Nanomaterial Gas Sensors for Online Monitoring System of Fruit Jams.

Jams are appreciated worldwide and have become a growing market, due to the greater attention paid by consumers for healthy food. The selected products for this study represent a segment of the European market that addresses natural products without added sucrose or with a low content of natural sugars. This study aims to identify volatile organic compounds (VOCs) that characterize three flavors of fruit and five recipes using gas chromatography-mass spectrometry (GC-MS) and solid-phase micro-extraction (SPME) analysis. Furthermore, an innovative device, a small sensor system (S3), based on gas sensors with nanomaterials has been used; it may be particularly advantageous in the production line. Results obtained with linear discriminant analysis (LDA) show that S3 can distinguish among the different recipes thanks to the differences in the VOCs that are present in the specimens, as evidenced by the GC-MS analysis. Finally, this study highlights how the thermal processes for obtaining the jam do not alter the natural properties of the fruit.

Acute, nonfatal intoxication with trichloroethylene.

Nonfatal acute inhalation of trichloroethylene (TRI) at work was described. The subject, male, 54 years old, was drawn unconscious by a metal-degreasing machine and immediately sheltered in intensive care unit. Other than basic life support and common laboratory indices, blood and urine were collected to measure dose and kidney effect parameters such as TRI in blood and urine, trichloroethanol (TCE) and trichloroacetic acid (TCA) in urine, and total urinary proteins (TUP), urinary glutamine synthetase (GS) and urinary N-acetyl-beta-D-glucosaminidase (NAG). Two hours after accident, TRI in blood was 9 mg/l, but after 38 h it was below 1 mg/l. TCE and TCA have a peak 11 and 62 h after poisoning, respectively. Acute renal involvement was revealed by a peak of urinary proteins and enzymes 7 h after exposure with a second peak 74 h after. Seven day after hospitalisation the patient was dismissed with complete recovery. This nonfatal intoxication with TRI shows that the exposure was approximately 150 ppm, three times the ACGIH TLV (50 ppm) and that kidney was the only organ affected. Urinary enzymes, in particular GS, are good indices to monitor transient effects of TRI on the kidney.

Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2-mediated theophylline metabolism by fluvoxamine.

BACKGROUND AND OBJECTIVES: In vivo inhibition of cytochrome P450 (CYP) 1A2 by fluvoxamine causes a reduction in the clearance of the high-extraction drug lidocaine, which decreases in proportion to the degree of liver dysfunction. The objectives of this study were (1) to evaluate the effect of liver cirrhosis on the inhibition by fluvoxamine of the metabolic disposition of theophylline, a CYP1A2 substrate with a low-extraction ratio, to assess whether decreased sensitivity to CYP1A2 inhibition in liver disease is a general characteristic of CYP1A2 substrates, regardless of their pharmacokinetic properties, and (2) to investigate the mechanism(s) underlying the effect of liver dysfunction on CYP1A2 inhibition. METHODS: The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild liver dysfunction (Child class A) and 10 with severe liver dysfunction (Child class C), according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 7 days; in the other phase they received one 50-mg fluvoxamine dose for 2 days and two 50-mg fluvoxamine doses, 12 hours apart, in the next 5 days. On day 6, 4 mg/kg of theophylline was administered orally 1 hour after the morning fluvoxamine dose. Concentrations of theophylline and its metabolites, 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid, were then measured in plasma and urine up to 48 hours. RESULTS: Fluvoxamine-induced inhibition of theophylline clearance decreased from 62% in healthy subjects to 52% and 12% in patients with mild cirrhosis and those with severe cirrhosis, respectively. CYP1A2-mediated formations of 3-methylxanthine and 1-methyluric acid were almost totally inhibited in control subjects, whereas they were only reduced by one third in patients with Child class C cirrhosis. Inhibition of 1,3-dimethyluric acid formation, which is catalyzed by CYP1A2 and CYP2E1, progressively decreased from 58% in healthy subjects to 43% and 7% in patients with mild cirrhosis and those with severe cirrhosis, respectively. CONCLUSIONS: The effect of liver dysfunction on the inhibition of CYP1A2-mediated drug elimination is a general phenomenon, independent of the pharmacokinetic characteristics of the CYP1A2 substrate. Therefore, for any drug metabolized by CYP1A2, the clinical consequences of enzyme inhibition are expected to become less and less important as liver function worsens. Two mechanisms, as follows in order of importance, are responsible for the effect of liver dysfunction: (1) decreased sensitivity to fluvoxamine of CYP1A2-mediated biotransformations in the cirrhotic liver, probably resulting from reduced uptake of the inhibitory drug, and (2) reduced hepatic expression of CYP1A2, which makes its contribution to overall drug elimination less important.

Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function.

OBJECTIVES: This study was designed (1) to evaluate the effect of a cytochrome P450 (CYP) 1A2 inhibitor, fluvoxamine, on the pharmacokinetics of intravenous lidocaine and its 2 pharmacologically active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), to confirm recent in vitro results indicating that CYP1A2 is the main isoform responsible for lidocaine biotransformation and (2) to assess whether liver function has any influence on the fluvoxamine-lidocaine interaction. METHODS: The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild (Child grade A) and 10 with severe (Child grade C) liver dysfunction, according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 6 days; in the other phase they received 50 mg fluvoxamine for 2 days and 100 mg fluvoxamine for the next 4 days. On day 6, a 1-mg/kg lidocaine dose was administered intravenously 2 hours after the last dose of fluvoxamine or placebo. Plasma concentrations of lidocaine, MEGX, GX, and fluvoxamine were measured up to 12 hours after lidocaine injection. RESULTS: The effects of fluvoxamine coadministration were dependent on liver function. Lidocaine clearance was decreased on average by 60% (from 12.1 mL/min.kg to 4.85 mL/min.kg, P <.001) in healthy subjects and by 44% (from 9.83 mL/min.kg to 5.06 mL/min.kg, P <.001) in patients with mild liver dysfunction, with proportional increases in terminal half-lives, whereas virtually no effect was produced in patients with severe liver dysfunction (4.21 mL/min.kg versus 3.65 mL/min.kg, P >.05). Analogous effects were observed on MEGX and GX formation kinetics, which were drastically impaired in healthy subjects and patients with mild liver cirrhosis but virtually unaffected in patients with severe cirrhosis. CONCLUSION: CYP1A2 is the enzyme principally responsible for the metabolic disposition of lidocaine in subjects with normal liver function. The extent of fluvoxamine-lidocaine interaction decreases as liver function worsens, most likely because of the concomitant decrease in the hepatic level of CYP1A2. These observations indicate that results obtained in healthy subjects cannot be extended a priori to patients with liver dysfunction, but the clinical consequences of inhibition of drug metabolism must also be assessed in such patients.

