Thalidomide-induced sensory polyneuropathy and electrophysiological study of the sural nerve as a screening diagnosis: a case report

Polineuropatia é uma condição clínica freqüente com sintomatologia debilitante e o tratamento depende fundamentalmente da etiologia. Inúmeras são as causas possíveis deste tipo de distúrbio e o diagnóstico etiológico nem sempre é fácil. Neste relato de caso descrevemos um caso de um paciente com mieloma múltiplo que evoluiu com polineuropatia puramente sensitiva, comprovada por estudo eletrofisiológico, induzida por talidomida.Polyneuropathy is a common clinical condition with debilitating symptoms whose treatment depends on etiology. There are numerous possible causes of this type of disorder and the etiological diagnosis is not always easy. In this case report we describe a case of a patient with multiple myeloma who developed purely sensory polyneuropathy, confirmed by electrophysiological study, induced by thalidomide

Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis.

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A4 and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA

Wettability and corrosion of [NTf2] anion-based ionic liquids on steel and PVD (TiN, CrN, ZrN) coatings

Thewetting and corrosion behavior of three bis(trifluoromethylsulfonyl)imide-based ionic liquids: 1-Dodecyl-3- methylimidazolium bis(trifluoromethylsulfonyl)imide [C12MIM][NTf2], tributylmethylammonium bis(trifluoromethylsulfonyl)imide [N4441][NTf2] and methyltrioctylammonium bis(trifluoromethylsulfonyl)imide [N1888][NTf2] are tested in this research. The surface tension was measured for temperatures of 293–353 K resulting in the expected linearly decreasing behavior with temperature increase. In addition, contact angle measurements were made on AISI 52100 steel and three coatings (TiN, CrN and ZrN) obtained by PVD technique, finding the regular behavior in hydrophobic (non-polar) systems: high contact angles led to high surface tensions. Complementary parameters like spreading parameter and polarity fraction were calculated to enhance the wetting evaluation of these ionic liquids. [N1888][NTf2]/TiN resulted as the best IL-surface combination for a good wettability, due to the higher dispersion of the charge on the large size cation in this IL and the higher values of total and polar component of the surface free energy for this coating. Finally, SEM-EDS analysis determined that [N1888][NTf2]/ZrN was the best option in order to avoid corrosion problems. The evaporation of water, present as impurity in the ionic liquids, was found the main reason because of corrosion did not occur in the tests carried out at 100 °C

High fat diet modifies the association of lipoprotein lipase gene polymorphism with high density lipoprotein cholesterol in an Asian Indian population

Background Single nucleotide polymorphisms (SNPs) in lipoprotein lipase gene (LPL) have been shown to influence metabolism related to lipid phenotypes. Dietary factors have been shown to modify the association between LPL SNPs and lipids; however, to date, there are no studies in South Asians. Hence, we tested for the association of four common LPL SNPs with plasma lipids and examined the interactions between the SNPs and dietary factors on lipids in 1,845 Asian Indians. Methods The analysis was performed in 788 Type 2 diabetes cases and 1,057 controls randomly chosen from the cross-sectional Chennai Urban Rural Epidemiological Study. Serum triacylglycerol (TAG), serum total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Dietary intake was assessed using a semi-quantitative food frequency questionnaire. The SNPs (rs1121923, rs328, rs4922115 and rs285) were genotyped by polymerase chain reaction followed by restriction enzyme digestion and 20% of samples were sequenced to validate the genotypes obtained. Statistical Package for Social Sciences for Windows version 22.0 (SPSS, Chicago, IL) was used for statistical analysis. Results After correction for multiple testing and adjusting for potential confounders, SNPs rs328 and rs285 showed association with HDL-C (P = 0.0004) and serum TAG (P = 1×10−5), respectively. The interaction between SNP rs1121923 and fat intake (energy %) on HDL-C (P = 0.003) was also significant, where, among those who consumed a high fat diet (28.4 ± 2.5%), the T allele carriers (TT + XT) had significantly higher HDL-C concentrations (P = 0.0002) and 30% reduced risk of low HDL-C levels compared to the CC homozygotes. None of the interactions on other lipid traits were statistically significant. Conclusion Our findings suggest that individuals carrying T allele of the SNP rs1121923 have increased HDL-C levels when consuming a high fat diet compared to CC homozygotes. Our finding warrants confirmation in prospective studies and randomized controlled trials

Perfil de dispensação da toxina botulínica para tratamento da espasticidade: dados nacionais brasileiros

