Nutrição parenteral: panorama das amostras analisadas no Instituto Nacional de Controle de Qualidade em Saúde

Background and objectives: Total parenteral nutrition (TPN) has great clinical importance in malnutrition treatment and prevention in patients with digestive problems. Although good practices for handling TPN are well established, contamination of these products still occurs, and this product remains listed as a higher risk drug by the Institute for Safe Medication Practices. The present study aimed to obtain an overview of the documentary data of the parenteral nutrition samples sent to the National Institute for Quality Control in Health (INCQS) of Fundação Oswaldo Cruz. Methods: This is a qualitative descriptive and quantitative study carried out based on a cross-section of TPN samples analyzed from 2000 to 2016. Results: A total of TPN 134 samples were sent during the study period. 11.20% of the samples were sent in 2001, 0.80% in 2005, 8.20% in 2006, 16.40% in 2007, 63.40% in 2013. Six samples (4.5%) were canceled and 113 submitted to sterility testing, resulting in 13.3% unsatisfactory samples. Conclusion: During the study period, four suspected events of enterobacterial contamination in TPNs administered to patients were reported, three of which have not yet been described in the scientific literature. For the safety of patients using TPN to be guaranteed, it is suggested that the norms that regulate TPN therapy be reviewed and updated, and programs to monitor the quality of these preparations should be established.Justificativa e objetivos: A Nutrição Parenteral Total (NPT) possui grande importância clínica no tratamento e prevenção da desnutrição de pacientes com problemas no sistema digestório. Apesar das boas práticas de manipulação de NPT estarem bem estabelecidas, a contaminação desses produtos ainda ocorre, e esse produto permanece como um medicamento de alto risco pelo Institute for Safe Medication Practices. O presente estudo teve como objetivo obter um panorama sobre os dados documentais das amostras de nutrição parenteral encaminhadas ao Instituto Nacional de Controle de Qualidade em Saúde da Fundação Oswaldo Cruz. Métodos: Foi realizado um estudo qualitativo descritivo e quantitativo com base em um coorte transversal de amostras de NPT analisadas no período de 2000 a 2016. Resultados: Foram encaminhadas 134 amostras de NPT no período do estudo. A distribuição por ano foi: 11,20 % das amostras foram encaminhadas em 2001, 0,80 % em 2005, 8,20 % em 2006, 16,40 % em 2007, 63,40 % em 2013. Seis amostras (4,5 %) foram canceladas e 113 submetidas ao ensaio de esterilidade, resultando em 13,3 % de amostras insatisfatórias. Conclusão: No período do estudo, quatro eventos suspeitos de contaminação bacteriana por enterobactérias em NPTs administradas em pacientes foram relatados, sendo três deles ainda não descritos na literatura. Para que a segurança dos pacientes que fazem uso de NPT seja garantida, sugere-se que as normas que regulamentam a terapia com NPT sejam revisadas e atualizadas e sejam estabelecidos programas de monitoramento da qualidade dessas preparações

Clinically early-stage CSPα mutation carrier exhibits remarkable terminal stage neuronal pathology with minimal evidence of synaptic loss

Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (AD-ANCL) is a multisystem disease caused by mutations in the DNAJC5 gene. DNAJC5 encodes Cysteine String Protein-alpha (CSPα), a putative synaptic protein. AD-ANCL has been traditionally considered a lysosomal storage disease based on the intracellular accumulation of ceroid material. Here, we report for the first time the pathological findings of a patient in a clinically early stage of disease, which exhibits the typical neuronal intracellular ceroid accumulation and incipient neuroinflammation but no signs of brain atrophy, neurodegeneration or massive synaptic loss. Interestingly, we found minimal or no apparent reductions in CSPα or synaptophysin in the neuropil. In contrast, brain homogenates from terminal AD-ANCL patients exhibit significant reductions in SNARE-complex forming presynaptic protein levels, including a significant reduction in CSPα and SNAP-25. Frozen samples for the biochemical analyses of synaptic proteins were not available for the early stage AD-ANLC patient. These results suggest that the degeneration seen in the patients with AD-ANCL reported here might be a consequence of both the early effects of CSPα mutations at the cellular soma, most likely lysosome function, and subsequent neuronal loss and synaptic dysfunction

