RESUMO
Background: The measurement of fecal inflammatory biomarkers among individuals presenting to care with diarrhea could improve the identification of bacterial diarrheal episodes that would benefit from antibiotic therapy. We reviewed prior literature in this area and describe our proposed methods to evaluate 4 biomarkers in the Enterics for Global Health (EFGH) Shigella surveillance study. Methods: We systematically reviewed studies since 1970 from PubMed and Embase that assessed the diagnostic characteristics of inflammatory biomarkers to identify bacterial diarrhea episodes. We extracted sensitivity and specificity and summarized the evidence by biomarker and diarrhea etiology. In EFGH, we propose using commercial enzyme-linked immunosorbent assays to test for myeloperoxidase, calprotectin, lipocalin-2, and hemoglobin in stored whole stool samples collected within 24 hours of enrollment from participants in the Bangladesh, Kenya, Malawi, Pakistan, Peru, and The Gambia sites. We will develop clinical prediction scores that incorporate the inflammatory biomarkers and evaluate their ability to identify Shigella and other bacterial etiologies of diarrhea as determined by quantitative polymerase chain reaction (qPCR). Results: Forty-nine studies that assessed fecal leukocytes (n = 39), red blood cells (n = 26), lactoferrin (n = 13), calprotectin (n = 8), and myeloperoxidase (n = 1) were included in the systematic review. Sensitivities were high for identifying Shigella, moderate for identifying any bacteria, and comparable across biomarkers. Specificities varied depending on the outcomes assessed. Prior studies were generally small, identified red and white blood cells by microscopy, and used insensitive gold standard diagnostics, such as conventional bacteriological culture for pathogen detection. Conclusions: Our evaluation of inflammatory biomarkers to distinguish diarrhea etiologies as determined by qPCR will provide an important addition to the prior literature, which was likely biased by the limited sensitivity of the gold standard diagnostics used. We will determine whether point-of-care biomarker tests could be a viable strategy to inform treatment decision making and increase appropriate targeting of antibiotic treatment to bacterial diarrhea episodes.
RESUMO
The aim of the present study was to extract and characterize bioactive components from separate body organs of Holothuria leucospilota. Preliminary qualitative assessment of the crude extracts was positive for phenols, terpenoids, carbohydrates, flavonoids, saponins, glycosides, cardiac glycosides, steroids, phlobatannins, and tannins in all body organs evaluated. Phenolics were the most abundant group of bioactives accounting for approximately 80%. The extraction solvent mixtures that yielded most compounds evaluated were methanol/acetone (3:1, v:v) and methanol/distilled water (3:1, v:v). In other analyses, GC-MS data revealed diverse metabolic and biologically active compounds, where those in high concentrations included 2-Pentanone, 4-hydroxy-4-methyl- among the ketones; phenol- 2,4-bis(1,1-dimethylethyl)-, a phenol group; and 2-Chlorooctane, a hydrocarbon. Among FA and their methyl/ethyl esters, n-hexadecanoic acid, 5,8,11,14-eicosatetraenoic acid ethyl ester (arachidonic acid), and 5,8,11,14,17-eicosapentaenoic acid methyl ester (EPA) were among the most abundant FAMEs accounting for approximately 50% of the subgroups measured. Data from GC-FID analysis revealed methyl laurate (C12:0), methyl myristate (C14:0), methyl palmitate (C16:0), and methyl stearate (18:0) methyl esters as the most abundant saturated FA, whereas cis-9-oleic methyl ester (C18:1) and methyl linoleate (C18:2) were found as the major monounsaturated FA and PUFA FAMEs, respectively, in the body wall of the species. Taken together, the extraction and characterization of different categories of metabolically and biologically active compounds in various organ extracts of H. leucospilota suggest that the species is potentially a rich source of cholesterol-lowering, antioxidant, antimicrobial, and anticancer agents. These substances are known to benefit human health and assist in disease prevention. These findings justify the use of sea cucumbers in traditional folklore medication and the current interest and attention focused on the species to mine for bioactives in new drugs research.
