,Mice ,Cell Movement ,Neoplasms ,Mice, Inbred BALB C ,Neovascularization, Pathologic ,Brain Neoplasms ,Glioma ,Recombinant Proteins ,Drug Combinations ,Oncology ,Proteoglycans ,Collagen ,medicine.symptom ,Growth inhibition ,Ratón ,Mice, Nude ,Biology ,Peptides, Cyclic ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,Cell Proliferation ,Cell growth ,Microcirculation ,Proteins ,medicine.disease ,PHEX Phosphate Regulating Neutral Endopeptidase ,Disease Models, Animal ,chemistry ,Microscopy, Fluorescence ,Immunology ,Cancer research ,Endothelium, Vascular ,Laminin ,Angiogenesis and Invasion ,Platelet factor 4 ,Neoplasm Transplantation - Abstract
Purpose: We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth. Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR). Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined. Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.
- Published
- 2004
136. IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo
- Author
-
Lorenzo, Bello, Valeria, Lucini, Carlo, Giussani, Giorgio, Carrabba, Mauro, Pluderi, Francesco, Scaglione, Giustino, Tomei, Roberto, Villani, Peter McL, Black, Andreas, Bikfalvi, Rona S, Carroll, Bello, L, Lucini, V, Giussani, C, Carrabba, G, Pluderi, M, Scaglione, F, Tomei, G, Villani, R, Black, P, Bikfalvi, A, and Carroll, R
- Subjects
Neoplasm Invasivene ,Neovascularization, Pathologic ,Brain Neoplasms ,Animal ,Cell Survival ,Mice, Nude ,Antineoplastic Agents ,Glioma ,Integrin alphaVbeta3 ,Peptides, Cyclic ,Antineoplastic Agent ,Brain Neoplasm ,Mice ,Cell Movement ,Cell Adhesion ,Tumor Cells, Cultured ,Animals ,Humans ,Oligopeptide ,Neoplasm Invasiveness ,Endothelium, Vascular ,Oligopeptides ,Cell Division ,Neoplasm Transplantation ,Human - Abstract
OBJECTIVE: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates, the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS201 on human malignant gliomas. METHODS: The in vitro effects of IS201. were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS201 was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS: IS201 reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS201 strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS201 induced endothelial and tumor cell apoptosis. In vivo, when IS201 was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS201 inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo
- Published
- 2003
137. LOCAL INTRACEREBRAL DELIVERY OF ENDOGENOUS INHIBITORS BY OSMOTIC MINIPUMPS EFFECTIVELY SUPPRESSES GLIOMA GROWTH IN VIVO
- Author
-
Carlo, Giussani, Giorgio, Carrabba, Mauro, Pluderi, Valeria, Lucini, Marilou, Pannacci, Dario, Caronzolo, Francesco, Costa, Matteo, Minotti, Giustino, Tomei, Roberto, Villani, Rona S, Carroll, Andreas, Bikfalvi, Lorenzo, Bello, Giussani, C, Carrabba, G, Pluderi, M, Lucini, V, Pannacci, M, Caronzolo, D, Costa, F, Minotti, M, Tomei, G, Villani, R, Carroll, R, Bikfalvi, A, and Bello, L
- Subjects
Mice, Inbred BALB C ,Brain Neoplasms ,Animal ,Molecular Sequence Data ,Mice, Nude ,Infusion Pumps, Implantable ,Recombinant Protein ,Platelet Factor 4 ,Immunohistochemistry ,Xenograft Model Antitumor Assays ,Peptide Fragments ,Recombinant Proteins ,Brain Neoplasm ,Mice ,Peptide Fragment ,Hemopexin ,Tumor Cells, Cultured ,Animals ,Humans ,Cattle ,Amino Acid Sequence ,Neoplasm Recurrence, Local ,Glioblastoma ,Cell Division ,Human - Abstract
The systemic administration of endogenous inhibitors significantly reduced the growth of human glioma in vivo, but required the production of a large amount of biologically active protein. In this study we reduced the amount of protein needed and optimized the therapeutical response by delivering the endogenous inhibitors locally into the brain by osmotic minipumps. Human hemopexin fragment of MMP-2 or COOH-terminal fragment of platelet factor-4 were delivered locally and continuously into the brain of mice implanted intracranially with glioma cells, by osmotic minipumps connected to an intracranial catheter. Local delivery of human hemopexin fragment of MMP-2 and COOH-terminal fragment of platelet factor-4 significantly inhibited the growth of well-established malignant glioma in nude and BALB/C mice. When the inhibitors were given at the same concentration, the efficacy of the local delivery was much higher than that reached with the systemic administration, both when the inhibitor was administered daily or continuously by s.c. minipumps. Moreover, the local delivery reduced the amount of protein needed to reach a significant therapeutic response. Intracerebral delivery maintained a long-term control of glioma growth and inhibited glioma recurrence in a surgical resection model. Treatment showed no side effects. Histochemical analysis of tumors showed that the tumor growth inhibition was the result of a decrease in tumor vasculature and a change in tumor vessel morphology. Our data demonstrate that local intracerebral delivery of endogenous inhibitors effectively inhibits malignant glioma growth and reduces the amount of protein needed to reach a therapeutical response.
