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Biomedical subjects

S Floris

Publications and source records attributed to S Floris.

At least 19 recordsLinked to original sources
PubMed2004

Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients.

Osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within multiple sclerosis (MS) lesions. Recently, we demonstrated that OPN plasma levels were elevated in active relapsing-remitting (RR) MS patients. In this longitudinal study, a trend was observed for OPN serum levels in relation to clinical exacerbations. Moreover, OPN protein levels were significantly elevated 1 month prior to increase of gadolinium (Gd)-enhancing lesion number, whereas no relation was observed between OPN levels and increase in Gd-enhancing lesion volume. Although no robust relation between OPN and disease activity was observed, these data suggest that OPN levels are elevated prior to increased disease activity in RR MS patients.

Adult↗
PubMed2004

[Duloxetine in the treatment of urinary incontinence in women].

Urinary incontinence is a disease able to decrease the quality of life of affected women. It shows a prevalence of about 35% among adult women. Pharmacological treatment can be used when pelvic floor muscle training has failed or when it could be better to postpone or avoid surgery. Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor (SNRI), can act effectively in treating stress urinary incontinence.

Adrenergic Uptake Inhibitors↗
PubMed2003

Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study.

Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive cellular infiltration in the development of acute experimental allergic encephalomyelitis (EAE), the animal correlate of multiple sclerosis. Cerebrovascular leakage and monocytes infiltrates were separately monitored by quantitative in vivo MRI during the course of the disease. Magnetic resonance enhancement of the contrast agent gadolinium diethylenetriaminepentaacetate (Gd-DTPA), reflecting vascular leakage, occurred concomitantly with the onset of neurological signs and was already at a maximal level at this stage of the disease. Immunohistochemical analysis also confirmed the presence of the serum-derived proteins such as fibrinogen around the brain vessels early in the disease, whereas no cellular infiltrates could be detected. MRI further demonstrated that Gd-DTPA leakage clearly preceded monocyte infiltration as imaged by the contrast agent based on ultra small particles of iron oxide (USPIO), which was maximal only during full-blown EAE. Ultrastructural and immunohistochemical investigation revealed that USPIOs were present in newly infiltrated macrophages within the inflammatory lesions. To validate the use of USPIOs as a non-invasive tool to evaluate therapeutic strategies, EAE animals were treated with the immunomodulator 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, lovastatin, which ameliorated clinical scores. MRI showed that the USPIO load in the brain was significantly diminished in lovastatin-treated animals. Data indicate that cerebrovascular leakage and monocytic trafficking into the brain are two distinct processes in the development of inflammatory lesions during multiple sclerosis, which can be monitored on-line with MRI using USPIOs and Gd-DTPA as contrast agents. These studies also implicate that USPIOs are a valuable tool to visualize monocyte infiltration in vivo and quantitatively assess the efficacy of new therapeutics like lovastatin.

Animals↗
PubMed2001

Uterine perfusion and hormonal pattern in patients with polycystic ovary syndrome.

PURPOSE: To evaluate whether polycystic ovary syndrome (PCOS) patients with different pulsatility index (PI) of uterine artery showed differences in their hormonal pattern. METHODS: Eighty-eight PCOS-affected patients and 15 controls were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL, estradiol, and androgens concentration determination; and BMI evaluation during early follicular phase. RESULTS: The mean PI of uterine artery of PCOS patients was significantly higher than control group (2.97 +/- 0.9 vs. 1.89 +/- 0.2 respectively). The distribution of the PI'values was significantly different in the PCOS-affected patients and in control group. The plasma levels of DHEAS and BMI were significantly higher in PCOS patients with PI > or = 3 than in PCOS patients with PI < 3. CONCLUSION: High resistance in the uterine artery is present in PCOS patients, but a wide range PI values of uterine artery is present. BMI and DHEAS seem to be factors interfering with uterine perfusion.

Adult↗
PubMed2001

Evidence that cyproterone acetate improves psychological symptoms and enhances the activity of the dopaminergic system in postmenopause.

