Open access articles by Roberto Scatena
Current Medicinal Chemistry
Nitric oxide is becoming an increasingly important signalling molecule implicated in a growing nu... more Nitric oxide is becoming an increasingly important signalling molecule implicated in a growing number of physiological and pathophysiological processes. Moreover, with the recent advances in nitric oxide biochemistry, many well known drugs have been shown to act totally or partially by modulating NO metabolism with varying therapeutic results. The classic organic nitrates have been shown to exhibit beneficial therapeutic but suffer from some well known pitfalls (tolerability induction, abrupt cephalea and hypotension). Similarly, sydnonimines, another well known class of NO donor drugs, have a characteristically low therapeutic index (i.e., cyanide toxicity). At present, pharmacological researchers are designing and synthesising various chemical compounds capable of modulating NO metabolism for therapeutic purposes that also possess an optimal therapeutic index. Specifically, various new classes of NO donors are under intense pharmacological investigation (such as S-nitrosothiols, diazeniumdiolates, furoxans, zeolites and so on), each characterised by a particular pharmacokinetic and pharmacodynamic profile. To know the pharmacological development of these new NO donor drugs could help to ameliorate the use of these molecules in various therapeutic protocols. In fact, the pharmacologically modulated nitric oxide release showed to have an important therapeutic impact in the treatment of diseases such as arteriopathies, various acute and chronic inflammatory conditions, and several degenerative diseases. At present, the most important obstacle in the field of new NO donor drugs seems to be carefully targeting NO release to a particular tissue at an optimal concentration, so as to achieve a beneficial action and to limit possible toxic effects.
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Papers by Roberto Scatena
Journal of Medicinal Chemistry, 2002
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Journal of Medicinal Chemistry, 2002
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Scientific Reports, 2015
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Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1989
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The cooperative effect of inositol hexakisphosphate (IHP), bezafibrate (BZF), and clofibric acid ... more The cooperative effect of inositol hexakisphosphate (IHP), bezafibrate (BZF), and clofibric acid (CFA) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous human hemoglobin (HbNO) has been investigated quantitatively. In the presence of IHP, BZF, and CFA, the X-band EPR spectra and the absorption spectra in the Soret region of HbNO display the same basic characteristics described in the presence of 2,3-diphosphoglycerate (2,3-DPG), which have been attributed to a low affinity conformation of the tetramer. Addition to HbNO of two allosteric effectors together (such as IHP and BZF, or IHP and CFA) further stabilizes the low affinity conformation of the ligated hemoprotein (i.e., HbNO). Moreover, in the presence of saturating amounts of IHP, the affinity of BZF and CFA for HbNO increases by about fifteenfold. Likewise, in the presence of both IHP and BZF, as well as in IHP and CFA, the oxygen affinity for ferrous human hemoglobin (Hb) is reduced with respect to that observed in the presence of IHP, BZF, or CFA alone, which in turn is lower than that reported in the absence of any allosteric effector. All the data were obtained at pH 7.0 (in 1.0 x 10(-1) M N-[2-hydroxyethyl]-piperazine-N'-[2-ethanesulfonic acid]/NaOH buffer system plus 1.0 x 10(-1) M NaCl), as well as at 100 K and/or 20 degrees C. The results here reported represent clearcut evidence for the cooperative and specific (i.e., functionally relevant) binding of IHP, BZF, and CFA to Hb.
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Journal of Cellular and Molecular Medicine, 2005
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Expert Opinion on Investigational Drugs, 2005
The discovery of the multiple physiological and pathophysiological processes in which nitric oxid... more The discovery of the multiple physiological and pathophysiological processes in which nitric oxide (NO) is involved has promoted a great number of pharmacological researches to develop new drugs that are capable of influencing NO production directly and/or indirectly for therapeutic purposes (i.e, NO-releasing drugs, NO-inhibiting drugs, and phosphodiesterase V inhibitors). In particular, the so-called NO donor drugs could actually have an important therapeutic effect in the treatment of many diseases such as arteriopathies (atherosclerosis and its sequelae, arterial hypertension and some forms of male sexual impotence), various acute and chronic inflammatory conditions (colitis, rheumatoid arthritis and tissue remodelling), and several degenerative diseases (Alzheimer's disease and cancer). The old organic nitrates show some well-known pitfalls including the induction of tolerance and acute side effects related to abrupt vasodilation such as cephalea and hypotension, which limit their therapeutic indications. A low therapeutic index (i.e., peroxynitrite toxicity) has always characterised the sydnonimines class. A series of interesting new classes of NO donors are under intense pharmacological investigation and scrutiny (S-nitrosothiols, diazeniumdiolates and NO hybrid drugs), each characterised by a particular pharmacokinetic and pharmacodynamic profile. The most important obstacle in the field of NO donor drugs is represented by the difficulty in targeting NO release, and thereby its effects, to a particular tissue.
