Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due to its strong association with nervous system malformation (microcephaly) of fetuses in pregnant women infected by ...the virus. Signs and symptoms of ZIKV infection are often mistaken with other common viral infections. Since transmission may occur through biological fluids exchange and coitus, in addition to mosquito bite, this condition is an important infectious disease. Thus, understanding the mechanism of viral infection has become an important research focus, as well as providing potential targets for assertive clinical diagnosis and quality screening for hemoderivatives. Within this context, the present work analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV-infected group. Samples underwent direct-infusion mass spectrometry and statistical analysis, where eight markers related to the pathophysiological process of ZIKV infection were elected and characterized. Among these, Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an attempt to induce autophagy of the infected cells. However, this finding is concerning about hypertensive individuals under treatment with inhibitors of the Renin-Angiotensin System (RAS), which could reduce this response against the virus and exacerbate the symptoms of the infection. Moreover, one of the most abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also elected in the present study as an infection biomarker. Considered an important pathogen receptor at membrane's outer layer, this finding represents the importance of gangliosides for ZIKV infection and its association with brain tropism. Furthermore, a series of phosphatidylinositols were also identified as biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this mechanism. Finally, these pathways may also be understood as potential targets to be considered in pharmacological intervention studies on ZIKV infection management.
O objetivo do presente trabalho foi avaliar o processo de conciliação medicamentosa na admissão hospitalar, transferência interna e alta dos pacientes da enfermaria de um Hospital de Ensino.
Estudo ...longitudinal descritivo, retrospectivo, aprovado pelo Comitê de Ética em Pesquisa da sob o CAAE 06213518.8.0000.52430. A coleta de dados acerca do perfil sociodemográfico e clínico do paciente foi realizada a partir dos registros em prontuário e formulários da unidade de farmácia clínica, os quais foram analisados categórica e quantitativamente, bem como as discrepâncias encontradas. Foram quantificadas as intervenções farmacêuticas e sua aceitação ou não pela equipe clínica. Realizou se análise quali-quantitativa das orientações de alta. Os dados obtidos foram tabulados em Microsoft Excel® e os resultados mensurados através de estatística descritiva.
Foram realizadas 118 conciliações, entre julho/2019 a agosto/2020, obtidos de 80 pacientes, sendo 48,75% com idade superior a 60 anos. Os diagnósticos mais frequentes foram linfoma (38,75%) e mieloma múltiplo (17,5%). Das 118 conciliações realizadas, 80 (67,8%) foram de admissão e 38 (32,2%) de transferências. As fontes de informação mais consultadas foram o paciente e prescrição do setor/instituição de transferência. Foram conciliados 621 medicamentos, os quais apresentaram 310 discrepâncias, sendo 219 justificadas e 91 não justificadas. Dentre as classificações das não justificadas, a 3A (omissão do medicamento em uso pelo paciente) apontou-se como mais frequente. Foram realizadas 52 orientações de alta, não sendo possível realizar 42 orientações por motivo de alta não programada.
O processo de Conciliação Medicamentosa (CM) pode ser definido como um mecanismo de revisão do tratamento do paciente, antes e depois de transições no cuidado. Farmacêuticos clínicos podem realizar a CM com o objetivo de otimizar a farmacoterapia e assegurar a segurança do paciente hospitalizado.
O estudo mostrou ser uma ferramenta eficaz, que contribuiu para segurança do paciente hospitalizado, bem como, promoveu a qualidade das informações sobre os medicamentos em uso pelos mesmos.
Conciliação medicamentosa; Hematologia; Eventos adversos; Erros de medicação; Segurança do paciente.
