A structure-based proposal for a comprehensive myotoxic mechanism of phospholipase A(2)-like proteins from viperid snake venoms

Envenomation via snakebites is an important public health problem in many tropical and subtropical countries that, in addition to mortality, can result in permanent sequelae as a consequence of local tissue damage, which represents a major challenge to antivenom therapy. Venom phospholipases A(2) (PLA(2)s) and PLA(2)-like proteins play a leading role in the complex pathogenesis of skeletal muscle necrosis, nevertheless their precise mechanism of action is only partially understood. Recently, detailed structural information has been obtained for more than twenty different members of the PLA(2)-like myotoxin subfamily. In this review, we integrate the available structural, biochemical and functional data on these toxins and present a comprehensive hypothesis for their myotoxic mechanism. This process involves an allosteric transition and the participation of two independent interaction sites for docking and disruption of the target membrane, respectively, leading to a five-step mechanism of action. Furthermore, recent functional and structural studies of these toxins complexed with ligands reveal diverse neutralization mechanisms that can be classified into at least three different groups. Therefore, the data summarized here for the PLA(2)-like myotoxins could provide a useful molecular basis for the search for novel neutralizing strategies to improve the treatment of envenomation by viperid snakes. (C) 2014 Elsevier B.V. All rights reserved.

Phenotypic and functional evaluations of peripheral blood monocytes from chronic-form paracoccidioidomycosis patients before and after treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A produção científica sobre diagnóstico de enfermagem NANDA no Brasil: revisão integrativa da literatura-UNESP – Botucatu

Concern about the identity of nursing professionals has existed since Florence Nightingale. The exercise of the nursing profession must be based on scientific principles so that the actual health problems of a given community can be assessed and actions targeted at improving the population’s quality of life can be designed from such assessments. This problem assessment is referred to as Nursing Diagnosis. NANDA defines diagnosis as “a clinical judgment about individual, family or community responses to actual or potential health problems/life processes. Nursing diagnosis provides the basis for selection of nursing interventions to achieve outcomes for which nurses are accountable”. The present study aimed at investigating the scientific production on Nursing Diagnosis (NANDA). This is an literature review. For data collection, an instrument that addressed the following items was used: identification of original articles and evaluation of their objectives, methodological characteristics, results and conclusion. In the present review, 15 articles that met the inclusion criteria were analyzed. They were all authored by nurses. Four articles addressed obstetrics, puerperium and neonatology, and the diagnosis of an unsatisfactory breastfeeding process was observed in 100% of cases. As regards chronic diseases, four articles were found, and two exclusively addressed diabetes, with a main diagnosis of an ineffective control of the therapeutic regimen. Three articles addressed the elderly, and the main diagnosis found was hindered mobility in more than 90% of cases. As regards, sexually transmitted diseases, one article was found with three diagnoses with 100% for disturbed sleep patterns, infection risk and ineffective protection. As to patients with sequelae, two articles were identified, and the diagnoses found were hindered physical mobility, with 100%; self-care deficit for... (Complete abstract click electronic access below)

Surgical treatment of type I neuritis in a teenage boy with borderline tuberculoid leprosy

Exacerbation of the immune response against Mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. Early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. We report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. The pain was associated with paresthesias in the ulnar edge and left ulnar claw. After evaluation, the diagnosis was changed to borderline tuberculoid leprosy accompanied with neuritis of the left ulnar nerve. Early neurolysis resulted in rapid reduction of the pain and recovery of motor function.

Poisoning after ingestion of pufferfish in Brazil: report of 11 cases

In this brief communication the authors report eleven cases of human poisoning caused by ingestion of pufferfish meat. Three patients (two children and one adult) were seriously affected. The circumstances that precipitated the poisoning are discussed as well as the clinical aspects observed. No deaths were registered and the patients did not present sequelae after the episode.

Effects of Yersinia enterocolitica O:3 derivatives on B lymphocyte activation in vivo

The potential sequelae of intestinal infection with Yersinia enterocolitica include reactive arthritis, erythema nodosum, Reiter's syndrome and other autoimmune diseases. The role of the immune response in the pathogenesis of these diseases has not been fully defined, but autoimmune manifestations may be a consequence of the increase in autoantibodies as a result of polyclonal B-cell activation induced by Yersinia. We investigated the effects of Y enterocolitica 0:3 derivatives on B lymphocyte activation in vivo. Groups of five specific pathogen free (SPF) Swiss mice were inoculated with bacterial cell extract, Yersinia outermembrane proteins (Yops) or lipopolysaccharide (LPS) obtained from Y enterocolitica 0:3 and their immunoglobulin-secreting spleen cells were detected by isotype-specific protein A plaque assay. The presence of specific anti-Yersinia antibodies and autoantibodies was determined in mouse sera by ELISA. In all experiments a marked increase in the number of secretory cells of different isotypes was observed as early as the third day after inoculation. IgG and IgM anti-Yersinia antibodies were detected in the sera of all inoculated mice, and autoantibodies against myosin in the sera of those inoculated with bacterial cell extract. The sera from animals stimulated with LPS reacted with myelin, actin and laminin, while the sera from mice inoculated with Yops reacted with myelin, thyroglobulin and cardiolipin. These results suggest that SPF Swiss mice inoculated with any one of the Y enterocolitica derivatives tested exhibited polyclonal activation of B lymphocytes as a result of stimulation by various bacterial components and not only LPS stimulation.