- Published
- 2003
138. A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain
- Author
-
Valeria Lucini, Franco Fraschini, Morten Møller, Simona Capsoni, Bojidar Stankov, Stankov, B, Møller, M, Lucini, V, Capsoni, Simona, and Fraschini, F.
- Subjects
Male ,Cerebellum ,medicine.medical_specialty ,Pituitary gland ,GTP' ,Endocrinology, Diabetes and Metabolism ,Carnivora ,Receptors, Melatonin ,Hippocampus ,Socio-culturale ,Receptors, Cell Surface ,Melatonin ,Endocrinology ,Dogs ,Internal medicine ,medicine ,Animals ,Circadian rhythm ,Receptor ,Chemistry ,Brain ,General Medicine ,Circadian Rhythm ,medicine.anatomical_structure ,Autoradiography ,Female ,Pars tuberalis ,medicine.drug - Abstract
Stankov B, Møller, M, Lucini V, Capsoni S, Fraschini F. A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain. Eur J Endocrinol 1994;131:191–200. ISSN 0804–4643 Dogs kept under controlled photoperiodic conditions of 12 h light and 12 h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[125I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in this species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. The eosinophils in the adenohypophysis and the neural lobe were devoid of binding. Heavily labeled were the external laminar and the mitral cell layers of the olfactory bulbs, but no binding was detected in the filae nervi olfactorii or tractus olfactorius. The hypothalamic suprachiasmatic nuclei were discernible clearly. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant (ic50) in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 5′-O-(3-thiotriphosphate) (GTPΓS) led to a consequential decrease in the binding density. The specific binding observed in other areas (hippocampus, frontal, parietal, occipital cortex and cerebellum) was rather weak, diffuse and could not be attributed to a particular layer; the apparent ic50 for melatonin was about 1 μmol/l, and co-incubation with GTPΓS did not modify the binding density. Collectively, these data show that the dog posesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species. Bojidar Stankov, Chair of Chemotherapy, Department of Pharmacology, University of Milan, 32 Via Vanvitelli, 20129 Milano, Italy
- Published
- 1994
139. Autoradiographic localization of putative melatonin receptors in the brain of two old world primates: Cercopithecus aethiops and Papio ursinus
- Author
-
B. Gridelli, Gabriele Biella, Franco Fraschini, Stefano Gatti, Simona Capsoni, Valeria Lucini, J. Fauteck, Bojidar Stankov, Bruno Cozzi, Stankov, B, Capsoni, Simona, Lucini, V, Fauteck, J, Gatti, S, Gridelli, B, Biella, G, Cozzi, B, and Fraschini, F.
