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Biomedical subjects

A Bartoli

Publications and source records attributed to A Bartoli.

At least 55 records · Page 3Linked to original sources
PubMed1997

The influence of dosage, age, and comedication on steady state plasma lamotrigine concentrations in epileptic children: a prospective study with preliminary assessment of correlations with clinical response.

The effects of age, dosage, and type of comedication on plasma lamotrigine (LTG) concentrations and the relationship between plasma drug levels and clinical response were evaluated in a prospective study of 45 patients, aged 3 to 38 years, with epilepsy uncontrolled by conventional anticonvulsant therapy. Six of the 45 patients were on single-drug therapy, and 39 were on two to five concurrently administered antiepileptic drugs when LTG was added. Thirteen patients were assessed at three or more LTG dosage levels. Within individuals, steady state plasma LTG concentrations increased linearly with increasing daily dosage over the examined dose range (25 to 575 mg/day or 0.75 to 21 mg/kg.day). Among patients also receiving enzyme-inducing agents, such as carbamazepine, barbiturates, or phenytoin, plasma LTG concentrations normalized to a 1 mg/kg daily dose were lower in children aged 3 to 6 years (0.30 +/- 0.17 microgram/ml; n = 6) than in the older children (0.43 +/-0.18 microgram/ml; n = 12) and adolescents/adults (0.68 +/- 0.26 microgram/ml; n = 10). In patients treated with valproate, the age dependency of plasma LTG was less evident, possibly because of a smaller sample size and the confounding effect of comedication. Within any given age group, dose-normalized LTG concentrations were about five-fold higher in patients comedicated with valproic acid than in those comedicated with enzyme inducers. Twenty patients showed a favorable response (with a > or = 40% reduction in seizure frequency compared with the pre-LTG period) and continued on long-term treatment. Plasma drug concentrations in these apparent responders were highly variable and did not differ significantly from those observed in nonresponders (6.6 +/- 5.2 versus 4.8 +/- 3.3 microgram/ml). These findings show that plasma LTG concentrations exhibit a wide interindividual variability under the influence of age and type of comedication, but they are predictably related to dosage within individual patients. Although there was no apparent relationship between drug levels and clinical response in this difficult-to-treat population, further studies on the potential value of monitoring plasma LTG concentrations are indicated.

Adolescent↗
PubMed1997

A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers.

PURPOSE: This study was conducted to determine whether vigabatrin affects in vivo indices of hepatic microsomal enzyme activity and the pharmacokinetics of steroid oral contraceptives in healthy subjects. METHODS: Under double-blind conditions, 13 female healthy volunteers received, in random order and with a washout interval of > or = 4 weeks, two oral 4-week treatments with vigabatrin (VGB) (maintenance dosage, 3,000 mg daily) and placebo, respectively. The clearance and half-life of antipyrine (a broad marker of drug oxidation capacity), the urinary excretion of 6-beta-hydroxycortisol (a selective marker of cytochrome CYP3A-mediated oxidation), and the activity of serum gamma-glutamyltransferase (a nonspecific index of microsomal enzyme activity) were determined after 3 weeks of each treatment. The single-dose kinetics of a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel were also determined after 3 weeks of treatment by specific radioimmunologic assays. RESULTS: VGB treatment had no influence on antipyrine clearance (28 +/- 5.6 vs. 30 +/- 4.5 ml/h/kg on placebo), antipyrine half-life (15.5 +/- 3.5 vs. 14.1 +/- 2.1 h), urinary 6-beta-hydroxycortisol excretion (488 +/- 164 vs. 470 +/- 228 nmol/ day), 6-beta-hydroxycortisol-to-cortisol concentration ratio (6.8 +/- 3.1 vs. 6.1 +/- 3.1) and serum gamma-glutamyltransferase activity (12 +/- 3 vs. 11 +/- 3 IU/L). No difference in pharmacokinetic parameters between VGB and placebo sessions were found for ethinyl estradiol (half-life, 12.5 +/- 3.2 vs. 13.9 +/- 3.2 h; AUC, 874 +/- 301 vs. 939 +/- 272 ng/ L/h) and levonorgestrel (half-life, 17.7 +/- 5.2 vs. 23.1 +/- 9.8 h; AUC, 27.5 +/- 9.6 vs. 30.0 +/- 12.0 micrograms/L/h). Two subjects, however, showed a 50 and a 39% reduction in ethinyl estradiol AUC during VGB treatment. CONCLUSIONS: At therapeutic dosages, VGB did not modify in vivo indices of hepatic microsomal enzyme activity and did not interfere significantly with the CYP3A-mediated metabolism of ethinyl estradiol and levonorgestrel. Based on these data, VGB is unlikely to affect consistently the efficacy of steroid oral contraceptives or interact pharmacokinetically with drugs that are eliminated mainly by oxidative pathways, particularly those involving cytochrome CYP3A.