The psychological symptoms assessed with a validated psychometric scale, SCL-90, were significantly higher in postmenopausal women (PMW; 60 subjects) than in premenopausal women (20 subjects). In the same PMW, the activity of the dopaminergic system, assessed with the PRL response to the dopamine-blocking agent sulpiride, was significantly lower than that in premenopausal women. During a period of 12 weeks the 60 PMW were randomly divided into 3 groups: no treatment (group A; n = 20), treatment with estradiol (E(2)) alone (patches with a E(2) release of 50 microg/24 h; group B; n = 20), and treatment with hormonal replacement therapy [estradiol valerate (EV) at a daily dose of 2 mg for 11 days and EV at the same daily doses plus cyproterone acetate (CPA) at a daily dose of 1 mg/day for 10 days; group C; n = 20). At the 12th week of the observation, only in group C women were the psychological symptoms significantly decreased, and the indirect evaluation of the dopaminergic system activity through PRL response to sulpiride showed a significant increase. During the same period, no changes in testosterone levels were observed in any group of PMW, whereas a significant increase in E(2) levels was found in both groups B and C. Although it is likely that the improvement in psychological symptoms with EV and CPA was due to progestin, we cannot rule out the possibility that greater estrogen exposure may have played a role.

Adult↗
PubMed2000

Evidence that treatment with monophasic oral contraceptive formulations containing ethinylestradiol plus gestodene reduces bone resorption in young women.

The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound (gestodene, GES, 75 microg) but different doses of ethinylestradiol (EE2) (20 or 30 microg) differently influences specific markers of bone resorption (urinary levels of pyridinoline (PYR) and dexoxypyridinoline (D-PYR)). During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women (subjects of the same age group with normal menstrual cycle who did not use contraception). In women taking pills with 20 or 30 microg EE2, the levels of sex hormone-binding globulin (SHBG) significantly increased during treatment in comparison with baseline, whereas in the same time period no changes occurred in control women. These findings suggest that similar to the pill containing 30 microg EE2, the lower dosage of the EE2 pill (20 microg) is also capable of reducing bone resorption. Twenty and 30 microg EE2 pills exert the same biological estrogenic effect. In fact, SHBG levels significantly increased with both pills. However, an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone cannot be excluded. Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects, these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice.

Adult↗
PubMed2000

Allopregnanolone synthesis in cerebellar granule cells: roles in regulation of GABA(A) receptor expression and function during progesterone treatment and withdrawal.

Rat cerebellar granule cells were cultured for 5 days with progesterone, resulting in the conversion of progesterone to allopregnanolone, a potent and efficacious modulator of gamma-aminobutyric acid (GABA) type-A receptors, as well as in decreases in the abundance of GABA(A) receptor alpha(1), alpha(3), alpha(5), and gamma(2) subunit mRNAs. These effects were accompanied by decreases in the efficacies of diazepam and the beta-carboline DMCM with regard to modulation of GABA-evoked Cl(-) currents. Withdrawal from such progesterone treatment resulted in a rapid and selective increase in the abundance of the GABA(A) alpha(4) subunit mRNA that was associated with a restoration of receptor sensitivity to the negative modulatory action of DMCM, a positive receptor response to flumazenil, and continued reduced responsiveness of receptors to diazepam. Prevention of allopregnanolone synthesis by the 5alpha-reductase inhibitor finasteride also prevented the changes in both GABA(A) receptor gene expression and receptor function elicited by progesterone treatment and withdrawal.

Animals↗
PubMed1999

Changes in the gene expression of GABAA receptor subunit mRNAs in the septum of rats subjected to pentylenetetrazol-induced kindling.