- Subjects
Male ,Pituitary gland ,medicine.medical_specialty ,Receptors, Melatonin ,Hippocampus ,Socio-culturale ,Biology ,Binding, Competitive ,Melatonin ,Internal medicine ,Cortex (anatomy) ,Chlorocebus aethiops ,medicine ,Animals ,Neurotransmitter metabolism ,Brain Chemistry ,General Neuroscience ,Brain ,Ligand (biochemistry) ,Receptors, Neurotransmitter ,medicine.anatomical_structure ,Endocrinology ,Guanosine 5'-O-(3-Thiotriphosphate) ,Pituitary Gland ,Median eminence ,Autoradiography ,Female ,Pars tuberalis ,Papio ,medicine.drug - Abstract
The distribution of putative melatonin receptors in the brains of two Old World primates of the superfamily Catarrhina, Cercopithecus aethiops and Papio ursinus, was characterized using 2-[125I]iodomelatonin autoradiography. The specific binding demonstrated a discrete distribution pattern. The median eminence was intensely labelled, and examination at the light microscopic level demonstrated that the binding was confined to the small layer of cells comprising the pars tuberalis of the pituitary gland. The collar of pars distalis, present in the baboon (Papio ursinus), was diffusely labelled. No binding was detected in the pars distalis proper or the neural lobe of the pituitary gland. The binding in the suprachiasmatic nuclei was weaker, but well discernible. Diffuse faint specific binding was found in the frontal cortex and the dentate gyrus of the hippocampus. Two non-neural sites expressed strong, well-delineated binding: the walls of some brain blood vessels (the vertebral and spinal arteries, the inferior cerebellar and acoustic arteries, the basilar, pericallosal, internal carotid arteries, the arteries forming the circle of Willis) and the choroid plexuses. Binding in the arteries of the circle of Willis, the pars tuberalis and the suprachiasmatic nuclei was readily displaceable. Addition of 1 microM unlabelled 2-iodomelatonin following 45 min of preincubation with the radioactive ligand completely abrogated the binding. Co-incubation with guanosine 5'-O-(3-thiotriphosphate) led to a significant decrease in the apparent binding density in the pars tuberalis and abolished binding in the suprachiasmatic nuclei, but was without effect on the binding in the walls of the adjacent arteries, forming the circle of Willis, in the cortex and in the hippocampus. This qualitative distribution pattern demonstrates that in the two primate species studied, melatonin high-affinity, G-protein-linked binding sites are present in the pars tuberalis and the hypothalamic suprachiasmatic nuclei, and that melatonin may be acting as a synchronizer of the endogenous pacemakers' circadian activity, apart from its possible reproductive effects at the level of pars tuberalis, where the highest receptor density was observed. The strongly labelled arterial walls, and the flimsy labelled cortex and hippocampus, expressed different characteristics: though the binding was readily reversible, it was apparently not regulated by a guanine nucleotide-binding protein.
- Published
- 1993
140. Localization and characterization of melatonin binding sites in the brain of the rabbit (Oryctolagus cuniculus) by autoradiography and in vitro ligand-receptor binding
- Author
-
Bruno Cozzi, Pietro Fumagalli, Franco Fraschini, Jan Fauteck, Bojidar Stankov, Simona Capsoni, Valeria Lucini, Stankov, B, Cozzi, B, Lucini, V, Capsoni, Simona, Fauteck, J, Fumagalli, P, and Fraschini, F.
