Epstein Barr Virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> peptides are recognized in sera and cerebrospinal fluid of MS patients

Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF. An intrathecal specific synthesis of IgG against MBP and their EBV and MAP homologous as indicated by the antibody index was observed in MS patients. The humoral response against EBV, MAP, MBP and IRF5 was significantly higher in MS patients compared to OND both in serum and in CSF. The higher presence of antibodies against MBP and their MAP and EBV homologous in CSF during relapses suggests a possible role of the pathogens in enhancing inflammation

Serum BAFF levels, methypredsinolone therapy, Epstein-Barr virus and <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> infection in Multiple Sclerosis patients

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease

Combining HLA-DRB1-DQB1 and <i>Mycobacterium avium subspecies paratubercolosis</i> (MAP) antibodies in Sardinian multiple sclerosis patients: associated or independent risk factors?

Background: Amongst Sardinians the human leukocyte antigen (HLA) DRB1-DQB1 haplotypes *15:02-*06:01, *16:01-*05:02, *14:01-4-*05:03 are protective for multiple sclerosis (MS), while *13:03-*03:01, *04:05-*03:01, *03:01-*02:01, *15:01-*06:02 and Mycobacterium avium subspecies paratubercolosis (MAP) are predisposing factors. We studied the correlation between MAP and HLA. Methods: Five hundred thirty-one patients were searched for anti-MAP2694 antibodies, DRB1-DQB1 genotyping was performed. The haplotypes were classified as predisposing, neutral or protective. Results: Anti-MAP2694 were found in 23 % of subjects carrying one protective HLA versus 32 % without (p = 0.04). Conclusions: We showed a lower frequency of Abs in patients with protective HLA. These haplotypes could have a protective role for both MS and MAP

Quality assessment of information about medications in primary care electronic patient record (EPR) systems

Background Many different brands of primary care electronic patient record (EPR) software are available to general practitioners (GPs). Their ability to support GPs in improving prescribing varies greatly. Objective To assess, using a ten-item tool, the quality of drug information provided by EPR software to support the appropriateness of prescriptions and to propose a list of quality standards for this type of application. Methods The eight EPR programmes most used in general practice in Italy were assessed by a multidisciplinary team using the ten-item tool. The tool evaluated information on single drugs and drug safety and information on prescription rules in force. Results Out of eight EPR programmes assessed, none scored more than 55% of the maximum possible score. Two achieved scores higher than 50%, one scored 48%, four ranged from 32% to 39% and one obtained 22%. Information on drug safety, such as the ability to detect interactions, to monitor laboratory parameters or to get updated information on drug safety was particularly limited. None of the eight EPR programmes contained drug information for patients, but two of them contained drug advertising. Conclusions This project highlighted the poor quality of drug information provided by these EPR programmes. The ten-item tool seems suitable for assessing their quality. Based on this analysis, we have proposed a set of ten quality standards for prescribing software

Effects of Pregnancy and Breastfeeding on Clinical Outcomes and MRI Measurements of Women with Multiple Sclerosis: An Exploratory Real-World Cohort Study

Pregnancy represents an important event for women with multiple sclerosis (MS) and is often accompanied by post-partum disease reactivation. To date, the influence of this reproductive phase on long-term MS outcomes is still largely unexplored. The objective of the study was characterise a large real-world cohort of women with MS to evaluate the effects of pregnancy and breastfeeding on short- and long-term clinical and magnetic resonance imaging (MRI) outcomes while exploring the relationships with MRI measurements of brain atrophy

Inhibition of Morphine- and Ethanol-Mediated Stimulation of Mesolimbic Dopamine Neurons by Withania somnifera

Morphine- and ethanol-induced stimulation of neuronal firing of ventral tegmental area (VTA) dopaminergic neurons and of dopamine (DA) transmission in the shell of the nucleus accumbens (AcbSh) represents a crucial electrophysiological and neurochemical response underlying the ability of these compounds to elicit motivated behaviors and trigger a cascade of plasticity-related biochemical events. Previous studies indicate that the standardized methanolic extract of Withania somnifera roots (WSE) prevents morphine- and ethanol-elicited conditioned place preference and oral ethanol self-administration. Aim of the present research was to investigate whether WSE may also interfere with the ability of morphine and ethanol to stimulate VTA dopaminergic neurons and thus AcbSh DA transmission as assessed in male Sprague- Dawley rats by means of patch-clamp recordings in mesencephalic slices and in vivo brain microdialysis, respectively. Morphine and ethanol significantly stimulated spontaneous firing rate of VTA neurons and DA transmission in the AcbSh. WSE, at concentrations (200–400 mg/ml) that significantly reduce spontaneous neuronal firing of VTA DA neurons via a GABAA- but not GABAB-mediated mechanism, suppressed the stimulatory actions of both morphine and ethanol. Moreover, in vivo administration of WSE at a dose (75 mg/kg) that fails to affect basal DA transmission, significantly prevented both morphine- and ethanol-elicited increases of DA in the AcbSh. Overall, these results highlight the ability of WSE to interfere with morphine- and ethanolmediated central effects and suggest a mechanistic interpretation of the efficacy of this extract to prevent the motivational properties of these compounds

Continuous infusion versus bolus injection of furosemide in critically ill patients. A systematic review and meta-analysis

Introduction. Fluid overload and a positive fluid balance are common in the intensive care unit (ICU). Furosemide is frequently administered to increase urine output. A bolus injection is the traditional mode of administration, but many concerns have been raised about possible intravascular volume fluctuations, toxicity and enhanced tolerance. Furosemide related adverse effects can be enhanced in critically ill patients. Continuous infusion should allow better hemodynamic stability, less side effects and an easier achievement of the desired diuretic effect. We performed a systematic review and meta-analysis to compare the effects and complications of continuous furosemide infusion with those of bolus injections in critically ill patients in the ICU. Methods. Studies were searched in PubMed (updated January 2009). Backward snowballing of included papers was performed. International experts were contacted for further studies. The inclusion criteria were: random allocation to treatment, comparison of furosemide bolus vs continuous infusion, performed in surgical or intensive care patients. The exclusion criteria were: non-parallel design randomized trials, duplicate publications, non-human experimental studies, no outcome data. Results. Four eligible randomized clinical trials were identified, including 129 patients (64 to continuous infusion and 65 to bolus treatment). Continuous perfusion was not associated with a significant reduction in risk of mortality as compared to bolus injection Conclusions. Furosemide in continuous perfusion was not associated with a significant reduction in risk of hospital mortality as compared to bolus administration in critically ill patients in ICU, but existing data are insufficient to confidently assess the best way to administer furosemide . Applying a protocol to drive furosemide therapy could be more relevant than the chosen mode of administration