Effect of metal ions on the reactions of the cumyloxyl radical with hydrogen atom donors. Fine control on hydrogen abstraction reactivity determined by Lewis acid-base interactions.

A time-resolved kinetic study on the effect of metal ions (M(n+)) on hydrogen abstraction reactions from C-H donor substrates by the cumyloxyl radical (CumO(•)) was carried out in acetonitrile. Metal salt addition was observed to increase the CumO(•) β-scission rate constant in the order Li(+) > Mg(2+) > Na(+). These effects were explained in terms of the stabilization of the β-scission transition state determined by Lewis acid-base interactions between M(n+) and the radical.

Reactions of the cumyloxyl and benzyloxyl radicals with strong hydrogen bond acceptors. Large enhancements in hydrogen abstraction reactivity determined by substrate/radical hydrogen bonding.

A kinetic study on hydrogen abstraction from strong hydrogen bond acceptors such as DMSO, HMPA, and tributylphosphine oxide (TBPO) by the cumyloxyl (CumO(•)) and benzyloxyl (BnO(•)) radicals was carried out in acetonitrile. The reactions with CumO(•) were described in terms of a direct hydrogen abstraction mechanism, in line with the kinetic deuterium isotope effects, k(H)/k(D), of 2.0 and 3.

Transcranial direct current stimulation ameliorates tactile sensory deficit in multiple sclerosis.

Background: Deficit of tactile sensation in patients with MS is frequent and can be associated with interference with daily life activities. Transcranial direct current stimulation (tDCS) showed to increase tactile discrimination in healthy subjects.

Objective: In the present study, we investigated whether tDCS may be effective in ameliorating tactile sensory deficit in MS patients.

Interleukin-1β causes anxiety by interacting with the endocannabinoid system.

Interleukin-1β (IL-1β) is involved in mood alterations associated with inflammatory illnesses and with stress. The synaptic basis of IL-1β-induced emotional disturbances is still unknown. To address the possible involvement of the endocannabinoid system in IL-1β-induced anxiety, we performed behavioral and neurophysiological studies in mice exposed to stress or to intracerebroventricular injections of this inflammatory cytokine or of its antagonist.

Hydrogen abstraction from cyclic amines by the cumyloxyl and benzyloxyl radicals. The role of stereoelectronic effects and of substrate/radical hydrogen bonding.

A kinetic study on the hydrogen abstraction reactions from cyclic amines and diamines (pyrrolidines, piperidines, morpholines, and piperazines) by the cumyloxyl (CumO(•)) and benzyloxyl (BnO(•)) radicals was carried out. The reactions with CumO(•) were described in all cases as direct hydrogen abstractions. The differences in the hydrogen abstraction rate constant (k(H)) were explained in terms of the different number of abstractable hydrogen atoms, the operation of stereoelectronic effects, and, with the morpholines, on the basis of polar effects.

Abnormal NMDA receptor function exacerbates experimental autoimmune encephalomyelitis.

Background And Purpose: Glutamate transmission is dysregulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. A characteristic of EAE is increased glutamate transmission associated with up-regulation of AMPA receptors. However, little is known about the role of NMDA receptors in the synaptic modifications induced by EAE.

Tissue inhibitor of metalloproteinase-3 regulates inflammation in human and mouse intestine.

Background & Aims: Tissue inhibitor of metalloproteinases (TIMP)-3 is an inhibitor of matrix metalloproteinases, which regulates tissue inflammation, damage, and repair. We investigated the role of TIMP-3 in intestinal inflammation in human beings and mice.

Methods: We used real-time polymerase chain reaction and flow cytometry to measure levels of TIMP-3 in intestine samples from patients with Crohn's disease (CD) and those without (controls).

Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab.

Background And Purpose: Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity.

Methods: In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers.

Inverse energy cascade in three-dimensional isotropic turbulence.

We study the statistical properties of homogeneous and isotropic three-dimensional (3D) turbulent flows. By introducing a novel way to make numerical investigations of Navier-Stokes equations, we show that all 3D flows in nature possess a subset of nonlinear evolution leading to a reverse energy transfer: from small to large scales. Up to now, such an inverse cascade was only observed in flows under strong rotation and in quasi-two-dimensional geometries under strong confinement.

A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation.

Background: Multiple sclerosis (MS) patients discontinuing natalizumab treatment are at risk of disease reactivation. No clinical or surrogate parameters exist to identify patients at risk of post-natalizumab MS reactivation.

Objective: To determine the role of natalizumab-induced lymphocytosis and of Akt polymorphisms in disease reactivation after natalizumab discontinuation.

Interleukin-21 in immune and allergic diseases.

Interleukin-21 (IL-21), a cytokine produced by various subsets of activated CD4+ T cells, plays a major role in the control of innate and adaptive immune responses. IL-21 biological activity is mediated by binding of the cytokine to a heterodimeric receptor, composed of a specific subunit, termed IL-21 receptor (IL-21R), and the common γ-chain, that is shared with IL-2, IL-4, IL-7, IL-9 and IL-15 receptors. IL-21 stimulates the proliferation of CD4+ and CD8+ T lymphocytes and regulates the profile of cytokines secreted by these cells, drives the differentiation of B cells into memory cells and Ig-secreting plasma cells, and enhances the activity of natural killer cells.

Th17-related cytokines in inflammatory bowel diseases: friends or foes?

T helper (Th)17 cells and other interleukin (IL)-17-producing cells are supposed to play critical roles in several human immune-mediated diseases, including Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man. Th17 cells infiltrate massively the inflamed intestine of IBD patients and in vitro and in vivo studies have shown that Th17-type cytokines may trigger and amplify multiple inflammatory pathways. Nonetheless, some Th17-related cytokines, such as interleukin (IL)-17A and IL-22, may target gut epithelial cells and promote the activation of counter-regulatory mechanisms.

Short interval intracortical facilitation correlates with the degree of disability in multiple sclerosis.

Background: The Expanded Disability Status Scale (EDSS) is the most widely used measure of disability in MS, however because of its limitations surrogate markers of clinical disability progression are of high interest. Transcranial magnetic stimulation (TMS) measures of demyelination and cortical excitability correlate with disability levels in MS.

Objective: Aim of this study was testing whether paired pulse (pp) TMS represents a reliable surrogate marker to measure clinical disability in MS.

Inflammation inhibits GABA transmission in multiple sclerosis.

Abnormal glutamate-dependent synaptic excitation contributes to neuronal damage in multiple sclerosis (MS). Little is known about the involvement of the GABA system in this disorder. Here we found that cerebrospinal fluid (CSF) from MS patients with enhanced brain lesions on magnetic resonance imaging inhibited GABA transmission in mouse brain slices.

[Acute hospital care for the elderly in Italy: comparison between 2001 and 2006].

The continous health expenditure increase in developed countries is often related with the acute hospital care of the elderly. To monitor the characteristics of elderly acute hospital care included the expenditure trend is crucial in order to identify the appropriateness of this care. The aim of this study is to describe quality and quantity of in-hospital care use of elderly population in Italy in 2006 and to compare the results with the same information gathered for 1996 and 2001.

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

Background & Aims: The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use.

Methods: In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered.

Memory disorders in patients with cerebral tumors.

In patients with cerebral tumors, deficits in declarative episodic memory typically result from damage to structures of the Papez circuit. These deficits can arise directly from the action of the tumor mass or indirectly from the surgical intervention. Memory deficits are also frequently seen in patients who show no direct involvement of the Papez circuit.

Kinetic solvent effects on hydrogen abstraction from phenol by the cumyloxyl radical. Toward an understanding of the role of protic solvents.