- Subjects
Male ,medicine.medical_specialty ,Pituitary gland ,Characterization ,Hypothalamus ,Receptors, Melatonin ,Socio-culturale ,Rabbit ,In Vitro Techniques ,Biology ,Distribution ,Ligands ,Melatonin receptor ,Iodine Radioisotopes ,Melatonin ,Binding site ,GTP-Binding Proteins ,Internal medicine ,medicine ,Animals ,Brain Chemistry ,General Neuroscience ,Brain ,Ligand (biochemistry) ,Molecular biology ,Receptors, Neurotransmitter ,Olfactory bulb ,Endocrinology ,medicine.anatomical_structure ,Guanosine 5'-O-(3-Thiotriphosphate) ,Melatonin binding ,Autoradiography ,Rabbits ,Pars tuberalis ,medicine.drug - Abstract
The distribution and the properties of the melatonin binding sites were characterized in the brain of the rabbit by combined use of autoradiography and in vitro ligand-receptor binding. Autoradiography revealed widespread specific binding in the brain. The pars tuberalis of the pituitary gland, suprachiasmatic nuclei, ventromedial hypothalamic nuclei, tapetum, hippocampus, indusium griseum, cingulate gyrus, cortex and the choroid plexus were intensely labelled. Diffuse specific binding was recorded in the olfactory bulb and the anterior hypothalamus. Series of in vitro ligand-receptor binding experiments, using the anterior hypothalamus, confirmed that the binding was of high affinity and specificity. Coincubation with a non-hydrolyzable GTP analogue provoked a shift in the binding affinity, the numerical values of the K d increasing from 20–30 pM to 280–300 pM. Apparently the melatonin receptor in the rabbit brain is linked to its second messenger via a G protein, similarly to what has been described for the brain of other vertebrates.
- Published
- 1991
141. Melatonin signal transduction and mechanism of action in the central nervous system: Using the rabbit cortex as a model
- Author
-
Bojidar Stankov, Bruno Cozzi, Valeria Lucini, J. Fauteck, C. Panara, Simona Capsoni, Gabriele Biella, Franco Fraschini, Stankov, B, Biella, G, Panara, C, Lucini, V, Capsoni, Simona, Fauteck, J, Cozzi, B, and Fraschini, F.
- Subjects
Male ,medicine.medical_specialty ,Receptors, Melatonin ,Socio-culturale ,Posterior parietal cortex ,Biology ,In Vitro Techniques ,Melatonin receptor ,gamma-Aminobutyric acid ,Melatonin ,Endocrinology ,Cortex (anatomy) ,Internal medicine ,Parietal Lobe ,medicine ,Cyclic AMP ,Premovement neuronal activity ,Animals ,Virulence Factors, Bordetella ,gamma-Aminobutyric Acid ,Binding Sites ,Receptors, GABA-A ,Receptors, Neurotransmitter ,medicine.anatomical_structure ,Pertussis Toxin ,Cerebral cortex ,Melatonin binding ,Rabbits ,medicine.drug ,Signal Transduction - Abstract
The cortex of the rabbit (Oryctolagus cuniculus) is rich in melatonin binding sites, and particularly abundant is the parietal cortex. Consequently, we characterized the putative melatonin receptor in the parietal cortex by a series of in vitro ligand-receptor binding experiments and biochemical and electrophysiological studies. The in vitro saturation and competition experiments demonstrated that the binding in the crude cortical membrane preparations was of high affinity and specificity. Guanine nucleotides (GDP, GTP, and GTP gamma S) inhibited the specific 2-[125I]iodomelatonin binding in a dose-dependent manner. Coincubation with a nonhydrolyzable GTP analog provoked a shift in the binding affinity; the numerical values of the Kd increased from 20-30 to 200-600 pM. Melatonin, in nanomolar concentrations, was able to inhibit the forskolin-stimulated accumulation of cAMP in parietal cortex explants, and preincubation with pertussis toxin counteracted this effect of melatonin. Apparently, the melatonin binding site in the rabbit parietal cortex is linked to its second messenger via a pertussis toxin-sensitive G-protein, probably of the inhibitory Gi class, similar to what has been described for different parts of the brain of other vertebrates. The experiments on the spontaneous firing activity of single neurons in the third to fourth layer of the parietal cortex in anesthetized animals showed that melatonin and its potent agonist 2-iodomelatonin exhibited gamma-aminobutyric acid (GABA)-like effects and were able alone, in nanomolar concentrations, to significantly slow the neuronal firing activity. Moreover, both melatonin and 2-iodomelatonin potentiated the effect of GABA on the neuronal activity, leading to powerful inhibition of the tested neurons. Undoubtedly, the binding site in the rabbit parietal cortex possesses all of the characteristics of a functional receptor. We suggest that melatonin is involved in the control of fundamental cortical functions and that it acts in concert with GABA, one of the two major inhibitory neurotransmitters in the central nervous system.