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American Journal of Physiology-cell Physiology, 2007
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Iubmb Life, 2004
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European Journal of Pharmacology, 2007
Peroxisome proliferator activated receptors (PPARs) are a class of nuclear receptors now actively... more Peroxisome proliferator activated receptors (PPARs) are a class of nuclear receptors now actively investigated for their involvement in lipid and glucidic metabolism, immune regulation and cell differentiation. Drugs binding and activating PPARs are therefore attracting attention for their potential therapeutic role in various diseases like type 2 diabetes, dyslipidemias, atherosclerosis, obesity (i.e., metabolic syndrome). Agonists of these receptors have been
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Biophysical Chemistry, 1998
A minor hemoglobin component of human red cell hemolysate, HbA1c, is the result of the non-enzyma... more A minor hemoglobin component of human red cell hemolysate, HbA1c, is the result of the non-enzymatic reaction of glucose with the α-amino groups of the valine residues at the N-terminus of the β-chains of human hemoglobin. In this paper, the effect of protons, chloride and 2,3-diphosphoglycerate (DPG) on the functional properties of HbA1c has been investigated in some details. Moreover,
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Biomedical Chromatography - BIOMED CHROMATOGR, 1993
The separation of reduced and oxidized glutathione at an absolute sensitivity of about 100 pg by ... more The separation of reduced and oxidized glutathione at an absolute sensitivity of about 100 pg by micellar electrokinetic capillary chromatography without derivatization is described. The time required for the separation is less than 10 min (the time between two following injections is about 15 min). The separation is characterized by high efficiency and good reliability. A partition mechanism is responsible for the high resolution observed. The method was utilized for the analysis of commercial preparations of glutathione and a good agreement with the expected results was obtained; the oxidation of the commercial glutathione in solution was easily analysed.
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PROTEOMICS - CLINICAL APPLICATIONS, 2010
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PROTEOMICS – CLINICAL APPLICATIONS, 2008
The recent development of compounds that induce cell differentiation in various types of cancer c... more The recent development of compounds that induce cell differentiation in various types of cancer cells has enabled the molecular mechanisms governing this kind of induced cancer regression to be investigated. Moreover, this approach to investigating the pathophysiology of neoplasia represents a promising experimental model for proteomic analysis of cancer cells. Modulating neoplastic cell differentiation grade may reveal cytodifferentiation-related protein expression changes, and doing so in vitro has the advantage of less biological variation. Hence, this analysis brings attention to molecular targets of the so-called differentiating factors (i.e., retinoids, hybrid polar compounds, tyrosine kinase inhibitors, etc.) as well as proteins that are frequently associated with differentiation/dedifferentiation processes. The in vitro study of these proteins and of their pathogenetic roles in cancer may ultimately result in the discovery of cancer biomarkers with diagnostic, prognostic, and therapeutic applications.
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PPAR Research, 2008
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Journal of Bioluminescence and Chemiluminescence, 1998
Non-enzymatic glycosylation (NEG) of collagen has been previously shown to significantly influenc... more Non-enzymatic glycosylation (NEG) of collagen has been previously shown to significantly influence the reactive oxygen metabolism (ROM) of phagocytic cells in healthy subjects. Considering the role of NEG in the pathophysiology of diabetes, we have further analysed the oxidative metabolism of polymorphonuclear cells (PMNs) and monocytes in 23 patients with non-insulin dependent diabetes mellitus in order to better elucidate a possible pathogenic role of NEG of the extracellular matrix in long-term complications of diabetes. Experiments were performed in triplicate on native-collagen and glycated-collagen coated vials, using a chemiluminescence (CL) assay. Results show that PMNs from diabetic patients display a significant increased basal and zymosan-induced CL activity with respect to controls that are not related to the glycation state of the substrate. Conversely, the CL activity of monocytes induced by zymosan shows a decrease in diabetic patients with respect to healthy volunteers (p < 0.05). Moreover, monocyte CL was reduced by the glycated matrix, both in healthy volunteers and in diabetic subjects (p < 0.05 and p < 0.01, respectively). These data highlight a complex role of phagocytic leukocytes in the pathophysiology of extracellular matrix alterations secondary to NEG that are typically present in clinical conditions such as diabetes or ageing.
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Journal of Bioluminescence and Chemiluminescence, 1996
The pathophysiology of the acquired extracellular matrix alterations, like non-enzymatic glycosyl... more The pathophysiology of the acquired extracellular matrix alterations, like non-enzymatic glycosylation (NEG) of proteins secondary to diabetes or ageing, is not well characterized, particularly considering its relationship with leukocytes. We have analysed the influence of collagen NEG on the fundamental function of phagocytic cells, i.e. the production of reactive oxygen species (ROS). To this aim, we considered the activity of polymorphonuclear leukocytes and monocytes incubated in the presence of both non-glycated and glycated collagen. ROS production was monitored by chemi-luminescence (CL), a standardized and sensitive assay of phagocytes oxidative metabolism. All experiments were performed in triplicate on collagen-coated and glycated collage-coated vials. Results showed that PMNs ROS metabolism appeared unrelated to the glycation state of the substrate. Conversely, data regarding zymosan-induced CL by monocytes indicated a significant and intriguing decrease in reactive oxygen metabolism, which appeared greatly compromised by the glycation state of the matrix (monocytes in collagen, 197.4 +/- 31.2 vs. monocytes in glycated collagen, 138.0 +/- 20.4; p < 0.001 expressed as counts/cell/60 min). These data highlight the different role of polymophonuclear and monocytic phagocytes in the pathophysiology of the acquired extracellular matrix alteration secondary to non-enzymatic glycosylation (NEG) of proteins.
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Journal of Molecular Biology, 1996
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Open access articles by Roberto Scatena
Papers by Roberto Scatena