Pietro Lo Giudice - Academia.edu (original) (raw)

Papers by Pietro Lo Giudice

Background Impaired wound healing represents a high cost for health care systems. Endothelial dys... more Background Impaired wound healing represents a high cost for health care systems. Endothelial dys-function characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascul...

Cardiovascular Drugs and Therapy, 2016

Purpose The myocardium is largely dependent upon oxidation of fatty acids for the production of A... more Purpose The myocardium is largely dependent upon oxidation of fatty acids for the production of ATP. Cardiac contractile abnormalities and failure have been reported after acute emotional stress and there is evidence that catecholamines are responsible for acute stress-induced heart injury. We hypothesized that carnitine deficiency increases the risk of stressinduced heart injury. Methods Carnitine deficiency was induced in Wistar rats by adding 20 mmol/L of sodium pivalate to drinking water (P). Controls (C) received equimolar sodium bicarbonate and a third group (P + Cn) received pivalate along with 40 mmol/L carnitine. After 15 days, 6 rats/group were used to evaluate function of isolated hearts under infusion of 0.1 μM isoproterenol and 20 rats/group were submitted to a single subcutaneous administration of 50 mg/kg isoproterenol. Results Isoproterenol infusion in C markedly increased the heart rate, left ventricular (LV) systolic pressure and coronary flow rate. In P rats, isoproterenol increased the heart rate and LV systolic pressure but these increases were not paralleled by a rise in the coronary flow rate and LV diastolic pressure progressively increased. Subcutaneous isoproterenol induced 15 % mortality rate in C and 50 % in P (p < 0.05). Hearts of surviving P rats examined 15 days later appeared clearly dilated, presented a marked impairment of LV function and a greater increase in tumor necrosis factor α (TNFα) levels. All these detrimental effects were negligible in P + Cn rats. Conclusions Our study suggests that carnitine deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress.

Journal of Inorganic Biochemistry, 2014

The reactions of ruthenium(III) chloride trihydrate with piroxicam (H 2 PIR) and tenoxicam (H 2 T... more The reactions of ruthenium(III) chloride trihydrate with piroxicam (H 2 PIR) and tenoxicam (H 2 TEN), two widely used non-steroidal anti-inflammatory drugs, afforded [Ru III Cl 2 (H 2 PIR)(HPIR)],•1, and [Ru III Cl 2 (H 2 TEN)(HTEN)],•2. Both compounds were obtained as pure green solids through purification via flash column chromatography. Characterizations were accomplished through UV-vis and IR spectroscopy, potentiometry and HPLC. Quantum mechanics and density functional computational methods were applied to investigate their respective molecular structures. The experimental and computational results are in agreement with a pseudo-octahedral coordination where the two chlorido ligands are in trans positions (apical) and the two trans-N,O chelating oxicam ligands occupy the equatorial sites. Both compounds revealed an acceptable solubility and stability profile upon dissolution in a standard buffer at physiological pH. Nonetheless, the addition of biologically occurring reducing agents caused spectral changes. The two complexes manifested a poor reactivity with the model proteins cytochrome c and lysozyme: no evidence for adduct formation was indeed obtained based on a standard ESI MS analysis; in contrast, some significant reactivity with serum albumin was proved spectrophotometrically. Remarkably, both study compounds revealed pronounced anti-edema effects in vivo suggesting that the pharmacological actions of the ligands are mostly retained; in addition, they were less irritating than piroxicam on the gastric mucosa when the coordination compounds and free oxicam were administered at the same overall molar concentration of the ligand. Overall, the present results point out that ruthenium coordination may represent an effective strategy to improve the pharmacological properties of oxicam drugs reducing their undesired side effects.

PloS one, 2015

Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction ch... more Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VE...

Anticancer research

Oxaliplatin (OHP) is severely neurotoxic and induces the onset of a disabling sensory peripheral ... more Oxaliplatin (OHP) is severely neurotoxic and induces the onset of a disabling sensory peripheral neuropathy. Acetyl-L-carnitine (ALC), a natural compound with neuroprotective action, was tested to determine whether it plays a protective role in OHP-induced neuropathy. Peripheral neuropathy was induced in Wistar rats, and the effect of OHP alone or in combination with ALC was assessed, using behavioral and neurophysiological methods. Moreover, ALC interference on OHP antitumor activity was investigated using several in vitro and in vivo models. ALC-co-treatment reduced the neurotoxicity of OHP when it was coadministered. Furthermore, the administration-of OHP, once OHP-induced neuropathy was established, significantly mitigated its severity. Finally, experiments in different tumor systems indicated that ALC does not interfere with the antitumor effects of OHP. ALC is effective in the prevention and treatment of chronic OHP-induced peripheral neurotoxicity in an experimental rat model.

Clinical cancer research : an official journal of the American Association for Cancer Research, Jan 15, 2003

Antineoplastic drugs belonging to platinum or taxane families are severely neurotoxic, inducing t... more Antineoplastic drugs belonging to platinum or taxane families are severely neurotoxic, inducing the onset of disabling peripheral neuropathies with different clinical signs. Acetyl-L-carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms. In this study we have tested the hypothesis that ALC may have a protective role on cisplatin and paclitaxel-induced neuropathy. Sensory nerve conduction velocity (SNCV) was measured in rats before, at end, and after an additional follow-up period from treatments with cisplatin, paclitaxel, or with the respective combination with ALC. In addition, serum from treated animals was collected to measure the levels of circulating NGF, and left sciatic nerves were processed for light and electron microscope observations. ALC interference on cisplatin and paclitaxel antitumor activity and protective mechanisms were investigated using several in vitro and in vivo models. ALC cotreatment was able to s...

Pharmacological Research, 1990

Digestive Diseases and Sciences, 1999

The effect of the nonsteroidal antiinflammatorydrug (NSAID) amtolmetin guacyl (AMG) on the gastri... more The effect of the nonsteroidal antiinflammatorydrug (NSAID) amtolmetin guacyl (AMG) on the gastricmucosa was studied in the rat by means of histologicaland functional techniques. AMG administered at 50-300 mg/kg intragastrically was virtuallydevoid of gastrolesive properties after either acute orrepeated treatment. By contrast, its metabolite,tolmetin (TOL, 15-60 mg/kg, intragastrically) caused dose-dependent gastric damage after bothtreatments. Light and electron microscopy revealed thatAMG

Journal of Molecular and Cellular Cardiology, 1988

Journal of Molecular and Cellular Cardiology, 1989

Journal of Cardiovascular Pharmacology, 2000

There is strong evidence that autonomic imbalance plays an important role in progression of heart... more There is strong evidence that autonomic imbalance plays an important role in progression of heart failure. Analysis of heart rate variability (HRV) has achieved substantial acceptance as a noninvasive method for the assessment of autonomic tone. The purpose of this investigation was to study HRV in an experimental model of heart failure using cardiomyopathic (BIO TO.2) hamsters. Animals showed an autonomic imbalance of cardiac control that seems due to attenuation of parasympathetic activity and an enhanced sympathetic tone. The reduction of parasympathetic activity in BIO TO.2 hamsters is suggested by (a) the reduction of the high-frequency (HF) spectrum, and (b) the lack of atropine to generate a response. The increased sympathetic activity is indicated by (a) the decreased time-domain indexes, (b) the increased LF/HF ratio of the power spectrum, and (c) the alteration of HRV indexes induced by propranolol. These results support the notion that in heart failure, there is a similar autonomic imbalance in both human and hamster and suggest that the cardiomyopathic hamster is a suitable experimental model for studying the involvement of the autonomic nervous system in the progression of heart failure.

European Journal of Pharmacology, 1990

Digestive and Liver Disease, 2002

See Commentary on paps 35X3-5 I Background. The novel non-steroidal anti-inflammatory drug amtolm... more See Commentary on paps 35X3-5 I Background. The novel non-steroidal anti-inflammatory drug amtolmetin guacyl has been shown to possess markedly reduced ulcerogenie effects and nitric oxide-mediated gastroprotective activity against the damage induced by ethanol in the rat. Aims. To investigate, in the rat, the role of nitric oxide and of inducible nitric oxide synthase isoform in the protective effect of amtolmetin guacyl against the gastric damage induced by ethanol. Methods. The effects of amtolmetin guacyl on gastric transmucosal potential difference and on gastric mucosal blood flow were investigated in the anaesthetised rat; myeloperoxidase activity inducible and endothelial nitric oxide synthase protein content were determined in rat gastric mucosal homogenates. The anti-inflammatory drug tolmetin and the bacterial lipopolysaccharide from Escherichia coli were studied for comparison. Results. In the anaesthetised rat, amtolmetin guacyl, but not tolmetin, reduced by approximately 50% the fall in gastric potential difference and, to a lesser extent, the macroscopic damage induced by ethanol. The effect of amtolmetin guacyl on transmucosal potential difference was prevented by the selective inducible nitric oxide synthase inhibitor 14OOW In amtolmetin guacyl-treated rats, 1400 W decreased gastric mucosal blood flow, whereas it was inactive in vehicle-and tolmetintreated animals. In gastric mucosal homogenates, both amtolmetin guacyl and lipopolysaccharide, but not tolmetin, increased inducible, but not endothelial, nitric oxide synthase protein content, as revealed by Western immunoblotting. Conclusions. These data confirm that amtolmetin guacyl is a non-steroidal anti-inflammatory agent devoid of gastrolesive properties, that can actually reduce the damaging effects of ethanol through the increase in nitric oxide production, via the inducible isoform of nitric oxide synthase.