Structural basis for the inhibition of a phospholipase A2-like toxin by caffeic and aristolochic acids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência dos polimorfismos Taql e Bsml do gene do receptor de vitamina D no surgimento de infecção, tempo de internação e mortalidade em pacientes queimados

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Localized periodontal disease induced by bacterial plaque and palatal radicular groove: treatment and considerations

The palatal radicular groove is a morphological tooth defect, which act as local predisposing risk factor favoring accumulation of the bacterial plaque, permitting microbial invasion via root groove way, directly into periodontal structures. A patient diagnosed with palatal radicular groove and a localized periodontal disease was treated by procedures to control bacterial action and procedures to eliminate local predisposing risk factor. To treat the periodontal bone defect a sequelae of periodontal disease, a guided tissue regeneration technique was applied by using allograft and xenograft materials associated with a resorbable demineralized bovine cortical bone membrane. The objective of surgical regenerative procedure was to recover the periodontal tissues nearly as they were before periodontal disease destruction.

Periodontite ulcerativa necrosante: tratamento fisico da superficie radicular com Er YAG laser

Necrotizing ulcerative periodontitis is associated with bacteria and predisposing risk factors. The treatment is centered in elimination and/or control of the bacteria and predisposing risk factors. However the disease acute phase could induce sequelae as periodontal tissue destruction which may be treated by periodontal surgical procedures.

O conceito de saúde geral e bucal na visão dos cuidadores de idosos

The aim of this study was to analyze the perception of elderly caregivers in relation to the meaning of general and oral health and about oral health status of the institutionalized aged. It was performed a qualitative study, using Discourse of Collective Subject method. It were interviewed 42 caregivers who worked in longterm care facilities of Araçatuba City, SP and Passo Fundo City, RS – Brazil, applying a structured questionnaire. The interviews were recorded and transcript to be performed the qualitative analysis. The answers were analyzed and them it was elaborated the discourses of collective subject (DCS). Oral health, according to caregivers, was hygiene habits and good diet, while the absence of oral health was sequelae of oral diseases. It's possible to note that older means of health were being substituted by new perceptions of quality of life and is very divergent between older professionals and those who graduated during last two decades. However, according to caregivers, this health perception as quality of life was not included in Dentistry, where the old mean "absence of symptoms" was prevalent. For part of them, the institutionalized elderly have no oral health and the only way to improve their condition was through clinical attendance.

Efeitos da radioterapia sobre as condições bucais de pacientes oncológicos

This study evaluated the oral conditions of 50 cancer patients undergoing head and neck radiotherapy (RT). Clinical examinations were performed before treatment, immediately after 30 days after RT and 6 months after conclusion of RT. Periodontal conditions were evaluated using the criteria of the Periodontal Screening and Recording (SRP) and the need for dental treatment were determined. The presence of xerostomia, mucositis and other side effects of RT were also evaluated. Soon after the beginning of RT, the irradiated patients of radiotherapy developed severe mucositis, dermatitis, dysgeusia, xerostomia and, to a lesser extent, candidosis. After completion of radiotherapy, 68% of patients had level III or IV mucositis. It was found that the development of mucositis hinders oral hygiene and these factors contribute to exacerbate inflammation of periodontal tissues. The data from this study evidenced that the main cause of desertion of RT and of severity of sequelae of RT depends on the oral conditions of patients before starting treatment and the absence of previous dental treatment prior RT.

Implante de queratinócitos autólogos em úlceras de membros inferiores de pacientes com seqüelas de hanseníase

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

THE INFLUENCE OF CHILDHOOD ABUSE ON LONGITUDINAL COURSE OF RECOVERY IN PSYCHIATRIC REHABILITATION

Background: Empirical outcome studies have identified specific symptomatic, cognitive, emotional and functional sequelae of childhood abuse in people with severe mental illness (SMI). These findings illuminate the need for an integrated understanding of biological, psychological, environmental, and developmental aspects of SMI. Purpose: The purpose of the present study includes the following: 1) to examine reliability and validity of the comprehensive child abuse rating system in a sample of individuals with SMI, 2) to examine the influence of childhood abuse severity on recovery of psychotic symptoms, neurocognition and social-cognition, and social functioning in people with SMI during 12 months of inpatient psychiatric rehabilitation, and 3) to examine moderating effects of social cognition on the relationship between severity of different types of child abuse history and social functioning. Results: In Study I (N=171), the child abuse rating system produced reliable ratings and some subtypes of child abuse history were related to poorer premorbid functioning and cognition, higher overall psychiatric symptoms, and lower social functioning. In Study II (N=161), the longitudinal factor pattern invariance of the measures of social functioning, externality, and psychiatric symptoms were confirmed across 3 time points (e.g., at admission, at 6 months, and at 12 months). In addition, significant but varied linear relationships between subtypes of child abuse and each level of assessment of functioning were identified. In Study III (N=143), the results showed that higher baseline social inference, independent of history of child physical abuse (CPA), played a protective role in improvements in social functioning. High externality appeared to be counter-therapeutic for individuals with no history of CPA but protective for individuals with a more severe history of CPA. Conclusion: The child abuse rating system appears to provide reliable and valid assessment of subtypes of child abuse history of individuals with SMI. Considering the extreme heterogeneity in both SMI and child maltreatment, the current finding sheds light on providing individualized treatment and assessment planning for individuals with SMI and a history of childhood abuse.

Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EPTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the fast multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome.