Maurizio Campo - Academia.edu (original) (raw)
Papers by Maurizio Campo
Frontiers in Allergy
Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from t... more Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with drugs. DIP includes phototoxicity and photoallergy. A phototoxic reaction is obtained when topical and systemic drugs or their metabolites absorb light inducing a direct cellular damage, while a photoallergic reaction takes place when the interaction between drugs and ultraviolet radiations causes an immune cutaneous response. Clinically, phototoxicity is immediate and appears as an exaggerated sunburn, whereas photoallergy is a delayed eczematous reaction. DIP may show several clinical subtypes. In this mini-review we report the pathogenetic mechanisms and causative drugs of DIP. We offer a detailed description of DIP clinical features in its classical and unusual subtypes, such as hyperpigmentation/dyschromia, pseudoporphyria, photo-onycolysis, eruptive teleangiectasia, pellagra-like reaction, lichenoid reaction, phot...
Biomedicines, 2021
miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeu... more miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (−18.5%), DBP (−18%), HDL-C and LDL-C (+3% and −5.42%), glucose (−2.15%), BMI (−3.23%), fibrinogen (−11%), CRP (−17.5%,), AIx (−49.1%) PWV (−32.2%), and monocyte miR expression (miR...
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Biomolecules, 2019
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An int... more β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduce...
Pharmacological Research Communications, 1988
Identification of paraoxonase 3 gene (PON3) missense mutations in a population of southern Italy
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2004
PON gene family includes at least three members termed PON1, PON2 and PON3, and it is mapped on h... more PON gene family includes at least three members termed PON1, PON2 and PON3, and it is mapped on human chromosome 7q21-q22. PON1 and PON3 gene products are constituents of high density lipoprotein (HDL) and have many enzymatic properties and antioxidant activity. PONs are proposed to participate in the prevention of low density lipoprotein (LDL) oxidation. PON1 and PON2 genes have missense polymorphisms, but, to date, no missense variants are reported in PON3 gene. In this work we explored the existence of genetic variants within the PON3 coding sequences. Five point mutations were identified by direct sequencing of genomic DNA derived from 250 randomly selected DNA samples of 1143 blood donors living in southern Italy. Three were silent mutations, while two were missense mutations that give rise to amino acid substitutions at positions 311 (S>T) and 324 (G>D). The missense variations in the DNA of the 1143 samples had frequencies of 0.22% (5 out of 2286 alleles) for the S311T mutation, and 0.57% (13 out of 2286 alleles) for the G324D mutation. The effect of these variants on the metabolic activity of paraoxonase 3 remains to be further evaluated.
Evaluation of putative cytotoxic activity of crude extracts from Onopordum acanthium leaves and Spartium junceum flowers against the U-373 glioblastoma cell line
Pakistan journal of pharmaceutical sciences, 2015
Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leave... more Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leaves and Spartium junceum flowers were tested for cytotoxic effects against glioblastoma U-373 tumour cells. Onopordum acanthium extract was found to be ~5 times more cytotoxic than Spartium junceum (IC50 values of 309 and 1602μg/ml, respectively). Similar to most chemotherapeutic agents killing through the intrinsic pathway, Onopordum killed the cells via apoptosis, which was confirmed by the activation of caspase-3. Spartium exerted its weak cytotoxic effect, presumably by a caspase-independent, non-apoptotic form of necrotic-like programmed cell death. Onopordum acanthium is considered a promising plant for the researchers investigating putative biological activities, particularly antitumour and immune-related activity.
Fluvoxamine-induced alterations in plasma concentrations of imipramine and desipramine in depressed patients
International journal of clinical pharmacology research, 1993
The effect of fluvoxamine maleate, 100 mg/day for 10 days, on plasma concentrations of tricyclic ... more The effect of fluvoxamine maleate, 100 mg/day for 10 days, on plasma concentrations of tricyclic antidepressants was studied in 15 depressed patients on maintenance therapy with imipramine (7 pts.) or desipramine (8 pts.). In the subgroup treated with imipramine, plasma levels of imipramine increased significantly (p < 0.001) during fluvoxamine coadministration, while levels of desipramine were not modified. Addition of fluvoxamine to patients on a stable desipramine dosage regimen resulted in a slight, but statistically not significant, increase in desipramine plasma concentrations. These results suggest that fluvoxamine is a potent inhibitor of imipramine demethylation, while it has a weak effect on the hydroxylation of desipramine.