Defective proteostasis in induced pluripotent stem cell models of frontotemporal lobar degeneration

Impaired proteostasis is associated with normal aging and is accelerated in neurodegeneration. This impairment may lead to the accumulation of protein, which can be toxic to cells and tissue. In a subset of frontotemporal lobar degeneration with tau pathology (FTLD-tau) cases, pathogenic mutations in the microtubule-associated protein tau (MAPT) gene are sufficient to cause tau accumulation and neurodegeneration. However, the pathogenic events triggered by the expression of the mutant tau protein remain poorly understood. Here, we show that molecular networks associated with lysosomal biogenesis and autophagic function are disrupted in brains from FTLD-tau patients carrying a MAPT p.R406W mutation. We then used human induced pluripotent stem cell (iPSC)-derived neurons and 3D cerebral organoids from patients carrying the MAPT p.R406W mutation and CRISPR/Cas9, corrected controls to evaluate proteostasis. MAPT p.R406W was sufficient to induce morphological and functional deficits in the lysosomal pathway in iPSC-neurons. These phenotypes were reversed upon correction of the mutant allele with CRISPR/Cas9. Treatment with mTOR inhibitors led to tau degradation specifically in MAPT p.R406W neurons. Together, our findings suggest that MAPT p.R406W is sufficient to cause impaired lysosomal function, which may contribute to disease pathogenesis and serve as a cellular phenotype for drug screening

Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons

In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. Fil: Benitez, Bruno A.. Harvard Medical School; Estados UnidosFil: Belálcazar, Helen M.. Harvard Medical School; Estados UnidosFil: Anastasia Gonzalez, Agustin. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mamah, Daniel. Washington University in St. Louis; Estados UnidosFil: Zorumski, Charles. Washington University in St. Louis; Estados UnidosFil: Masco, Daniel Hugo. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Herrera, Daniel. Harvard Medical School; Estados UnidosFil: de Erausquin, Gabriel Alejandro. Harvard Medical School; Estados Unido

Gastrointestinal parasites in captive and free-ranging Cebus albifrons in the Western Amazon, Ecuador

Currently, there is a lack of surveys that report the occurrence of gastrointestinal parasites in the whiteheaded capuchin monkey (Cebus albifrons). We therefore assessed the presence and richness (= number of different parasite genera) of parasites in C. albifrons in wildlife refuges (n = 11) and in a free-ranging group near a human village (n = 15) in the Ecuadorian Amazon. In the 78 samples collected (median of 3 samples per animal), we identified a total of 6 genera of gastrointestinal parasites, representing protozoa, nematodes, acanthocephalans and cestodes. We observed a high prevalence (84%) across the 26 individuals, with the most prevalent parasite being Strongyloides sp. (76.9%), followed by Hymenolepis sp. (38.5%) and Prosthenorchis elegans (11.5%). We found Entamoeba histolytica/dispar/moskovskii/nuttalli and Capillaria sp. in only a minority of the animals (3.8%). In addition, we observed unidentified strongyles in approximately one-third of the animals (34.6%). We found a total of 6 parasite genera for the adult age group, which showed higher parasite richness than the subadult age group (5) and the juvenile age group (3). Faecal egg/cyst counts were not significantly different between captive and free-ranging individuals or between sexes or age groups. The free-ranging group had a higher prevalence than the captive group; however, this difference was not significant. The only genus common to captive and free-ranging individuals was Strongyloides sp. The high prevalence of gastrointestinal parasites and the presence of Strongyloides in both populations support results from previous studies in Cebus species. This high prevalence could be related to the high degree of humidity in the region. For the free-ranging group, additional studies are required to gain insights into the differences in parasite prevalence and intensity between age and sex groups. Additionally, our study demonstrated that a serial sampling of each individual increases the test sensitivity