Search PubMed⌕ Search

Biomedical subjects

F Bono

Publications and source records attributed to F Bono.

At least 19 recordsLinked to original sources
PubMed2006

Bilateral transverse sinus stenosis predicts IIH without papilledema in patients with migraine.

BACKGROUND: The headache profile of patients with idiopathic intracranial hypertension without papilledema (IIHWOP) may be indistinguishable from that of migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in patients with migraine is unknown. OBJECTIVE: To detect the frequency of BTSS in adult patients with migraine and to investigate whether the presence of BTSS identifies patients with IIHWOP. METHODS: In a prospective study from December 2000 to November 2005, 724 consecutive patients with recurrent headaches who fulfilled International Headache Society diagnostic criteria for migraine underwent cerebral MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 70 age-matched control subjects. RESULTS: Six hundred seventy-five of the 724 patients with migraines had normal MRV. Seventy of these 675 patients underwent LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724 patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF pressures within normal limits. CSF pressure was normal in both patients and controls with normal MRV. CONCLUSIONS: Of patients with migraine, 6.7% had bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic intracranial hypertension without papilledema (IIHWOP). These results suggest that patients with migraine who present bilateral transverse sinus stenosis on cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

Adult↗
PubMed2005

Transverse sinus stenoses persist after normalization of the CSF pressure in IIH.

BACKGROUND: Bilateral transverse sinus (TS) stenosis has been found in more than 90% of patients with idiopathic intracranial hypertension (IIH). OBJECTIVE: To evaluate whether TS stenosis changed after normalization of CSF pressure in patients with IIH during medical treatment. METHODS: Fourteen consecutive patients with IIH with bilateral TS stenosis on cerebral MR venography (MRV) during the medical treatment were studied. Patients were followed for over a 6-year period. During the follow-up, patients underwent repeated lumbar punctures (LPs) and cerebral MRV. MRV was always performed before each LP. RESULTS: TS stenosis persisted in all the patients during the follow-up. In 9 of 14 (64%) patients with IIH, CSF pressure normalized during medical treatment. CONCLUSIONS: Transverse sinus (TS) stenoses, as revealed by MR venography, persist in patients with idiopathic intracranial hypertension after normalization of CSF pressure, suggesting the lack of a direct relationship between the caliber of TS and CSF pressure.

Acetazolamide↗
PubMed2004

Nerve growth factor-induced protein kinase C stimulation contributes to TrkA-dependent inhibition of p75 neurotrophin receptor sphingolipid signaling.

Previous studies have established that reciprocal interactions between the low-affinity p75 nerve growth factor (NGF) receptor (p75(NTR)) and the high-affinity TrkA NGF receptor can dictate the cellular response to NGF. As the most important interaction, TrkA signaling was found to inhibit p75(NTR)-mediated sphingomyelinase (SMase) stimulation, ceramide production, and apoptosis. However, the mechanism by which TrkA counteracts p75(NTR)-coupled sphingolipid signaling is still unclear. Considering the stimulatory effect of NGF on protein kinase C (PKC) activity, we investigated the role of PKC in TrkA/p75(NTR) signaling interaction. In this study, we found that, in SK-N-BE cells, which selectively express p75(NTR), phorbol ester-induced PKC stimulation resulted in the abrogation of SMase stimulation and ceramide production induced by NGF. Moreover, in SK-N-BE neuroblastoma cells, which selectively express TrkA, NGF stimulated global PKC activity through two independent pathways involving phospholipase Cgamma (PLCgamma) and phosphoinositide-3 kinase (PI3K). In SH-SY5Y, another neuroblastoma cell line, which coexpresses TrkA and p75(NTR), NGF induced PKC stimulation through a TrkA/PI3K signaling pathway, whereas there was no ceramide production. However, in these cells, the inhibition of TrkA, PI3K, and PKC resulted in the restoration of NGF-induced ceramide production. Thus, our study demonstrates for the first time that TrkA interferes with p75(NTR) signaling through a PI3K/PKC-dependent mechanism.

Cell Line, Tumor↗
PubMed2004

A novel Notch3 gene mutation not involving a cysteine residue in an Italian family with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to accumulating neurologic deficits and dementia. CADASIL has been linked to nucleotide substitutions and deletions in the Notch3 gene. All the mutations described until now lead to unpaired cysteine residue in the epidermal growth factor-like repeats. The authors report a family with CADASIL carrying a deletion in the Notch3 gene that did not involve a cysteine residue.

Adult↗
PubMed2004

Gene conversion events in adult-onset spinal muscular atrophy.

OBJECTIVE: To investigate the possible occurrence of a conversion event in three patients with adult-onset spinal muscular atrophy (SMA) type IV, which represents the mildest form within the spectrum of the SMA phenotype. MATERIAL AND METHODS: We observed three patients with adult onset SMA and apparent isolated deletion of telomeric survival motor neuron (SMN1) exon 7. To distinguish between a deletion and a sequence conversion event of exon 7, these patients were analyzed in greater detail by a simple PCR-based assay. RESULTS: Analysis by DdeI digestion showed products for both telomeric and centromeric copies of exon 8. These findings indicated a gene conversion event as the site for primer R111 was retained at least in one of two alleles. CONCLUSIONS: These results provide first evidence that a conversion event may be also associated with adult-onset SMA, and further support the notion that a gene conversion event is usually associated with a milder SMA phenotype and a later onset of disease.

Adult↗
PubMed2003

Cerebral MR venography of transverse sinuses in subjects with normal CSF pressure.

Flow artifacts or anatomic variants of venous sinuses often make MR venography (MRV) interpretation difficult. The authors investigated cerebral MRV in 111 subjects with normal CSF pressure to identify the most common flow abnormalities of transverse sinuses (TS). Disturbance of venous outflow in one transverse sinus was commonly observed in 30% of subjects whereas flow abnormalities of both TS occurred in 2 of 111 individuals. Subjects with flow gaps in both TS should undergo lumbar puncture to exclude increased CSF pressure.

Adolescent↗
PubMed2003

Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand.

The peripheral benzodiazepine receptor (PBR), has been recently shown to play a key role in the regulation of the mitochondrial process leading to apoptosis, which occurs during cardiac ischemia. The present work shows that SSR180575, a novel PBR ligand of potential interest in pathological cardiovascular indications, irreversibly and specifically binds with high affinity on both rat heart mitochondria and on a cell line transfected with the human PBR (K(d)=1.95+/-0.22 and 4.58+/-0.83nM, respectively). In conclusion, SSR180575 is a specific and potent PBR ligand which irreversible binding to PBR appears of high interest in various therapeutic indications where apoptosis occurs.

Acetamides↗
PubMed2003

Effect of SanOrg123781A, a synthetic hexadecasaccharide, on clot-bound thrombin and factor Xa in vitro and in vivo.

Factor (F)Xa and thrombin bound to the clot during its formation contribute to the propensity of thrombi to activate the coagulation system. The aim of this work was to study the inhibition of clot-bound FXa and clot-bound thrombin by SanOrg123781A, a synthetic hexadecasaccharide that enhances the inhibition of thrombin and FXa by antithrombin (AT). SanOrg123781A, designed to exhibit low non-specific binding to proteins other than AT, was compared with heparin. In buffer, heparin and SanOrg123781A inhibited FXa and thrombin at similar concentrations [concentration inhibiting 50% (IC50) of Xa and IIa activity were, respectively: heparin 120 +/- 7 and 3 +/- 1 ng mL-1; SanOrg123781A 77 +/- 5 and 4 +/- 1 ng mL-1]. In human plasma, the activity of both compounds was reduced, although the activity of heparin was much more affected than that of SanOrg123781A (IC50 values for inhibition of FXa and FIIa activity were, respectively: heparin 100 +/- 5 and 800 +/- 40 ng mL-1; SanOrg123781A 10 +/- 5 and 30 +/- 3 ng mL-1). We demonstrated, in agreement with our previous results, that the procoagulant activity of the clot is essentially due to clot-bound FXa and to some extent to clot-bound thrombin. We showed that heparin and SanOrg123781A were able to inhibit fragment F1+2 generation induced by clot-bound FXa with IC50 values of 2 +/- 0.5 micro g mL-1 and 0.6 +/- 0.2 micro g mL-1, respectively. Both compounds also inhibited clot-bound thrombin activity, the IC50 values of heparin and SanOrg123781A being 1 +/- 0.01 micro g mL-1 and 0.1 +/- 0.1 micro g mL-1, respectively. Moreover, both heparin and SanOrg123781A significantly inhibited fibrinopeptide A generated by the action of clot-bound thrombin on fibrinogen but also by free thrombin generated from prothrombin by clot-bound FXa with IC50 values of 4 +/- 0.6 and 1 +/- 0.1 micro g mL-1, respectively. As with clot-bound enzymatic activities, SanOrg123781A was three times more active than heparin in vivo on fibrinogen accretion onto a pre-existing thrombus and as activators of recombinant tissue-type plasminogen activator-induced thrombolysis. In conclusion, due to the specific activities of SanOrg123781A, this compound is much more active than heparin in the presence of plasma proteins, on clot-bound enzymes and in in vivo models of thrombosis/thrombolysis.

Animals↗
PubMed2002

Obesity does not induce abnormal CSF pressure in subjects with normal cerebral MR venography.

Obesity has been shown to increase lumbar CSF pressure in healthy subjects. The authors studied lumbar CSF opening pressure in 18 obese, 33 overweight, and 49 nonoverweight subjects with normal MRI and MR venography (MRV) of the brain. No subject had a CSF pressure above 200 mm H2O. Obesity does not cause abnormal CSF pressure in subjects with normal MRV. Individuals with a CSF pressure higher than 200 mm H2O should undergo MRV to exclude cerebral venous thrombosis.

Adolescent↗
PubMed2002

Pharmacokinetics of new synthetic heparin mimetics.

