Sars-CoV2 infection in pregnant women with multiple sclerosis.

Background: In the general population, maternal SARS-CoV-2 infection during pregnancy is associated with worse maternal outcomes; however, only one study so far has evaluated COVID-19 clinical outcomes in pregnant and postpartum women with multiple sclerosis, showing no higher risk for poor COVID-19 outcomes in these patients.

Objective: In this multicenter study, we aimed to evaluate COVID-19 clinical outcomes in pregnant patients with multiple sclerosis.

Methods: We recruited 85 pregnant patients with multiple sclerosis who contracted COVID-19 after conception and were prospectively followed-up in Italian and Turkish Centers, in the period 2020-2022.

Anatomical variants of the circle of willis and brain lesions in migraineurs.

Background: Some reports demonstrated vascular alterations in brain magnetic resonance imaging (MRI) in migraineurs and a relationship between circle of Willis (Circle) variants and lacunar brain infarcts. We examined anomalies of the whole circle of Willis and their relationship with vascular brain lesions in migraineurs, to identify any possible vascular mechanism in migraine.

Methods: We studied, with a cohort controlled study, the circle of Willis in migraineurs seen consecutively in our Headache Center, and in non-headache controls, using angio-MRI of the brain.

Short-term treatment of relapsing remitting multiple sclerosis patients with interferon (IFN)-beta1B transiently increases the blood levels of interleukin (IL)-6, IL-10 and IFN-gamma without significantly modifying those of IL-1beta, IL-2, IL-4 and tumour necrosis factor-alpha.

We have studied the impact of short-term treatment with interferon (IFN)-beta1b of relapsing remitting (RR) multiple sclerosis (MS) patients' blood levels of type 1 and type 2 cytokines such as IFN-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10 and tumour necrosis factor (TNF)-alpha. These cytokines were measured by solid-phase ELISA. Serum samples were obtained prior to, and 2 and 12 hours after beginning of the treatment and 48 h after the last of 5 s.

Natural interferon-beta treatment of relapsing-remitting and secondary-progressive multiple sclerosis patients. A two-year study.

Objectives: To evaluate clinical and MRI effects of natural interferon beta treatment in both relapsing-remitting (RR) and secondary-progressive (SP) multiple sclerosis patients.

Material And Methods: A double-blind, randomized trial of natural interferon beta (nIFN-beta) in 58 ambulatory patients with RR and 40 with SP multiple sclerosis. Forty-nine patients (29 RR and 20 SP) were treated with intramuscular nIFN-beta6 MIU three times a week for 24 months and 49 control patients were treated with placebo.

Neuropsychological, neuroradiological and clinical findings in multiple sclerosis. A 3 year follow-up study.

Cognitive impairment is a frequent feature in multiple sclerosis patients. To assess its evolution in comparison with clinical and neuroradiological evolution, we followed up 57 multiple sclerosis patients over a 3-year period. During this time EDSS deteriorated significantly but not the MRI lesional load nor the cognitive test performance; nevertheless both at the beginning and at the end of the follow-up neuropsychological results showed a significant correlation with both EDSS and lesional load.

HPLC analysis of cyclic adenosine diphosphate ribose and adenosine diphosphate ribose: determination of NAD+ metabolites in hippocampal membranes.

Cyclic adenosine diphosphate-ribose (cADPR) and ADPR were separated by high-performance liquid chromatography (HPLC) on a CarboPac PA-1 column at strong basic pH and quantitated by a pulsed amperometric detector. Although this HPLC method was quite sensitive and highly reproducible, it did not allow the separation of cADPR from guanosine monophosphate (GMP) which, when present, could be removed by ion-affinity chromatography, using gel-immobilized Fe3+ columns. Crude synaptic membranes from rat hippocampi were incubated with nicotinamide adenine dinucleotide (NAD) and acidic extracts were subject to HPLC analysis after neutralization.

[3H]aniracetam binds to specific recognition sites in brain membranes.

[3H]Aniracetam bound to specific and saturable recognition sites in membranes prepared from discrete regions of rat brain. In crude membrane preparation from rat cerebral cortex, specific binding was Na+ independent, was still largely detectable at low temperature (4 degrees C), and underwent rapid dissociation. Scatchard analysis of [3H]aniracetam binding revealed a single population of sites with an apparent KD value of approximately 70 nM and a maximal density of 3.

(2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine positively modulates metabotropic glutamate receptors coupled to polyphosphoinositide hydrolysis in rat hippocampal slices.

In rat hippocampal slices, the novel metabotropic glutamate receptor (mGluR) ligand, (1S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) enhanced the stimulation of polyphosphoinositide (PPI) hydrolysis elicited by quisqualate or by submaximal concentrations of ibotenate or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). The enhancing effect of DCG-IV was (i) specific for mGluR agonists, (ii) restricted to hippocampal slice preparation, (iii) reversible, and (iv) not subject to homologous desensitization, in addition, DCG-IV did not interact with L-2-amino-4-phosphonobutanoate (AP4), a noncompetitive antagonist of mGluRs coupled to PPI hydrolysis in brain slices [32]. The action of DCG-IV on quisqualate-stimulated PPI hydrolysis was insensitive to antagonists of ionotropic glutamate receptors and did not appear to be a consequence of a reduction in the intracellular levels of cAMP [14].

Interaction between metabotropic receptors and purinergic transmission in rat hippocampal slices.

Inhibition of forskolin-stimulated cAMP formation by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) in rat hippocampal slices was partially obliterated by the adenosine-depleting enzyme, adenosine deaminase, or by the adenosine receptor agonist, 5'-(N-ethylcarboxamido)-adenosine, suggesting that activation of metabotropic glutamate receptors (mGluRs) modulates the release of endogenous adenosine. Consistent with this hypothesis, forskolin stimulated the release of purines from rat hippocampal slices, and this effect was reduced by 1S,3R-ACPD. To establish which transduction pathway is involved in the modulation of forskolin-stimulated purine release, we have tested the novel mGluR2 agonist, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), which reduced forskolin-stimulated cAMP formation but, as opposed to 1S,3R-ACPD, did not stimulate polyphosphoinositide hydrolysis.

Characterization of metabotropic glutamate receptors negatively linked to adenylyl cyclase in brain slices.

We have characterized the pharmacological profile of activation of metabotropic glutamate receptors negatively linked to adenylyl cyclase (mGluR decreases cAMP) in brain slices. Among the putative mGluR agonists, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), were the most potent inhibitors of forskolin-stimulated cAMP formation in hippocampal slices, followed by ibotenate, L-2-amino-3-phosphonopropionate (AP3), quisqualate, L-glutamate and beta-N-methylamino-L-alanine (BMAA). Inhibition of forskolin-stimulated cAMP formation by DL-2-amino-4-phosphonobutanoate (AP4) was biphasic, suggesting that the drug interacts with more than one mGluR decreases cAMP subtype.

(2s,1'R,2'R,3'R)-2-(2,3-Dicarboxycyclopropyl) glycine enhances quisqualate-stimulated inositol phospholipid hydrolysis in hippocampal slices.

In adult rat hippocampal slices, (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) did not affect the basal hydrolysis of polyphosphoinositides but dramatically enhanced (EC50 value = 30 nM) the stimulation of [3H]inositol monophosphate (InsP) formation by quisqualate, without substantially affecting the stimulation produced by maximal concentrations of 1S,3R-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) or carbamylcholine. alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) was virtually devoid of activity on [3H]InsP formation, either in the absence or presence of DCG-IV. These results suggest that DCG-IV acts, directly or indirectly, as a positive modulator of metabotropic glutamate receptors in the rat hippocampus.