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Biomedical subjects

F Mattioli

Publications and source records attributed to F Mattioli.

At least 19 recordsLinked to original sources
PubMed2006

Interindividual variability in the absorption of ciprofloxacin and hydrocortisone from continent ileal reservoir for urine.

OBJECTIVE: The neobladder created with a detubularized segment of ileum as standard treatment for the transitional cell carcinoma of the bladder may permit absorption of drugs. As a consequence, on the one hand the elimination of drugs excreted in the urine may be delayed and a change of dosage may be required, and on the other hand the intravesical administration of a drug may produce blood levels capable of inducing unwanted systemic effects. The purpose of the present study was to explore the possibility of drug absorption from a continent ileal reservoir for urine. METHODS: The possibility of drug re-absorption from a continent ileal reservoir for urine was studied in 12 patients with well functioning reservoirs after a time interval of 3 months from surgery and also, in 7 of them, 6 months later. Saline solutions of ciprofloxacin or hydrocortisone were instilled and maintained in the reservoir for 2 h, and drug concentrations in plasma were measured 1 and 2 h after instillation. RESULTS: Both ciprofloxacin and to a lower extent hydrocortisone were adsorbed from the reservoir, but with large interindividual variability. A comparison of the plasma concentrations produced by the two drugs 3 and 9 months after creation of the new bladder revealed that after 9 months the absorption was decreased in 3 patients, substantially unchanged in 2, and increased in 2. CONCLUSIONS: The results of this study show that both ciprofloxacin, chosen for its use as possible radiosensitizing agent in bladder cancer patients, and hydrocortisone, chosen as an example of lypofilic endogenous compound, can be absorbed through the intestinal mucosa of a continent ileal reservoir, but to a different extent and with high interindividual variability.

Administration, Intravesical↗
PubMed2004

Serum lamivudine levels in the presence of a lamivudine-resistant HBV mutant.

BACKGROUND/AIMS: Lamivudine efficiently inhibits hepatitis B virus replication and has been used to treat hepatitis B virus recurrence after orthotopic liver transplantation. Although effective, its use is hampered by viral breakthrough due to the appearance of hepatitis B virus drug-resistant strains. Aims of this work were to evaluate the inter- and intra-individual variations of lamivudine serum levels and the effects on the drug levels of the lamivudine-resistant hepatitis B virus mutant infection. METHODS: Serum lamivudine concentration was measured by high-performance liquid chromatography. Polymerase chain reaction analysis and sequencing analysis of the reverse transcriptase area of the polymerase was performed on each sample using specific primers. A polymerase chain reaction-enzyme-linked immunosorbent assay was used to differentiate between wild-type hepatitis B virus and lamivudine-resistant hepatitis B virus strain. RESULTS: Lamivudine serum levels presented minor inter- and intra-individual fluctuations along time, with an important increase at the time of the hepatitis flare-up due to the hepatitis B virus mutant presence. When the wild-type hepatitis B virus briefly reappeared as a mixed population, the titre of lamivudine dropped to below the detection level. CONCLUSIONS: While lamivudine serum levels appears stable when the anti-viral efficacy is fully achieved, important fluctuations are present according to the type of viral population, with a considerable decrease possibly due to the presence of the wild-type virus.

Anti-HIV Agents↗
PubMed2000

4-Dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol-4-yl)butan-1-ols: synthesis and evaluation of analgesic, anti-inflammatory and platelet anti-aggregating activities.

A number of 4-dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol-4-yl)butan-1-ols 2a-n were synthesized and tested in vivo for anti-inflammatory and analgesic activities and in vitro for platelet anti-aggregating activity. Dimethylaminoderivatives 2b, e, g showed good analgesic activity; almost all of them had strong platelet anti-aggregating properties at a final concentration of 1 x 10(-3) M; pyrazoles 2c, d, f-h showed weak anti-inflammatory activity.

Analgesics↗
PubMed2000

1,8-Naphthyridines IV. 9-substituted N,N-dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4]triazolo[4,3-a][1, 8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities.

The title compounds (8) were synthesized through the cyclocondensation of the corresponding N-substituted 4-amino-2-chloro-1,8-naphthyridine-3-carboxamides (4) with the proper hydrazides, in order to evaluate their anti-inflammatory and anti-aggressive properties. Several compounds 8 exhibited high anti-inflammatory activity (carrageenin-induced paw edema assay in the rat) along with appreciable anti-aggressive properties (isolation-induced aggressiveness test in mice). With respect to anti-inflammatory activity, the most active compounds (8n and 8c) produced a 61% edema inhibition at the 25 mg/kg dose, and 50 or 35% inhibition, respectively, at the 12.5 mg/kg dose. The structure-activity relationships are discussed.