142. Fetal aortic valvuloplasty as the first step in a complex therapeutic strategy.
- Author
-
Grinenco S, Aiello HA, Meller CH, Lucini V, Nápoli N, Trentacoste L, Córdoba A, Saenz Tejeira M, Osuna JM, Barretta J, Villa AB, Marantz P, and Otaño L
- Subjects
- Humans, Female, Pregnancy, Hypoplastic Left Heart Syndrome therapy, Hypoplastic Left Heart Syndrome surgery, Balloon Valvuloplasty methods, Ultrasonography, Prenatal, Infant, Newborn, Retrospective Studies, Fetal Diseases therapy, Adult, Fetal Therapies methods, Aortic Valve Stenosis surgery, Aortic Valve Stenosis therapy
- Abstract
Background: Fetal aortic valvuloplasty (FAV) is proposed to prevent hypoplastic left heart syndrome due to fetal critical aortic stenosis., Objective: to report our experience on FAV as the first step in a complex therapeutic strategy., Method: Series of patients with FAV over an 18-year period., Results: 27 FAVs were performed in 26 fetuses, with technical success in 82% (22/27) and periprocedural fetal demise in 22% (6/27), decreasing to 15% in the second half-cohort. Loss to follow-up was due to birth or postnatal therapy in other centers (5) and termination of pregnancy (1), A normal-sized LV at birth was observed in 46% (6/13), 4 neonates underwent aortic valvuloplasty and 2 cardiac surgeries, with 5/6 achieving biventricular circulation at 28 days, and 3 transplant-free survival at mid-term follow-up. The 7/13 born with a borderline LV underwent LV rehabilitation strategy, with survival at 28 days in 4/7 and at mid-term in 3: one with biventricular circulation, one with a ventricle-and-a-half repair, and one lost to follow-up., Conclusion: FAV was feasible in most cases, with no maternal complications, and biventricular circulation at 28 days in ∼40% of survivors. After FAV, a diverse range of postnatal cardiac interventions are performed, reflecting the challenging innovation in current cardiovascular therapy., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
143. Local Diagnostic Reference Levels for Pediatric Interventional Cardiology Procedures in Argentina.
- Author
-
Azcurra P, Leyton F, Lucini V, Rivarola M, Trentacoste L, Marques A, Chiabrando J, Seropian I, Mundo N, Ubeda C, and Agatiello C
- Abstract
The aim of this work was to propose a preliminary local diagnostic reference levels (DRL) for pediatric interventional cardiology (PIC) procedures in Argentina, for different ranges of age and weight. This work has been conducted in the framework of the "Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean" (OPRIPALC) program coordinated by the World Health Organization and the Pan American Health Organization in cooperation with the International Atomic Energy Agency to ensuring that radiation exposures of pediatric patients are the minimum necessary during fluoroscopy-guided interventional procedures. The local DRL values presented in this paper by weight group and age group were 7.1 Gy·cm
2 (<5 kg), 10.7 Gy·cm2 (5-15 kg), 18.0 Gy·cm2 (15-30 kg), 15.9 Gy·cm2 (30-50 kg), and 28.2 Gy·cm2 (50-80 kg) and 5.3 Gy·cm2 (<1), 11.2 Gy·cm2 (1 to 5<), 19.6 Gy·cm2 (5 to 10<), and 21.4 Gy·cm2 (10 to 16<), respectively. Our dose results are among the values found in other international studies; however, there is great potential for dose optimization.- Published
- 2023
- Full Text
- View/download PDF
144. 2-Arylmelatonin analogues: Probing the 2-phenyl binding pocket of melatonin MT 1 and MT 2 receptors.
