The real usefulness and indication for migraine diagnosis of neurophysiologic evaluation.

According to IHS criteria, a correct clinical history is fully adequate for a diagnosis of migraine. Patients usually perform many useless instrumental and laboratoristic exams and specialistic evaluations. In particular, electroencephalogram (EEG) is often prescribed as a first-line study in migraine patients.

Frovatriptan versus almotriptan for acute treatment of menstrual migraine: analysis of a double-blind, randomized, cross-over, multicenter, Italian, comparative study.

The objective of the study was to compare the efficacy and safety of frovatriptan and almotriptan in women with menstrually related migraine (IHS Classification of Headache disorders) enrolled in a multicenter, randomized, double-blind, cross-over study. Patients received frovatriptan 2.5 mg or almotriptan 12.

Multipotent MAO and cholinesterase inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amine.

The synthesis, pharmacological evaluation and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amines 1-7 of type I, and 9-12 of type II, designed as multipotent inhibitors able to simultaneously inhibit monoamine oxidases (MAO-A/B) as well as cholinesterase (AChE/BuChE) enzymes, as potential drugs for the treatment of Alzheimer's disease, are described. Indole derivatives 1-7 of type I are well known MAO inhibitors whose capacity to inhibit AChE and BuChE was here investigated for the first time. As a result, compound 7 was identified as a MAO-B inhibitor (IC(50) = 31 ± 2 nM) and a moderately selective eqBuChE inhibitor (IC(50) = 4.

The rapid and direct determination of ATPase activity by ion exchange chromatography and the application to the activity of heat shock protein-90.

Adenosine nucleotides are involved as substrates or co-factors in several biochemical reactions, catalyzed by enzymes, which modulate energy production, signal transduction and cell proliferation. We here report the development and optimization of an ion exchange liquid chromatography (LC) method for the determination of ATP, ADP and AMP. This method is specifically aimed at the determination of the ATP-ase activity of human heat shock protein 90 (Hsp90), a molecular chaperone that has emerged as target enzyme in cancer therapy.

The First Dual ChE/FAAH Inhibitors: New Perspectives for Alzheimer's Disease?

The treatment of Alzheimer's disease (AD) still remains an area of significant unmet need, with drugs that only target the symptoms of the disease. Therefore, there is considerable need for disease-modifying therapies. The complex etiology of AD prompts scientists to develop multitarget strategies to combat causes and symptoms.

Vascular predictors of cognitive decline in patients with mild cognitive impairment.

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index.

Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases.

A family of huprine-tacrine heterodimers has been developed to simultaneously block the active and peripheral sites of acetylcholinesterase (AChE). Their dual site binding for AChE, supported by kinetic and molecular modeling studies, results in a highly potent inhibition of the catalytic activity of human AChE and, more importantly, in the in vitro neutralization of the pathological chaperoning effect of AChE toward the aggregation of both the β-amyloid peptide (Aβ) and a prion peptide with a key role in the aggregation of the prion protein. Huprine-tacrine heterodimers take on added value in that they display a potent in vitro inhibitory activity toward human butyrylcholinesterase, self-induced Aβ aggregation, and β-secretase.

Synthesis of monomeric derivatives to probe memoquin's bivalent interactions.

Eight monomeric congeners, related to the multitarget lead candidate memoquin, were prepared and evaluated at multiple targets to determine their profile against Alzheimer's disease. 2-4 bind to AChE with similar low nanomolar affinities and function as effective inhibitors of amyloid aggregation. The most potent monovalent ligand 2 also inhibits BACE-1 in vitro and APP metabolism in primary chicken telencephalic neurons.

Cystamine-tacrine dimer: a new multi-target-directed ligand as potential therapeutic agent for Alzheimer's disease treatment.

Alzheimer's disease (AD) is the most common cause of dementia, clinically characterized by loss of memory and progressive deficits in different cognitive domains. An emerging disease-modifying approach to face the multifactorial nature of AD may be represented by the development of Multi-Target Directed Ligands (MTDLs), i.e.

Synthesis and biological assessment of diversely substituted furo[2,3-b]quinolin-4-amine and pyrrolo[2,3-b]quinolin-4-amine derivatives, as novel tacrine analogues.

The synthesis and pharmacological analyses of a number of furo[2,3-b]quinolin-4-amine, and pyrrolo[2,3-b]quinolin-4-amine derivatives are reported. Thus, we synthesized diversely substituted tacrine analogues 1-11 and 12-16 by Friedländer-type reaction of readily available o-amino(furano/pyrrolo)nitriles with suitable and selected cycloalkanones. The biological evaluation of furanotacrines1-11 and pyrrolotacrine13 showed that these are good, in the micromolar range, and highly selective inhibitors of BuChE.

Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer's disease.

Lipoic acid (LA) is a natural antioxidant. Its structure was previously combined with that of the acetylcholinesterase inhibitor tacrine to give lipocrine (1), a lead compound multitargeted against Alzheimer's disease (AD). Herein, we further explore LA as a privileged structure for developing multimodal compounds to investigate AD.

Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers.

The multifactorial nature of Alzheimer's disease (AD) offers us a textbook example where parental compounds, mostly marketed, are modified with the aim of improving and/or conferring two or even more biological activities to contrast or less frequently revert the disease's symptoms. This is the case of tacrine and its dimeric derivative bis(7)-tacrine which, for instance, paved the way for the development of a broad collection of very interesting homo- and heterodimeric structures, conceived in light of the emerging multi-target approach for AD-related drug discovery. As a contribution to the topic, we report here the design, synthesis and biological evaluation of 12 compounds referable to bis(7)-tacrine.

Oxidative stress in ischaemic stroke.

Background: Production of reactive oxygen species after ischaemic stroke may enhance tissue damage through multiple molecular pathways.

