65 results on '"A. M. Gasco"'
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2. N-substituted analogues of S-nitroso-<scp> N </scp> -acetyl-<scp>D</scp> ,<scp>L</scp> -penicillamine: chemical stability and prolonged nitric oxide mediated vasodilatation in isolated rat femoral arteries
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Anthony R. Butler, A. M. Gasco, David J. Webb, Francesca A Mazzei, Roberta Fruttero, Giulia Caron, Iain R. Greig, Robert A. Field, Ian L. Megson, and S Morton
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Male ,Endothelium ,Stereochemistry ,Vasodilation ,In Vitro Techniques ,Pharmacology ,Nitric Oxide ,Nitric oxide ,Neocuproine ,chemistry.chemical_compound ,medicine ,Animals ,Nitric Oxide Donors ,Rats, Wistar ,Penicillamine ,Snap ,Water ,Biological activity ,1-Octanol ,Hydrogen-Ion Concentration ,Rats ,Femoral Artery ,medicine.anatomical_structure ,Solubility ,chemistry ,Papers ,Endothelium, Vascular ,medicine.drug ,Blood vessel - Abstract
Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl-D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator effects in endothelium-denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might influence chemical stability and duration of vascular action of S-nitrosothiols. Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was confirmed by electrochemical detection at 37 degrees C. Bolus injections of SNAP (10 microl; 10(-8)-10(-3) M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400-500 g), caused concentration-dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium-intact vessels but failed to recover to pre-injection pressures at moderate and high concentrations (10(-6)-10(-3) M) in those denuded of endothelium. This sustained effect (> 1 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium-denuded vessels; subsequent slow decomposition within the tissue generates sufficient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage.
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- 1999
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3. [Untitled]
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Dario Ghigo, A. Di Stilo, Roberta Fruttero, Sonja Visentin, Claudio Medana, A. M. Gasco, and Amalia Bosia
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Pharmacology ,chemistry.chemical_classification ,Organic Chemistry ,Furoxan ,Pharmaceutical Science ,Biological activity ,Vasodilation ,Nitric oxide ,Cytosol ,chemistry.chemical_compound ,Enzyme ,chemistry ,Biochemistry ,Mechanism of action ,medicine ,Molecular Medicine ,Structure–activity relationship ,Pharmacology (medical) ,medicine.symptom ,Biotechnology - Abstract
Purpose. To investigate the effect of benzofusion on NO donor properties and related biological activities of the furoxan system. The biological properties considered were the ability to increase the cytosolic levels of cGMP in C6 cells and vasodilation.
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- 1999
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4. New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities
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Giuseppe Ermondi, Clara Cena, Di Stilo A, A. M. Gasco, Sonja Visentin, and Alberto Gasco
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Male ,Dihydropyridines ,Nifedipine ,Stereochemistry ,Vasodilator Agents ,Aorta, Thoracic ,In Vitro Techniques ,Furazan ,Binding, Competitive ,Chemical synthesis ,Muscle, Smooth, Vascular ,Nitrone ,Radioligand Assay ,Structure-Activity Relationship ,chemistry.chemical_compound ,Nitrendipine ,Quinoxalines ,Drug Discovery ,medicine ,Animals ,Structure–activity relationship ,Nitric Oxide Donors ,Enzyme Inhibitors ,Rats, Wistar ,Cerebral Cortex ,chemistry.chemical_classification ,Oxadiazoles ,Calcium channel ,Furoxan ,Calcium Channel Blockers ,Rats ,Methylene Blue ,chemistry ,Guanylate Cyclase ,Molecular Medicine ,Methylene blue ,Muscle Contraction ,medicine.drug - Abstract
A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Affinities to 1, 4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [3H]nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of EC50iGC/EC50 ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1, 4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.
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- 1998
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5. Glutathione potentiates cGNP synthesis induced by the two phenylfuroxancarbonitrile isomers in RFL-6 cells
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Clara Cena, Alberto Gasco, Amalia Bosia, Dario Ghigo, A. Di Stilo, and A. M. Gasco
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Chemistry ,Organic Chemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Glutathione ,Biochemistry ,Cellular mechanism ,chemistry.chemical_compound ,medicine.anatomical_structure ,Drug Discovery ,medicine ,Molecular Medicine ,Fibroblast ,Molecular Biology ,Intracellular ,Guanylate cyclase - Abstract
The cellular mechanism of bioactivation underlying guanylate cyclase activation by the pair of phenylfuroxancarbonitrile isomers 2a, b was investigated. In cultured rat lung fibroblast (RFL-6 cells) it was principally dependent on intracellular thiols.
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- 1996
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6. The Furoxan System as a Useful Tool for Balancing 'Hybrids' with Mixed .alpha.1-Antagonist and NO-like Vasodilator Activities
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A. M. Gasco, A. Di Stilo, Roberta Fruttero, and Donatella Boschi
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Male ,Magnetic Resonance Spectroscopy ,Nitrile ,Stereochemistry ,Vasodilator Agents ,Alpha (ethology) ,In Vitro Techniques ,Nitric Oxide ,Chemical synthesis ,Nitric oxide ,Norepinephrine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Prazosin ,medicine ,Animals ,Cysteine ,Adrenergic alpha-Antagonists ,Antihypertensive Agents ,Aorta ,Oxadiazoles ,Furoxan ,Antagonist ,Rats ,chemistry ,Oxyhemoglobins ,Molecular Medicine ,Piperidine ,Muscle Contraction ,medicine.drug - Abstract
The design of new vasodilator derivatives in which two different pharmacophoric groups are present in a single molecule has been pursued by substitution of NO-prodrug furoxan moieties for the furanylcarbonyl function in Prazosin, a well-known alpha 1-receptor antagonist. The aim was to obtain new antihypertensive agents in which two vasodilation mechanisms, alpha 1-antagonist and NO-mediated, can operate in an appropriate balance. The alpha 1-antagonist activity was assessed on rat aortic strips in the presence and in the absence of oxyhemoglobin (HbO2), a well-known scavenger of nitric oxide. The resulting hybrids displayed different pharmacological behaviors. When the 4-furoxanylcarbonyl system, bearing an ester or an amide function at the 3-position, was present (derivatives 7a,b), hybrids with predominant alpha 1-antagonist activity were obtained. By contrast, in the derivative 7c, in which the nitrile function is linked to the 3-position of the furoxan ring, the NO-mediated vasodilating properties are predominant. Finally, the (furoxanylsulfonyl)piperidine derivatives 13a,b showed NO vasodilation and alpha 1-antagonist activities in an appropriate balance. For the furoxan derivatives, the NO-dependent vasodilating ability, assessed on the K(+)-depolarized aortic strip, and the NO release features under the action of thiol cofactors are also discussed.
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- 1995
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7. Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia
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C, Gonzales, J, Leiva-Revilla, J, Rubio, M, Gasco, and G F, Gonzales
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Male ,Rats, Sprague-Dawley ,Zinc ,Plant Extracts ,Finasteride ,Prostate ,Prostatic Hyperplasia ,Animals ,Testosterone ,Organ Size ,Lepidium ,Rats - Abstract
Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca.
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- 2011
8. Evaluation of different doses of mashua (Tropaeolum tuberosum) on the reduction of sperm production, motility and morphology in adult male rats
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J, Leiva-Revilla, I, Cárdenas-Valencia, J, Rubio, F, Guerra-Castañón, P, Olcese-Mori, M, Gasco, and G F, Gonzales
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Male ,Rats, Sprague-Dawley ,Tropaeolum ,Dose-Response Relationship, Drug ,Sperm Count ,Plant Extracts ,Sperm Motility ,Animals ,Spermatozoa ,Rats - Abstract
Mashua is an edible-tuber crop that grows in the Andean region. Folk medicine describes the use of mashua to reduce reproductive function in men. The present study aimed: (i) to determine whether different doses of mashua (0.01, 0.1, 1 and 2 g kg(-1)) produced a dose-response reduction on sperm production and quality; and, (ii) to determine whether these anti-reproductive effects of mashua can be reversible after cessation of treatment (12 and 24 days of recovery time). Mashua-treated rats showed lower values of daily sperm production, epididymal and vas deferens sperm count and sperm motility; meanwhile, mashua increased the percentage of abnormal sperm morphology and epididymal sperm transit rate. The following variables follow a dose-response effect: sperm number in vas deferens, sperm motility and sperm transit rate. In addition, it was demonstrated that the reduction in reproduction function in male rats treated with mashua was reversible after 24 days of recovery time. Finally, lower doses mashua reduces sperm number and quality (motility and morphology), and these adverse effects on male reproductive system may be reversible after 24 days after cessation of the treatment.
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- 2011
9. Serum testosterone levels and score of chronic mountain sickness in Peruvian men natives at 4340 m
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G F, Gonzales, V, Tapia, M, Gasco, and C, Gonzales-Castañeda
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Adult ,Male ,Peru ,Humans ,Testosterone ,Altitude Sickness ,Middle Aged - Abstract
Life at high altitudes (4000 m) is associated with higher erythropoiesis. Haemoglobin ≥21 g dl(-1) is considered as excessive erythrocytosis and is a sign of chronic mountain sickness (CMS). The present study was designed to determine an association between serum testosterone (T) and serum oestradiol (E(2) ) levels with the score of CMS. One hundred and seventeen men natives from low altitude (150 m) and 103 men natives from high altitude (4340 m) were studied. The presence of breathlessness or palpitations, sleep disturbance, cyanosis, dilatation of veins, paraesthesia, headaches, tinnitus and Hb ≥21 g dl(-1) , have been included for the CMS score. Men living at high altitude had higher CMS score (P0.001), serum T (P0.05) and serum E(2) levels (P0.04) and had lower serum luteinising hormone levels (P0.005) than men living at sea level. At high altitude, the group with the highest CMS score (≥10) showed higher chronological age, SpO(2) , serum T and ratio T/E(2) than the group with CMS score of ≤4. Some symptoms of CMS as sleep disorders and paraesthesia were more related to high serum T level; cyanosis was more related to higher haemoglobin values. In conclusion, higher serum T levels were associated to higher scores of CMS.
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- 2011
10. Effect of the ethanolic extract from Fagara tessmannii on testicular function, sex reproductive organs and hormone level in adult male rats
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D, Massoma Lembè, M, Gasco, J, Rubio, S, Yucra, E Ngo, Sock, and G F, Gonzales
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Epididymis ,Male ,Ethanol ,Plant Extracts ,Seminal Vesicles ,Organ Size ,Genitalia, Male ,Weight Gain ,Rats ,Sperm Transport ,Testis ,Animals ,Testosterone ,Spermatogenesis ,Rutaceae - Abstract
The effect of ethanolic extract of Fagara tessmannii, wide medicinal plants used on reproductive function in South Cameroon, was investigated in male rats. Twenty male sexually experienced rats (four groups) were orally treated with vehicle, 0.01, 0.1, 1 g kg(-1) BW per day of F. tessmannii (equivalent to 16.67 g, 33.33 g, 50 g, 66.66 g kg(-1) dry raw material) for 14 days, the upper limit dose without any clinical sign of toxicity was 2 g kg(-1). Fagara tessmannii extract negatively affected weight of accessory organs and significantly affected body weight gain at dose 1 g kg(-1) (P0.05) in treated rats. The weight of epididymis and seminal vesicle significantly decreased at low doses (0.01 g kg(-1)) while the prostate weight decreased at all doses (P0.05). The transit of spermatozoa in cauda epididymidis significantly increased at lower dose of 0.01 g kg(-1) (P0.05). In addition, F. tessmannii extract affected neither daily sperm production (DSP) and DSP per g nor sperm count in vas deferens and epididymis. The length of stages IX-I of the seminiferous tubule and serum testosterone level increased dose-dependently following 14 days of treatment (P0.05). The results suggest that F. tessmannii, 14 days after treatment, may improve spermatogenesis, testosterone level and sperm transit in cauda epididymidis but negatively impair reproductive organ activities.
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- 2011
11. No-Mimetic Furoxans: Arylsulphonylfuroxans and Related Compounds
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A. M. Gasco, Giancarlo Folco, R. Ferioli, Maurizio Civelli, Stefano Bongrani, Roberta Fruttero, A. Fazzini, and Rosella Calvino
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Male ,Pharmacology ,Oxadiazoles ,Contraction (grammar) ,Platelet Aggregation ,Platelet aggregation test ,Stereochemistry ,Vasodilator Agents ,Furoxan ,Aorta, Thoracic ,Vasodilation ,In Vitro Techniques ,Furazan ,Muscle, Smooth, Vascular ,In vitro ,Nitric oxide ,Structure-Activity Relationship ,chemistry.chemical_compound ,chemistry ,Animals ,Humans ,Potency ,Rabbits ,Platelet Aggregation Inhibitors - Abstract
A new class of methylfuroxans and methylfurazans arylthio, arylsulphinyl and arylsulphonyl substituted, characterized by vasodilating and antiaggregatory properties, is described. Vasodilating activity, tested on rabbit aortic rings precontracted with 1 μM noradrenaline, is enhanced by N-oxidation of the furazan ring and is maximized by increase of the sulphur atom oxidation level. Compounds 4-methyl-3-(p-methoxyphenylsulphonyl) furoxan 6c , 3-phenyl-4-phenylsulphonylfuroxan 10 , 4-phenyl-3-phenylsulphonylfuroxan 11 and 3,4-bis(phenyl-sulphonyl)furoxan 12 (EC 50 values ranging between 0.055-1.07 μM), seem to be promising since they show the highest potency as well as maximal efficacy, causing complete reversal of noradrenaline induced contraction. The structure-activity relationship, observed in the platelet aggregation test, is substantially similar to that reported for the vasodilating activity, in line with the general profile of these drugs as putative NO-mimetic derivatives.
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- 1993
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12. Unsymmetrically Substituted Furoxans, XIV. Synthesis and Structure of a Trimer of the Furoxan System with High Vasodilator and Platelet Antiaggregatory Activity
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Antonella Di Stilo, Giovanni Sorba, A. M. Gasco, Roberta Fruttero, Alberto Gasco, and P. Sabatino
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chemistry.chemical_classification ,Stereochemistry ,Organic Chemistry ,Furoxan ,Trimer ,Biological activity ,Crystal structure ,Nitrone ,chemistry.chemical_compound ,chemistry ,Molecule ,Physical and Theoretical Chemistry ,Chemical decomposition ,Derivative (chemistry) - Abstract
The synthesis and structure of a trimer 5 of the furoxan system are reported. The probable origin of this derivative is the dimerization of the intermediate 4-phenyl-3-furoxancarbonitrile oxide (4) obtained by decomposition of the corresponding nitrolic acid 3. The title compound shows a high level of activity as vasodilator and inhibitor of platelet aggregation.