- Author
-
Mari M, Elisi GM, Bedini A, Lucarini S, Retini M, Lucini V, Scaglione F, Vincenzi F, Varani K, Castelli R, Mor M, Rivara S, and Spadoni G
- Subjects
- Ligands, Molecular Dynamics Simulation, Melatonin analogs & derivatives, Melatonin chemistry, Melatonin metabolism, Receptor, Melatonin, MT1 chemistry, Receptor, Melatonin, MT1 metabolism, Receptor, Melatonin, MT2 chemistry, Receptor, Melatonin, MT2 metabolism
- Abstract
In crystal structures of melatonin MT
1 and MT2 receptors, a lipophilic subpocket has been characterized which accommodates the phenyl ring of the potent agonist 2-phenylmelatonin. This subpocket appears a key structural element to achieve high binding affinity and selectivity for the MT2 receptor. A series of 2-arylindole ligands was synthesized to probe the requirements for the optimal occupation and interaction with the 2-phenyl binding pocket. Thermodynamic integration simulations applied to MT1 and MT2 receptors in complex with the α-naphthyl derivative provided a rationale for the MT2 -selectivity and investigation on the binding mode of a couple of atropisomers allowed to define the available space and arrangement of substituents inside the subpocket. Interestingly, more hydrophilic 2-aza-substituted compounds displayed high binding affinity and molecular dynamics simulations highlighted polar interaction with residues from the subpocket that could be responsible for their potency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)- Published
- 2022
- Full Text
- View/download PDF
145. Effects of Levofloxacin, Aztreonam, and Colistin on Enzyme Synthesis by P. aeruginosa Isolated from Cystic Fibrosis Patients.
- Author
-
Pani A, Lucini V, Dugnani S, Schianchi A, and Scaglione F
- Abstract
(1) Background: Cystic fibrosis (CF) is characterized by chronic pulmonary inflammation and persistent bacterial infections. P. aeruginosa is among the main opportunistic pathogens causing infections in CF. P. aeruginosa is able to form a biofilm, decreasing antibiotic permeability. LOX, a lipoxygenase enzyme, is a virulence factor produced by P. aeruginosa and promotes its persistence in lung tissues. The aim of this study is to evaluate if antibiotics currently used for aerosol therapy in CF are able to interfere with the production of lipoxygenase from open isolates of P. Aeruginosa from patients with CF. (2) Methods: Clinical isolates of P. aeruginosa from patients with CF were grown in Luria broth (LB). Minimum inhibitory concentration (MIC) was performed and interpreted for all isolated strains according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. We selected four antibiotics with different mechanisms of action: aztreonam, colistin, amikacin, and levofloxacin. We used human pulmonary epithelial NCI-H929 cells to evaluate LOX activity and its metabolites according to antibiotic action at increasing concentrations. (3) Results: there is a correlation between LOX secretion by clinical isolates of P. aeruginosa and biofilm production. Levofloxacin exhibits highly significant inhibitory activity compared to the control. Amikacin also exhibits significant inhibitory activity against LOX production. Aztreonam and colistin do not show inhibitory activity. These results are also confirmed for LOX metabolites. (4) Conclusions: among the evaluated antibiotics, levofloxacin and amikacin have an activity on LOX secretion.
- Published
- 2022
- Full Text
- View/download PDF
146. Erdosteine enhances antibiotic activity against bacteria within biofilm.
- Author
-
Pani A, Lucini V, Dugnani S, and Scaglione F
- Subjects
- Anti-Bacterial Agents pharmacology, Biofilms, Extracellular Polymeric Substance Matrix, Microbial Sensitivity Tests, Thioglycolates, Thiophenes, Methicillin-Resistant Staphylococcus aureus
- Abstract
Bacterial biofilms form on inert and living surfaces and display high levels of resistance to antibiotics, making it difficult to eradicate biofilm-related infections. Erdosteine, a thiol-based drug used in the treatment of acute and chronic respiratory diseases, has multiple pharmacodynamic properties (mucolytic, anti-inflammatory, antioxidant), suggesting that it may have potential in controlling biofilm-related infections. This in vitro study aimed to evaluate the effects of erdosteine in combination with different antibiotics against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) biofilms. Biofilm production/mass and bacterial viability were measured using crystal violet absorbance and resorufin resonance, respectively, in young (6 h) and mature (24 h) biofilms incubated with antibiotics [at concentrations from 0 to 200 times the minimum inhibitory concentration (MIC)] for 24 h in the absence or presence of erdosteine (2, 5 and 10 mg/L). In 6-h MRSA biofilms, vancomycin and linezolid displayed concentration-dependent reductions in biofilm mass and viability, which was enhanced in the presence of increasing concentrations of erdosteine. Similar results were seen for amoxicillin/clavulanate and levofloxacin against 6-h MSSA biofilms. Antibiotics alone had reduced efficacy against 24-h biofilms, while the effect of the erdosteine-antibiotic combination was significantly greater against 24-h biofilms (MRSA and MSSA). These results suggest that erdosteine enhances the activity of the antibiotic by facilitating its penetration into biofilms and by disrupting the extracellular polymeric substance matrix, which should be confirmed with further studies. The potential clinical value of erdosteine in treating biofilm-related infections warrants further investigation., Competing Interests: Competing interests FS has received speaking fees from GSK, Pfizer and MSD in the past 3 years. All other authors declare no competing interests., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
147. A Hybrid Strategy for Geometrical Reshaping of the Main Pulmonary Artery and Transcatheter Pulmonary Valve Replacement.