Pharmacokinetics of oligosaccharides displaying various affinities for antithrombin (AT) allowed us to show that there was a close relationship between the plasma half-life of these antithrombotic oligosaccharides and their affinity for AT. Recently, we have described new heparin mimetics comprising an AT binding domain and a thrombin binding domain separated by a neutral methylated saccharide sequence. These compounds displayed strong anti-Xa and antii-IIA activities and, in contrast to heparin, escaped neutralisation by platelet factor 4. The aim of this work was to compare the pharmacokinetics of several of these heparin mimetics in rats. These compounds differed by their length, charge and affinity for AT (AT-binding domain). The results obtained indicate that the prolongation of the AT binding domain did not modify significantly their affinities for AT. However, an increase in the number of charges leads to a decrease in the half-life. When a methylated spacer was added in order to minimise the non-specific interactions to other proteins, half-lives of the heparin mimetic were in the same range than that of the pentasaccharide used as an AT binding domain. In conclusion, this study shows the influence of the charge of the oligosaccharides on their pharmacokinetics and underlinesthe importance of minimising their non-specific binding to plasma proteins in order to obtain compounds with predictive pharmacokinetics.

Animals↗
PubMed2002

The structure of synthetic oligosaccharides in relation to factor IXa inhibition.

We investigated the effect of various oligosaccharides (OS) on the inhibition of factor IXa by antithrombin (AT) in a purified system. The OS comprised the AT-binding pentasaccharide sequence prolonged by saccharide chains with various lengths and charges. We show that factor IXa inhibition depended on the molecular weight of the OS. Factor IXa was not inhibited by the AT-binding pentasaccharide alone, but was inhibited if it was prolonged by a sulphated dodecasaccharide at the non-reducing end. The overall charge was also important since factor IXa inhibition was negligible if the pentasaccharide was prolonged by a non-sulphated dodecasaccharide. Using compounds containing a non-sulphated spacer, we showed that the central part of the OS was not critical. This study therefore demonstrates that the minimal OS structure necessary for catalysing factor IXa inhibition by AT is close to that required for catalysing thrombin inhibition.

Antithrombin III↗
PubMed2001

Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia.

Deprivation of oxygen (hypoxia) and/or glucose (hypoglycemia) represents a serious stress that affects cellular survival. The hypoxia-inducible transcription factor-1alpha (HIF-1alpha), which has been implicated in the cellular response to hypoxia (Semenza, G. L. (1999) Annu. Rev. Cell Dev. Biol. 15, 551-578), mediates apoptosis during hypoxia (Halterman, M. W., Miller, C. C., and Federoff, H. J. (1999) J. Neurosci. 19, 6818-6824 and Carmeliet, P., Dor, Y., Herbert, J. M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., Koch, C. J., Ratcliffe, P., Moons, L., Jain, R. K., Collen, D., and Keshet, E. (1998) Nature 394, 485-490), but the function of its homologue HIF-2alpha remains unknown. Therefore, the role of HIF-2alpha in cellular survival was studied by targeted inactivation of the HIF-2alpha gene (HIF-2alpha(-/-)) in murine embryonic stem (ES) cells. In contrast to HIF-1alpha deficiency, loss of HIF-2alpha did not protect ES cells against apoptosis during hypoxia. Both HIF-1alpha(-/-) and HIF-2alpha(-/-) ES cells were, however, resistant to apoptosis in response to hypoglycemia. When co-cultured with wild type ES cells, HIF-2alpha(-/-) ES cells became rapidly and progressively enriched in hypoglycemia but not in hypoxia. Thus, HIF-1alpha and HIF-2alpha may have distinct roles in responses to environmental stress, and despite its name, HIF-2alpha may be more important in the survival response to environmental variables other than the level of oxygen.

Animals↗
PubMed2001

Cerebral venous thrombosis and isolated intracranial hypertension without papilledema in CDH.

BACKGROUND: There is evidence that patients with chronic daily headache (CDH) may have isolated intracranial hypertension without papilledema (IHWOP). Recent studies have emphasized that isolated IH may be due to cerebral venous thrombosis (CVT). OBJECTIVE: To detect the occurrence of CVT in patients with CDH. METHODS: The authors investigated the occurrence of CVT in 114 consecutive patients with CDH by using MR venography (MRV). A portion of these patients underwent a lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in 28 age-matched control subjects. RESULTS: In all the control subjects, both MRV and CSF pressure were normal. One hundred three of the 114 patients with CDH had normal MRV. Twenty-seven (Group 1) of these 103 patients underwent LP, and all of them had normal CSF pressure. Eleven (9.6%) of the 114 patients with CDH had CVT of one or both transverse sinuses. Six of these 11 patients had flowing abnormalities of one transverse sinus (Group 2), whereas the remaining five patients showed involvement of both transverse sinuses (Group 3). The CSF pressure of Group 2 was higher than that of either Group 1 or the control subjects, and one of the six patients showed isolated IHWOP. Patients of Group 3 displayed the highest CSF pressure, and four of five had isolated IHWOP. The headache profiles of patients with CDH and CVT did not differ from those of patients with CDH but normal MRV. CONCLUSIONS: CVT, as detected by MRV, occurred in 9.6% of patients who presented with CDH. Almost half of the patients with CVT had isolated IHWOP. These results suggest that MRV may be a useful tool for selecting patients with CDH who should have LP to exclude isolated IHWOP.

Adult↗