Mario Giorgi | University of Pisa (original) (raw)

Papers by Mario Giorgi

American Journal of Animal and Veterinary Sciences

… of pharmaceutical and …, 2008

Research in Veterinary Science

Toxins

A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous d... more A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous determination of 17 mycotoxins in swine, poultry and dairy feeds using stable isotope dilution (13C-ISTD) and (ultra)-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A simple QuEChERS-based method (quick, easy, cheap, effective, rugged and safe) was developed consisting of soaking with a solution of 1% formic acid followed by extraction with acetonitrile, clean-up with C18 sorbent and finally adding 13C-ISTD before the UHPLC-MS/MS analysis. The chromatographic condition was optimized for separation and detection of the 17 mycotoxins using gradient elution. The method’s performance complied with the SANTE/11813/2017 standard and had mean recovery accuracies in the range 70%–120% and precision testing of % relative standard deviation (RSD) ≤ 20%. The limit of detection and limit of quantification values ranged from 0.25 to 40.0 ng/g and 0.5 to 100.0 ng/g, respe...

Journal of Veterinary Pharmacology and Therapeutics

Journal of Veterinary Science

Journal of Veterinary Pharmacology and Therapeutics

Journal of Veterinary Pharmacology and Therapeutics

Journal of Food and Drug Analysis

Journal of veterinary pharmacology and therapeutics, 2018

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary m... more Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment, four-phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC-UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approxima...

Journal of food protection, Sep 1, 2017

The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and other fruit-base... more The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and other fruit-based products. Pesticides are a group of chemicals abundantly used in agriculture to maximize productivity by protecting crops from pests and weeds. Because of their harmful health effects, PAT and pesticides are strictly monitored. The current study was undertaken to investigate the significance of PAT and pyrethroid insecticide contamination in a variety of fruit juices in Bangkok. To do this, a total of 200 fruit juice samples, consisting of 40 samples each of apple, apricot, peach, pineapple, and grape juice, were collected from supermarkets in Bangkok, Thailand. PAT contamination in a variety of fruit juices was detected using validated liquid chromatography-tandem mass spectrometry, and pyrethroid insecticides (cypermethrin, cyfluthrin, and flumethrin) were analyzed using a gas chromatography equipped with micro-electron capture detector. The survey found that PAT concentrations were ...

Veterinary Anaesthesia and Analgesia, 2017

To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep ... more To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation. Prospective randomized controlled study. A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg(-1)). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography. Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes. Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia.

Research in veterinary science, Jan 12, 2017

The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage ... more The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage in the target animals is increasingly being recognized as vital for maximizing efficacy and minimizing the risk of resistance, so this study aimed to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) of levofloxacin in broilers. Using a parallel study design, each group of animals (n=20) received 5mg/kg of levofloxacin intravenously (IV) and orally (PO). Plasma, serum and tissues were collected for PK and PD studies. Plasma concentrations of levofloxacin were determined by HPLC. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined against E. coli, isolated in clinical broilers. Ex vivo antibacterial activity was evaluated using the time killing method. Mean values of terminal half-life for IV and PO groups were 6.93 and 8.09h, respectively. Following oral administration, the peak plasma concentration was achieved at 0.88h (Tmax). Mean v...

Toxicon, 2016

Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, ... more Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0.5 mg/kg bodyweight. FX caused the up-regulation of Bax, Bid, Trp53, and Caspase-9 mRNA but the relative expression of Fas, TNF, and Caspase-8 remained unchanged. Furthermore, we also determined the toxicity of FX in Jurkat T-cells. FX exhibited a concentration- and time-dependent inhibition of cell viability. Thus, incubation time and FX concentration influence the percentage of apoptotic cells. These data suggested that treatment with low dosage of FX can induce apoptosis in lymphocytes through an effect on Bax, Bid, Trp53, and Caspase-9 and therefore the mitochondrial apoptotic pathway.