- Author
-
Lugones I, Barbosa JD, Schvartz G, Ackerman J, Laudani V, Vitorino AM, Lucini V, and Garay F
- Subjects
- Cardiac Catheterization, Humans, Pulmonary Artery diagnostic imaging, Pulmonary Artery surgery, Treatment Outcome, Heart Valve Prosthesis, Heart Valve Prosthesis Implantation, Pulmonary Valve diagnostic imaging, Pulmonary Valve surgery, Pulmonary Valve Insufficiency diagnostic imaging, Pulmonary Valve Insufficiency surgery
- Abstract
Transcatheter pulmonary valve replacement has become an attractive alternative to surgical approach in patients with dysfunctional right ventricular outflow tract. However, in certain cases, an unfavorable anatomy might complicate optimal valve deployment and stability. Several techniques have been described to reshape the landing zone and allow proper implantation of the transcatheter valve. Among them, the hybrid approach has gained attention as an interesting method for off-pump pulmonary valve replacement in patients with dilated right ventricular outflow tract. But to date, there is no standardized method to resize and reshape the landing zone for the stented valve. Here, we describe a reproducible method based on simple geometric rules to allow adequate remodeling of the main pulmonary artery to the desired dimensions in a single attempt, followed by perventricular implantation of a Venus P-valve.
- Published
- 2021
- Full Text
- View/download PDF
148. Chiral Recognition of Flexible Melatonin Receptor Ligands Induced by Conformational Equilibria.
- Author
-
Elisi GM, Bedini A, Scalvini L, Carmi C, Bartolucci S, Lucini V, Scaglione F, Mor M, Rivara S, and Spadoni G
- Subjects
- Acetamides chemistry, Crystallography, X-Ray, Humans, Ligands, Magnetic Resonance Spectroscopy, Molecular Docking Simulation, Stereoisomerism, Thermodynamics, Molecular Conformation, Receptor, Melatonin, MT1 chemistry, Receptor, Melatonin, MT2 chemistry
- Abstract
N -anilinoethylamides are a class of melatoninergic agents with the aniline portion mimicking the indole ring of the natural ligand and the ethylamide chain reproducing that of melatonin. The simplest compound in this class, N -{2-[(3-methoxyphenyl)methylamino]ethyl}acetamide (UCM793), has nanomolar binding affinity for MT
1 and MT2 membrane receptors. To explore the effect of chain conformation on receptor binding, a methyl group was inserted on the methylene alpha or beta to the amide nitrogen and conformational equilibria were investigated by NMR spectroscopy and molecular dynamics simulations. Receptor affinity was conserved only for the beta-methyl derivative, which also showed significant stereoselectivity, with the ( S ) enantiomer being the eutomer. Molecular dynamics simulations, validated by NMR spectroscopy, showed that the beta-methyl group affects the conformational preferences of the ethylamide chain. Docking into the receptor crystal structure provides a rationale for the observed chiral recognition, suggesting that the ( S )-beta-methyl group favors the conformation that better fits the receptor binding site.- Published
- 2020
- Full Text
- View/download PDF
149. Identification of Bivalent Ligands with Melatonin Receptor Agonist and Fatty Acid Amide Hydrolase (FAAH) Inhibitory Activity That Exhibit Ocular Hypotensive Effect in the Rabbit.
