Early regional cerebral grey matter damage predicts long-term cognitive impairment phenotypes in multiple sclerosis: a 20-year study.

Despite grey matter atrophy in cortical and subcortical regions has been related to cognitive impairment in multiple sclerosis, only a few studies evaluated its predictive value for alterations in the long-term. We aimed to determine early predictors of cognitive status after 20 years of multiple sclerosis. In this longitudinal retrospective study, participants underwent a 1.

Enteropathogenic and Multidrug-Resistant -Carrying Isolates from Dogs and Cats.

Enteropathogenic (EPEC) are pathogens associated with gastrointestinal illnesses. Dogs and cats can harbor EPEC, and antimicrobial resistance may impair necessary treatments. This study characterized strains from dogs and cats, focusing on phylogroup classification, virulence factors, and antimicrobial resistance profiles.

Cortical lesions at diagnosis predict long-term cognitive impairment in multiple sclerosis: A 20-year study.

Background And Purpose: Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, few studies (and with conflicting results) have evaluated early predictors of CI in the long term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.

Methods: We investigated in 170 MS patients the relationship between clinical/magnetic resonance imaging (MRI) data at diagnosis and cognitive status almost 20 years after MS onset.

Two years' effect of dimethyl fumarate on focal and diffuse gray matter pathology in multiple sclerosis.

Background: Data on the effect of dimethyl fumarate (DMF) on focal and diffuse gray matter (GM) damage, a relevant pathological substrate of multiple sclerosis (MS)-related disability are lacking.

Objective: To evaluate the DMF effect on cortical lesions (CLs) accumulation and global and regional GM atrophy in subjects with relapsing-remitting MS.

Methods: A total of 148 patients (mean age 38.

CSF TNF and osteopontin levels correlate with the response to dimethyl fumarate in early multiple sclerosis.

Background: Disease activity in the first years after a diagnosis of relapsing-remitting multiple sclerosis (RRMS) is a negative prognostic factor for long-term disability. Markers of both clinical and radiological responses to disease-modifying therapies (DMTs) are advocated.

Objective: The objective of this study is to estimate the value of cerebrospinal fluid (CSF) inflammatory markers at the time of diagnosis in predicting the disease activity in treatment-naïve multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF).

CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis.

Introduction And Methods: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis.

Results: PVALB gene expression was downregulated in MS (fold change = 3.

"Better explanations" in multiple sclerosis diagnostic workup: A 3-year longitudinal study.

Background: The exclusion of other diseases that can mimic multiple sclerosis (MS) is the cornerstone of current diagnostic criteria. However, data on the frequency of MS mimics in real life are incomplete.

Methods: A total of 695 patients presenting with symptoms suggestive of MS in any of the 22 RIREMS centers underwent a detailed diagnostic workup, including a brain and spinal cord MRI scan, CSF and blood examinations, and a 3-year clinical and radiologic follow-up.

The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons.

Objective: The prevalence of peripheral artery disease (PAD) increases with aging and is higher in persons with metabolic syndrome and diabetes. PAD is associated with adverse outcomes, including frailty and disability. The protective effect of testosterone and sex hormone binding globulin (SHBG) for diabetes in men suggests that the biological activity of sex hormones may affect PAD, especially in older populations.

The hormonal pathway to cognitive impairment in older men.

In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline.

Morning increase of whole blood viscosity in obstructive sleep apnea syndrome.

Objective: Patients affected by obstructive sleep apnea syndrome (OSAS) have an increased risk of cardiovascular diseases such as stroke and myocardial infarction. The pathophysiological mechanisms leading to increased vascular risk are still matter of debate. A relative morning hyperviscosity could be one of the leading mechanisms of cardiovascular morbidity which is actually known to be especially high in the morning hours.

Relationship of sleep interictal epileptiform discharges to sigma activity (12-16 Hz) in benign epilepsy of childhood with rolandic spikes.

Objective: The activation of interictal epileptic discharges (IEDs) by NREM sleep is a well-known phenomenon in benign epilepsy of childhood with rolandic spikes (BECRS). The activating properties of NREM sleep on IEDs have been attributed to increased synchronization within thalamocortical neurons. During NREM sleep two synchronizing mechanisms lead to the appearance of spindles and delta waves on the EEG.

A quantified analysis of sleep electroencephalography in anorectic adolescents.

Background: Previous studies on sleep characteristics in anorexia nervosa have led to controversial results. This may be due to either the heterogeneity of the samples studied or to an intrinsic inadequacy of the scoring criteria. To obtain a more detailed analysis we have investigated sleep characteristics in a group of adolescents affected by anorexia nervosa using spectral analysis techniques.

Comparison between visual scoring of cyclic alternating pattern (CAP) and computerized assessment of slow EEG oscillations in the transition from light to deep non-REM sleep.

Ten healthy volunteers (six men and four women) aged between 20 and 30 years underwent a nocturnal polygraphic recording on paper and on tape. Spectral analysis was accomplished and EEG sleep scored according to standard criteria and to the guidelines for the identification of cyclic alternating pattern (CAP). The initial 25 min of sleep, starting from the first clear-cut k-complex and ending within stage 4, was subdivided into five consecutive blocks of 5 min each.