Adult↗
PubMed1997

[Intestinal invagination in adults: 3 case reports].

The Authors report their experience in the surgical management of three adults affected by intussusception. The different symptoms and different diagnostic approach, compared to those of childhood, induced the Authors to some evaluations on pathophysiology of intussusception in adults. On the basis of the different pathogenesis some differential criteria between the two forms are stressed, finally suggesting a systematic surgical approach in adults.

Adult↗
PubMed1997

["Hepatoid" gastric tumor].

In this study the Authors describe two cases of hepatoid adenocarcinoma of the stomach: one is characterized by the presence of alpha-fetoprotein (AFP) high levels of the serum both pre and post-operating and by the very positive response to the adjuvant chemotherapy (how the return to the normality of such values demonstrates). The other is instead characterized by the presence of post operating hepatic metastasis, event which is very frequent in this kind of neoplasm, but presents many problems concerning the differential histological diagnostics with the primitive hepatocarcinoma (problems which are nowadays not completely solved). Moreover the Authors relate to this study the revision of the international literature of the main characteristics and of prognosis of this particular and rare neoplasm.

Adenocarcinoma↗
PubMed1996

Dexamethasone modulates CD2 expression.

Glucocorticoid hormones (GCs) are able to modulate leukocyte activity. We studied the effect of dexamethasone (DEX) on the expression of CD2, an adhesion molecule involved in T-lymphocyte homing and activation. Results of flow cytometry analysis and immunoprecipitation with anti-CD2 monoclonal antibodies (mAbs) indicated that in vitro treatment with DEX augments CD2 expression in transformed T-cell lines. This effect correlated with a rapid increase in the mRNA and was inhibited by actinomycin-D (AD). The DEX-induced CD2 augmentation was transient, peaked at days 1-2 and returned to the levels of untreated controls at days 3-4. It was a dose-dependent phenomenon, mediated by the GC receptor (GCR), because it was inhibited by the GCR antagonist RU486, and was not induced by other steroids such as testosterone and progesterone. This CD2 modulation could presumably contribute to GC-induced effects on T-cell activity.

Animals↗
PubMed1996

Effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics in epileptic patients.

1. To assess the effect of enzyme inducing anticonvulsants on ethosuximide pharmacokinetics, plasma ethosuximide concentrations after a single oral dose (500 mg) of the drug were compared in 12 healthy control subjects and 10 epileptic patients receiving chronic therapy with phenobarbitone, phenytoin and/or carbamazepine. 2. Compared with controls, epileptic patients showed markedly shorter ethosuximide half-lives (29.0 +/- 7.8 vs 53.7 +/- 14.3 h, means +/- s.d., P < 0.001) and higher apparent oral clearance (CL/F) values (15.3 +/- 3.8 vs 9.2 +/- 1.9 ml kg-1 h-1, P < 0.001). The apparent volume of distribution (V/F) of ethosuximide was slightly lower in the patients than in controls (0.6 +/- 0.1 vs 0.7 +/- 0.1 l kg-1, P < 0.05). 3. These findings provide evidence that ethosuximide elimination is increased by enzyme inducing anticonvulsants, the effect probably being mediated by stimulation of cytochrome CYP3A activity. 4. The enhancement of ethosuximide clearance in patients comedicated with enzyme inducing anticonvulsants is likely to be clinically relevant. Higher ethosuximide dosages will be required to achieve therapeutic drug concentrations in these patients.

Adult↗
PubMed1996

The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a comparative study in Caucasian and Chinese subjects using phenacetin as a marker substrate.

To assess potential ethnic and gender-related differences in the expression of cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2 substrate) and its metabolite paracetamol were compared in 20 Caucasian and 20 Chinese subjects after administration of a single oral 900 mg phenacetin dose. Peak plasma concentrations and apparent oral clearance values for phenacetin did not differ between the two groups (geometric means: 3.4 micrograms/ml and 1.56 ml h-1 kg-1, respectively, for Caucasians vs. 4.7 micrograms/ml and 1.25 ml h-1 kg-1, respectively, for Chinese, after excluding one Caucasian with aberrantly low plasma phenacetin values). Pharmacokinetic parameters for metabolically derived paracetamol were also similar in the two groups. When subjects were divided into subgroups according to gender, phenacetin apparent oral clearance values were found to be lower in Chinese women compared with both Chinese men and Caucasian subjects of either sex. It is concluded that there are no major interethnic differences in the expression of CYP1A2-related activity between Caucasians and Chinese, although Chinese women as a subgroup may exhibit comparatively lower enzyme activity.

