Aptamers for pharmaceuticals and their application in environmental analytics

Aptamers are single-stranded DNA or RNA oligonucleotides, which are able to bind with high affinity and specificity to their target. This property is used for a multitude of applications, for instance as molecular recognition elements in biosensors and other assays. Biosensor application of aptamers offers the possibility for fast and easy detection of environmental relevant substances. Pharmaceutical residues, deriving from human or animal medical treatment, are found in surface, ground, and drinking water. At least the whole range of frequently administered drugs can be detected in noticeable concentrations. Biosensors and assays based on aptamers as specific recognition elements are very convenient for this application because aptamer development is possible for toxic targets. Commonly used biological receptors for biosensors like enzymes or antibodies are mostly unavailable for the detection of pharmaceuticals. This review describes the research activities of aptamer and sensor developments for pharmaceutical detection, with focus on environmental applications

Pulsed heat shocks enhance procollagen type I and procollagen type III expression in human dermal fibroblasts

Background: The formation of wrinkles is associated with degeneration of the collagen matrix. For regeneration of the matrix, fibroblasts need to be stimulated in producing new collagen. Aims: In this study, the effect of short-pulsed heat shocks on gene expression of procollagen type I, procollagen type III, heat shock protein (hsp)27, hsp47 and hsp70 and on the expression of remodeling markers, procollagen type I carboxy-terminal peptide (P1P) and carboxy-terminal telopeptide of type I (ICTP), of human dermal fibroblasts in vitro, is investigated. Materials and Methods: Temperatures of 45 °C and 60 °C were used for the heat shocks. The proliferation rates, viability and metabolic activity were measured directly after the pulsed heat shocks and quantitative PCR was performed at five different time points after the heat shocks. Enzyme Immuno Assays were performed to determine the concentrations of P1P and ICTP. Results: A decreased proliferation rate of the 60 °C heat shocked cells was shown, whereas the viability and metabolic activity did not differ. Furthermore, gene expressions were upregulated in both 45 °C and 60 °C heat-shocked cells. However, remodeling marker analyses showed a larger amount of collagen produced by 60 °C heat-shocked cells. Conclusion: It can be concluded that these findings, together with upregulation in gene expression, show that it is possible to stimulate the cells to produce more collagen with short-pulsed heat shock

Systematic Review: Diagnostic Accuracy of Biomarkers of Alcohol Use in Patients With Liver Disease

BACKGROUND AND AIMS: Alcohol-related liver disease is the most frequent cause of cirrhosis and a major indication for liver transplantation. Several alcohol use biomarkers have been developed in recent years and are already in use in several centers. However, in patients with liver disease their diagnostic performance might be influenced by altered biomarker formation by hepatic damage, altered excretion by kidney dysfunction and diuretics use, and altered deposition in hair and nails. We systematically reviewed studies on the diagnostic accuracy of biomarkers of alcohol use in patients with liver disease and performed a detailed study quality assessment. METHODS: A structured search in PubMed/Medline/Embase databases was performed for relevant studies, published until April 28, 2019. The risk of bias and applicability concerns was assessed according to the adapted quality assessment of diagnostic accuracy studies-2 (QUADAS-2) checklist. RESULTS: Twelve out of 6,449 studies met inclusion criteria. Urinary ethyl glucuronide and urinary ethyl sulfate showed high sensitivity (70 to 89 and 73 to 82%, respectively) and specificity (93 to 99 and 86 to 89%, respectively) for assessing any amount of alcohol use in the past days. Serum carbohydrate-deficient transferrin showed low sensitivity but higher specificity (40 to 79 and 57 to 99%, respectively) to detect excessive alcohol use in the past weeks. Whole blood phosphatidylethanol showed high sensitivity and specificity (73 to 100 and 90 to 96%, respectively) to detect any amount of alcohol use in the previous weeks. Scalp hair ethyl glucuronide showed high sensitivity (85 to 100%) and specificity (97 to 100%) for detecting chronic excessive alcohol use in the past 3 to 6 months. Main limitations of the current evidence are the lack of an absolute gold standard to assess alcohol use, heterogeneous study populations, and the paucity of studies. CONCLUSIONS: Urinary and scalp hair ethyl glucuronide are currently the most validated alcohol use biomarkers in patients with liver disease with good diagnostic accuracies. Phosphatidylethanol is a highly promising alcohol use biomarker, but so far less validated in liver patients. Alcohol use biomarkers can complement each other regarding diagnostic time window. More validation studies on alcohol use biomarkers in patients with liver disease are needed.status: publishe