Search

Your search keyword '"drug effects/enzymology/genetics"' showing total 3 results
Start Over Descriptor "drug effects/enzymology/genetics"
3 results on '"drug effects/enzymology/genetics"'

1. The γ-Secretase Modulator CHF5074 Restores Memory and Hippocampal Synaptic Plasticity in Plaque-Free Tg2576 Mice

Author

Marina Pizzi, Claudia Balducci, Luciana Giardino, Alessandro Usiello, Arturo R. Viscomi, Gino Villetti, Giuseppe Nisticò, Bruno P. Imbimbo, Annamaria Lanzillotta, Gianluigi Forloni, Luca Lorenzini, Alessandro Giuliani, Ilenia Sarnico, Lydia Mare, Simone Ottonello, Sandra Sivilia, Laura Calzà, Bisan Mehdawy, Robert Nisticò, Balducci, C, Mehdawy, B, Mare, L, Giuliani, A, Lorenzini, L, Sivilia, S, Giardino, L, Calzà, L, Lanzillotta, A, Sarnico, I, Pizzi, M, Usiello, Alessandro, Viscomi, Ar, Ottonello, S, Villetti, G, Imbimbo, Bp, Nisticò, G, Forloni, G, Nisticò, R., C. Balducci, B. Mehdawy, L. Mare, A. Giuliani, L. Lorenzini, S. Sivilia, L. Giardino, L. Calzà, A. Lanzillotta, I. Sarnico, M. Pizzi, A. Usiello, A.R. Viscomi, S. Ottonello, G. Villetti, B.P. Imbimbo, G. Nisticò, and G. Forloni and R. Nisticò

Subjects
Cyclopropanes, Hippocampus, Plaque, Amyloid, drug effects/genetics/physiology, drug effects/enzymology/physiology, Pharmacology, Inbred C57BL, Transgenic, Mice, Cricetinae, Medicine, Fear conditioning, Amyloid Precursor Protein Secretases, Animals, Female, Flurbiprofen, Humans, Memory, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Synapses, Plaque, chemistry.chemical_classification, General Neuroscience, Settore BIO/14, Long-term potentiation, General Medicine, Alzheimer's disease, Psychiatry and Mental health, Clinical Psychology, antagonists /&/ inhibitors/genetics/metabolism/physiology, Animals, Cricetinae, Cyclopropanes, pharmacology/therapeutic use, Female, Flurbiprofen, analogs /&/ derivatives/pharmacology/therapeutic use, Hippocampus, drug effects/enzymology/physiology, Humans, Memory Disorders, drug therapy/enzymology/genetics, Memory, drug effects/physiology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, drug effects/genetics/physiology, Plaque, Amyloid, Synapses, drug effects/enzymology/genetics, LTP, analogs /&/ derivatives/pharmacology/therapeutic use, Genetically modified mouse, Amyloid, Transgene, drug therapy/enzymology/genetics, amyloid-β, pharmacology/therapeutic use, gamma secretase modulator, Recognition memory, business.industry, antagonists /&/ inhibitors/genetics/metabolism/physiology, fear conditioning, drug effects/physiology, Enzyme, chemistry, Geriatrics and Gerontology, business
Abstract

Abnormal amyloid-β (Aβ) production and deposition is believed to represent one of the main causes of Alzheimer's disease (AD). γ-Secretase is the enzymatic complex responsible for Aβ generation from its precursor protein. Inhibition or modulation of γ-secretase represents an attractive therapeutic approach. CHF5074 is a new γ-secretase modulator that has been shown to inhibit brain plaque deposition and to attenuate memory deficit in adult AD transgenic mice after chronic treatment. To date, it is not known whether the positive behavioral effects of this compound also occur in young transgenic mice without plaque deposition. Here, we evaluated the effects of acute and subchronic treatment with CHF5074 on contextual and recognition memory and on hippocampal synaptic plasticity in plaque-free Tg2576 mice. We found that at 5 months of age, contextual memory impairment was significantly attenuated after acute subcutaneous administration of 30 mg/kg CHF5074. At 6 months of age, recognition memory impairment was fully reversed after a 4-week oral treatment in the diet (≈60 mg/kg/day). These cognitive effects were associated with a reversal of long-term potentiation (LTP) impairment in the hippocampus. A significant reduction in brain intraneuronal AβPP/Aβ levels and hyperphosphorylated tau, but no change in soluble or oligomeric Aβ levels was detected in Tg2576 mice showing functional recovery following CHF5074 treatment. We conclude that the beneficial effects of CHF5074 treatment in young transgenic mice occurred at a stage that precedes plaque formation and were associated with a reduction in intraneuronal AβPP/Aβ and hyperphosphorylated tau.