Aggression↗
PubMed2000

Evaluation of flutamide genotoxicity in rats and in primary human hepatocytes.

Flutamide, an effective competitive inhibitor of the androgen receptor used orally for palliative treatment of prostatic carcinoma and regulation of prostatic hyperplasia was evaluated for its genotoxic effects in the intact rat and in primary cultures of human hepatocytes. Negative responses were obtained in all the in vivo assays as well as in the in vitro assay. In rats given a single oral dose of 500 mg/kg flutamide, fragmentation and repair of liver DNA were absent, and no increase was observed in the frequency of micronucleated hepatocytes. In the liver of rats given flutamide as initiating agent at the dose of 500 mg/kg/week for 6 successive weeks, gamma-glutamyltraspeptidase-positive foci were detected only in 3 of 10 rats. There was no evidence of a promoting effect on the development of aberrant crypt foci in rats given 100 mg/kg flutamide on alternate days for 8 successive weeks. In primary cultures of human hepatocytes from one male and one female donor DNA fragmentation as measured by the Comet assays, and DNA repair synthesis as revealed by quantitative autoradiography, were absent after a 20 hr exposure to flutamide concentrations ranging from 18 to 56 microM. Taken as a whole, our results seem to indicate that flutamide is a non-genotoxic drug.

Androgen Antagonists↗
PubMed2000

DNA damage induced by 3,3'-dimethoxybenzidine in liver and urinary bladder cells of rats and humans.

3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye industry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder mucosa of intact rats. A similar modest dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic DMB concentrations ranging from 56 to 180 microM. Replicating rat hepatocytes displayed a modest increase in the frequency of micronucleated cells after a 48-h exposure to 100 and 180 microM concentrations. In primary cultures of human urinary bladder mucosa cells exposed for 20 h to 100 and 180 microM DMB, the Comet assay revealed a clear-cut increase of DNA fragmentation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, these results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary bladder might be the consequence of pharmacokinetic behavior.

Administration, Oral↗
PubMed1999

Confabulation and delusional misidentification: a four year follow-up study.

We describe a patient, AZ, who showed, in addition to an amnesic syndrome which eventually improved, longstanding confabulation and delusional misidentification following bilateral frontal and right temporal post-traumatic lesions. Confabulation appeared in personal recollections and on long-term verbal memory testing. Misidentification concerned mainly his wife and house. During the four year follow-up AZ's confabulation progressively shrinked so as to become restricted to verbal memory tasks. By contrast, misidentification persisted. General semantic memory was unimpaired throughout, while performance on frontal tests was initially poor and partly improved in time. We argue that confabulation and misidentification, though often intermingled and occurring after similar lesion pattern, should be considered as different neuropsychological entities.

Amnesia↗
PubMed1999

Interactions between cholecystokinin and opioids in the isolated guinea-pig ileum.

1. Although cholecystokinin octapeptide sulphate (CCK-8) activates the opioid system of isolated guinea-pig ileum (GPI) whether it activates the mu- or kappa-system, or both, remains unclear. Neither is it known whether CCK-8 influences the withdrawal responses in GPI preparations briefly exposed to opioid agonists. This study was designed to clarify whether CCK-8 activates mu- or kappa-opioid systems or both; and to investigate its effect on the withdrawal contractures in GPI exposed to mu- or kappa-agonists and on the development of tolerance to the withdrawal response. 2. In GPI exposed to CCK-8, the selective kappa-antagonist nor-binaltorphimine elicited contractile responses that were concentration-related to CCK-8 whereas the selective mu-antagonist cyprodime did not. 3. In GPI preparations briefly exposed to the selective mu-agonist, dermorphin, or the selective kappa-agonist, U-50, 488H, and then challenged with naloxone, CCK-8 strongly enhanced the withdrawal contractures. 4. During repeated opioid agonist/CCK-8/opioid antagonist tests tolerance to opioid-induced withdrawal responses did not develop. 5. These results show that CCK-8 preferentially activates the GPI kappa-opioid system and antagonizes the mechanism(s) that control the expression of acute dependence in the GPI.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Genotoxicity testing of potassium canrenoate in cultured rat and human cells.

Potassium canrenoate (PC), a competitive aldosterone antagonist used as a diuretic and in the treatment of hypertension, was examined for its capacity to produce genotoxic effects in cultured rat and human cells. At subtoxic concentrations (10-90 microM) PC was found to induce a dose-dependent degree of DNA fragmentation, as detected by the Comet assay, and of DNA repair synthesis, as measured by quantitative autoradiography, in primary cultures of hepatocytes from rat and human donors of both genders. In rat hepatocytes both DNA fragmentation and DNA repair were more marked after 3 h than after 20 h exposure and in cultures from females than from males. In human hepatocytes from one male and two female donors, PC caused a similar effect in terms of DNA fragmentation, whereas DNA repair was detected in cultures from only two of the same three donors and was less marked than in rat hepatocytes. A modest but statistically significant increase in micronucleated cells was present in primary cultures of replicating rat hepatocytes exposed to 10 or 30 microM PC for 48 h, the response being, in this case also, more evident in females than in males. In contrast, PC did not induce micronucleus formation in human hepatocytes from two female donors. Any evidence of DNA fragmentation and micronucleus formation was absent in cultured human lymphocytes. Taken as a whole these findings support the hypothesis that hepatocytes activate PC to DNA-damaging reactive species. PC induced the observed genotoxic effects at concentrations close to those produced in humans by the administration of therapeutic doses, but these effects were as a whole more marked in rat than in human hepatocytes. Since PC shares the 17-hydroxy-3-oxopregna-4,6-diene structure with cyproterone acetate, chlormadinone acetate and megestrol acetate, previously found to be genotoxic to both rat and human hepatocytes, the potential carcinogenic hazard of this type of steroids cannot be neglected.

Adult↗
PubMed1998

Evaluation of omeprazole genotoxicity in a battery of in vitro and in vivo assays.

Omeprazole, a proton pump inhibitor of wide use in the treatment of gastric acid-related disorders, was evaluated for its genotoxic effects in both rat and human cultured cells and in the intact rat. DNA repair synthesis, as revealed by autoradiography, was detected in primary cultures of metabolically competent rat hepatocytes exposed to concentrations ranging from 10 to 100 mg/l, but the responses cannot be considered as clearly positive. Under the same experimental conditions any significant evidence of DNA repair was absent in primary hepatocytes from two human donors. At the same concentrations a modest but dose-related increase of micronucleated cells, that reached the level of statistical significance at 33 mg/l, was present in primary rat hepatocytes and in one of two human donors. In human lymphocytes exposed to subtoxic concentrations ranging from 0.78 to 12.5 mg/l a reproducible concentration dependent clastogenic effect was absent. In partially hepatectomized female rats treated with a single p.o. dose of 1000 mg/kg, the frequency of micronucleated cells was 5.2-fold higher than in controls in the liver, but only 2.0-fold higher in polychromatic erythrocytes of the bone marrow. In rats of the same sex given azoxymethane as initiator of colon carcinogenesis the oral administration for 8 successive weeks of 10 mg/kg omeprazole on alternate days increased the response to azoxymethane, as indicated by the occurrence in colon mucosa of a modest but statistically significant increase in both the average number and size of aberrant crypt foci. Taken as a whole, our results suggest that omeprazole behaves as a weak genotoxic agent for the rat liver. Reliable information about the potential genotoxic risk to humans requires further studies on primary cells from a wide number of donors.

Adult↗
PubMed1998

Evaluation of auramine genotoxicity in primary rat and human hepatocytes and in the intact rat.

Auramine, a dye previously found to be a liver carcinogen in both mice and rats, was evaluated for its DNA-damaging and clastogenic activities in primary cultures of rats and human hepatocytes and for the induction of DNA single-strand breaks in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In contrast, neither rat nor human hepatocytes displayed an increased frequency of micronuclei after a 48-h exposure to the same auramine concentrations. In rats given a single oral dose of 125, 250 or 500 mg kg-1 auramine, the Comet assay revealed a significant increase in the frequency of DNA lesions in the liver and in the urinary bladder mucosa, the effect being slightly more marked in the liver. Taken as a whole and compared with previous findings, these results suggest that auramine is biotransformed into reactive species in target organs of both rats and humans, and that this dye might play by itself the main role in the increased incidence of bladder cancer which has been judged as causally related to its manufacture.

Animals↗
PubMed1998

Effects of reduced glutathione and n-acetylcysteine on lidocaine metabolism in cimetidine treated rats.

The aim of this work was to evaluate the effects of exogenous glutathione (GSH) and N-acetylcysteine (NAC) on the formation of monoethylglycinexylidide (MEGX) from lidocaine in rats with and without the administration of cimetidine. GSH and NAC were administered intraperitoneally (i.p.) (1 mmol/kg) 1 hour before treatment with cimetidine (0.5 mmol/kg) or saline, and 1 hr later all rats were injected i.p. with lidocaine (1 mg/kg). Blood samples were drawn 30 min after the lidocaine injection. MEGX and lidocaine serum concentrations were determined by means of fluorescence polarization immuno-assay using the TDX system. Cimetidine produced a decrease in MEGX levels (from 210 +/- 18 to 164 +/- 13 ng/mL) and a parallel increase in lidocaine levels (from 73 +/- 22 to 172 +/- 47 ng/mL), consistent with cytochrome P-450 3A inhibition. Both GSH and NAC produce a significant decrease in MEGX levels (151 +/- 16 and 139 +/- 14 ng/mL, respectively), but no significant increase in lidocaine levels were found. As compared to the cimetidine group, pre-treatment using either GSH or NAC with cimetidine produced a marked decrease in lidocaine levels (37 +/- 27 and 63 +/- 28 ng/mL, respectively) and no modification of MEGX levels (155 +/- 12 and 165 +/- 22 ng/mL, respectively). These results suggest that GSH and NAC might accelerate the lidocaine metabolism while counteracting the inhibitory effect of cimetidine.

Acetylcysteine↗
PubMed1997

Surveillance after colorectal cancer surgery.

Early diagnosis of local and distant recurrences of colorectal cancer remains difficult and there is no agreement on the effectiveness of follow-up in these patients. The aim of this study is to assess the value of our method of follow-up. We consider 239 patients with colorectal cancer and at least 2 years follow-up following radical resection. A local recurrence appeared in 26 patients (10.9%), a distant metastasis in 41 (17.1%), while in seven (2.9%) local and distant recurrences appeared simultaneously. Local recurrence was detected because of an increase in carcinoembryonic antigen (CEA) level in 15 patients (57.7%), during a scheduled endoscopy in four (15.4%) and because of symptoms in seven (26.9%). In seven patients (26.9%) a radical resection was possible. Distant metastases were detected by CEA levels in 20 patients (48.8%), by ultrasonography (U.S.) in 12 (29.3%) and by chest X-ray in five (12.2%). In 13 of 26 patients with liver metastases a resection was performed. This study shows that few patients benefit from follow-up and only CEA levels and liver U.S. performed intensively between 15 and 36 months after surgery are useful in early detection of recurrences. A modification of the follow-up to the single patient, according to the stage, location and grading of cancer, could improve the results, so lowering the costs of this expensive practice.

Barium Sulfate↗
PubMed1997

Testing of p-dichlorobenzene and hexachlorobenzene for their ability to induce DNA damage and micronucleus formation in primary cultures of rat and human hepatocytes.

The genotoxicity of p-dichlorobenzene (DCB) and hexachlorobenzene (HCB) was evaluated in primary cultures of rat and human hepatocytes. DNA fragmentation was measured by the alkaline elution technique and clastogenic activity by the increase in micronucleus formation. In rat hepatocytes, exposure to concentrations of DCB ranging from 0.56 to 3.2 mM and of HCB from 0.1 to 0.56 mM did not induce any significant increase in the frequency of DNA breaks but consistently produced a statistically significant increase in the frequency of micronucleated cells. In human hepatocytes, under the same experimental conditions, the response to DCB was negative in terms of both DNA fragmentation and clastogenic effect, whereas HCB produced a significant increase in the frequency of both DNA breaks and micronuclei. Taken as a whole these results suggest that of the two pesticides examined only HCB should be considered as a weak genotoxic carcinogen.

Adolescent↗
PubMed1997

Penetration of oral cefuroxime axetil into the human aqueous humor.

The purpose of this study was to investigate the penetration into the aqueous humor of cefuroxime after a single oral dose as cefuroxime axetil. Fourteen patients scheduled for cataract extraction received a single oral dose of cefuroxime axetil corresponding to 500 mg of cefuroxime 2-8 h preoperatively. Aqueous humor samples were obtained at the beginning of the cataract surgery and blood samples were drawn at the time of anesthesia. Cefuroxime levels were determined by high-performance liquid chromatography. The aqueous levels were (mean +/- SEM) 0.48 +/- 0.13 microgram/ml from 3 to 8 h after administration. Serum levels averaged 3.80 +/- 0.58 micrograms/ml. These data indicate that detectable levels of cefuroxime, exceeding the MIC of some bacterial species that frequently cause intraocular infections, may be achieved in uninflamed eyes after a low dose of cefuroxime axetil.

Administration, Oral↗