Acetaminophen↗
PubMed1996

[Evaluation of risk factors in oncologic surgery].

The Authors carried on a retrospective study of risks factors in oncologic surgery based on a univariate analysis. The study includes 337 patients hospitalized for neoplastic pathology from January 1991 to June 1995. In agreement with Literature the most important risks factors were represented by associated pathologies, TNM staging and ASA classification. The opportunity of a correct preoperative evaluation of risks factors is recommended to assure the best conditions for the surgical patient and to rescue to surgery patients otherwise considered not surgically manageable.

Adolescent↗
PubMed1996

[Primary biliary peritonitis without perforation in childhood: etiopathogenetic evaluations and 2 case reports].

The Authors review biliary peritonitis. After some evaluations on etiopathogenesis, biliary peritonitis without perforation in childhood is discussed. The rarity of this form is considered as well as etiopathological hypothesis, difficulties of diagnosis and surgical management. Two cases of primary biliary peritonitis without perforation observed and operated in two children are reported.

Bile↗
PubMed1995

CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis.

Anti-CD3 monoclonal antibodies (MoAbs) and glucocorticoid hormones (GCH) induce apoptosis in immature thymocytes and peripheral T lymphocytes. This process is inhibited by a number of growth factors, including interleukin-2 (IL-2), IL-3, and IL-4, indicating that signals generated by membrane receptors can modulate the survival of lymphoid cells. To investigate whether signals activated by adhesion receptors have a similar activity, we analyzed the effect of CD44 (Pgp-1) adhesion molecule receptor stimulation on T-cell apoptosis induced by three stimuli (anti-CD3 MoAbs, dexamethasone [DEX] treatment, and exposure to ultraviolet irradiation [UV]) on a 3DO T-cell line. The results show that CD44 engagement, either by hyaluronic acid (HA) or anti-CD44 MoAbs, inhibits DNA fragmentation and apoptosis induced by DEX and anti-CD3 MoAbs, whereas that induced by UV, a p53-dependent phenomenon, was not inhibited. Furthermore, the antiapoptotic effect exerted through CD44 activation does not seem related to overexpression of bcl-2 or to have appreciable effects on cell proliferation. Our results indicate that adhesion molecules modulate T-cell survival by counteracting apoptosis induced by DEX or anti-CD3 MoAbs.

Animals↗
PubMed1995

T cell receptor iota an alternatively spliced product of the T cell receptor zeta gene.

It has been previously suggested that three alternative splicings of the murine T cell receptor (TCR) zeta gene are involved in the regulation of TCR/CD3 transduction signals. We here describe a new alternative splicing of this gene (TCR iota), cloned by reverse transcriptase-polymerase chain reaction, that is encoded by exons 1-7 and 10. The protein putatively encoded by TCR iota mRNA differs in its carboxy terminus from that coded by TCR0 as a consequence of the reading frame shift of exon 10. The possible role of this new splicing in TCR modulation is briefly discussed.

Amino Acid Sequence↗
PubMed1995

[Peripheral nerve tumors of the thoracic wall: 2 case reports].

The Authors discuss about thoracic wall neoplasms examining in particular neurogenic tumors, their origin, most frequent locations, and biological behaviour. Two cases are reported and preoperative diagnosis as well as surgical techniques and results obtained are discussed.

Adult↗
PubMed1994

Heterogeneous secretory response of phagocytes from different anatomical districts to the dimorphic fungus Candida albicans.

In the present study, we have examined the ability of phagocytes from different anatomical districts to discriminate between the two morphogenetic forms of Candida albicans. We have demonstrated that resident peritoneal macrophages (RP-M phi) and thioglycollate-elicited peritoneal macrophages (TP-M phi) were able to distinguish between the hyphal (H-Candida) and the yeast (Y-Candida) form of the fungus, since TNF production was observed only upon exposure of RP-M phi and TP-M phi to H-Candida. In contrast, splenic macrophages (S-M phi), bone marrow-derived macrophages (BM-M phi) and polymorphonuclear neutrophils (PMN) did not discriminate between the two forms because S-M phi and PMN produced TNF regardless of the morphogenetic status of the fungus, while BM-M phi did not. Under the same experimental conditions, we failed to observe IL-1 production from any of the phagocytic cell populations examined, with the exception of PMN. This implies that the interaction between phagocytes and C. albicans triggers differential secretory responses depending upon the morphogenetic status of the fungus and the anatomical localization of the immune cells.

Animals↗
PubMed1994

Pharmacokinetic and pharmacodynamic studies following single and multiple doses of rolafagrel, a novel inhibitor of thromboxane synthase, in normal volunteers.