Materials And Methods: In this study, we examined the serum levels of lipoperoxide and hydroperoxide, conjugated dienes and total antioxidant capacity levels in 50 patients with acute ischaemic stroke (T0) to evaluate the possibility to use them as specific biochemical markers for cerebral ischaemia. Determinations were repeated after a month (T1) to correlate their relative changes with clinical evolution.

The role of instrumental examinations in delayed migraine diagnosis.

Patients affected by migraine without aura very often consult different specialists who, misunderstanding the correct diagnosis, submit them to different instrumental examinations. The objective of the study was to assess if each instrumental examination was really useful for a faster migraine definition, or on the contrary, it increased the time delay for a correct diagnosis. We enrolled 300 consecutive patients referring to our Headache Center with a first diagnosis of migraine without aura and submitted them to a face-to-face interview about time from disease's onset to a correct diagnosis.

The role of carotid atherosclerosis in Alzheimer's disease progression.

The aim of this 12-month prospective study was to establish whether severe internal carotid artery stenosis is associated with faster progression of the cognitive impairment in patients with Alzheimer's disease (AD). Four hundred and eleven patients with AD underwent extracranial carotid Doppler ultrasound evaluation. Cerebrovascular reactivity to hypercapnia was measured by means of the breath-holding index (BHI) in those with severe carotid artery stenosis using transcranial Doppler ultrasonography.

A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine.

The objective of this study was to evaluate patients' satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.

Kinetic characterization of amyloid-beta 1-42 aggregation with a multimethodological approach.

Extensive evidence suggests that the self-assembly of amyloid-beta peptide (Aβ) is a nucleation-dependent process that involves the formation of several oligomeric intermediates. Despite neuronal toxicity being recently related to Aβ soluble oligomers, results from aggregation studies are often controversial, mainly because of the low reproducibility of several experimental protocols. Here a multimethodological study that included atomic force microscopy (AFM), transmission electron microscopy (TEM), fluorescence microscopy (FLM), mass spectrometry techniques (matrix-assisted laser desorption/ionization time-of-flight [MALDI-TOF] and electrospray ionization quadrupole time-of-flight [ESI-QTOF]), and direct thioflavin T (ThT) fluorescence spectroscopy were enabled to set up a reliable and highly reproducible experimental protocol for the characterization of the morphology and dimension of Aβ 1-42 (Aβ42) aggregates along the self-assembly pathway.

Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation.

The leading mechanistic theory of Alzheimer's disease (AD) is the "amyloid hypothesis" which states that the accumulation of the amyloid β protein (Aβ), and its subsequent aggregation into plaques, is responsible for the initiation of a cascade of events resulting in neurodegeneration and dementia. The anti-amyloid disease-modifying approach, based on the decrease in the production of Aβ, gained thus a paramount importance. The aim of this study was the design and synthesis of a new series of acetylcholinesterase inhibitors (AChEIs) endowed with anti-Aβ aggregating capability.

Multitargeted drugs discovery: balancing anti-amyloid and anticholinesterase capacity in a single chemical entity.

Memoquin (1) is a lead compound multitargeted against Alzheimer's disease (AD). It is an AChE inhibitor, free-radical scavenger, and inhibitor of amyloid-β (Aβ) aggregation. A new series of 1 derivatives was designed and synthesized by linking its 2,5-diamino-benzoquinone core with motifs that are present in the structure of known amyloid binding agents like curcumin, the benzofuran derivative SKF64346, or the benzothiazole bearing compounds KHG21834 and BTA-1.

Early activation of intracranial collateral vessels influences the outcome of spontaneous internal carotid artery dissection.

Background And Purpose: the effectiveness of different treatments for internal carotid artery (ICA) dissection has not been well defined. Lack of early prognostic indicators may represent a major problem in adequately identifying the most appropriate option for treatment. This study aimed at evaluating the influence of patients' vascular risk profiles and of early cerebral hemodynamic changes in determining the clinical evolution after ICA dissection.

Diagnosis of carotid arterial injury in major trauma using a modification of Memphis criteria.

Background: Incidence of Blunt Cerebrovascular Injuries (BCVI) after head injury has been reported as 0.5-1% of all admissions for blunt trauma, with a high stroke and mortality rate. The purpose of this study is to evaluate if a modification of Memphis criteria could improve the rate of BCVI diagnosis.

Prognostic implications of post-stress ejection fraction decrease detected by gated SPECT in the absence of stress-induced perfusion abnormalities.

Purpose: The prognostic meaning of a post-stress ejection fraction (EF) decrease detected by perfusion gated SPECT is still unclear.We therefore followed up patients with post-stress EF decrease in the absence of stress-induced perfusion abnormalities.

Methods: We prospectively enrolled 57 consecutive patients with post-stress EF drop ≥ 5 EF units and summed difference score (SDS) ≤ 1.

Time delay from onset to diagnosis of migraine.

Objective: To investigate the factors involved in the delayed diagnosis of migraine without aura among patients attending a tertiary center for headache diagnosis and management.

Methods: Two hundred consecutive patients were divided into 3 groups according to the time elapsed from the first clinical manifestations and the diagnosis of migraine at our center.

Results: The interval was <1 year in 16.

Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates.

A new family of dual binding site acetylcholinesterase (AChE) inhibitors has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced β-amyloid (Aβ) aggregation and β-secretase (BACE-1), and to cross the blood-brain barrier. The new heterodimers consist of a unit of racemic or enantiopure huprine Y or X and a donepezil-related 5,6-dimethoxy-2-[(4-piperidinyl)methyl]indane moiety as the active site and peripheral site to mid-gorge-interacting moieties, respectively, connected through a short oligomethylene linker. Molecular dynamics simulations and kinetics studies support the dual site binding to AChE.