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- 1993
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13. ChemInform Abstract: X-Ray and NMR Structural Study of Acylglyoximes and Related Substances
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Rosella Calvino, Roberta Fruttero, P. Sabatino, A. M. Gasco, and B. Ferrarotti
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Crystallography ,Chemistry ,X-ray ,Organic chemistry ,General Medicine - Published
- 2010
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14. ChemInform Abstract: Unsymmetrically Substituted Furoxans. Part 14. Synthesis and Structure of a Trimer of the Furoxan System with High Vasodilator and Platelet Antiaggregatory Activity
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Roberta Fruttero, Alberto Gasco, A. M. Gasco, A. Di Stilo, P. Sabatino, and Giovanni Sorba
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chemistry.chemical_compound ,chemistry ,Stereochemistry ,Furoxan ,Trimer ,Platelet ,Vasodilation ,General Medicine - Published
- 2010
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15. ChemInform Abstract: Use of Nitric Oxide Releasing Furoxan System in the Design of 'Hybrids' : Substitution of Furoxan Moieties for the Furan Ring in Prazosin
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Donatella Boschi, Alberto Gasco, Marco Orsetti, A. Di Stilo, A. M. Gasco, Roberta Fruttero, and Giovanni Sorba
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chemistry.chemical_compound ,chemistry ,Furan ,Substitution (logic) ,Furoxan ,Prazosin ,medicine ,Organic chemistry ,General Medicine ,Ring (chemistry) ,Medicinal chemistry ,medicine.drug ,Nitric oxide - Published
- 2010
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16. ChemInform Abstract: The Reduction of Benzofuroxans by Ferrous Salts and by Thiophenol
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A. M. Gasco, A. Marcello Gasco, and Claudio Medana
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Reduction (complexity) ,chemistry.chemical_compound ,chemistry ,Thiophenol ,Inorganic chemistry ,Ferrous salts ,Organic chemistry ,General Medicine - Published
- 2010
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17. ChemInform Abstract: Mesomeric Dipole Moments. Part 13. Dipole Moments and Electron Distribution of Furoxans (I) and Furazans (II)
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Otto Exner, Roberta Fruttero, A. M. Gasco, and Václav Všetečka
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Dipole ,Computational chemistry ,Chemistry ,General Medicine ,Atomic physics ,Electron distribution - Published
- 2010
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18. ChemInform Abstract: Unsymmetrically Substituted Furoxans. Part 15. Bromination of Dimethylfuroxan and Related Compounds with NBS
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Alberto Gasco, Donatella Boschi, and A. M. Gasco
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Substitution reaction ,Chemistry ,Halogenation ,Organic chemistry ,General Medicine - Published
- 2010
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19. ChemInform Abstract: Synthesis and Structural Characterization of the Trimeric Furoxan (= Furazan 2-Oxide) System, a New Potent Vasodilating Moiety
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Claudio Medana, Clara Cena, A. M. Gasco, A. Di Stilo, Alberto Gasco, and Giuseppe Ermondi
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chemistry.chemical_compound ,chemistry ,Furoxan ,Oxide ,Moiety ,General Medicine ,Furazan ,Combinatorial chemistry ,System a - Published
- 2010
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20. ChemInform Abstract: Furoxan Derivatives as NO-Donors
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Claudio Medana, Giovanni Sorba, A. M. Gasco, A. Di Stilo, and Roberta Fruttero
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chemistry.chemical_compound ,chemistry ,Furoxan ,Organic chemistry ,General Medicine ,Combinatorial chemistry ,No donors - Published
- 2010
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21. ChemInform Abstract: Unsymmetrically Substituted Furoxanes. Part 17. Structural Investigations in Benzenesulfonylfuroxan Derivatives and Related Compounds
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A. M. Gasco, Roberta Fruttero, Marco Lucio Lolli, Giovanni Sorba, and Giuseppe Ermondi
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Chemistry ,Organic chemistry ,General Medicine - Published
- 2010
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22. ChemInform Abstract: Characterization of Furoxancarbonitriles as a New Class of Vasodilators
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A. M. Gasco, A. Di Stilo, Alberto Gasco, Claudio Medana, Piero A. Martorana, Donatella Boschi, and K. Schoenafinger
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Chemistry ,General Medicine ,Combinatorial chemistry ,Characterization (materials science) - Published
- 2010
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23. HONDURAS: VALIDANDO LAS AREAS ESTRATÉGICAS DEL PLAN DE GRADUACIÓN DE USAID
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Merce M. Gasco and Quesada, Nora
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- 2008
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24. Identification of 2,3-diaminophenazine and of o-benzoquinone dioxime as the major in vitro metabolites of benzofuroxan
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Giorgio Grosa, Barbara Rolando, A. M. Gasco, Roberta Fruttero, Ubaldina Galli, and G. Gervasio
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Male ,Health, Toxicology and Mutagenesis ,Toxicology ,Biochemistry ,Models, Biological ,Cofactor ,Cytosol ,Benzoquinones ,Animals ,Rats, Wistar ,Incubation ,Cells, Cultured ,Pharmacology ,chemistry.chemical_classification ,Benzoxazoles ,Chromatography ,biology ,General Medicine ,Metabolism ,Benzoquinone ,In vitro ,Rats ,chemistry ,Models, Chemical ,biology.protein ,Thiol ,Microsome ,Microsomes, Liver ,Phenazines - Abstract
1. The results of an in vitro study of the metabolism of benzofuroxan using either cytosolic or microsomal fractions obtained from rat liver are reported. 2. Benzofuroxan was incubated with an appropriate volume of cytosol or microsomal suspension; control incubations were performed without the beta-nicotinamide adenine dinucleotide phosphate-generating system or, alternatively, by using the subcellular fractions inactivated by heating. Incubation mixtures were analysed by high-performance liquid chromatography. Two principal metabolites (M1, M2) were identified in the cytosolic fraction only. The dependence of M2 formation on thiol cofactors, incubation time and protein concentration was examined. 3. The two metabolites were isolated and characterized by their 1H-, 13C-nuclear magnetic resonance, infrared and mass spectra. The structures of o-benzoquinonedioxime (2) and 2,3-diaminopleuozuc (3), were arranged to M1 and M2 respectively. The proposed structures were confirmed by the identity of the metabolites with authentic samples obtained by synthesis. X-ray analysis showed that the dioxime metabolite had an amphy configuration. 4. A metabolic scheme for the formation of the two products is proposed.
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- 2004
25. New potential uroselective NO-donor alpha1-antagonists
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Donatella Boschi, A. M. Gasco, Di Stilo A, Motta G, Elena Poggesi, Gian Cesare Tron, Leonardi A, and Roberta Fruttero
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Male ,Stereochemistry ,medicine.drug_class ,Muscle Relaxation ,Alpha (ethology) ,Carboxamide ,Nitrous Acid ,CHO Cells ,In Vitro Techniques ,Chemical synthesis ,Binding, Competitive ,chemistry.chemical_compound ,Radioligand Assay ,Vas Deferens ,Receptors, Adrenergic, alpha-2 ,Cricetinae ,Receptors, Adrenergic, alpha-1 ,Drug Discovery ,medicine ,Animals ,Humans ,Nitric Oxide Donors ,Adrenergic alpha-Antagonists ,Cerebral Cortex ,Oxadiazoles ,Chemistry ,Furoxan ,Antagonist ,Vas deferens ,Biological activity ,Muscle, Smooth ,In vitro ,Rats ,medicine.anatomical_structure ,Chromones ,Receptors, Serotonin ,Molecular Medicine ,Receptors, Serotonin, 5-HT1 ,HeLa Cells - Abstract
A recent uroselective alpha(1)-adrenoceptor antagonist, REC15/2739, has been joined with nitrooxy and furoxan NO-donor moieties to give new NO-donor alpha(1)-antagonists. All the compounds studied proved to be potent and selective ligands of human cloned alpha(1a)-receptor subtype. Derivatives 6 and 7 were able to relax the prostatic portion of rat vas deferens contracted by (-)-noradrenaline because of both their alpha(1A)-antagonist and their NO-donor properties.