Investigational New Drugs, 2016

The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharm... more The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharmacokinetic profiles, of oral metronomic vinorelbine (VNR) plus dexamethasone (DEX) in metastatic castration-resistant prostate cancer (mCRPC) patients. Fourty-one patients (92 % chemotherapy-resistant) received 30 mg/day VNR p.o. thrice a week plus 1 mg/day DEX p.o. until disease progression. Plasma soluble B cell antigen 7 homolog 3 (sB7-H3), vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1), were measured by ELISA. Plasma VNR was detected using a LC-MS-MS system. The fraction of patients free of progression, defined by criteria of the Prostate Cancer Clinical Trials Working Group 2, at 3 months was 61 %. PSA decrease ≥50 % from baseline was observed in 35 % of patients. Median PFS and OS were 4 months (95 % CI, 2.8-6.9) and 17.5 months (95 % CI, 10.8-24.5), respectively. Toxicity was mild, and no grade 4 toxicities were found. The mean plasma VNR Cmax ranged from 1 to 2.7 ng/ml (Tmax 1.1 h) and no evidence of drug accumulation was found. A moderate relationship was found between plasma sB7-H3 and PSA values (r = 0.565; P = 0.0094) at the baseline. Increased PFS (11.3 vs. 2.8 months; P = 0.0298) was observed in patients with sB7-H3 levels <30.25 ng/mL. Plasma VEGF AUC0-24day increased in non-responders (P < 0.0001), whereas responders maintained higher plasma TSP-1 AUC0-24day (P = 0.0063). In conclusion, metronomic VNR plus DEX showed favourable activity, and a low toxicity profile, in mCRPC patients. Plasma sB7-H3, VEGF and TSP-1 levels are potential pharmacodynamic markers at the reached low plasma concentrations of vinorelbine metronomically administered.

Journal of food protection, Jul 1, 2016

One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected... more One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected from supermarkets in Bangkok, Thailand. Deoxynivalenol (DON) and aflatoxin B1 (AFB1) contamination in these products was analyzed using a validated liquid chromatography-tandem mass spectrometry method. The limit of quantification values of DON and AFB1 in the instant noodles and bread were 2 and 1 ng g(-1), respectively. The survey found that DON was quantifiable in 40% of collected samples, in 2% of noodles (0.089 μg g(-1)), and in 78% of breads (0.004 to 0.331 μg g(-1)). AFB1 was below the limit of quantification of the method in all of the tested samples. The results suggest that the risk of DON exposure via noodles and breads is very low in urban areas of Thailand. No risk can be attributable to AFB1 exposure in the same food matrices, but further studies with a larger sample size are needed to confirm these data.

Medycyna Weterynaryjna, 2012

Medycyna Weterynaryjna, 2014

American Journal of Animal and Veterinary Sciences

… of pharmaceutical and …, 2008

Research in Veterinary Science

Toxins

A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous d... more A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous determination of 17 mycotoxins in swine, poultry and dairy feeds using stable isotope dilution (13C-ISTD) and (ultra)-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A simple QuEChERS-based method (quick, easy, cheap, effective, rugged and safe) was developed consisting of soaking with a solution of 1% formic acid followed by extraction with acetonitrile, clean-up with C18 sorbent and finally adding 13C-ISTD before the UHPLC-MS/MS analysis. The chromatographic condition was optimized for separation and detection of the 17 mycotoxins using gradient elution. The method’s performance complied with the SANTE/11813/2017 standard and had mean recovery accuracies in the range 70%–120% and precision testing of % relative standard deviation (RSD) ≤ 20%. The limit of detection and limit of quantification values ranged from 0.25 to 40.0 ng/g and 0.5 to 100.0 ng/g, respe...