The physiatrists specialized in treating spasticity were brought together for a panel discussion about the use of botulinum toxin (BT) in the public system in different states of Brazil. The data analyzed during the discussion of Datasus demonstrate a low-demand profile of the product dispensed by the Unified Health System (SUS), with heterogeneity in the distribution of TB in the Brazilian states. This scenario seems to be set up mainly for lack of a properly planned public policy, such as lack of unification and standardization of distribution centers, the lack or inadequacy of TB compensation proceeding to treatment centers, in a standardized manner by SUS and shortage of trained doctors to do it together with the lack of qualified multidisciplinary rehabilitation centers. The use of botulinum toxin for therapeutic purposes in Brazil began in the 90s, to treat dystonia and spasticity. It is currently employed in different clinical conditions; however, despite growing demand and indications over the years, there are few reports or publications on its use and benefit to patients served by the Unified Health System (SUS). To address this issue, in May 2015, in São Paulo, physiatrists from different states of Brazil met and discussed the relevance of botulinum toxin in treating spasticity.Os fisiatras especializados no tratamento de espasticidade foram reunidos para um painel de discussão a respeito do uso de toxina botulínica (TB) na rede pública de diferentes estados do Brasil. Os dados analisados durante a discussão do Datasus demonstram um baixo perfil de demanda desse produto dispensado pelo Sistema Único de Saúde (SUS), com uma heterogeneidade na distribuição da TB nos estados brasileiros. Esse quadro parece se configurar principalmente por falta de uma política pública devidamente planejada, como a falta de unificação e normatização dos centros de distribuição, pela falta ou inadequação da remuneração do procedimento de aplicação da TB aos centros de tratamento, de modo padronizado pela tabela SUS e escassez de médicos capacitados para realizá-lo junto à falta de centros de reabilitação multidisciplinar habilitados. O uso de toxina botulínica com finalidade terapêutica no Brasil teve início nos anos 90, para tratamento de distonia e de espasticidade. Atualmente, é empregada em diferentes condições clínicas, porém, apesar da crescente demanda e indicações ao longo dos anos, há poucos relatos ou publicações sobre seu uso e benefício para pacientes atendidos pela Sistema Único de Saúde (SUS). Para abordar esse tema, em maio de 2015, na cidade de São Paulo, fisiatras de diferentes estados do Brasil se encontraram e discutiram a relevância da toxina botulínica no tratamento de espasticidade

Pathogen-Induced Proapoptotic Phenotype and High CD95 (Fas) Expression Accompany a Suboptimal CD8+ T-Cell Response: Reversal by Adenoviral Vaccine

MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination

A transcriptomic analysis of Echinococcus granulosus larval stages:implications for parasite biology and host adaptation

The cestode Echinococcus granulosus--the agent of cystic echinococcosis, a zoonosis affecting humans and domestic animals worldwide--is an excellent model for the study of host-parasite cross-talk that interfaces with two mammalian hosts. To develop the molecular analysis of these interactions, we carried out an EST survey of E. granulosus larval stages. We report the salient features of this study with a focus on genes reflecting physiological adaptations of different parasite stages.We generated ~10,000 ESTs from two sets of full-length enriched libraries (derived from oligo-capped and trans-spliced cDNAs) prepared with three parasite materials: hydatid cyst wall, larval worms (protoscoleces), and pepsin/H(+)-activated protoscoleces. The ESTs were clustered into 2700 distinct gene products. In the context of the biology of E. granulosus, our analyses reveal: (i) a diverse group of abundant long non-protein coding transcripts showing homology to a middle repetitive element (EgBRep) that could either be active molecular species or represent precursors of small RNAs (like piRNAs); (ii) an up-regulation of fermentative pathways in the tissue of the cyst wall; (iii) highly expressed thiol- and selenol-dependent antioxidant enzyme targets of thioredoxin glutathione reductase, the functional hub of redox metabolism in parasitic flatworms; (iv) candidate apomucins for the external layer of the tissue-dwelling hydatid cyst, a mucin-rich structure that is critical for survival in the intermediate host; (v) a set of tetraspanins, a protein family that appears to have expanded in the cestode lineage; and (vi) a set of platyhelminth-specific gene products that may offer targets for novel pan-platyhelminth drug development.This survey has greatly increased the quality and the quantity of the molecular information on E. granulosus and constitutes a valuable resource for gene prediction on the parasite genome and for further genomic and proteomic analyses focused on cestodes and platyhelminths