Reações adversas a medicamentos em um hospital universitário no Brasil

The aim of this study is to characterize the patients and the ADR notified to a Pharmacovigilance Center at a universityhospital in Brazil. The ADR rate in hospitalized patients is 10% to 20% and the frequency of hospitalization due to ADR is 0,5%to 6,5%. The ADRs contribute to the increase of length in hospitalization and costs. Patient’s exposures have an increase inthe rate of mortality, although about 60% to 80% could be prevented. A descriptive study carried at a university hospital inNortheast of Brazil, where all the spontaneous notifications were analyzed during two years. For the process of notificationof ADR suspicions, WHO definition was used. After receiving the notification, ADR suspicions were analyzed and the causalityassessment was done by CFV staff members, using three different algorithms, and classified according to severity and type.Seventy eight ADR suspicions were spontaneously notified. The female gender represented 55% of cases. Black and mulattoraces represented 70%. The most frequent organ and system affected was the skin. Medicines most frequently involved inADR were anti-infectious agents followed by anti-parasitic agents. The causality assessment shows that the frequency ofcertain and probable ADRs were around 55%. ADRs severity was moderate in 41%, although more than 60% of all ADRs couldbe prevented. ADRs are a major problem and measures must be adopted to minimize them.O objetivo deste trabalho foi caracterizar os pacientes e as reações adversas a medicamentos (RAMs ) notificadas ao Centro deFarmacovigilância de um hospital universitário no Brasil. Sabe-se que a taxa de RAM em pacientes hospitalizados é de 10% a20% e que a frequência de hospitalização por RAM é de 0,5% a 6,5%. As RAMs contribuem para o aumento do tempo de internaçãoe dos custos em saúde. Os pacientes expostos às RAMs têm uma taxa de mortalidade aumentada, embora cerca de 60% a 80%sejam passíveis de prevenir. Um estudo descritivo foi conduzido em um hospital universitário do Nordeste do Brasil, onde todasas notificações espontâneas foram analisadas durante um período de dois anos. Para o processo de notificação das suspeitasde RAM, foi utilizada a definição de reação da OMS. Após o recebimento das notificações, as relações de causalidade dassuspeitas de RAM, foram analisadas pelos membros do CFV, com o uso de três algoritmos diferentes, e também classificadas deacordo com a gravidade e tipo. Setenta e oito suspeitas de RAM foram notificadas espontaneamente. O gênero femininorepresentou 55% dos casos. A raça mulata e a negra representaram 70%. O órgão e sistema mais frequentemente afetado foia pele, tendo os anti-infecciosos e antiparasitários como principais desencadeadores. Na análise da relação causal, as reaçõescertas e prováveis representaram cerca de 55%. As RAMs foram moderadas em 41% dos casos, embora mais de 60% fossempassíveis de prevenir, portanto evitáveis. As RAMs são um grande problema, e medidas devem ser adotadas para minimizá-las

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure

The Germ Cell Nuclear Proteins hnRNP G-T and RBMY Activate a Testis-Specific Exon

The human testis has almost as high a frequency of alternative splicing events as brain. While not as extensively studied as brain, a few candidate testis-specific splicing regulator proteins have been identified, including the nuclear RNA binding proteins RBMY and hnRNP G-T, which are germ cell-specific versions of the somatically expressed hnRNP G protein and are highly conserved in mammals. The splicing activator protein Tra2β is also highly expressed in the testis and physically interacts with these hnRNP G family proteins. In this study, we identified a novel testis-specific cassette exon TLE4-T within intron 6 of the human transducing-like enhancer of split 4 (TLE4) gene which makes a more transcriptionally repressive TLE4 protein isoform. TLE4-T splicing is normally repressed in somatic cells because of a weak 5′ splice site and surrounding splicing-repressive intronic regions. TLE4-T RNA pulls down Tra2β and hnRNP G proteins which activate its inclusion. The germ cell-specific RBMY and hnRNP G-T proteins were more efficient in stimulating TLE4-T incorporation than somatically expressed hnRNP G protein. Tra2b bound moderately to TLE4-T RNA, but more strongly to upstream sites to potently activate an alternative 3′ splice site normally weakly selected in the testis. Co-expression of Tra2β with either hnRNP G-T or RBMY re-established the normal testis physiological splicing pattern of this exon. Although they can directly bind pre-mRNA sequences around the TLE4-T exon, RBMY and hnRNP G-T function as efficient germ cell-specific splicing co-activators of TLE4-T. Our study indicates a delicate balance between the activity of positive and negative splicing regulators combinatorially controls physiological splicing inclusion of exon TLE4-T and leads to modulation of signalling pathways in the testis. In addition, we identified a high-affinity binding site for hnRNP G-T protein, showing it is also a sequence-specific RNA binding protein

Pediatric multiple sclerosis: update on diagnostic criteria, imaging, histopathology and treatment choices

Pediatric multiple sclerosis (MS) represents less than 5% of the MS population, but patients with pediatric-onset disease reach permanent disability at a younger age than adult onset patients. Accurate diagnosis at presentation and optimal long-term treatment is vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate pediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD) as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices