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1.
Antiviral Res ; 140: 13-17, 2017 04.
Article in English | MEDLINE | ID: mdl-28063994

ABSTRACT

The recent Zika virus (ZIKV) outbreak, which mainly affected Brazil and neighbouring states, demonstrated the paucity of information concerning the epidemiology of several flaviruses, but also highlighted the lack of available agents with which to treat such emerging diseases. Here, we show that heparin, a widely used anticoagulant, while exerting a modest inhibitory effect on Zika Virus replication, fully prevents virus-induced cell death of human neural progenitor cells (NPCs).


Subject(s)
Cytopathogenic Effect, Viral/drug effects , Heparin/pharmacology , Neural Stem Cells/drug effects , Neural Stem Cells/virology , Zika Virus/drug effects , Cell Death/drug effects , Drug Repositioning , Humans , Neural Stem Cells/pathology , Zika Virus/pathogenicity
2.
J Clin Endocrinol Metab ; 101(2): 653-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26647152

ABSTRACT

CONTEXT: Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed even after complete surgical removal without evidence of a recurrent or persistent tumor. OBJECTIVE: To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease. PATIENTS AND METHODS: We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose. RESULTS: Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2-7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH. CONCLUSIONS: For the first time, our results show the presence of a novel pitfall in the CT immunoassay: "macrocalcitonin." Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC.


Subject(s)
Calcitonin/blood , Carcinoma, Neuroendocrine/blood , Thyroid Neoplasms/blood , Adolescent , Adult , Aged , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/surgery , Chromatography, High Pressure Liquid , False Positive Reactions , Female , Goiter, Nodular/blood , Humans , Immunoassay , Iodide Peroxidase/blood , Male , Middle Aged , Mutation/genetics , Neoplasm Metastasis , Protein Precursors , Proto-Oncogene Proteins c-ret/blood , Proto-Oncogene Proteins c-ret/genetics , Thyroglobulin/analysis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/surgery , Thyroidectomy , Young Adult
3.
PLoS One ; 10(6): e0131105, 2015.
Article in English | MEDLINE | ID: mdl-26107959

ABSTRACT

Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology.


Subject(s)
Bone and Bones/chemistry , Glycosaminoglycans/analysis , Proteoglycans/analysis , Tooth/chemistry , Archaeology , Humans
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