IRFI-016, a new radical scavenger, limits ischemic damage following coronary artery occlusion in rats
Research communications in chemical pathology and pharmacology, 1992
The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new... more The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new radical scavenger were studied following six hours of myocardial ischemia, induced by left coronary artery occlusion in male rats. The loss of myocardial Creatinine Phosphokinase activity (CPK), myocardial Myeloperoxidase Activity (MPO), ECG, survival rate, and Pressure Rate Index (PRI) were evaluated in SHAM, control (vehicle i.p. injection) and IRFI-016 (200 mg/kg i.p., 30 minutes before occlusion) treated animals. CPK was significantly reduced and MPO significantly enhanced in the ischemic areas of the hearts obtained from vehicle treated rats when compared to SHAM operated ones. Pretreatment with IRFI-016 significantly attenuated (52%) loss of CPK activity in ischemic hearts and the increase in MPO activity, but did not increase PRI, thus indicating that this substance reduces the myocardial ischemic demand for oxygen. Occlusion of the coronary artery, furthermore, was associated wi...
Extracellular superoxide dismutase (EC-SOD) gene mutations screening in a sample of Mediterranean population
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2005
The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells an... more The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells and tissues. Extracellular SOD (EC-SOD/SOD3) is a major superoxide scavenger and it is located on cell surfaces and primarily in extracellular matrix, and binds heparan sulfates by its carboxyterminal portion. Human EC-SOD gene is located on chromosome 4 and comprises three exons and two introns. The SOD3 coding sequence is entirely located within exon 3 and has missense polymorphisms. The Arg213Gly mutation affects the function of the carboxyterminus and correlates with several diseases. In this work, we explored genetic variants within EC-SOD gene of subjects living in southern Italy. Four new variations were detected: one was silent mutation, while three were missense variations that give rise to amino acid substitutions at position 131 (F&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C), 160 (V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;L) and 202 (R&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;L) in the mature product. The Arg213Gly variant was not found. The missense mutations in the DNA of assayed 2400 chromosomes had frequencies of 5.34% for the F131C variation, 0.25% for the V160L variation and 0.84% for the R202L variation. The effect of these alterations on the metabolic activity and diseases remains to be further explained.
OBJECTIVES The purpose of this study was to evaluate the value of platelet reactivity (PR) in pre... more OBJECTIVES The purpose of this study was to evaluate the value of platelet reactivity (PR) in predicting the response to treatment and outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention assisted by glycoprotein (GP) IIb/IIIa inhibition. BACKGROUND There is limited prognostic information on the role of spontaneous or drug-modulated PR in STEMI patients. METHODS The PR was measured with Platelet Function Analyzer (PFA)-100 and light transmission aggregometry (LTA) using adenosine diphosphate as agonist in 70 consecutive STEMI patients at entry (PR-T0), 10 min after GP IIb/IIIa bolus (PR-T1), and discharge (PR-T2) and in 30 stable angina (SA) patients (PR-SA). Complete platelet inhibition (CPI) was based on closure time Ͼ300 s by PFA-100 and percentage inhibition of platelet aggregation Ͼ95% by LTA. Clinical, electrocardiographic, and angiographic responses to treatment during 1-year follow-up were collected. RESULTS According to both techniques, PR-T0 was higher than: 1) PR-T2 and PR-SA; 2) in those without CPI at T1; and 3) in patients with final Thrombolysis In Myocardial Infarction (TIMI) flow grade Ͻ3. The PR-T0 assessed with PFA-100 correlated with: 1) corrected TIMI frame count (r ϭ Ϫ0.6, p Ͻ 0.001); 2) ST-segment resolution (r ϭ 45, p Ͻ 0.001); and 3) creatine kinase-MB (r ϭ Ϫ0.47, p Ͻ 0.001). At 1 year, patients with high PR-T0 showed an adjusted 5-to 11-fold increase in the risk of death, reinfarction, and target vessel revascularization (hazard ratio [HR] 11, 95% confidence interval [CI] 1.5 to 78 [p ϭ 0.02] in PFA-100; HR 5.2, 95% CI 1.1 to 23 [p ϭ 0.03] in LTA). CONCLUSIONS The PR at entry affects response to GP IIb/IIIa inhibition, mechanical treatment, and long-term outcome in STEMI patients undergoing primary intervention.
Journal of Chromatography B: Biomedical Sciences and Applications, 1998
An isocratic high-performance liquid chromatography (HPLC) method with ultraviolet detection for ... more An isocratic high-performance liquid chromatography (HPLC) method with ultraviolet detection for the simultaneous determination of clozapine and its two major metabolites in human plasma is described. Analytes are concentrated from alkaline plasma by liquid-liquid extraction with n-hexane-isoamyl alcohol (75:25, v / v). The organic phase is back-extracted with 150 ml of 0.1 M dibasic phosphate (pH 2.2 with 25% H PO). Triprolidine is used as internal standard. For the 3 4 chromatographic separation the mobile phase consisted of acetonitrile-0.06 M phosphate buffer, pH 2.7 with 25% phosphoric acid (48:52, v / v). Analytes are eluted at a flow-rate of 1.0 ml / min, separated on a 25034.60 mm I.D. analytical column packed with 5 mm C silica particles, and measured by UV absorbance detection at 254 nm. The separation requires 6 7 min. Calibration curves for the three analytes are linear within the clinical concentration range. Mean recoveries were 92.7% for clozapine, 82.0% for desmethylclozapine and 70.4% for clozapine N-oxide. C. V. values for intra-and inter-day variabilities were #13.8% at concentrations between 50 and 1000 ng / ml. Accuracy, expressed as percentage error, ranged from 219.8 to 2.8%. The method was specific and sensitive with quantitation limits of 2 ng / ml for both clozapine and desmethylclozapine and 5 ng / ml for clozapine N-oxide. Among various psychotropic drugs and their metabolites, only 2-hydroxydesipramine caused significant interference. The method is applicable to pharmacokinetic studies and therapeutic drug monitoring.
Therapeutic Drug Monitoring, 1993
Phenobarbital Induces the 2-Hydroxylation of Desipramine
Therapeutic Drug Monitoring, 1996
The kinetics of a single oral dose of desipramine (DMI; 100 mg) were studied in eight epileptic p... more The kinetics of a single oral dose of desipramine (DMI; 100 mg) were studied in eight epileptic patients chronically treated with phenobarbital (PB) and in eight drug-free healthy controls. All subjects were extensive metabolizers with respect to the genetically determined CYP2D6-related metabolic polymorphism. Compared with controls, epileptic patients exhibited lower peak plasma DMI concentrations (74 +/- 24 vs. 107 +/- 32 nmol/L; means +/- SD, p < 0.05), smaller DMI area-under-the-curve values (1,943 +/- 461 vs. 3,234 +/- 1,145 nmol L-1 h; p < 0.01), and shorter DMI elimination half-lives (15.1 +/- 2.1 vs. 20.6 +/- 3.4 h; p < 0.01). The proportion of the dose excreted as 2-hydroxydesipramine (2-OH-DMI) was significantly higher in the patients (54 +/- 8 vs. 40 +/- 9%; p < 0.05). In one single poor metabolizer volunteer, a 3-week treatment with PB was associated with no major changes in DMI kinetics, but the urinary excretion of 2-OH-DMI tended to increase. These results suggest that PB is an inducer of the 2-hydroxylation of DMI, a reaction primarily catalyzed by CYP2D6, but do not provide further information on the specific P450 isoenzyme(s) being induced.
Innate Immunity, 2009
Hyaluronan is a biological polysaccharide that may exist in different degrees of polymerization. ... more Hyaluronan is a biological polysaccharide that may exist in different degrees of polymerization. Several investigations reported that low molecular mass hyaluronan may have pro-inflammatory activity, while high molecular mass hyaluronan can exert beneficial effects. Starting from these data, the aim of this study was to investigate the effect of hyaluronan of different molecular mass in mouse articular chondrocyte cultures stimulated with lipopolysaccharide (LPS). Inflammation was induced in chondrocytes by acute treatment with 2.0 µg/ml LPS. High levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ and iNOS gene expression and their related proteins were found in chondrocytes 24 h after treatment with LPS. High concentrations of NO, NF-κB activation, IκBα phosphorylation and apoptosis, evaluated by the increase in caspase-3 expression and its related protein amount were also produced by LPS stimulation. In contrast, LPS reduced aggrecan and collag...
Changes in urine volume and urinary electrolyte excretion after intracerebroventricular injection of arecoline and hemicholinium-3
Life Sciences, 1991
Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, w... more Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, which appears to be atropine-sensitive and, perhaps, independent from the renal innervation. However the role of cholinergic neurons in central control of renal function is not well understood. The purpose of this study was to further investigate whether brain acetylcholine stores are able to influence kaliuresis and natriuresis in conscious rats. Therefore, the renal response to cholinergic drugs was examined in Wistar rats which underwent to a 0.15 M NaCl solution (saline) load administered by gavage. Central injection of arecoline, a muscarinic agonist, produced a dose-dependent reduction in water diuresis and a highly significant increase in sodium excretion within two hours from the oral saline load. An intracerebroventricular (ICV) injection of methylatropine completely blocked both the antidiuretic and the natriuretic response induced by arecoline. Hemicholinium-3 (HC), centrally administered at a dose (34.8 nmol) known to be capable of inducing a maximal depletion of brain acetylcholine, elicited a time-dependent antidiuretic effect accompanied by a highly significant reduction in potassium and sodium urinary excretion. Therefore, we suggest that brain cholinergic neurons are involved in the regulation of the electrolyte balance.
Antioxidant Activity of Chondroitin Sulfate
Chondroitin Sulfate: Structure, Role and Pharmacological Activity, 2006
Publisher Summary Molecules in biological systems often perform more than one function. Many stru... more Publisher Summary Molecules in biological systems often perform more than one function. Many structures have the ability to scavenge free radicals, acting in living organisms as antioxidants, although their main biological function is different. During oxidative stress, the increase in the concentration of these molecules seems to be a biological response that in synergism with the other antioxidant defense systems may protect cells from oxidation. Among these structures, chondroitin sulfate (CS) has increasingly attracted the interest of many research groups. This chapter discusses the action of CSs in reducing molecular damage caused by free radicals and associated oxygen reactants. The chondroitin‐4‐sulfate exerts higher antioxidant activity than chondroitin‐6‐sulfate. The specific sulfation pattern seems to play a central role in the inhibitory activity of these molecules on free radicals because the suggested mechanism is entrapment by the chelation of those metal cations, such as Fe 2+ and Cu 2+ , which, in turn by Fenton's reaction, are responsible of reactive oxygen species production. Chondroitin sulfate's protection on a wide variety of molecules (i.e., lipids, proteins, and DNA) and in various cells from different organs is documented in several in vitro and in vivo experimental studies.
Cell Biochemistry and Function, 2014
The aim of this study was to investigate the involvement of exchange proteins directly activated ... more The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB inhibition although EPAC seems to be more involved than PKA.
Life Sciences, 2004
We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) ind... more We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1h (IL-1h) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 F 0.03 nmol/mg protein; KA + LVT = 0.13 F 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 F 0.2 nmol/mg protein; KA + LVT = 0,33 F 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 F 1 Amol/g protein; KA + LVT = 15 F 2 Amol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 F 0.8 Amol/g protein; KA + LVT = 13 F 0.3 Amol/g protein; P < 0.05), reduced brain IL-1h mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuroprotective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.
Veterinary Research Communications, 2003
Frontiers in Allergy
Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from t... more Drug-induced photosensitivity (DIP) is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, mostly ultraviolet A, with drugs. DIP includes phototoxicity and photoallergy. A phototoxic reaction is obtained when topical and systemic drugs or their metabolites absorb light inducing a direct cellular damage, while a photoallergic reaction takes place when the interaction between drugs and ultraviolet radiations causes an immune cutaneous response. Clinically, phototoxicity is immediate and appears as an exaggerated sunburn, whereas photoallergy is a delayed eczematous reaction. DIP may show several clinical subtypes. In this mini-review we report the pathogenetic mechanisms and causative drugs of DIP. We offer a detailed description of DIP clinical features in its classical and unusual subtypes, such as hyperpigmentation/dyschromia, pseudoporphyria, photo-onycolysis, eruptive teleangiectasia, pellagra-like reaction, lichenoid reaction, phot...
Biomedicines, 2021
miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeu... more miR profile could be associated to CV risk, and also to prognosis/outcome in response to therapeutic approach. We aimed to evaluate if anti-hypertensive drugs enalapril, losartan or olmesartan have effects on monocyte miR profile in essential hypertensives without target organ involvement. For this purpose, 82 hypertensives and 49 controls were included; we evaluated SBP/DBP, lipid profile, glucose, CRP, fibrinogen, arterial stiffness indices (PWV; AIx), and cIMT at baseline (T0) and after 24 weeks of treatment (T1). Subjects with LDL-C ≥ 160 mg/dL, TG ≥ 200 mg/dL, BMI ≥ 30, and other additional CV risk factors were excluded. Patients who were prescribed to receive once-a-day enalapril 20 mg, losartan 100 mg or olmesartan 20 mg were eligible for the study. At T1, we found a significant improvement of SBP (−18.5%), DBP (−18%), HDL-C and LDL-C (+3% and −5.42%), glucose (−2.15%), BMI (−3.23%), fibrinogen (−11%), CRP (−17.5%,), AIx (−49.1%) PWV (−32.2%), and monocyte miR expression (miR...
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Biomolecules, 2019
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An int... more β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 μg/100 μL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 μL) or its vehicle (100 μL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-ĸB mRNA expression and reduce...
Pharmacological Research Communications, 1988
Identification of paraoxonase 3 gene (PON3) missense mutations in a population of southern Italy
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2004
PON gene family includes at least three members termed PON1, PON2 and PON3, and it is mapped on h... more PON gene family includes at least three members termed PON1, PON2 and PON3, and it is mapped on human chromosome 7q21-q22. PON1 and PON3 gene products are constituents of high density lipoprotein (HDL) and have many enzymatic properties and antioxidant activity. PONs are proposed to participate in the prevention of low density lipoprotein (LDL) oxidation. PON1 and PON2 genes have missense polymorphisms, but, to date, no missense variants are reported in PON3 gene. In this work we explored the existence of genetic variants within the PON3 coding sequences. Five point mutations were identified by direct sequencing of genomic DNA derived from 250 randomly selected DNA samples of 1143 blood donors living in southern Italy. Three were silent mutations, while two were missense mutations that give rise to amino acid substitutions at positions 311 (S&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T) and 324 (G&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;D). The missense variations in the DNA of the 1143 samples had frequencies of 0.22% (5 out of 2286 alleles) for the S311T mutation, and 0.57% (13 out of 2286 alleles) for the G324D mutation. The effect of these variants on the metabolic activity of paraoxonase 3 remains to be further evaluated.
Evaluation of putative cytotoxic activity of crude extracts from Onopordum acanthium leaves and Spartium junceum flowers against the U-373 glioblastoma cell line
Pakistan journal of pharmaceutical sciences, 2015
Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leave... more Crude hydromethanolic (80% methanol) extracts produced by maceration of Onopordum acanthium leaves and Spartium junceum flowers were tested for cytotoxic effects against glioblastoma U-373 tumour cells. Onopordum acanthium extract was found to be ~5 times more cytotoxic than Spartium junceum (IC50 values of 309 and 1602μg/ml, respectively). Similar to most chemotherapeutic agents killing through the intrinsic pathway, Onopordum killed the cells via apoptosis, which was confirmed by the activation of caspase-3. Spartium exerted its weak cytotoxic effect, presumably by a caspase-independent, non-apoptotic form of necrotic-like programmed cell death. Onopordum acanthium is considered a promising plant for the researchers investigating putative biological activities, particularly antitumour and immune-related activity.
Fluvoxamine-induced alterations in plasma concentrations of imipramine and desipramine in depressed patients
International journal of clinical pharmacology research, 1993
The effect of fluvoxamine maleate, 100 mg/day for 10 days, on plasma concentrations of tricyclic ... more The effect of fluvoxamine maleate, 100 mg/day for 10 days, on plasma concentrations of tricyclic antidepressants was studied in 15 depressed patients on maintenance therapy with imipramine (7 pts.) or desipramine (8 pts.). In the subgroup treated with imipramine, plasma levels of imipramine increased significantly (p < 0.001) during fluvoxamine coadministration, while levels of desipramine were not modified. Addition of fluvoxamine to patients on a stable desipramine dosage regimen resulted in a slight, but statistically not significant, increase in desipramine plasma concentrations. These results suggest that fluvoxamine is a potent inhibitor of imipramine demethylation, while it has a weak effect on the hydroxylation of desipramine.
IRFI-016, a new radical scavenger, limits ischemic damage following coronary artery occlusion in rats
Research communications in chemical pathology and pharmacology, 1992
The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new... more The effects of IRFI-016 [2(2,3 Dihydro-5-Acetoxy 4,6,7-Trimethyl-Benzofuranyl) acetic acid] a new radical scavenger were studied following six hours of myocardial ischemia, induced by left coronary artery occlusion in male rats. The loss of myocardial Creatinine Phosphokinase activity (CPK), myocardial Myeloperoxidase Activity (MPO), ECG, survival rate, and Pressure Rate Index (PRI) were evaluated in SHAM, control (vehicle i.p. injection) and IRFI-016 (200 mg/kg i.p., 30 minutes before occlusion) treated animals. CPK was significantly reduced and MPO significantly enhanced in the ischemic areas of the hearts obtained from vehicle treated rats when compared to SHAM operated ones. Pretreatment with IRFI-016 significantly attenuated (52%) loss of CPK activity in ischemic hearts and the increase in MPO activity, but did not increase PRI, thus indicating that this substance reduces the myocardial ischemic demand for oxygen. Occlusion of the coronary artery, furthermore, was associated wi...
Extracellular superoxide dismutase (EC-SOD) gene mutations screening in a sample of Mediterranean population
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2005
The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells an... more The main role of superoxide dismutases (SODs) is to eliminate reactive oxygen species in cells and tissues. Extracellular SOD (EC-SOD/SOD3) is a major superoxide scavenger and it is located on cell surfaces and primarily in extracellular matrix, and binds heparan sulfates by its carboxyterminal portion. Human EC-SOD gene is located on chromosome 4 and comprises three exons and two introns. The SOD3 coding sequence is entirely located within exon 3 and has missense polymorphisms. The Arg213Gly mutation affects the function of the carboxyterminus and correlates with several diseases. In this work, we explored genetic variants within EC-SOD gene of subjects living in southern Italy. Four new variations were detected: one was silent mutation, while three were missense variations that give rise to amino acid substitutions at position 131 (F&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;C), 160 (V&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;L) and 202 (R&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;L) in the mature product. The Arg213Gly variant was not found. The missense mutations in the DNA of assayed 2400 chromosomes had frequencies of 5.34% for the F131C variation, 0.25% for the V160L variation and 0.84% for the R202L variation. The effect of these alterations on the metabolic activity and diseases remains to be further explained.
OBJECTIVES The purpose of this study was to evaluate the value of platelet reactivity (PR) in pre... more OBJECTIVES The purpose of this study was to evaluate the value of platelet reactivity (PR) in predicting the response to treatment and outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention assisted by glycoprotein (GP) IIb/IIIa inhibition. BACKGROUND There is limited prognostic information on the role of spontaneous or drug-modulated PR in STEMI patients. METHODS The PR was measured with Platelet Function Analyzer (PFA)-100 and light transmission aggregometry (LTA) using adenosine diphosphate as agonist in 70 consecutive STEMI patients at entry (PR-T0), 10 min after GP IIb/IIIa bolus (PR-T1), and discharge (PR-T2) and in 30 stable angina (SA) patients (PR-SA). Complete platelet inhibition (CPI) was based on closure time Ͼ300 s by PFA-100 and percentage inhibition of platelet aggregation Ͼ95% by LTA. Clinical, electrocardiographic, and angiographic responses to treatment during 1-year follow-up were collected. RESULTS According to both techniques, PR-T0 was higher than: 1) PR-T2 and PR-SA; 2) in those without CPI at T1; and 3) in patients with final Thrombolysis In Myocardial Infarction (TIMI) flow grade Ͻ3. The PR-T0 assessed with PFA-100 correlated with: 1) corrected TIMI frame count (r ϭ Ϫ0.6, p Ͻ 0.001); 2) ST-segment resolution (r ϭ 45, p Ͻ 0.001); and 3) creatine kinase-MB (r ϭ Ϫ0.47, p Ͻ 0.001). At 1 year, patients with high PR-T0 showed an adjusted 5-to 11-fold increase in the risk of death, reinfarction, and target vessel revascularization (hazard ratio [HR] 11, 95% confidence interval [CI] 1.5 to 78 [p ϭ 0.02] in PFA-100; HR 5.2, 95% CI 1.1 to 23 [p ϭ 0.03] in LTA). CONCLUSIONS The PR at entry affects response to GP IIb/IIIa inhibition, mechanical treatment, and long-term outcome in STEMI patients undergoing primary intervention.