Chemical kindling was induced in rats by long-term administration of pentylenetetrazol (PTZ) (30 mg/kg three times a week for 9 weeks). The effects of such kindling on the abundance of transcripts encoding subunits of the gamma-aminobutyric acid type A (GABAA) receptor in the brain were measured by RNase protection assay. Kindled rats were examined either 3 or 30 days after discontinuation of PTZ treatment. The amounts of gamma2L and gamma2S subunit mRNAs were significantly increased in the hippocampus and cerebral cortex of kindled rats 3 and 30 days after treatment discontinuation, compared with those observed in control rats, and these effects were prevented by the concomitant administration of the anticonvulsant abecarnil. In contrast, the amounts of alpha1 and beta2 subunit mRNAs in these two brain regions did not differ significantly between kindled and control rats. The abundance of alpha1, beta2, gamma2L and gamma2S subunit mRNAs was decreased in the septum of rats 3 or 30 days after discontinuation of treatment with PTZ either alone or in combination with abecarnil. The amounts of none of the four subunit mRNAs measured differed significantly between the striatum or frontal cortex of kindled rats and control rats 3 days after drug discontinuation. Immunohistochemical analysis with antibodies to choline acetyltransferase revealed a marked decrease in the number of cholinergic neurons in the septum of kindled rats 30 days after discontinuation of PTZ treatment; this effect was not prevented by the administration of abecarnil. These results suggest that long-term treatment with PTZ induces a loss of GABAA receptors in the septum.

Animals↗
PubMed1999

Increased abundance of GABAA receptor subunit mRNAs in the brain of Long-Evans Cinnamon rats, an animal model of Wilson's disease.

The abundance of mRNAs encoding various subunits of the gamma-aminobutyric acid type A (GABAA) receptor was examined in different regions of the brain of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease (WD). The measurements were performed at two different stages of disease: at 9 weeks of age, when no symptoms are evident, and at 15 weeks of age, when 90% of the animals develop jaundice. The amounts of the gamma2L and gamma2S subunit mRNAs in the striatum, cerebellum, and cerebral cortex of LEC rats at 9 weeks of age were increased (+25 to +35%) compared with those in LE rats of the same age; these differences were no longer apparent in 15-week old animals. The amount of alpha1 subunit mRNA was also significantly increased (+30%) in the cerebellum of LEC rats at 9 weeks of age; although a smaller increase (+20%) was still evident at 15 weeks of age, this was not statistically significant. The amount of beta2 subunit mRNA was increased in the cerebellum (+32%) and hippocampus (+21%) of LEC rats at 9 weeks of age, but no differences with LE rats were apparent at 15 weeks. The onset of isoniazid-induced seizures in LEC rats at 9 weeks of age was significantly delayed compared with that in LE rats. These results demonstrate abnormal expression of GABAA receptor subunit genes in the brain of LEC rats, and they suggest that this altered expression is associated with an increase in GABAergic tone.

Aging↗
PubMed1999

Effect of chronic administration of cabergoline on uterine perfusion in women with polycystic ovary syndrome.

OBJECTIVE: To confirm whether patients with polycystic ovary syndrome (PCOS) have a reduction in uterine perfusion and to verify whether chronic administration of cabergoline can decrease this high vascular resistance. DESIGN: Prospective randomized trial. SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy. PATIENT(S): Thirty patients were enrolled in the study: 20 affected by PCOS and 10 healthy controls. Patients with PCOS were randomly assigned to one of two treatments for 3 months: oral administration of cabergoline (0.5 mg) every week or oral administration of placebo every week. INTERVENTION(S): All patients underwent transvaginal ultrasonography associated with Doppler flow measurement of the uterine artery, and serum hormone concentrations were determined during the early follicular phase. In women with PCOS, Doppler flow measurement and hormonal assessment were repeated in the early follicular phase of the third month of treatment. MAIN OUTCOME MEASURE(S): Pulsatility index of the uterine artery before and during treatment. RESULT(S): The mean pulsatility index of the uterine artery in patients with PCOS was significantly higher than that of the control group (3.29+/-0.5 and 2.01+/-0.2, respectively). Patients with PCOS treated with cabergoline showed a significant increase in uterine perfusion, with a pulsatility index of 3.14+/-0.6 before and 2.39+/-0.5 during the treatment. No difference was found in patients with PCOS treated with placebo. CONCLUSION(S): Patients with PCOS have high resistance in the uterine arteries, but chronic administration of cabergoline can increase uterine perfusion.

Administration, Oral↗
PubMed1998

Molecular and functional adaptation of the GABA(A) receptor complex during pregnancy and after delivery in the rat brain.

The abundance of gamma-aminobutyric acid receptor type A (GABAA receptor) subunit mRNAs and polypeptides as well as muscimol-stimulated 36Cl- uptake were measured in rat cerebral cortex or hippocampus at various times during pregnancy and after delivery. RNase protection assays revealed that the amount of the gamma2L subunit mRNA decreased progressively during pregnancy, in the cerebral cortex and hippocampus, and then returned to control values around the time of delivery. A similar pattern was observed for the alpha5 subunit mRNA in the cerebral cortex, whereas no significant changes were apparent for alpha1, alpha2, alpha3, alpha4, beta1, beta2, beta3 and gamma2S subunit mRNAs. The amounts of gamma2 and alpha1 proteins in the cerebral cortex were measured by immunoblot analysis; whereas the abundance of gamma2 protein decreased during pregnancy, no change was detected in the amount of alpha1 protein. Evaluation for functional significance of the down-regulated gamma2 and alpha5 subunit was made by determining the GABAA receptor function assessed by measurement of muscimol-stimulated 36Cl- uptake in cerebral cortical membrane vesicles. Muscimol-induced 36Cl- uptake was markedly reduced during of pregnancy compared with rats in oestrus. At this same time, the potentiating effects of diazepam and allopregnanolone on muscimol stimulation of 36Cl- uptake also were reduced. In contrast, the effects of muscimol, allopregnanolone and diazepam were significantly increased, relative to animals in oestrus, after delivery.

Allosteric Regulation↗
PubMed1998

Composite cerebrospinal fluid score in relapsing-remitting and secondary progressive multiple sclerosis.

We investigated whether cerebrospinal fluid (CSF) analysis may differentiate between relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). In 17 RR and 16 SP patients we determined: albumine CSF/PB ratio; mononuclear cell (MNC) number, CD4+, CD8+, and B1+ subsets, CD4+/CD8+ ratio; IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indexes; myelin basic protein; neuron-specific enolase (NSE); S100; and lactate. For each parameter the statistical distance was calculated. Then, using linear discriminant analysis, we computed a discriminant score, including only variables with a P value less than or equal to 0.15: albumin CSF/PB ratio, MNC number, IgM, IgM index, C3, C4, NSE, S100, and lactate. The discriminant score allocated all 17 RR patients to the RR group and 15 of 16 SP patients to the SP group. We conclude that RR and SP MS patients differ with respect to CSF profile and that in individual patients a composite CSF score may differentiate between RR and SP MS.

Adult↗
PubMed1996

Chronic ethanol intoxication enhances [3H]CCPA binding and does not reduce A1 adenosine receptor function in rat cerebellum.

The effects of acute and chronic treatment with ethanol on the function of A1 adenosine receptor in the rat cerebellar cortex were investigated. Acute administration of ethanol (0.5-5 g/kg) had no effect on the binding of the A1-receptor agonist [3H]2-chloro-N6-cyclopentyladenosine ([3H]CCPA) or that the antagonist [3H]8-cyclopentyl-1-3-dipropylxanthine ([3H]DPCPX) in rat cerebellar cortical membranes. Rats were rendered ethanol dependent by repeated forced oral administration of ethanol (12-18 g/kg per day) for 6 days. [3H]CCPA binding was increased by 23% in cerebellar cortical membranes prepared from rats killed 3 h after ethanol withdrawal compared with saline-treated animals. The increase in [3H]CCPA binding was still apparent 12-24 h after the last ethanol administration, but was no longer detectable 3-6 days after ethanol withdrawal. In contrast, the binding of [3H]DPCPX was not modified in the cerebellar cortex of rats killed at various times after ethanol withdrawal. The acute administration of CCPA [0.25-1 mg/kg, intraperitoneally (IP)] suppressed the tremors and audiogenic seizures apparent 24 h after ethanol withdrawal. Moreover, repeated coadministration of CCPA (0.5 mg/kg, IP, four times daily) and ethanol did not prevent the generation of audiogenic seizures during withdrawal but completely prevented mortality. Finally, CCPA antagonized with similar potencies and efficacies the isoniazid-induced convulsions observed in control and ethanol-withdrawn rats. These results indicate that long-term treatment with intoxicating doses of ethanol enhances [3H]CCPA binding but does not reduce the anticonvulsant efficacy of CCPA or the function of A1 adenosine receptors.