Published
2011
Full Text
View/download PDF

2. No pol mutation is associated independently with the lack of immune recovery in patients infected with HIV and failing antiretroviral therapy

Author

Gianotti, N1, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Collaborators Giacometti A, ARCA database i. n. i. t. i. a. t. i. v. e., Butini, L, del Gobbo, R, Tacconi, D, Corbelli, G, Zanussi, S, Monno, L, Punzi, G, Maggiolo, F, Callegaro, A, Calza, L, Re, Mc, Pristerà, R, Turconi, P, Mandas, A, Tini, S, Carnevale, G, Paolini, E, Amadio, G, Sighinolfi, L, Zuccati, G, Morfini, M, Manetti, R, Di Pietro, M, Bartalesi, F, Colao, G, Tosti, A, Di Biagio, A, Setti, M, Trezzi, M, Orani, A, Pardelli, R, De Gennaro, M, Chiodera, A, Scalzini, A, Palvarini, L, Almi, P, Todaro, G, Gianotti, N, Cicconi, P, Rusconi, S, Gismondo, Mr, Biondi, Ml, Capetti, A, Boeri, E, Pecorari, M, Mussini, C, Santirocchi, M, Brustia, D, Ravanini, P, Dal Bello, F, Romano, N, Mancuso, S, Calzetti, C, Maserati, R, Baldanti, F, Francisci, D, Parruti, G, Polilli, E, Sacchini, D, Martinelli, C, Consolini, R, Vatteroni, L, Vivarelli, A, Nerli, A, Lenzi, L, Magnani, G, Ortolani, P, Andreoni, M, Palamara, G, Fimiani, C, Palmisano, L, Antinori, A, Vullo, Vincenzo, Turriziani, O, Perno, Cf, Montano, M, Cenderello, G, Gonnelli, A, Romano, L, Palumbo, M, Delle Foglie, P, Rossi, C, Poletti, F, Mondino, V, Malena, M, Lattuada, E., Gianotti, N, Galli, L, Zazzi, M, Ghisetti, V, Bonora, S, Micheli, V, Meraviglia, P, Corsi, P, Bruzzone, B, Menzo, S, Di Giambenedetto, S, De Luca, A, Filice, G, Penco, G, Castagna, A, Mancuso, S, Gianotti N, Galli L, Zazzi M, Ghisetti V, Bonora S, Micheli V, Meraviglia P, Corsi P, Bruzzone B, Menzo S, Di Giambenedetto S, De Luca A, Filice G, Penco G, Castagna A, Giacometti A, Butini L, del Gobbo R, Tacconi D, Corbelli G, Zanussi S, Monno L, Punzi G, Maggiolo F, Callegaro A, Calza L, Re MC, Pristerà R, Turconi P, Mandas A, Tini S, Carnevale G, Paolini E, Amadio G, Sighinolfi L, Zuccati G, Morfini M, Manetti R, Di Pietro M, Bartalesi F, Colao G, Tosti A, Di Biagio A, Setti M, Trezzi M, Orani A, Pardelli R, De Gennaro M, Chiodera A, Scalzini A, Palvarini L, Almi P, Todaro G, Cicconi P, Rusconi S, Gismondo MR, Biondi ML, Capetti A, Boeri E, Pecorari M, Mussini C, Santirocchi M, Brustia D, Ravanini P, Dal Bello F, Romano N, Mancuso S, Calzetti C, Maserati R, Baldanti F, Francisci D, Parruti G, Polilli E, Sacchini D, Martinelli C, Consolini R, Vatteroni L, Vivarelli A, Nerli A, Lenzi L, Magnani G, Ortolani P, Andreoni M, Palamara G, Fimiani C, Palmisano L, Antinori A, Vullo V, Turriziani O, Perno CF, Montano M, Cenderello G, Gonnelli A, Romano L, Palumbo M, Delle Foglie P, Rossi C, Poletti F, Mondino V, Malena M, Lattuada E., Gianotti, Nicola, Galli, Laura, Zazzi, Maurizio, Ghisetti, Valeria, Bonora, Stefano, Micheli, Valeria, Meraviglia, Paola, Corsi, Paola, Bruzzone, Bianca, Menzo, Stefano, Di Giambenedetto, Simona, De Luca, Andrea, Filice, Gaetano, Penco, Giovanni, and Castagna, Antonella

Subjects
Male, HIV Infections, Drug resistance, Logistic regression, Resistance to nucleoside reverse transcriptase inhibitor, CD4+ T-lymphocyte, Retrospective Studie, Immunopathology, Antiretroviral Therapy, Highly Active, Resistance to non-nucleoside reverse transcriptase inhibitor, genetics, Resistance to protease inhibitor, HIV Infection, resistance to nucleoside reverse transcriptase inhibitors, Viral, Sida, resistance to protease inhibitors, biology, Reverse-transcriptase inhibitor, Viral Load, Genes, pol, drug therapy/immunology/virology, Reverse Transcriptase Inhibitor, Infectious Diseases, Treatment Outcome, resistance to non-nucleoside reverse transcriptase inhibitors, Reverse Transcriptase Inhibitors, Female, Viral load, medicine.drug, Human, pol, Anti-HIV Agents, Antiretroviral Therapy, Viremia, Infectious Disease, Settore MED/17 - MALATTIE INFETTIVE, pharmacology/therapeutic use, Acquired immunodeficiency syndrome (AIDS), Virology, Drug Resistance, Viral, medicine, Humans, Highly Active, Retrospective Studies, pharmacology/therapeutic use, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, genetics, Female, Genes, pol, HIV Infections, drug therapy/immunology/virology, HIV-1, drug effects/enzymology/genetics, Humans, Male, Mutation, Retrospective Studies, Reverse Transcriptase Inhibitors, therapeutic use, Treatment Outcome, Viral Load, drug resistance, Anti-HIV Agent, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Genes, drug effects/enzymology/genetics, therapeutic use, Mutation, CD4+ T-lymphocytes, HIV-1
Abstract

An investigation was undertaken to determine whether specific pol mutations hinder long-term immune recovery regardless of virological response. In total, 826 patients with >50 HIV RNA copies/ml, who underwent genotypic resistance testing between 1 January 2000 and 31 December 2003 after >3 years of antiretroviral treatment, and were followed up for >3 years after genotypic resistance testing, were analyzed retrospectively. The outcome of the study was the lack of immune recovery after >3 years of follow-up, defined as a slope by linear regression 50 copies/ml divided by the number of HIV RNA measurements during follow-up. Logistic regression was used for univariable and multivariable analysis. Median (Q1, Q3) values at baseline were the following: age 40 (37, 45) years, years on antiretroviral therapy 4.45 (3.65, 5.47), HIV RNA 3.91 (3.39, 4.53) log 10 copies/ml, CD4+ T-cell 358 (211, 524)/μl. After 3.13 years of follow-up, 375 patients (45.4%) showed a lack of immune recovery. The risk of lack of immune recovery increased independently with increasing baseline CD4+ counts (OR=1.104 per 50-cell increase, 95% CI=1.069-1.142, P

Published
2011

3. Bacterial mutagenicity of cigarette smoke and its interaction with ethanol

Author

Anna Camoirano, R Balansky, L Gasparini, and S. De Flora

Subjects
Male, Salmonella typhimurium, Health, Toxicology and Mutagenesis, Polycyclic aromatic hydrocarbon, Toxicology, medicine.disease_cause, Ames test, chemistry.chemical_compound, Nitroreductase, Smoke, Prodrugs, Food science, Genetics (clinical), Biotransformation, chemistry.chemical_classification, biology, Smoking, Drug Synergism, Plants, Middle Aged, Enterobacteriaceae, urine, Pyrene, Female, Bacterial Proteins, Species Specificity, Acetyltransferases, Tobacco, Genetics, medicine, Escherichia coli, Humans, Ethanol, Mutagenicity Tests, toxicity, Nitroreductases, biology.organism_classification, Toxic, metabolism, Bacterial Proteins, metabolism, Biotransformation, Drug Synergism, Escherichia coli, drug effects/enzymology/genetics, Ethanol, toxicity, Female, Humans, Male, Middle Aged, Mutagenicity Tests, Mutagens, isolation /&/ purification/toxicity, Nitroreductases, metabolism, Plants, Toxic, Prodrugs, isolation /&/ purification/toxicity, Salmonella typhimurium, drug effects/enzymology/genetics, Smoke, adverse effects/analysis, Smoking, urine, Species Specificity, Tobacco, Plants, Toxic, chemistry, drug effects/enzymology/genetics, Nitrosamine, isolation /&/ purification/toxicity, adverse effects/analysis, metabolism, Mutagens
Abstract

The mutagenicities of mainstream cigarette smoke (CS), a cigarette smoke condensate (CSC) and smokers' urines were investigated by using batteries of Salmonella typhimurium and Escherichia coli strains. The S9-mediated mutagenicity of CSC was remarkably enhanced when using nitroreductase- and especially O-acetyltransferase-overproducing derivatives of the classical strains TA98 and TA100, with the following rank of sensitivity: YG1024 > YG1029 > YG1021 > TA98NR > YG1026 > TA98 > TA100 > TA100-DNP6 > TA100NR > TA98-1,8-DNP6. With YG1024, a doubling of spontaneous revertants was observed with as little as 1/110 of the smoke condensate recovered from one cigarette under our experimental conditions. Similarly, the S9-mediated mutagenicity of mainstream CS was considerably increased in YG1024 and YG1029, the O-acetyltransferase-overproducing derivatives of TA98 and TA100, respectively. In the absence of S9 mix, the concentrates of 23 urine specimens from five smokers failed to revert S. typhimurium TA98 and YG1024, and were equitoxic in E. coli WP2 and its repair-deficient counterpart CM871 (uvrA-, recA-, lexA-). In the presence of S9 mix, all specimens were mutagenic, with an average YG1024:TA98 ratio of 6.6:1. These patterns suggest that the bacterial mutagenicity of smoke-associated complex mixtures is mainly due to aromatic amines. The mutagenicities of other typical constituents of CS, i.e. the polycyclic aromatic hydrocarbon benzo[a]pyrene (BP) and the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), were not appreciably enhanced in the O-acetyltransferase-overproducing strain YG1029, compared to its parental strain TA100. Moreover, BP and NNK induced less than additive mutagenic responses when combined at high doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1995

Catalog

Books, media, physical & digital resources
See catalog results