- Author
-
Spadoni G, Bedini A, Furiassi L, Mari M, Mor M, Scalvini L, Lodola A, Ghidini A, Lucini V, Dugnani S, Scaglione F, Piomelli D, Jung KM, Supuran CT, Lucarini L, Durante M, Sgambellone S, Masini E, and Rivara S
- Subjects
- Amidohydrolases metabolism, Animals, Ligands, Male, Molecular Structure, Ocular Hypotension metabolism, Ocular Hypotension pathology, Protein Conformation, Rabbits, Rats, Rats, Wistar, Structure-Activity Relationship, Amidohydrolases antagonists & inhibitors, Antihypertensive Agents chemistry, Antihypertensive Agents pharmacology, Intraocular Pressure drug effects, Ocular Hypotension drug therapy, Receptors, Melatonin agonists
- Abstract
Activation of melatonin receptors and inhibition of fatty acid amide hydrolase (FAAH) have both shown potential benefits for the treatment of glaucoma. To exploit the combination of these biological activities in single therapeutic agents, we designed dual-acting compounds sharing the pharmacophore elements required for the two targets, in search for balanced potencies as MT
1 /MT2 agonists and FAAH inhibitors. In particular, the N-anilinoethylamide scaffold, previously developed for melatonergic ligands, was decorated at meta position with a polymethylene linker bound to an O-arylcarbamate group, substituted according to known structure-activity relationships for FAAH inhibition. For the most active series, the N-anilinoethylamide portion was also replaced with the indole scaffold of melatonin. O-Biphenyl-3-ylcarbamate derivatives were characterized by remarkable and balanced activity at both targets, in the nanomolar range for compound 29. Topical administration reduced elevated intraocular pressure in rabbits, with a longer action and improved efficacy compared to the reference compounds melatonin and URB597.- Published
- 2018
- Full Text
- View/download PDF
150. Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells.
- Author
-
Calastretti A, Gatti G, Lucini V, Dugnani S, Canti G, Scaglione F, and Bevilacqua A
- Subjects
- Antineoplastic Agents chemistry, Cell Line, Tumor, Humans, Male, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Receptors, Androgen genetics, Receptors, Androgen metabolism, Antineoplastic Agents toxicity, Cell Death drug effects, Cell Proliferation drug effects, Melatonin analogs & derivatives, Prostatic Neoplasms metabolism
- Abstract
Melatonin has been indicated as a possible oncostatic agent in different types of cancer, its antiproliferative role being demonstrated in several in vitro and in vivo experimental models of tumors. Specifically, melatonin was proven to inhibit cell growth of both androgen-dependent and independent prostate cancer cells, through various mechanisms. A number of melatonin derivatives have been developed and tested for their role in the prevention and treatment of neoplastic diseases. We recently proved the in vitro and in vivo anticancer activity of UCM 1037, a newly-synthetized melatonin analogue, on melanoma and breast cancer cells. In this study we evaluated UCM 1037 effects on cell proliferation, cell cycle distribution, and cytotoxicity in LNCaP, PC3, DU145, and 22Rv1 prostate cancer cells. We demonstrated significant dose- and time-dependent UCM 1037 antiproliferative effects in androgen-sensitive LNCaP and 22Rv1 cells. Data from flow cytometric studies suggest that UCM 1037 is highly cytotoxic in androgen-sensitive prostate cancer cells, although no substantial increase in the apoptotic cell fraction has been observed. UCM 1037 cytotoxic effects were much less evident in androgen-insensitive PC3 and DU145 cells. Experiments performed to gain insights into the possible mechanism of action of the melatonin derivative revealed that UCM 1037 down-regulates androgen receptor levels and Akt activation in LNCaP and 22Rv1 cells.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.