Adenosine↗
PubMed1995

Proconflict effect of carbon dioxide inhalation in rats.

The effect of brief inhalation of carbon dioxide (CO2) was studied in a conflict situation (Vogel test) in the rat. This treatment, which inhibits gamma-aminobutyric acid (GABA)-mediated transmission in rat brain and induces anxiety and panic attacks in humans, elicited a proconflict effect. Exposure of rats for 1 min to CO2 decreased by approximately 40% the number of licking periods in the test. This effect was abolished by prior administration of alprazolam (0.5 mg per kilogram of body mass, i.p.). Although these results may support a role for GABA-mediated transmission in the anxiogenic effect of CO2 inhalation, the possibility that different neurotransmitters other than GABA are involved in the action of CO2 can not be ruled out.

Administration, Inhalation↗
PubMed1994

2-Chloro-N6-cyclopentyladenosine (CCPA), an adenosine A1 receptor agonist, suppresses ethanol withdrawal syndrome in rats.

The ability of 2-chloro-N6-cyclopentyladenosine (CCPA) to suppress ethanol withdrawal syndrome was tested in male rats rendered physically dependent on ethanol by intragastric administrations of ethanol (12-18 g/kg daily for 6 days). CCPA administered 24 hr after the last ethanol dose produced a dose-dependent inhibition of withdrawal signs such as tremors and audiogenically induced seizures, an effect prevented by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX).

Adenosine↗
PubMed1994

Imidazenil, a new partial agonist of benzodiazepine receptors, reverses the inhibitory action of isoniazid and stress on gamma-aminobutyric acidA receptor function.

The imidazobenzodiazepine 6-(2-bromophenyl)-8-fluoro-4H-imidazo-[1,5-a] [1,4]benzodiazepine-3-carboxamide (imidazenil) is a new anxiolytic and anticonvulsant ligand of the benzodiazepine recognition site that possesses the characteristics of a partial allosteric modulator of the gamma-aminobutyric acid (GABA) type A receptor. The effects of imidazenil on GABAA receptor function were examined both in vitro and in vivo. Imidazenil inhibited [3H] flumazenil binding to mouse cerebral cortical membranes in vitro with an IC50 of 0.9 nM, showing that this compound binds with high affinity to benzodiazepine receptors. However, imidazenil failed to modify t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to washed or unwashed mouse cortical membrane preparations. Furthermore, imidazenil injected i.p. into mice failed to affect [35S]TBPS binding subsequently measured in unwashed cortical membranes. In contrast, imidazenil reduced in a dose-dependent manner the increase in [35S]TBPS binding elicited by isoniazid (200 mg/kg s.c.), an effect mimicked by lorazepam and abecarnil++ but not by bretazenil. As expected, i.p. administration of lorazepam or abecarnil induced within 30 min a marked reduction in [35S]TBPS binding subsequently measured in unwashed cortical membranes of control mice. Moreover, imidazenil at a dose as low as 0.05 mg/kg (i.p.) delayed the onset of convulsions and death elicited by isoniazid and reduced significantly the number of mice exhibiting seizures. Accordingly, imidazenil also showed great potency in antagonizing the convulsions induced by pentylenetetrazole in rats. Imidazenil also completely abolished the increase in [35S]TBPS binding induced by foot-shock or exposure to carbon dioxide. Finally, imidazenil antagonized both in vitro and in vivo the effects of bretazenil or lorazepam on GABAA receptor function.

Animals↗
PubMed1988

[Paradoxical fluoride phenomena in a Sardegna district].

The authors in epidemiologic research on dental caries of primary-school children in a village having optimufluorotic water, put in evidence fluorine paradox phenomena founding high percentual of cariopatic subjects.

Adolescent↗