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. Forty active relapsing–remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12–18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. Results 62.5% of patients were relapse‐free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post‐natalizumab– GA therapy is not associated with clinical deterioration. Conclusions Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting.

Opioid‐like antinociceptive effects of oral administration of a lectin purified from the seeds of Canavalia brasiliensis

The objective of this study was to evaluate the antinociceptive effects of a lectin from Canavalia brasiliensis (ConBr) when administered orally to murine models of chemical and thermal nociception. ConBr up to 100 mg/kg produced significant and dose‐dependent antinociceptive effects: 81% reduction in abdominal writhing induced by 0.6% acetic acid; 26 and 52% reduction in early‐ and late‐stage paw licking, respectively, induced by 2.5% formalin; and 155% increase in reaction latency (heightened thermal pain threshold). In all models, the antinociceptive effect was reversed by the lectin‐binding carbohydrate α‐ d ‐methyl‐mannoside and by the nonselective opioid antagonist naloxone. The antinociceptive effect observed in the formalin test was inhibited by the δ‐selective antagonist naltrindole and the κ‐selective antagonist nor‐binaltorphimine but not by the μ‐selective antagonist cyprodime. In conclusion, when administered orally to Swiss mice, the ConBr lectin displayed antinociceptive activity, both peripheral and central, mediated by the opioid system and involving δ‐and κ‐receptors and the lectin domain.

Tie strength and family formation: Which personal relationships are influential?

On the basis of the analysis of qualitative interviews in Western Germany, it has been argued that personal relationships have a strong impact on individuals' family formation processes and childbearing intentions. Persons who influence individuals' childbearing choices were identified. Strong ties, such as among core family members (i.e., parents and siblings), are an important contributing factor, but the authors are also able to show that weak ties, such as those among colleagues and acquaintances, need to be considered when examining social influence on family formation processes. Apart from single network partners, influential groups of persons have been identified. Such groups serve as a comparative standard regarding the timing of having one's first child and subsequent children.

Current limits and future challenges in the management of renal dysfunction in patients with cirrhosis: report from the I nternational C lub of A scites

Advanced cirrhosis is often complicated by a multi organ failure syndrome which involves many different organs besides the liver. The high morbidity and mortality secondary to this clinical setting is often related to renal dysfunction, either alone or, more frequently, in combination with other organ dysfunction. A clear defintion of renal dysfunction, an accurate differential diagnostic process of its different phenotypes as well as of full understanding of its pathophysiological mechanisms are crucial to the development of strategies for the management of this complication. This article is based either on the more recent knowledge on renal dysfunction in advanced cirrhosis or current opinions among the members of the I nternational C lub of A scites ( ICA ) on the management of this complication, obtained through a survey and discussed during the EASL ‐ ICA J oint M eeting in B erlin in M arch 2011. It reviews critically our current knowledge and it outlines future perspectives, on the management of renal dysfunction in patients with cirrhosis.

Impact of chemiluminescent enzyme immunoassay screening for human parvovirus B 19 antigen in J apanese blood donors

Background To reduce the risk of human parvovirus B 19 ( B 19 V ) transmission through contaminated blood for transfusion and plasma‐derived products, the J apanese R ed C ross ( JRC ) B lood C enters introduced B19V antigen screening by chemiluminescent enzyme immunoassay ( CLEIA ‐ B19V ) in 2008.Study Design and Methods Donor samples that were positive by CLEIA ‐ B19V screening were tested for B19V DNA . The sensitivity of CLEIA ‐ B19V was tested using samples of all three genotypes and B19V DNA –positive donations. B19V DNA –positive donations and pooled plasma were quantitatively assayed for B19V DNA . B19V DNA –positive donations were phylogenetically analyzed by polymerase chain reaction direct sequencing. Results The sensitivity of CLEIA ‐ B19V was inferred to be approximately 6.3 log IU / mL with the genotype samples and 6.4 log IU / mL with B19V DNA –positive donor samples. Of 417 CLEIA ‐ B19V –positive samples from 1,035,560 donations in H okkaido, J apan, 101 were positive for B19V DNA . The 198 strains of B19V DNA –positive donations in H okkaido over the past 15 years clustered exclusively with Genotype 1. After introduction of CLEIA ‐B19V, the viral load for B19V DNA in all 772 pooled plasma for fractionation from donors in nationwide J apan did not exceed 4 log IU / mL . Conclusion CLEIA ‐ B19V can detect all three genotypes of B19V (viral load >6.3 log IU / mL ) and limit the viral load (<4 log IU / mL ) in pooled plasma, and thus such screening has further reduced the risk of transfusion‐transmitted B19V infection. These results show that CLEIA ‐ B19V screening at the JRC B lood C enters can be an alternative approach to comply with recommendations regarding B19V in the United States and E urope.

Detection of Leishmania infantum , the etiological agent of visceral leishmaniasis, in Lutzomyia neivai , a putative vector of cutaneous leishmaniasis

Usefulness of a novel system for measuring glucose area under the curve while screening for glucose intolerance in outpatients

Aims/Introduction To realize the effectiveness of a novel system for measuring glucose area under the curve ( AUC ) using minimally invasive interstitial fluid extraction technology ( MIET ), outpatients undergoing oral glucose tolerance tests ( OGTT ) were investigated for the efficacy of screening for glucose intolerance using this system. Materials and Methods Fifty outpatients scheduled to undergo a 75‐g OGTT for medical reasons were recruited to the study. An area of skin on the forearm was pretreated with microneedle arrays before the application of hydrogels for interstitial fluid extraction. Plasma glucose ( PG ) levels were measured every 30 min for 2 h to calculate reference (actual) AUC . The AUC was predicted by MIET on the basis of glucose extracted by the hydrogel using sodium ion levels as the internal standard. Results Good correlation between MIET ‐predicted and reference AUC s obtained using PG levels was confirmed for a wide AUC range. By introducing a threshold level for AUC to separate glucose intolerance with peak glucose ≥180 mg/dL from normal glucose tolerance, the system was demonstrated to provide better screening accuracy compared with conventional methods that use H b A 1c and fasting PG levels. The results of a questionnaire‐based survey administered to the subjects suggested that this system was readily accepted by the majority as a painless monitoring method. Conclusions The findings suggest that our glucose AUC measurement system using MIET would be useful for screening of glucose intolerance. In the future, this system may prove to be a useful aid as a screen for glucose intolerance before performing an OGTT for diagnosis.