Journal of Chromatography B: Biomedical Sciences and Applications, 1998
An isocratic high-performance liquid chromatography (HPLC) method with ultraviolet detection for ... more An isocratic high-performance liquid chromatography (HPLC) method with ultraviolet detection for the simultaneous determination of clozapine and its two major metabolites in human plasma is described. Analytes are concentrated from alkaline plasma by liquid-liquid extraction with n-hexane-isoamyl alcohol (75:25, v / v). The organic phase is back-extracted with 150 ml of 0.1 M dibasic phosphate (pH 2.2 with 25% H PO). Triprolidine is used as internal standard. For the 3 4 chromatographic separation the mobile phase consisted of acetonitrile-0.06 M phosphate buffer, pH 2.7 with 25% phosphoric acid (48:52, v / v). Analytes are eluted at a flow-rate of 1.0 ml / min, separated on a 25034.60 mm I.D. analytical column packed with 5 mm C silica particles, and measured by UV absorbance detection at 254 nm. The separation requires 6 7 min. Calibration curves for the three analytes are linear within the clinical concentration range. Mean recoveries were 92.7% for clozapine, 82.0% for desmethylclozapine and 70.4% for clozapine N-oxide. C. V. values for intra-and inter-day variabilities were #13.8% at concentrations between 50 and 1000 ng / ml. Accuracy, expressed as percentage error, ranged from 219.8 to 2.8%. The method was specific and sensitive with quantitation limits of 2 ng / ml for both clozapine and desmethylclozapine and 5 ng / ml for clozapine N-oxide. Among various psychotropic drugs and their metabolites, only 2-hydroxydesipramine caused significant interference. The method is applicable to pharmacokinetic studies and therapeutic drug monitoring.
Therapeutic Drug Monitoring, 1993
Phenobarbital Induces the 2-Hydroxylation of Desipramine
Therapeutic Drug Monitoring, 1996
The kinetics of a single oral dose of desipramine (DMI; 100 mg) were studied in eight epileptic p... more The kinetics of a single oral dose of desipramine (DMI; 100 mg) were studied in eight epileptic patients chronically treated with phenobarbital (PB) and in eight drug-free healthy controls. All subjects were extensive metabolizers with respect to the genetically determined CYP2D6-related metabolic polymorphism. Compared with controls, epileptic patients exhibited lower peak plasma DMI concentrations (74 +/- 24 vs. 107 +/- 32 nmol/L; means +/- SD, p < 0.05), smaller DMI area-under-the-curve values (1,943 +/- 461 vs. 3,234 +/- 1,145 nmol L-1 h; p < 0.01), and shorter DMI elimination half-lives (15.1 +/- 2.1 vs. 20.6 +/- 3.4 h; p < 0.01). The proportion of the dose excreted as 2-hydroxydesipramine (2-OH-DMI) was significantly higher in the patients (54 +/- 8 vs. 40 +/- 9%; p < 0.05). In one single poor metabolizer volunteer, a 3-week treatment with PB was associated with no major changes in DMI kinetics, but the urinary excretion of 2-OH-DMI tended to increase. These results suggest that PB is an inducer of the 2-hydroxylation of DMI, a reaction primarily catalyzed by CYP2D6, but do not provide further information on the specific P450 isoenzyme(s) being induced.
Innate Immunity, 2009
Hyaluronan is a biological polysaccharide that may exist in different degrees of polymerization. ... more Hyaluronan is a biological polysaccharide that may exist in different degrees of polymerization. Several investigations reported that low molecular mass hyaluronan may have pro-inflammatory activity, while high molecular mass hyaluronan can exert beneficial effects. Starting from these data, the aim of this study was to investigate the effect of hyaluronan of different molecular mass in mouse articular chondrocyte cultures stimulated with lipopolysaccharide (LPS). Inflammation was induced in chondrocytes by acute treatment with 2.0 µg/ml LPS. High levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ and iNOS gene expression and their related proteins were found in chondrocytes 24 h after treatment with LPS. High concentrations of NO, NF-κB activation, IκBα phosphorylation and apoptosis, evaluated by the increase in caspase-3 expression and its related protein amount were also produced by LPS stimulation. In contrast, LPS reduced aggrecan and collag...