A time-resolved kinetic study of the hydrogen atom abstraction reactions from phenol by the cumyloxyl radical (CumO(•)) was carried out in different solvents. The hydrogen atom abstraction rate constant (k(H)) was observed to decrease by almost 3 orders of magnitude on going from isooctane to MeOH. In TFE, MeCN/H(2)O 2:1, and MeOH, the measured k(H) values were lower than expected on the basis of the Snelgrove-Ingold (SI) equation that correlates log k(H) to the solvent hydrogen bond acceptor (HBA) ability parameter β(2)(H).

Phase I clinical trial of Smad7 knockdown using antisense oligonucleotide in patients with active Crohn's disease.

In the gut of patients with Crohn's disease (CD), high Smad7 blocks the immune-suppressive activity of transforming growth factor (TGF)-β1, thereby contributing to amplify inflammatory signals. In vivo in mice, knockdown of Smad7 with a Smad7 antisense oligonucleotide (GED0301) attenuates experimental colitis. Here, we provide results of a phase 1 clinical, open-label, dose-escalation study of GED0301 in patients with active, steroid-dependent/resistant CD, aimed at assessing the safety and tolerability of the drug.

Prediction of cardiovascular events by inflammatory markers in patients undergoing carotid stenting.

Objective: To assess whether inflammatory markers predict atherosclerotic disease activity after carotid treatment in patients with severe carotid stenosis and nonsignificant coronary artery disease undergoing carotid stenting.

Patients And Methods: From March 1, 2004, to September 30, 2005, a total of 55 consecutive patients (mean ± SD age, 69±8.3 years; 26 men) with severe carotid stenosis and nonsignificant coronary artery disease were treated with carotid stent implantation.

Th17-related cytokines: new players in the control of chronic intestinal inflammation.

Crohn's disease (CD) and ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD) in man, are thought to be caused by an excessive and poorly controlled immune response that is directed against components of the normal microflora. The exact sequence of events by which this pathological process is triggered and maintained is not fully understood, but studies in experimental models of IBD and data emerging from recent clinical trials indicate that T cell-derived cytokines are crucial mediators of the tissue damage. Although CD and UC have been traditionally considered two typical examples of T helper (Th)1 or Th2-associated disease respectively, it is now known that CD- and UC-related inflammation is also marked by enhanced production of cytokines made by a distinct subset of Th cells, termed Th17 cells.

Loss of striatal cannabinoid CB1 receptor function in attention-deficit / hyperactivity disorder mice with point-mutation of the dopamine transporter.

Abnormal dopamine (DA) transmission in the striatum plays a pivotal role in attention-deficit/hyperactivity disorder (ADHD). As striatal DA signalling modulates the endocannabinoid system (ECS), the present study was aimed at investigating cannabinoid CB1 receptor (CB1R) function in a model of ADHD obtained by triple point-mutation in the dopamine transporter (DAT) gene in mice, making them insensitive to cocaine [DAT cocaine-insensitive (DAT-CI) mice]. DAT-CI mice had a marked hyperactive phenotype, and neurophysiological recordings revealed that the sensitivity of CB1Rs controlling GABA-mediated synaptic currents [CB1Rs((GABA)) ] in the striatum was completely lost.

Understanding kinetic solvent effects on hydrogen abstraction reactions from carbon by the cumyloxyl radical.

A kinetic study of the hydrogen abstraction reactions from tetrahydrofuran (THF) and cyclohexane (CHX) by the cumyloxyl radical was carried out in different solvents. With THF, a 4.5-fold decrease in rate constant (k(H)) was observed on going from isooctane to 2,2,2-trifluoroethanol.

Solitary skin metastasis from sarcomatoid carcinoma of the bladder: a case report.

Introduction: Cutaneous metastases from carcinomas of the bladder are very rare. They are related to advanced stages of the disease and have poor prognosis with low survival rates. The common treatment modality of cutaneous metastases from a primary bladder cancer is wide local excision followed by chemotherapy.