An integrated model of sleep regulation.

We present a new model of sleep regulation which integrates the two process model and the limit cycle reciprocal interaction model. In the two process model the interaction of a homeostatic process (S signal) and of a circadian process determines the timing of sleep and waking. In the limit cycle model, the NREM-REM sleep cycle is generated by the reciprocal interaction of two coupled cell population.

Ultradian aspects of sleep in narcolepsy.

Following a baseline night recording, 9 narcoleptic subjects and 9 sex and age-matched control subjects were maintained on 16 hours of diurnal sleep deprivation. Thereafter subjects were submitted to a 32 hour bed rest protocol in a sound-light attenuated room. The EEG was recorded and processed using a Fast Fourier Transform.

Dynamics of slow wave activity in narcoleptic patients under bed rest conditions.

Following a baseline night recording, 9 narcoleptic subjects and 9 sex- and age-matched control subjects were maintained on 16 h of diurnal sleep deprivation. Thereafter subjects were submitted to a 32 h bed rest protocol in a sound- and light-attenuated room. The EEG was recorded and processed by a Fast Fourier Transform.

Synthesis, absolute configuration, conformational analysis and binding affinity properties of enantiomeric forms of DAU 5750, a novel M1-M3 muscarinic receptor antagonist.

Both the enantiomeric forms of DAU 5750, a novel muscarinic receptor antagonist, have been synthesized in order to assess the relevance of configurational/conformational features for high affinity binding to muscarinic receptor subtypes. The attribution of absolute stereochemistry and conformational analysis by means of molecular modelling and NMR techniques are also reported.

Antagonistic properties of McNeil-A-343 at 5-HT4 and 5-HT3 receptors.

1. This study describes the in vitro interaction of the muscarinic ligand McNeil-A-343 with two 5-hydroxytryptamine (5-HT) receptor subtypes, the 5-HT4 and 5-HT3 receptors, using functional as well as radioligand binding studies. 2.

Medicinal chemistry of muscarinic agonists for the treatment of dementia disorders.

Alzheimer disease (AD) is a neurodegenerative disorder lacking an effective therapy. The etiology is controversial and among different drug strategies, the cholinergic approach has gained great interest owing to biochemical and pharmacological evidence of the crucial role of acetylcholine in cognitive functions. Several attempts exploiting the boosting of the cholinergic system are currently under way.

Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors.

We have investigated the in vivo motor stimulating and gastroprokinetic properties of the azabicycloalkyl benzimidazolone derivative BIMU 1 (3-ethyl-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride) and its binding profile at 5-hydroxytryptamine3 and 5-hydroxytryptamine4 receptors, in an attempt to assess the serotonergic mechanism underlying its prokinetic action.

Identification of serotonin 5-HT4 recognition sites in the porcine caudate nucleus by radioligand binding.

Specific binding for the serotonin 5-HT4 receptor (5-HT4R) radioligand [3H]GR 113808 was identified in pig caudate nucleus and characterized by serotonin subtype selective drugs. Binding was inhibited by serotonin and by synthetic indoles, benzamides and benzimidazolones known to characterize the 5-HT4R in functional tests. Rank order of potency of 5-HT4R antagonists was: GR 125487 (Ki, 0.

Synthesis and muscarinic activity of the chiral forms of methylenemuscarones.

The synthesis of the two pairs of enantiomers of methylenemuscarones 3 and 4 has been accomplished by using (R)- and (S)-lactic esters as starting materials. Due to the existence of different muscarinic receptor subtypes, the compounds were examined for their ability to bind membranes from cerebral cortex (M1), heart (M2), and salivary glands (M3) and were assayed in "in vitro" functional tests as well. The results of such an investigation put in evidence that, in both binding and functional tests, (-)-3 (2S,5S) and (-)-4 (2R,5S) were the eutomers and shared the stereochemistry of the eutomer of muscarone and allomuscarone respectively.

Characterization of BIBN 99: a lipophilic and selective muscarinic M2 receptor antagonist.

The present study was designed to characterize the receptor selectivity profile of the novel muscarinic M2 receptor antagonist BIBN 99 (5,11-dihydro-8-chloro-11-[[4-[3-[(2,2-dimethyl-1- oxopentyl)ethylamino]propyl]-1-piperidinyl]acetyl]-6H- pyrido[2,3-b][1,4]benzodiazepin-6-one). In radioligand binding studies BIBN 99 showed high affinity for m2/M2 sites (pKi = 7.52/7.

Therapeutic potential of CNS-active M2 antagonists: novel structures and pharmacology.

Clinical trials with muscarinic agonists or acetylcholine esterase inhibitors for the treatment of Alzheimer's dementia have shown disappointing or equivocal results. An alternative treatment of this disease is the development of drugs which enhance the release of acetylcholine. It is believed, that of the five muscarinic receptor subtypes so far identified in the brain, M2 receptors are located presynaptically in the cortex and hippocampus and upon stimulation inhibit the release of acetylcholine.