Effect of the CYP3A4 inhibitor erythromycin on the pharmacokinetics of lignocaine and its pharmacologically active metabolites in subjects with normal and impaired liver function.

AIMS: The objectives of this study were: (i) to evaluate the effect of a cytochrome P450 (CYP) 3A4 inhibitor, erythromycin, on the pharmacokinetics of intravenous lignocaine and its two pharmacologically active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX); (ii) to assess whether the effects of the erythromycin inhibitory action on lignocaine clearance and the results of the MEGX liver function test depend on liver functional status; and (iii) to determine the effects of both moderate and severe liver dysfunction on the disposition kinetics of lignocaine. METHODS: The study was carried out on 10 healthy volunteers, and 10 Child's class A and 10 class C cirrhotic patients, according to a double-blind, randomized, two-way crossover design. On day 1 of the investigation, all subjects received three oral doses of erythromycin (600 mg of the ethylsuccinate ester) or placebo, and two further doses on day 2. One hour after the fourth dose, subjects were given 1 mg kg-1 lignocaine intravenously. Timed plasma samples were then obtained until 12 h for determination of the concentrations of lignocaine, MEGX and GX. RESULTS: Erythromycin caused statistically significant, although limited, modifications of lignocaine and MEGX pharmacokinetic parameters. In healthy volunteers, lignocaine clearance was decreased from 9.93 to 8.15 ml kg-1 min-1[mean percentage ratio (95% CI), 82 (65-98)] and the half-life was prolonged from 2.23 to 02.80 h [mean percentage ratio (95% CI), 130 (109-151)]; MEGX area under the concentration-time curve from 0 h to 12 h was increased from 665 to 886 ng ml-1 h [mean percentage ratio (95% CI), 129 (102-156)]. Quantitatively similar modifications were observed in the two cirrhotic groups. GX concentrations were lowered in all study groups, although not to statistically significant extents. Erythromycin coadministration caused no appreciable interference with the results of the MEGX test. Only in patients with Child's grade C liver cirrhosis were lignocaine kinetic parameters significantly altered with respect to healthy volunteers. Thus, clearance was approximately halved, steady-state volume of distribution was increased, and terminal half-life was more than doubled. CONCLUSIONS: Although erythromycin only modestly decreases lignocaine clearance, it causes a concomitant elevation of the concentrations of its pharmacologically active metabolite MEGX. A pharmacodynamic study following lignocaine infusion to steady state appears necessary to assess the actual clinical relevance of these combined effects. The degree of liver dysfunction has no influence on the extent of the erythromycin-lignocaine interaction, whereas it markedly influences the extent of the changes in lignocaine pharmacokinetics. These findings indicate that no dose adjustment is needed in patients with moderate liver cirrhosis, whereas the lignocaine dose should be halved in patients with severe cirrhosis.

Diagnostic value of plasma cystatin C as a glomerular filtration marker in decompensated liver cirrhosis.

BACKGROUND: Plasma creatinine concentration and calculated creatinine clearance are of limited value as glomerular filtration rate (GFR) markers in patients with decompensated liver cirrhosis. We assessed plasma cystatin C as an indicator of GFR in such patients. METHODS: We studied 36 patients with decompensated liver cirrhosis and 56 noncirrhotic controls, both groups including individuals with normal and impaired renal function. GFR was measured in all individuals by inulin clearance, with values <72 mL x min(-1) x 1.73 m(-2) considered decreased. We measured cystatin C and creatinine in plasma and calculated (from plasma concentrations) and measured creatinine clearances, using for them decision points of 1.25 mg/L, 115 micromol/L, and 72 and 72 mL x min(-1) x 1.73 m(-2), respectively. RESULTS: Plasma cystatin C concentrations were similar in controls and cirrhotics and, at the usual cutpoint, could detect decreased GFR with similar sensitivities in the two groups (73% and 88%, respectively). Serum creatinine was markedly lower in cirrhotics and remained mostly within the reference interval at all GFR values; the diagnostic sensitivity of creatinine was much lower in cirrhotics than in controls (23% vs 64%). Lower diagnostic sensitivity was also observed for calculated creatinine clearance (53% vs 100% in controls), whereas similar sensitivities were found for measured creatinine clearance (86% and 81%) in controls and cirrhotics, respectively. ROC analysis showed that all four variables had similar diagnostic accuracies in cirrhotic patients. However, it also revealed that good diagnostic accuracies for plasma creatinine and calculated creatinine clearance can be obtained only if reference intervals different from those used for the general population are adopted. CONCLUSIONS: Plasma cystatin C concentration is an accurate GFR marker in cirrhotic patients. Plasma creatinine concentration and calculated creatinine clearance are of no practical value, as their reference values vary with the severity of the liver disease.