Journal of Veterinary Pharmacology and Therapeutics

Journal of Veterinary Science

Journal of Veterinary Pharmacology and Therapeutics

Journal of Veterinary Pharmacology and Therapeutics

Journal of Food and Drug Analysis

Journal of veterinary pharmacology and therapeutics, 2018

Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary m... more Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment, four-phase, unpaired, crossover study design. Blood was collected at predetermined times within 24 hr, and plasma was analyzed by a validated HPLC-UV method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC) min to 24 hr in all dogs. The highest concentrations of MAA were found in the i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar for i.v., i.m., and RC, and the concentrations were approxima...

Journal of food protection, Sep 1, 2017

The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and other fruit-base... more The mycotoxin patulin (PAT) is well known as a natural contaminant of apple- and other fruit-based products. Pesticides are a group of chemicals abundantly used in agriculture to maximize productivity by protecting crops from pests and weeds. Because of their harmful health effects, PAT and pesticides are strictly monitored. The current study was undertaken to investigate the significance of PAT and pyrethroid insecticide contamination in a variety of fruit juices in Bangkok. To do this, a total of 200 fruit juice samples, consisting of 40 samples each of apple, apricot, peach, pineapple, and grape juice, were collected from supermarkets in Bangkok, Thailand. PAT contamination in a variety of fruit juices was detected using validated liquid chromatography-tandem mass spectrometry, and pyrethroid insecticides (cypermethrin, cyfluthrin, and flumethrin) were analyzed using a gas chromatography equipped with micro-electron capture detector. The survey found that PAT concentrations were ...

Veterinary Anaesthesia and Analgesia, 2017

To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep ... more To evaluate the pharmacokinetics of two doses of tramadol during isoflurane anaesthesia in sheep and their ability to prevent the cardiovascular response induced by surgical stimulation. Prospective randomized controlled study. A total of 12 healthy sheep (mean weight, 47.5±7.9 kg) undergoing lumbar transpedicular intervertebral disk nucleotomy. Sheep were sedated with medetomidine, anaesthesia was induced with propofol and maintained with isoflurane at 1.5 vol.%. Baseline heart rate and blood pressure were measured and sheep were randomly assigned an intravenous injection of tramadol (4 or 6 mg kg(-1)). Fentanyl was injected as rescue analgesic if cardiovascular parameters were increased more than 20% compared to baseline. If those variables were below 20% of baseline, the concentration of isoflurane was gradually decreased until parameters returned to the original value. Blood collections were performed at pre-assigned times, and concentrations of tramadol and O-desmethyltramadol (M1) assessed by high-performance liquid chromatography. Time from premedication to anaesthesia induction, anaesthesia time, propofol dose and intraoperative body temperature were similar between doses. Cardiovascular variables remained between ±20% of baseline value, and no statistical difference was observed between treatments. Regardless of the dose of tramadol administered, arterial blood pressure was statistically higher than baseline 10 minutes after tramadol administration, but it gradually returned to previous values. A two-compartment model and a non-compartment model described the pharmacokinetics of tramadol and M1, respectively. Plasma concentrations of tramadol rapidly decreased in the first 2 hours for both doses with an elimination half-life of more than 40 minutes. The M1 maximum concentration was similar for both doses, and it was detected in plasma after 35 minutes. Both doses of tramadol provided adequate cardiovascular stability during spinal surgery in sheep. The pharmacokinetic variables may be used to plan the dosage regime during general anaesthesia.

Research in veterinary science, Jan 12, 2017

The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage ... more The use of antibiotics is necessary to treat bacterial diseases. Determination of optimal dosage in the target animals is increasingly being recognized as vital for maximizing efficacy and minimizing the risk of resistance, so this study aimed to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) of levofloxacin in broilers. Using a parallel study design, each group of animals (n=20) received 5mg/kg of levofloxacin intravenously (IV) and orally (PO). Plasma, serum and tissues were collected for PK and PD studies. Plasma concentrations of levofloxacin were determined by HPLC. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined against E. coli, isolated in clinical broilers. Ex vivo antibacterial activity was evaluated using the time killing method. Mean values of terminal half-life for IV and PO groups were 6.93 and 8.09h, respectively. Following oral administration, the peak plasma concentration was achieved at 0.88h (Tmax). Mean v...