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- 2003
26. Imatinib Mesylate in Desmoplastic Small Round Cell Tumour
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Alexia Bertuzzi, C. Gnocchi, M. Gasco, Gianni Bisogno, Armando Santoro, Alessandro Comandone, R. De Sanctis, Modesto Carli, and Andrea C. Ferrari
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Oncology ,medicine.medical_specialty ,Desmoplastic small-round-cell tumor ,Nausea ,business.industry ,medicine.drug_class ,Imatinib ,Hematology ,medicine.disease ,Tyrosine-kinase inhibitor ,Imatinib mesylate ,Tolerability ,Internal medicine ,medicine ,Clinical endpoint ,medicine.symptom ,business ,Progressive disease ,medicine.drug - Abstract
Introduction Desmoplastic small round cell tumor (DSRCT) is a very rare and aggressive mesenchymal neoplasia with an extremely poor prognosis. The typical translocation t(11;22) determines the overexpression of PDGF-Rα and β, responsible of clinical stromal fibrosis reaction constantly detected in abdominal lesions. We investigated the role of imatinib, as tyrosine kinase inhibitor of PDGF-R, in DSRCT. Patients and methods From August 2005 to June 2009 we enrolled patients (pts) with histologically proven diagnosis of DSRCT, refractory to conventional treatment. Inclusion criteria comprised immunohistochemical positivity of imatinib targets (PDGF-Rα and β). Treatment consisted of imatinib 400 mg p.o. daily. Primary endpoint of the study was objective response rate. Secondary endpoint was safety and tolerability assessment. Results Of the 13 enrolled patients, 8 pts were evaluable for response (4 screening failure and 1 never treated). Median age was 20 years (range, 9-32). M/F ratio was 7/1. ECOG PS was 0 in 6 pts. Median time from diagnosis was 24.5 months (range, 6-148). 75% of pts had metastatic disease. The primary site was abdominal-pelvic for all pts. PDGFRα and β were expressed with an heterogeneous intensity pattern. Objective responses at first radiological evaluation at 3 months were: stable disease in one pt (12.5%) and progressive disease in 7 (87.5%) pts. Treatment-related adverse events were G1-2 nausea/vomiting, fatigue and periorbital oedema. Conclusions In our limited case series, imatinib showed no efficacy in the treatment of DSRCT pts unresponsive to conventional therapy, despite molecular-based selection of pts. Probably to identify responder pts, it is necessary a more complex evaluation comprehensive of both levels of expression and activation of PDGFRα and β. Furthermore, enrolled pts were affected by advanced refractory disease, probably less responsive to target therapies. It would be hopeful a global effort to define a new combined approach based on the association of conventional chemotherapy and biological drugs. Disclosure C. Gnocchi: Novartis Patient Advocacy Manager. All other authors have declared no conflicts of interest.
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- 2012
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27. [Guidelines for basic and advanced cardiopulmonary resuscitation of children. Commission for Cardiopulmonary Resuscitation of the Spanish Society for Anesthesiology and Resuscitation]
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M, Gasco, T, Blanco, E, Teigel, J, García, A, Lahoz, J, Marco, J, Torres, and R, García-Guasch
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Age Factors ,Infant, Newborn ,Infant ,Arrhythmias, Cardiac ,Foreign Bodies ,Prognosis ,Cardiopulmonary Resuscitation ,Heart Arrest ,Airway Obstruction ,Catheters, Indwelling ,Heart Rate ,Child, Preschool ,First Aid ,Humans ,Brain Damage, Chronic ,Emergencies ,Child ,Algorithms - Published
- 2001
28. Metastatic breast cancer patients failing first-line, anthracycline-containing chemotherapy: is further therapy of benefit?
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E, Campora, G, Gardin, M, Gasco, R, Rosso, and L, Santi
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Salvage Therapy ,Antibiotics, Antineoplastic ,Time Factors ,Breast Neoplasms ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Quality of Life ,Humans ,Female ,Fluorouracil ,Treatment Failure ,Cyclophosphamide ,Epirubicin ,Retrospective Studies - Abstract
During the last 50 years median survival for metastatic breast cancer has not varied and remains 2-3.5 years. To assess the clinical benefit of salvage systemic therapy a retrospective analysis of metastatic breast cancer patients all homogeneously treated with a commonly used first-line anthacycline-containing cytotoxic regimen (FEC) was undertaken. The 140 patients in this report were among 375 entered in two consecutive multicenter randomized trials carried out from Dec. 1983 to Jan. 1990. All patients died during follow-up. Median number of salvage therapies was 3 (range 1-7). Response rate (CR and PR) was 41% with FEC and 7%, 3%, 15%, 0%, 14%, 0%, 0% in patients receiving salvage treatment line 1 to 7, respectively. Time to treatment failure (TTF) was 7.5 months for FEC and 3.5, 2.5, 2.1, 1.6, 2.1, 1.1, 1.6 months at first to seventh salvage treatment, respectively. Only a very small fraction of patients receiving first-line FEC respond to subsequent palliative treatment. The advantages of salvage therapy are unclear and must be weighed against the inconvenience, cost and morbidity of treatment. After first salvage therapy, patients should be considered for randomized trials comparing systemic antineoplastic therapy with best palliative care. Endpoints of all future clinical trials in metastatic breast cancer should include measurement of quality of life and accurate, sequential measurement of symptom control.
- Published
- 2000
29. Unsymmetrically substituted furoxans, XIII. Phenylfuroxancarbaldehydes and related compounds
- Author
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Alberto Gasco, A. M. Gasco, Roberta Fruttero, and Giovanni Sorba
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Ylide ,Organic Chemistry ,Furoxan ,Thermal equilibration ,Organic chemistry ,Physical and Theoretical Chemistry ,Aldehyde - Abstract
The synthesis and structure of the two isomeric phenylfuroxancarbaldehydes 7a and 7b, of the phenylfurazancarbaldehyde 6 and of the corresponding alcohols 3a, 3b and 5 are reported. Thermal equilibration of the furoxan derivatives and their oxidation to the corresponding carboxylic acids 8a and 8b are also discussed.
- Published
- 1991
- Full Text
- View/download PDF
30. Characterisation of furoxancarbonitriles as a new class of vasodilators
- Author
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A M, Gasco, D, Boschi, A, Di Stilo, C, Medana, A, Gasco, P A, Martorana, and K, Schönafinger
- Subjects
Male ,Oxadiazoles ,Magnetic Resonance Spectroscopy ,Swine ,Vasodilator Agents ,Hemodynamics ,Aorta, Thoracic ,In Vitro Techniques ,Nitric Oxide ,Mass Spectrometry ,Muscle, Smooth, Vascular ,Rats ,Nitriles ,Animals ,Rats, Wistar ,Intubation, Gastrointestinal - Abstract
The synthesis, structural characterization, NO-donor properties, and in vitro vasodilating activities of a series of furoxancarbonitriles 2, 17-22a, b are reported. Some derivatives (2b, 2a, 18b, 21b, 22b) are more potent vasodilating agents than sodium nitroprusside (SNP), the reference compound, some others display similar potency (17b, 19b, 20b). Log EC50 values fit well on the linear correlation log EC50 versus log C0.1(1 min) (namely the logarithm of the concentration able to release 2.6 mumol l-1 min-1 of NO) found in a previous work. The haemodynamic profile in anaesthetised pigs for some selected derivatives (2a, b, 19a, b) is also presented. These profiles are consistent with that known for another furoxan NO-donor (4-hydroxymethyl-3-furoxancarboxamide, CAS 1609) and suggest similar characteristic of in vivo NO-release.
- Published
- 1998
31. Vinorelbine as palliative therapy in advanced breast cancer
- Author
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M, Gasco, G, Gardin, L, Repetto, E, Campora, and R, Rosso
- Subjects
Adult ,Palliative Care ,Humans ,Breast Neoplasms ,Female ,Vinorelbine ,Middle Aged ,Vinblastine ,Antineoplastic Agents, Phytogenic ,Aged - Abstract
Thirty advanced breast cancer patients received Vinorelbine (VNB) according to two different schedules: a weekly i.v. bolus of 30 mg/m (14 patients) or a continuous infusion (CI) schedule comprising 8 mg i.v. bolus on day 1 followed by 8 mg/m2/die CI day 1 to 4, q 21 days (16 patients). 36% of patients had received at least two prior chemotherapy regimens for advanced disease and 57% had been treated with anthracycline-based palliative therapy. The overall response rate (CR + PR) was 33% (soft tissue 57%, bone 17%, viscera 29%). The main toxicities were neutropenia and abdominal pain. Vinorelbine is effective in pretreated advanced breast cancer patients.
- Published
- 1997
32. Radioimmunoguided surgery after primary treatment of locally advanced breast cancer
- Author
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Paolo Meszaros, Sergio Bertoglio, M Gasco, F. Cafiero, Pierluigi Percivale, M. Gipponi, E. Campora, Fausto Badellino, and Giuseppe Canavese
- Subjects
Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Mammary gland ,Breast Neoplasms ,Modified Radical Mastectomy ,Monoclonal antibody ,Breast cancer ,Antigen ,Monitoring, Immunologic ,Humans ,Medicine ,Radioimmunoguided surgery ,Aged ,business.industry ,Carcinoma, Ductal, Breast ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Primary tumor ,Surgery ,medicine.anatomical_structure ,Oncology ,Immunohistochemistry ,Female ,Radiology ,business - Abstract
PURPOSE To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.
- Published
- 1996
33. Mitoxantrone in elderly women with advanced breast cancer: a phase II study
- Author
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L, Repetto, C, Simoni, A, Venturino, V, Biancardi, M, Gasco, E, Campora, and R, Rosso
- Subjects
Aged, 80 and over ,Humans ,Antineoplastic Agents ,Breast Neoplasms ,Female ,Mitoxantrone ,Aged - Abstract
Comorbidity has important implications in older breast cancer patients. Whether elderly patients are more likely to have a decreased tolerance to antineoplastic agents is still a question of debate. Chemotherapy-naive women with metastatic or locally advanced breast cancer agedor = 68 years entered a phase II trial of Mitoxantrone given day 1 q 21 days. The dose of the drug was dependent on performance status (PS) and number of "minor" comorbid conditions: patients with ECOG PS = 2 and/oror = 2 comorbid conditions received 10 mg/m2 and those with PS2 and2 comorbid conditions received 14 mg/m2. Twenty-seven patients, median age 77 years (range 68-86), received a median number of 5 courses (range 1-9). All 27 patients were evaluable for toxicity and 23 cases (patients receiving at least 3 courses) were evaluable for response. Partial response was observed in 6/23 cases (26%) and median duration of response was 6 months (range 3-9). Median overall survival was 8 months (range 2-34). Among cases receiving 10 mg/m2, 4 PR, 4 SD and 2 P were observed and in cases treated with 14 mg/m2, 2 PR, 5 SD and 6 P occurred. Treatment was well tolerated and no grade 4 toxicity was encountered. Mitoxantrone is an effective and well-tolerated regimen in elderly breast cancer patients presenting with comorbid conditions.
- Published
- 1995
34. The cyano-NNO-azoxy function in the design of an irreversible label for alpha 1 adrenoreceptors
- Author
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A. M. Gasco, Clara Cena, A. Di Stilo, Claudio Medana, Marco Orsetti, and Giovanni Sorba
- Subjects
Azoxy ,Male ,medicine.medical_specialty ,Adrenergic receptor ,Irreversible antagonist ,Clinical Biochemistry ,Pharmaceutical Science ,Adrenergic ,Aorta, Thoracic ,In Vitro Techniques ,Biochemistry ,Medicinal chemistry ,Norepinephrine (medication) ,chemistry.chemical_compound ,Norepinephrine ,medicine.artery ,Internal medicine ,Receptors, Adrenergic, alpha-1 ,Drug Discovery ,medicine ,Prazosin ,Moiety ,Thoracic aorta ,Animals ,Rats, Wistar ,Molecular Biology ,Adrenergic alpha-Antagonists ,Cerebral Cortex ,Organic Chemistry ,Rats ,Endocrinology ,chemistry ,Drug Design ,Adrenergic alpha-1 Receptor Antagonists ,Molecular Medicine ,medicine.drug - Abstract
A potential α 1 -adrenergic irreversible antagonist 6, containing the cyano-NNO-azoxy function was synthesized and tested. The effects of norepinephrine on rat thoracic aorta were irreversibly blocked by this compound at the concentration of 1 × 10 −5 M after 60 minutes. Binding studies showed that 6, at 1 × 10 −6 M, did not modify the K D of Prazosin and caused a 30% decrease of the B max . Substitution in 6 of the bis (2-chloroethyl)amino moiety for the cyano-NNO-azoxy function afforded 7 which behaves as an irreversible antagonist able to change K D of Prazosin without influencing B max .
- Published
- 1995
35. Superiority of Choi vs Recist Criteria in Evaluating Outcome of Advanced Soft Tissue Sarcoma (STS) Patients Treated with Sorafenib
- Author
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Armando Santoro, Romano Fabio Lutman, R. De Sanctis, Laura Giordano, M. Gasco, P. Magnoni, and Alexia Bertuzzi
- Subjects
Sorafenib ,medicine.medical_specialty ,Chemotherapy ,Tumor size ,Anthracycline ,business.industry ,medicine.medical_treatment ,Soft tissue sarcoma ,Hematology ,RELAPSED DISEASE ,medicine.disease ,Tumor response ,Gastroenterology ,Oncology ,Internal medicine ,medicine ,In patient ,business ,medicine.drug - Abstract
Background Objective tumor response may be underestimated by RECIST criteria, since biological agents can cause metabolic response (necrosis) not related to tumor size. For this reason, CHOI criteria were designed to evaluate both tumor density and size. We compared CHOI and RECIST criteria in evaluating response to sorafenib in patients with advanced STS, treated within a phase II trial. The objective was to compare CHOI and RECIST criteria and to relate response to progression-free (PFS) and overall survival (OS). Patients and methods Sixty one advanced STS patients received sorafenib 400 mg twice daily for progressive or relapsed disease after anthracycline-based chemotherapy. Treatment was continued until progression or major toxicity. Contrast-enhanced CT was performed every 3 months. Thirty patients were evaluable for response, according to both RECIST and CHOI criteria. Results A total of 30 patients were included in the analysis. According to RECIST, we observed 1 (3%) complete response (CR), 1 (3%) partial remission (PR), 18 (60%) stable diseases (SD) and 10 (34%) progressive diseases (PD) at 3 months. According to CHOI, we observed 1 (3%) CR, 10 (34%) PR, 5 (16%) SD and 14 (47%) PD. The agreement between the two techniques was low (cohen Kappa: 0.36; CI 95%, 0.17-0.55). Of the 18 pts with SD according to RECIST, a total of 13 (72%) pts were reallocated to responder (8 PR, 44%) and non-responder (5 PD, 28%) groups, while only in 5 cases SD was confirmed using CHOI criteria. Median PFS and OS for SD RECIST pts were 8.3 and 22.7 months, respectively. In these 18 pts, we compared median PFS and OS of responders (CR + PR, n= 8) vs non-responders (SD + PD, n= 10) according to CHOI criteria. PFS was 11.2 vs 7.9 (p= 0.05), and OS 23.3 vs 15 months (p= 0.21). Conclusions Our analysis suggests that CHOI criteria may be helpful to define response to a biological treatment in STS. According to CHOI criteria, SD pts as defined by RECIST could be better divided in two subgroups (responders and non-responders) with a different outcome. Therefore, CHOI criteria may have an early significant predictive value for PFS in STS pts treated with biological agents. Disclosure All authors have declared no conflicts of interest.