Changes in urine volume and urinary electrolyte excretion after intracerebroventricular injection of arecoline and hemicholinium-3
Life Sciences, 1991
Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, w... more Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, which appears to be atropine-sensitive and, perhaps, independent from the renal innervation. However the role of cholinergic neurons in central control of renal function is not well understood. The purpose of this study was to further investigate whether brain acetylcholine stores are able to influence kaliuresis and natriuresis in conscious rats. Therefore, the renal response to cholinergic drugs was examined in Wistar rats which underwent to a 0.15 M NaCl solution (saline) load administered by gavage. Central injection of arecoline, a muscarinic agonist, produced a dose-dependent reduction in water diuresis and a highly significant increase in sodium excretion within two hours from the oral saline load. An intracerebroventricular (ICV) injection of methylatropine completely blocked both the antidiuretic and the natriuretic response induced by arecoline. Hemicholinium-3 (HC), centrally administered at a dose (34.8 nmol) known to be capable of inducing a maximal depletion of brain acetylcholine, elicited a time-dependent antidiuretic effect accompanied by a highly significant reduction in potassium and sodium urinary excretion. Therefore, we suggest that brain cholinergic neurons are involved in the regulation of the electrolyte balance.
Antioxidant Activity of Chondroitin Sulfate
Chondroitin Sulfate: Structure, Role and Pharmacological Activity, 2006
Publisher Summary Molecules in biological systems often perform more than one function. Many stru... more Publisher Summary Molecules in biological systems often perform more than one function. Many structures have the ability to scavenge free radicals, acting in living organisms as antioxidants, although their main biological function is different. During oxidative stress, the increase in the concentration of these molecules seems to be a biological response that in synergism with the other antioxidant defense systems may protect cells from oxidation. Among these structures, chondroitin sulfate (CS) has increasingly attracted the interest of many research groups. This chapter discusses the action of CSs in reducing molecular damage caused by free radicals and associated oxygen reactants. The chondroitin‐4‐sulfate exerts higher antioxidant activity than chondroitin‐6‐sulfate. The specific sulfation pattern seems to play a central role in the inhibitory activity of these molecules on free radicals because the suggested mechanism is entrapment by the chelation of those metal cations, such as Fe 2+ and Cu 2+ , which, in turn by Fenton's reaction, are responsible of reactive oxygen species production. Chondroitin sulfate's protection on a wide variety of molecules (i.e., lipids, proteins, and DNA) and in various cells from different organs is documented in several in vitro and in vivo experimental studies.
Cell Biochemistry and Function, 2014
The aim of this study was to investigate the involvement of exchange proteins directly activated ... more The aim of this study was to investigate the involvement of exchange proteins directly activated by cyclic adenosine (ADO) monophosphate (EPAC) in 4-mer hyaluronan (HA) oligosaccharide-induced inflammatory response in mouse normal synovial fibroblasts (NSF). Treatment of NSF with 4-mer HA increased Toll-like receptor-4, TNF-alpha and IL-1beta mRNA expression and of the related proteins, as well as nuclear factor kappaB (NF-kB) activation. Addition to NSF, previously stimulated with 4-mer HA oligosaccharides, of ADO significantly reduced NF-kB activation, TNF-alpha and IL-1beta expression. The pre-treatment of NSF with cyclic ADO monophosphate and/or PKA and/or EPAC-specific inhibitors significantly inhibited the anti-inflammatory effect exerted by ADO. In particular, the EPAC inhibitor reduced the ADO effect to a major extent than the PKA inhibitor. These results mean that both PKA and EPAC pathways are involved in ADO-induced NF-kB inhibition although EPAC seems to be more involved than PKA.
Life Sciences, 2004
We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) ind... more We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1h (IL-1h) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 F 0.03 nmol/mg protein; KA + LVT = 0.13 F 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 F 0.2 nmol/mg protein; KA + LVT = 0,33 F 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 F 1 Amol/g protein; KA + LVT = 15 F 2 Amol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 F 0.8 Amol/g protein; KA + LVT = 13 F 0.3 Amol/g protein; P < 0.05), reduced brain IL-1h mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuroprotective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.
Veterinary Research Communications, 2003