Toxicon, 2016

Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, ... more Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0.5 mg/kg bodyweight. FX caused the up-regulation of Bax, Bid, Trp53, and Caspase-9 mRNA but the relative expression of Fas, TNF, and Caspase-8 remained unchanged. Furthermore, we also determined the toxicity of FX in Jurkat T-cells. FX exhibited a concentration- and time-dependent inhibition of cell viability. Thus, incubation time and FX concentration influence the percentage of apoptotic cells. These data suggested that treatment with low dosage of FX can induce apoptosis in lymphocytes through an effect on Bax, Bid, Trp53, and Caspase-9 and therefore the mitochondrial apoptotic pathway.

Investigational New Drugs, 2016

The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharm... more The aim of the present study was to evaluate clinical activity, and the pharmacodynamic and pharmacokinetic profiles, of oral metronomic vinorelbine (VNR) plus dexamethasone (DEX) in metastatic castration-resistant prostate cancer (mCRPC) patients. Fourty-one patients (92 % chemotherapy-resistant) received 30 mg/day VNR p.o. thrice a week plus 1 mg/day DEX p.o. until disease progression. Plasma soluble B cell antigen 7 homolog 3 (sB7-H3), vascular endothelial growth factor (VEGF), and thrombospondin-1 (TSP-1), were measured by ELISA. Plasma VNR was detected using a LC-MS-MS system. The fraction of patients free of progression, defined by criteria of the Prostate Cancer Clinical Trials Working Group 2, at 3 months was 61 %. PSA decrease ≥50 % from baseline was observed in 35 % of patients. Median PFS and OS were 4 months (95 % CI, 2.8-6.9) and 17.5 months (95 % CI, 10.8-24.5), respectively. Toxicity was mild, and no grade 4 toxicities were found. The mean plasma VNR Cmax ranged from 1 to 2.7 ng/ml (Tmax 1.1 h) and no evidence of drug accumulation was found. A moderate relationship was found between plasma sB7-H3 and PSA values (r = 0.565; P = 0.0094) at the baseline. Increased PFS (11.3 vs. 2.8 months; P = 0.0298) was observed in patients with sB7-H3 levels <30.25 ng/mL. Plasma VEGF AUC0-24day increased in non-responders (P < 0.0001), whereas responders maintained higher plasma TSP-1 AUC0-24day (P = 0.0063). In conclusion, metronomic VNR plus DEX showed favourable activity, and a low toxicity profile, in mCRPC patients. Plasma sB7-H3, VEGF and TSP-1 levels are potential pharmacodynamic markers at the reached low plasma concentrations of vinorelbine metronomically administered.

Journal of food protection, Jul 1, 2016

One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected... more One hundred wheat product samples (50 instant noodle samples and 50 bread samples) were collected from supermarkets in Bangkok, Thailand. Deoxynivalenol (DON) and aflatoxin B1 (AFB1) contamination in these products was analyzed using a validated liquid chromatography-tandem mass spectrometry method. The limit of quantification values of DON and AFB1 in the instant noodles and bread were 2 and 1 ng g(-1), respectively. The survey found that DON was quantifiable in 40% of collected samples, in 2% of noodles (0.089 μg g(-1)), and in 78% of breads (0.004 to 0.331 μg g(-1)). AFB1 was below the limit of quantification of the method in all of the tested samples. The results suggest that the risk of DON exposure via noodles and breads is very low in urban areas of Thailand. No risk can be attributable to AFB1 exposure in the same food matrices, but further studies with a larger sample size are needed to confirm these data.

Medycyna Weterynaryjna, 2012

Medycyna Weterynaryjna, 2014