- Published
- 2012
- Full Text
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36. Furoxans as nitric oxide donors. 4-Phenyl-3-furoxancarbonitrile: thiol-mediated nitric oxide release and biological evaluation
- Author
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A. M. Gasco, A. Di Stilo, Claudio Medana, C. Ferretti, Giuseppe Ermondi, and Roberta Fruttero
- Subjects
Male ,Stereochemistry ,Vasodilator Agents ,Guanosine Monophosphate ,Aorta, Thoracic ,Nitric Oxide ,Cofactor ,Mass Spectrometry ,Nitric oxide ,chemistry.chemical_compound ,Norepinephrine ,Phenols ,Drug Discovery ,Animals ,Humans ,Sulfhydryl Compounds ,Isoxazole ,Rats, Wistar ,Lung ,chemistry.chemical_classification ,Oxadiazoles ,biology ,Thiophenol ,Biological activity ,Rats ,Enzyme Activation ,Vasodilation ,chemistry ,Thiolysis ,Guanylate Cyclase ,biology.protein ,Thiol ,Molecular Medicine ,Nitronate ,Platelet Aggregation Inhibitors - Abstract
4-Phenyl-3-furoxancarbonitrile (2) affords nitric oxide under the action of thiol cofactors. Two principal products were isolated in the reac- tion with thiophenol: the phenylcyanoglyoxime (6) and 5-amino-3-phenyl- 4-(phenylthio)isoxazole (7). Mechanisms which could account for the fo- rmation of these two products are discussed. Compound 2 is an efficient activator of the rat lung soluble guanylate cyclase, displays high va- sodilatory activity on strips of rat thoracic aorta precontracted with noradrenaline, and is a potent inhibitor of platelet aggregation
- Published
- 1994
37. THE REDUCTION OF BENZOFUROXANS BY FERROUS SALTS AND BY THIOPHENOL
- Author
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Claudio Medana, A. M. Gasco, and Alberto Gasco
- Subjects
inorganic chemicals ,Ferrous sulphate ,Reduction (complexity) ,chemistry.chemical_compound ,chemistry ,Yield (chemistry) ,Thiophenol ,Organic Chemistry ,Ferrous salts ,Catalysis ,Nuclear chemistry - Abstract
Treatment of benzofuroxan derivatives with ferrous sulphate in DMSO/water solution affords in high yield o-nitroanilines. o-Nitroaniline was also obtained by reduction of benzofuroxan with thiophenol in presence of catalytic amount of Fe2+ or Fe3+ salts.
- Published
- 1994
38. [Study of Navarra (PECNA). Correlation of arterial blood pressure, in a child-young population, with anthropometric and biochemical parameters]
- Author
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R, Elcarte López, I, Villa-Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzábal Irigoyen, A, Sola Mateos, C, García Ibero, A, Martínez González, F, Castiella Lafuente, and I, Ayensa Mezquiriz
- Subjects
Male ,Adolescent ,Statistics as Topic ,Age Factors ,Blood Pressure ,Myocardial Contraction ,Body Height ,Cholesterol ,Child, Preschool ,Humans ,Regression Analysis ,Female ,Child ,Triglycerides - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescent in Navarra, arterial blood pressure (BP) readings were taken in 5,829 children. These children, both males and females, between the ages of 4 and 17 years, were selected at random from the public and private school population in our community. The correlation between systolic blood pressure and diastolic blood pressure with anthropometric and biochemical parameters was analyzed. The correlation coefficient for systolic BP readings were always higher than those for diastolic BP. The highest correlations for both BP scores were found with weight, followed by height. Correlation with total weight parameters is superior to that found with body fat parameters. There were no significant correlations between BP and the lipid parameters. When analyzing multiple regression equations, we find that with only the child's weight and age, both systolic and diastolic BP can be predicted with correlation coefficients of 0.597 and 0.492, respectively. When doing a partial correlation analysis, the correlation between systolic BP and age, at a fixed height value, disappears; while the correlation of systolic BP with height remains when using a set age. This suggest that the best definition for hypertension is based on BP-height percentile, rather than BP-age.
- Published
- 1993
39. [The Navarra study. Prevalence of arterial hypertension, hyperlipidemia and obesity in the infant-child population of Navarra. Association of risk factors]
- Author
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R, Elcarte López, I, Villa Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzábal Irigoyen, A, Sola Mateos, A, Martínez González, T, Elcarte López, I, Ayensa Mezquiriz, and F, Castiella Lafuente
- Subjects
Male ,Adolescent ,Hypercholesterolemia ,Age Factors ,Hyperlipidemias ,Prognosis ,Lipoproteins, LDL ,Skinfold Thickness ,Cardiovascular Diseases ,Predictive Value of Tests ,Risk Factors ,Spain ,Child, Preschool ,Hypertension ,Prevalence ,Humans ,Female ,Obesity ,Child ,Lipoproteins, HDL - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, 5,829 children were studied. These children, of both sexes, were between 4 and 17 years of age and were selected at random from the public and private school population in Navarra. The prevalence of hypertension (HT) was 7.17 +/- 0.34%, hyperlipemia (LDL/HDL2.2) 15.70 +/- 0.49% and obesity (Quetelet I) 3.96 +/- 0.26%. Of the children and adolescents in Navarra 23.68% show some of these three associated risk factors. Obesity was significantly associated with HT and hyperlipemia, measured by LDL/HDL2.2 (but not when defined by cholesterol200 mg/dl). This association was greater when the pathology was defined by the Quetelet Index, rather than by the skinfold thickness. Hypertension was not associated with hypercholesterolemia (defined as LDL/HDL2.2). The association with hyperlipemia (measured by LDL/HDL) disappeared when the obesity effect was eliminated. It is deduced from these factors that if we don't take preventative health measures, the present children and adolescents from Navarra will suffer a high cardiovascular morbi-mortality when they become adults.
- Published
- 1993
40. [A study from Navarra. Hyperlipidemia V. What is the best definition of hyperlipemia in childhood and adolescence?]
- Author
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R, Elcarte López, I, Villa Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzábal Irigoyen, A, Sola Mateos, C, García Ibero, T, Elcarte López, M, Ferrer Giménez, and A, Fontaneda Estíbaliz
- Subjects
Male ,Adolescent ,Hypercholesterolemia ,Age Factors ,Coronary Disease ,Hyperlipidemias ,Lipoproteins, LDL ,Cholesterol ,Risk Factors ,Spain ,Child, Preschool ,Humans ,Mass Screening ,Female ,Child ,Lipoproteins, HDL - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes, between 4-17 years of age, and selected at random from the school population in our community. In this article, we analyze the different definitions for lipid risk during childhood, whether based on percentile values, according to age and sex of the child, of cholesterol, LDL/cholesterol, or risk quotients (C/HDL, LDL/HDL), or even on the absolute values of all of these parameters. An appropriate definition for hyperlipemia during childhood, once we know the average variations in the levels of lipids and lipoproteins according to age and sex, as well as the variations of the lipid risk prevalence according to its definition, would be: 1. Previous screening according to cholesterol serum levels: Values higher than the 70th percentile for each group according to age and sex: or higher than 185 mg/dl for children age 4 to 12 and 170 mg/dl for children age 13 to 17. 2. To calculate the LDL/HDL quotient among those selected children included in the definition of hyperlipemia when the quotient is higher than the 85th percentile for the patients age and sex, or it is higher than 2.2.