Microbiological and Physicochemical Quality Evaluation of Vacuum‐Packed Argentine Beef Imported into I taly

A total of 8 lots of vacuum‐packed bovine rump hearts ( G luteus medius muscle) imported in I taly from A rgentina were submitted to microbiological (total bacterial count, E nterobacteriaceae , P seudomonas spp., L actobacilli, sulfite‐reducing C lostridia, L isteria monocytogenes ) and physicochemical analyses ( pH , total volatile basic nitrogen, color measurement and shear force) after different storage times (35, 75 and 100 days). Lactobacilli were the predominant microbial population (about 6 log cfu/cm 2 ), causing a microbial stabilization and acidification of meat. Seventy‐three L actobacilli isolates were submitted to random amplified polymorphic DNA ‐polymerase chain reaction and identified, showing a high prevalence of L actobacillus sakei (in all the samples) and L actobacillus curvatus (in samples stored for 75 or 100 days). We observed high total volatile basic nitrogen levels (>27  mgN /100 g) in all the samples and a discoloration of beef after the opening of the packs. Our results suggest the need for a higher standardization of production conditions. Practical Applications Vacuum‐packed raw beef from A rgentina is globally commercialized, and it is frequently shipped to E uropean markets. Considering the perishability of this product and the very long shelf life assigned, the availability of microbiological and physicochemical data could be useful for quality evaluations purposes. Our data indicate that a long shelf life (3–4 months) is potentially achievable, but the application of the best hygienic practices during meat production and an optimal stabilization of microflora by the selection (or addition) of lactic acid bacteria must be assured. As protein degradation and microbial population showed to be stable during the shelf life, quality characteristics that are perceived by the consumer (such as color indexes) become important parameters for a proper evaluation of meat quality.

The role of angiogenin in pT1‐T2 tongue carcinoma neo‐angiogenesis and cell proliferation: an exploratory study

Background Angiogenin ( ANG ) is a member of the ribonuclease superfamily and of medical interest largely because it supports the growth of primary and metastatic malignancies. This study is the first to investigate the potential role of ANG in tongue carcinoma neo‐angiogenesis and cancer cell proliferation. Methods Angiogenin expression (in carcinoma cells and endothelial intratumor vessel cells), CD105‐assessed micro‐vessel density (MVD), and MIB‐1 expression were correlated with prognostic parameters in 28 primarily consecutively operated pT 1‐T2 tongue carcinomas (squamous cell carcinoma [SCC]). Whenever feasible, a computer‐based image analysis system was used for the immunohistochemical reaction analysis. Results No significant correlations emerged between ANG expression in the tongue carcinoma cells or endothelial intratumor vessel cells and tongue SCC recurrence rate or disease‐free survival ( DFS ). ANG expression was also unrelated to CD 105‐assessed MVD or MIB ‐1 expression. Conversely, CD 105‐assessed MVD correlated directly with recurrence rate ( P  = 0.02) and DFS was significantly shorter in cases with CD 105‐assessed MVD >167 micro‐vessels/mm 2 than in those with CD 105‐assessed MVD ≤167 micro‐vessels/mm 2 ( P  = 0.042). Conclusions Our results support the hypothesis that CD 105‐assessed MVD would be a valuable parameter for predicting which patients with tongue SCC are at greatest risk of disease recurrence. Despite our study results, the role of ANG in tongue carcinoma warrants further investigation in larger series.

Retinoic acid influences antero‐posterior positioning of peptidergic neurons in the planula larva of the hydrozoan C lava multicornis

Retinoic acid ( RA ) is a derivative of vitamin A known to be involved in the regulation of many developmental and physiological processes in chordates. Recently, evidence showing its presence and function in invertebrate deuterostomes and protostomes indicated the early evolutionary origin and conservation of the RA developmental machinery, with a key role also in neural differentiation. Moreover, it is known that retinoids can influence pattern specification in polyps of the hydroid H ydractinia echinata . The planula larvae of the hydrozoan C lava multicornis are characterized by a complex nervous system formed by a frontal neural plexus composed by two distinct peptidergic cell populations with antero‐posterior organization: a first, anterior‐most GLWamide immunoreactive ( GLW‐IR ) population and an RFamide immunoreactive ( RF‐IR ) cell belt just posterior to the first population. In contrast to most swimming planulae, C . multicornis larvae display a smooth gliding movement on the substrate, characterized by alternate bending of the anterior pole. We tested the effects of RA and of a RA antagonist on C . multicornis development by analyzing the nervous system organization and the photoresponsive behavior of larvae exposed to RA during their embryogenesis. After the exposure, the nervous system became completely disorganized, leading to the displacement of RFamide‐ IR cells. Moreover, RA ‐treated larvae did not exhibit the typical phototropic behavior of control specimens. Our results suggest that RA can alter the normal development of nervous elements in this hydroid species, supporting the hypothesis that the morphogenetic activity of RA predates the origin of chordates.