Diabetes Research and Clinical Practice, 2002

The present study was designed to characterize cardiac autonomic neuropathy in streptozotocin-ind... more The present study was designed to characterize cardiac autonomic neuropathy in streptozotocin-induced (45 mg/kg i.v.) diabetic rat by analysis of heart rate variability (HRV), and to assess, in this model, the effects of treatment with acetyl-L-carnitine (ALC). Heart rate was reduced in diabetic rats (332 9 22 vs. 411 935 beat per min; P B 0.0001). This bradycardia was partly reversed with ALC (369 9 52 beat per min; PB 0.05 vs. untreated). Both time-and frequency-domain parameters of HRV were significantly reduced in diabetic rats. The reduction of spectral power was around 50% at high frequencies and about 70% at low frequencies, suggesting a decrease of parasympathetic activity. Low/high frequency ratio was significantly decreased in diabetic rats suggesting decreased sympathetic tone, while nonlinear analysis indicated a reduction of the chaotic complexity of heart rate dynamics in diabetic rats. Standard deviation of heart rate in ALC-treated rats was significantly higher than in untreated diabetic rats (P B0.0001). ALC counteracts the reduction of the power spectrum observed in diabetic animals (P B 0.0005) normalizing the spectra profile. ALC restored chaotic complexity of heart rate dynamics. These results on the whole indicate that both sympathetic and parasympathetic cardiac tone were reduced significantly in diabetic rats and that ALC treatment prevents the development of autonomic neuropathy in streptozotocin-induced diabetes in rats.

Cardiovascular Drugs and Therapy, 1989

Cardiovascular Drugs and Therapy, 2011

Istaroxime is a new luso-inotropic compound. It exerts inotropic action by reducing Na+/K+-ATPase... more Istaroxime is a new luso-inotropic compound. It exerts inotropic action by reducing Na+/K+-ATPase activity, and simultaneously it stimulates sarcoplasmic reticulum Ca(2+)-ATPase function, thus also inducing lusitropic action. The aim of present study is to assess the effect of chronic istaroxime treatment on cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure. Bio TO.2 hamsters were daily treated, from 12 to 28 weeks of age, with 30 mg/kg/day oral istaroxime. Age-matched Bio TO.2 and Bio F1B hamsters were treated with vehicle and used as diseased and healthy controls. At the end of treatment, hearts function and autonomic cardiac control were evaluated. Hearts from vehicle-treated Bio TO.2 when compared with hearts from Bio F1B showed higher heart/body weight ratio, and lower left ventricular systolic pressure (LVSP), positive and negative derivative of LV pressure (dP/dT), coronary flow rate (CFR). Hearts from istaroxime-treated when compared with those of vehicle-treated hamsters, showed the reduction of heart/body weight ratio, and the increase of LVSP, of both positive and negative dP/dT, and of CFR. Autonomic cardiac control, evaluated by HRV analysis, indicated in vehicle-treated Bio TO.2 hamsters, when compared to healthy, a shift towards increased sympathetic and decreased parasympathetic activities. Istaroxime-treatment preserved parasympathetic activity. Chronic istaroxime improves cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure.

Biological Cybernetics, 1996

Most investigations into heart rate dynamics have emphasized continuous functions, whereas the he... more Most investigations into heart rate dynamics have emphasized continuous functions, whereas the heart beat itself is a discrete event. We present experimental evidence that by considering this quality, the dynamics may be appreciated as a result of singular dynamics arising out of non-Lipschitz formalisms. Markov process analysis demonstrates that heart beats may then be considered in terms of quantum-like constraints.

Antimicrobial Agents and Chemotherapy, 2010

Pentraxin 3 (PTX3) is an acute-phase glycoprotein with a nonredundant function in the host resist... more Pentraxin 3 (PTX3) is an acute-phase glycoprotein with a nonredundant function in the host resistance to Aspergillus fumigatus . PTX3 activity was evaluated against pulmonary aspergillosis in rats immunosuppressed with cortisone acetate. PTX3 enhanced the survival rate and reduced the lung fungal burden of infected rats in both therapeutic and prophylactic modalities. Thus, we extended the protective activity of PTX3 in pulmonary aspergillosis to corticosteroid-induced immunodeficiency, which is a relevant clinical condition in graft-versus-host disease and in solid organ transplant.