The assessment of drug taste is crucial for pediatric treatments so that formulations can be developed to enhance their effectiveness. In this study,
in vivo
and in vitro methods were applied to ...evaluate the taste of tablets of three drugs administered to children without taste-masking excipients to treat tropical diseases, namely artesunate-mefloquine (ASMQ), praziquantel (PZQ), and benznidazole (BNZ). In the first method, a model of rat palatability was adapted with recirculation to ensure sample dispersion, and the data were analyzed using ANOVA (single factor, 95%). The taste assessment results (
in vivo
) indicated an aversion to the three medicines, denoted by the animals retracting themselves to the bottom of the box after the first contact with the drugs. For the placebo samples, the animals behaved normally, indicating that taste perception was acceptable. The second method was based on the
in vitro
analysis of capacitance data from a homemade impedimetric electronic tongue. Consistent with the
in vivo
taste assessment results, the data points obtained with PZQ, ASMQ, and BNZ were far away from those of their placebos in a map built with the multidimensional projection technique referred to as Interactive Document Mapping (IDMAP). A combined analysis of the results with the two methods allowed us to confirm the bitterness of the three drugs, also pointing to electronic tongues as a promising tool to replace
in vivo
palatability tests.
Graphical abstract
Purpose
To assess collagen content and types in the rectus abdominis muscle of cadavers of different ages.
Methods
Forty fresh adult male cadavers within 24 h of death were obtained from an Institute ...of Legal Medicine and divided by age at death into Group 1 (mean age, 23.3 years; range, 18–30 years;
n
= 20) and Group 2 (mean age, 46.2 years; range, 31–60 years;
n
= 20). From each cadaver, samples of the rectus abdominis muscle measuring 1 cm
2
were collected 3 cm superiorly and 2 cm inferiorly to the umbilicus. Histological sections were prepared and stained with picrosirius red and Masson’s trichrome stain for visualization of total collagen fibers, and immunohistochemical analysis was performed to distinguish types I, II, III, IV and V collagen.
Results
No significant differences in total collagen were found between groups by Masson’s trichrome staining. However, picrosirius red staining revealed a significantly greater amount and higher concentration of total collagen and types I and III collagen in Group 1 than in Group 2 (
P
< 0.05). All but type II collagen were detected by immunohistochemistry in both groups. No significant difference in type IV collagen was found between groups. Type V collagen was detected by immunohistochemistry in both groups, but quantification was not possible due to background staining.
Conclusion
The amounts of types I and III collagen in the rectus abdominis muscle were significantly smaller in older subjects.
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•ZIKV neurological patients have increased Gas6 levels compared to controls.•Monocytes are the main sources of Gas6 and production is increased by ZIKV.•Gas6 correlate with increased ...SOCS1 expression suppressing type I interferon response.•GLA domain carboxylation of Gas6 is essential for ZIKV attachment to cell receptors.•ZIKV + rGas6 facilitates invasion and replication in placenta and mice fetal tissue.
Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.
Abstract Background Mesenchymal stem cells (MSCs) from human umbilical cord vein have great potential for use in cell therapy because of their ease of isolation, expansion, and differentiation, in ...addition to their relative acceptance from the ethical point of view. Obtaining the umbilical cord at birth does not present any risk to either mother or child. Objective To isolate and promote in vitro expansion and differentiation of MSCs from human umbilical cord vein into cells with a pancreatic endocrine phenotype. Methods Mesenchymal stem cells obtained from human umbilical cord vein via collagenase digestion were characterized at cytochemistry and fluorescent-activated cell sorting, and expanded in vitro. Differentiation of MSCs into an endocrine phenotype was induced using high-glucose (23 mmol/L) medium containing nicotinamide, exendin-4, and 2-mercaptoethanol. Expression of insulin, somatostatin, glucagon, and pancreatic and duodenal homeobox 1 was analyzed using immunofluorescence. Results Cells isolated from the umbilical cord vein were MSCs as confirmed at cytochemistry and fluorescent-activated cell sorting. Expression of somatostatin, glucagon, and pancreatic and duodenal homeobox 1 by differentiated cells was demonstrated using immunofluorescence. Insulin was not expressed. Conclusions The MSC differentiation protocol used in the present study induced expression of some endocrine markers. Insulin was not produced by these cells, probably because of incomplete induction of differentiation.