The pharmacokinetics and pharmacodynamics of rolafagrel (FCE 22178), a novel thromboxane synthase inhibitor, were evaluated after single and multiple oral doses in eight healthy volunteers. After a single dose (400 mg), the drug was absorbed rapidly, peak plasma concentrations being attained within 2 h in all subjects. Elimination followed a biphasic course, with a rapid initial decline followed after 12-24 h by a late phase with a terminal half-life of about 10 h. About 100% of the administered dose could be recovered in urine within 72 h, mostly in conjugated form. During multiple dosing (400 mg t.i.d. for 5 days), steady-state conditions were approached on day 2 and AUC values over a dosing interval were similar to those observed after a single dose (72.3 vs 76.3 micrograms.ml-1.h). Pharmacokinetic parameters calculated after multiple doses were similar to those observed after a single dose (Cmax: 20.1 vs 18.2 micrograms.ml-1; tmax: 1.2 vs 1.1 h; terminal half-life: 10.9 vs 11.4 h; CL: 85.2 vs 70.4 ml.h-1.kg-1; V: 1.23 vs 1.24 l.kg-1). Platelet generation of thromboxane B2, the stable breakdown product of thromboxane A2, was inhibited by 85% at a plasma rolafagrel concentration of about 4 micrograms.ml-1, and only a small increase in inhibition was observed at higher concentrations.

Administration, Oral↗
PubMed1994

Pattern of cytokine gene expression in brains of mice protected by picolinic acid against lethal intracerebral infection with Candida albicans.

Recently, we demonstrated that intracerebral (i.c.) administration of picolinic acid (PLA) confers protection against a lethal local challenge with the opportunistic pathogen Candida albicans. By histopathological studies, we show here that mice receiving PLA treatment survive challenge and no evidence of fungal invasion is found within the brain compartment. In contrast, PLA-untreated mice succumb to infection within 7-10 days and show massive brain colonization with extensive granulomatous reaction. By PCR analysis, we show that, unlike naive brains, PLA-treated brains show transient activation of TNF alpha, IL-1 beta and IL-6 genes. C. albicans infection results in high levels of all cytokine transcripts, the phenomenon being long-lasting in PLA-untreated brains, while gradually declining in PLA-treated brains. The only exception is IL-1 beta, whose levels remain high at the latest time-points tested, also in PLA-treated brains. Finally, IL-1 alpha, constitutively detectable in naive brains, is slightly enhanced by C. albicans challenge, regardless of prior treatment. These findings, together with the knowledge that PLA is a potent co-stimulus for macrophages, suggest the involvement of cytokine circuits, likely of macrophage origin, in anti-Candida resistance established by PLA at the cerebral level.

Animals↗
PubMed1994

CYP2D6-related oxidation polymorphism in Italy.

The distribution of the oxidation polymorphism related to cytochrome CYP2D6 (debrisoquine type) was determined in 246 healthy Italian volunteers. Phenotyping was based on HPLC determination of the dextrometorphan/dextrorphan concentration ratio (metabolic ratio) in urine samples collected over an 8 h interval following a single oral 30 mg dose of dextromethorphan hydrobromide. Urinary excretion of dextromethorphan showed a wide interindividual variability, ranging from < or = 0.04 to 3.9% and from 0.5 to 79.6% of the dose, respectively. Metabolic ratios ranged from < or = 0.001 to 6.6. Eleven of the 246 subjects showed a metabolic ratio greater than 0.30, indicating that 4.5% of the population could be ascribed to the poor metabolizer status. The frequency of the poor metabolizer phenotype in this population is within the range described for other Caucasian ethnic groups.

Cytochrome P-450 CYP2D6↗
PubMed1994

Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity, in healthy volunteers.

Omeprazole has been reported to increase cytochrome P450IA2 (CYP1A2) activity in vitro, but whether this effect also occurs in vivo is controversial. To clarify this issue, the effect of omeprazole (20 mg/day for 8 days) on the kinetics and metabolism of phenacetin, an in vivo marker of CYP1A2 activity, was examined in 10 healthy volunteers. The pharmacokinetic parameters of phenacetin and metabolically derived paracetamol on the 8th day of omeprazole administration were very similar to those observed in a control session in the absence of omeprazole administration, the only significant difference being a higher peak plasma phenacetin concentration during omeprazole treatment. It is concluded that at the dosage used omeprazole does not increase the rate of oxidative and conjugative reactions involved in the metabolism of phenacetin and paracetamol respectively. These data are consistent with the hypothesis that omeprazole is generally devoid of inducing effects on CYP1A2 activity in vivo, at least in a Caucasian population with a low prevalence of the omeprazole-mephenytoin poor metabolizer phenotype.

Acetaminophen↗