- Published
- 1993
41. [A study from Navarra. Hyperlipidemias. Avarage scores and percentiles for lipids and lipoproteins in a population of children and adolescents. Correlation with anthropometric parameters]
- Author
-
R, Elcarte López, I, Villa-Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzábal Irigoyen, A, Sola Mateos, C, García Ibero, T, Elcarte López, M, Ferrer Giménez, and A, Fontaneda Estíbaliz
- Subjects
Male ,Hyperlipoproteinemias ,Adolescent ,Anthropometry ,Lipoproteins ,Hypercholesterolemia ,Age Factors ,Hyperlipidemias ,Lipids ,Lipoproteins, LDL ,Spain ,Child, Preschool ,Humans ,Female ,Child ,Lipoproteins, HDL ,Triglycerides - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, the following parameters: total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and C/HDL and LDL/HDL risk quotients were determined in 5,829 children. These children, of both sexes and between the ages of 4 and 17 years, were selected at random from the school population in our community. Average values and percentiles of these parameters were obtained for each group according to age and sex as a previous step to define the health condition or "lipid risk" in our population. When determining the correlation of these biochemical parameters with the anthropometrical parameters of BP, age, weight, height, Quetelet Index, body mass surface, skinfold thickness and the percentage of subcutaneous fat (after the necessary logarithmic transformations, adjusted to each age and sex group by Z-scores) we find that none of the correlation coefficients are significant. The triglycerides and the HDL-cholesterol have a low, but significant. The triglycerides and the HDL-cholesterol have a low, but significantly, correlation with the other lipid parameters. The lipid risk quotient (C/HDL, LDL/HDL) shows a higher correlation with LDL-cholesterol than with total cholesterol.
- Published
- 1993
42. [The Navarra study (PECNA). Hyperlipidemia IV. Prevalence of hyperlipidemia in the infant- and juvenile population of Navarra. Variations based on age, gender and health care accessibility]
- Author
-
R, Elcarte López, I, Villa Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzabal Irigoyen, A, Sola Mateos, C, García Ibero, A, Martínez González, M, Ferrer Giménez, and A, Fontaneda Estíbaliz
- Subjects
Male ,Analysis of Variance ,Adolescent ,Hypercholesterolemia ,Age Factors ,Hyperlipidemias ,Health Services Accessibility ,Lipoproteins, LDL ,Sex Factors ,Risk Factors ,Spain ,Child, Preschool ,Prevalence ,Humans ,Female ,Child ,Lipoproteins, HDL - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes. These children were between 4 and 17 years of age and were randomly selected from the school population of our community. In this article, we analyze the prevalence of lipid risk, according to its different definitions, among children and adolescents in Navarra, and its variations related to age, sex and sanitary area. The prevalence of hypercholesterolemia (C200 mg/dl) among children and adolescents, aged 4 to 17 years, is very high: 21.07% +/- 0.54%. In spite of having high serum levels of HDL, the lipid risk measured by the risk quotient LDL/HDL2.2 is still very high: 15-70% +/- 0.49%. If we define the lipid risk during childhood and adolescence by the quotient LDL/HDL2.2, male adolescents turn out to be the group with the highest risk. This phenomenon coincides with the results of the epidemiological studies made among adults. Nevertheless, they do not coincide with these results if the lipid risk is defined by C200 mg/dl. In our opinion, during infancy and adolescence, the lipid risk is better defined by the quotient LDL/HDL2.2.
- Published
- 1993
43. [The Navarra study (PECNA). Hyperlipidemia III. Variations in the median HDL levels and lipid risk quotient in children and adolescents based on age and gender]
- Author
-
R, Elcarte López, I, Villa Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzabal Irigoyen, A, Sola Mateos, C, García Ibero, A, Martínez González, M, Ferrer Giménez, and A, Fonteneda Estíbaliz
- Subjects
Male ,Analysis of Variance ,Adolescent ,Hypercholesterolemia ,Age Factors ,Hyperlipidemias ,Lipoproteins, LDL ,Sex Factors ,Risk Factors ,Spain ,Child, Preschool ,Prevalence ,Humans ,Female ,Child ,Lipoproteins, HDL - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, lipids and lipoproteins were analyzed in 5,829 children of both sexes. The subjects were between 4 and 17 years of age and were selected at random from the school population in our community. In this article we analyze the variations in HDL-cholesterol and cholesterol/HDL and LDL/HDL risk quotients according to age and sex. Beginning at the age of 10, the HDL decreases in both sexes, although this decrease is more evident among males and they obtain levels lower than those during early childhood. Among females older than 14 there is a slight increase. Apparently the decrease in HDL among male adolescents is due to an increase in the production of testosterone during this stage of life. Both risk quotients decrease until the children are 10 years of age, after which they increase among males and stabilize or slightly decrease among females. For this reason, scores are higher for males during the last years of adolescence. The cardiovascular lipid risk increases with age and during adolescence in higher among males and depends more on the variations in HDL than on variations in cholesterol or LDL. We believe that the best definition for cardiovascular lipid risk during the infancy or adolescents is one which is based on the risk quotients.
- Published
- 1993
44. Pharmacochemistry of the furoxan ring: recent developments
- Author
-
R, Calvino, A, Di Stilo, R, Fruttero, A M, Gasco, G, Sorba, and A, Gasco
- Subjects
Blood Platelets ,Oxadiazoles ,Nifedipine ,Vasodilator Agents ,Guinea Pigs ,Prazosin ,In Vitro Techniques ,Calcium Channel Blockers ,Myocardial Contraction ,Heart Rate ,Animals ,Humans ,Cyclic GMP ,Platelet Aggregation Inhibitors - Abstract
In the present work recent results obtained in the pharmacochemistry of the furoxan system are reported. In particular, after a brief description of the salient points of the furoxan chemistry, the synthesis and the properties of a series of Nifedipine and Prazosin analogues, containing this heterocyclic system, are described. Since we observed that a few furoxan derivatives are able to elicit both a dose-dependent rise in platelet cGMP levels and to promote a dose-dependent inhibition of AA-induced [Ca++] rise, and that many substituted furoxans show potent vasodilating and antiaggregatory activity, the possibility of using the furoxan system as a lead in the design of new vasodilators is also discussed.
- Published
- 1993
45. [Study from Navarra. Variations in the average arterial blood pressure level according to age, gender and body height]
- Author
-
R, Elcarte López, I, Villa Elizaga, J, Sada Goñi, M, Gasco Eguiluz, M, Oyarzabal Irigoyen, A, Sola Mateos, A, Martínez González, T, Elcarte López, D, Serrano Tellechea, and R, Merino García
- Subjects
Male ,Adolescent ,Age Factors ,Blood Pressure ,Body Height ,Sex Factors ,Cardiovascular Diseases ,Predictive Value of Tests ,Reference Values ,Child, Preschool ,Hypertension ,Humans ,Female ,Child - Abstract
As part of an epidemiological study on cardiovascular risk factors among children and adolescents in Navarra, arterial blood pressure (BP) readings were taken in 5,829 children, including both sexes and aged between 4 and 17 years. The subjects were randomly selected from the public and private school population in our community. BP-age and BP-height percentiles were obtained for each sex and the physiological variations in BP according to these parameters was also analyzed. Systolic BP increased with age in both sexes throughout childhood. During adolescence, there is almost no variation in BP among girls, but in boys older than 13 years, there is a sudden increase. For this reason, boys have higher values than girls. Diastolic BP shows a linear increase in both sexes. BP increases with height in both sexes. In spite of the sudden rise in systolic BP among the boys taller than 145 cm, the increase in systolic BP in relationship to height is smaller and more homogeneous than the increase seen with age. As the BP variations with height are smaller and more homogeneous than those related to age, it is preferable to evaluate this parameter by BP-height rather than by BP-age.
- Published
- 1993
46. S35b, a new phenylsulfonylfuroxan compound, inhibits thrombin-induced synthesis of platelet-activating factor and prostacyclin in human endothelial cells
- Author
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Dario Ghigo, Federico Bussolino, Roberta Todde, P. Alessio, Gianpiero Pescarmona, Rosella Calvino, U. Till, Amalia Bosia, A. M. Gasco, R. Heller, and Roberta Fruttero
- Subjects
Umbilical Veins ,medicine.medical_specialty ,Immunology ,Prostacyclin ,Pharmacology ,Toxicology ,chemistry.chemical_compound ,Phospholipase A2 ,Thrombin ,Acetyltransferases ,1-Methyl-3-isobutylxanthine ,Internal medicine ,Cyclic AMP ,medicine ,Humans ,Pharmacology (medical) ,Iloprost ,Platelet Activating Factor ,Cyclic GMP ,Cells, Cultured ,Oxadiazoles ,Forskolin ,biology ,Platelet-activating factor ,Colforsin ,respiratory system ,Epoprostenol ,Enzyme Activation ,Endothelial stem cell ,Endocrinology ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Human umbilical vein endothelial cell ,Arachidonic acid ,Endothelium, Vascular ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Endothelial cells (EC) produce platelet activating factor (PAF) and prostacyclin (PGI2) in response to inflammatory agents such as thrombin. Upon cell stimulation a calcium-dependent phospholipase A2 (PLA2) is activated which hydrolyzes a membrane phospholipid to yield 1-0-alkyl-2-lyso-sn-glycero-3-phospho-choline (lyso-PAF) and free arachidonic acid. Lyso-PAF is in turn converted into PAF by a specific acetyltransferase and arachidonic acid is metabolized via cyclic endoperoxides to PGI2. In the present study we report that S35b (4-methyl-3-phenylsulfonylfuroxan), an new phenyl-sulfonylfuroxan compound with potent antiaggregatory effect, inhibits thrombin-induced PAF synthesis and acetyltransferase activation as well as PGI2 production in human umbilical vein endothelial cells (HUVEC) in a concentration dependent way. Additionally, we show that S35b stimulates the production of cyclic GMP (cGMP) in HUVEC in a concentration- and time-dependent manner. At high concentration, S35b potentiates the cAMP increase induced by iloprost or forskolin without having a significant influence on cAMP level itself. Potentiation of cAMP increase during agonist-induced EC stimulation seems not to be important for the effect of S35b on cellular function as the compound is active in inhibiting PAF production when endothelial cells are pretreated with indomethacin to block PGI2 synthesis. The increase of cGMP evoked by S35b may account for the effect on endothelial cell function.
- Published
- 1993
47. Synthesis and H2-antagonist properties of some 1,2,5-thiadiazole-1-oxide derivatives
- Author
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G, Sorba, A, Di Stilo, A M, Gasco, M, Gili, A, Gasco, and M, Orsetti
- Subjects
Cerebral Cortex ,Magnetic Resonance Spectroscopy ,Histamine H2 Antagonists ,Heart Rate ,Guinea Pigs ,Thiadiazoles ,Isoproterenol ,Animals ,Carbachol ,Muscle, Smooth ,In Vitro Techniques ,Histamine - Abstract
A series of 1,2,5-thiadiazole-1-oxide derivatives has been synthesized and studied for its H2-antagonist properties. These derivatives can be considered derived from classical H2-antagonists in which the structure was deeply modified in order to evidence the minimal structural requirements for the activity. It was found that it is sufficient to have the 1,2,5-thiadiazole-1-oxide ring substituted with an alkylamino moiety and with an aliphatic chain linked to the hydroxy or ether group to achieve compounds as active as cimetidine. A few considerations on the binding on guinea-pig cerebral cortex of a series of H2-antagonists with more and more simplified structures are also reported.
- Published
- 1992
48. Synthesis and cardiovascular properties of furazanyl-1,4-dihydropyridines and of furoxanyl analogues
- Author
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A M, Gasco, R, Fruttero, G, Sorba, A, Gasco, R, Budriesi, and A, Chiarini
- Subjects
Male ,Dihydropyridines ,Magnetic Resonance Spectroscopy ,Nifedipine ,Guinea Pigs ,Aorta, Thoracic ,Cardiovascular Agents ,In Vitro Techniques ,Calcium Channel Blockers ,Myocardial Contraction ,Muscle, Smooth, Vascular ,Heart Rate ,Heterocyclic Compounds ,Animals ,Female ,Muscle Contraction - Abstract
A series of furazanyl- and furoxanyl-1,4-dihydropyridines has been synthesized and tested for their cardiovascular activity. The new compounds showed a modest activity in comparison with nifedipine and some selectivity for the myocardial muscle. The most active compound was diethyl 1,4-dihydro-2,6-dimethyl-4-(3-phenyl-4-furoxanyl)-3,5-pyridine dicarboxylate, 4d.
- Published
- 1992
49. Novel genes mediating cisplatin resistance in head and neck cancer
- Author
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M. Gasco, N. Syed, H. Coley, I. Colantonio, M. Merlano, and T. Crook
- Subjects
Cisplatin ,Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Cisplatin resistance ,Head and neck cancer ,medicine.disease ,Novel gene ,Oncology ,medicine ,Cancer research ,Squamous Carcinomas ,Head and neck ,business ,medicine.drug - Abstract
e22135 Background: Chemo-radiotherapy with cisplatin-based regimens offers the possibility of cure to a subset of patients with surgically non-resectable squamous carcinomas of the head and neck (HNSCC), but outcome is frequently limited by acquired drug resistance. We have sought novel genes mediating cisplatin resistance in HNSCC. Methods: We derived in vitro cisplatin resistant variants of the HN5 HNSCC cell line and performed micro-array anaylsis to identify differentially expressed genes. Differences in gene expression were confirmed by qPCR and /or western blotting. Methylation-dependent transcriptional silencing of down-regulated genes was studied by bisulphate sequencing and methylation specific PCR. Selected genes were further analysed in a cohort of stage III and IV HNSCC patients treated with cisplatin-based chemo-radiotherapy. Results: We have identified a panel of genes in which changes in expression occur with acquisition of cisplatin resistance both in vitro and, some cases, in vivo. Up-regulated genes include TAOK1, BZW1 and RECQL, whereas down-regulated genes include FAM83D, PAFAH1B2, DLL1, ABPA1 and FH. Conclusions: We report the identification of a novel panel of genes which function as determinants of cisplatin sensitivity. Analysis of expression and/or epigenetic regulation of these genes may have clinical utility in prediction of patients likely to respond to highly toxic combined modality chemo-radiotherapy. No significant financial relationships to disclose.
- Published
- 2009
- Full Text
- View/download PDF
50. [Significance of cholesterol as a risk factor in children and adolescents]
- Author
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R, Elcarte López and M, Gasco Eguiluz
- Subjects
Male ,Adolescent ,Arteriosclerosis ,Lipoproteins ,Hypercholesterolemia ,Age Factors ,Hyperlipidemia, Familial Combined ,Coronary Disease ,Lipids ,Risk Factors ,Child, Preschool ,Humans ,Female ,Child - Abstract
Although nowadays there is still quite a controversy when it comes to accept that cardiovascular risk factors, e.g. hyperlipemias, exist right from paediatric age, we have already enough data to confirm this fact. First of all, it has been proved the presence of early atheroma injuries since paediatric age, as well as the relationship between lipid and lipoprotein serum levels and those injuries. Secondly, a clear tracking of those lipids during childhood reinforces this fact. And finally, the strong cholesterol and serum lipoproteins family aggregation actually confirm that hyperlipemias are a cardiovascular risk factor right from childhood.
- Published
- 1991
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