High Levels Of Hypoxanthine Research Articles

Electronic-free and low-cost wireless sensor tag for monitoring fish freshness

Real-time monitoring of fish products throughout the supply chain is critically important for proper tracking of fish quality and spoilage to eliminate food waste. However, most of the existing food freshness monitoring technologies are based on complex and costly sensors that lack specificity to direct biomarkers of product quality rendering them impractical for scalable low-cost production and integration into standard food packaging products. To address these issues, we present an electronic-free wireless sensor tag that can selectively monitor hypoxanthine (HX) as a specific biomarker to indicate the spoilage of fish products. The sensor tag is composed of a working and reference coil in a self-calibrating, dual-resonator configuration. The working coil is covered with a stimuli-responsive bilayer polymer structure that degrades only when high levels of HX are produced in spoiled fish products, resulting in a discernible change in the resonant characteristics of the coil. Detecting this change with respect to the reference antenna using a contactless external reader provides a differential mode of sensing to avoid environmental noise and enhance accuracy. The sensor fabrication process takes advantage of scalable and cost-effective manufacturing technologies including laser processing of metalized films and solution casting approaches. Systematic design of resonant coils and optimization of functional HX responsive coatings were performed to identify structures that provided the required spoilage detection threshold of (>2.25 mM HX) which is an indicator of fish spoilage in package products. As a proof of concept, the sensor tag’s performance was validated in a commercially packaged fish product, highlighting its ability to effectively differentiate spoiled products from fresh products in refrigerated conditions. The high selectivity exhibited by this technology puts forth a new platform that merges stimuli-responsive sensing with electronic-free wireless telemetry to develop biomarker-specific sensors for a wide range of intelligent food packaging applications.

The Role of Nucleases Cleaving TLR3, TLR7/8 and TLR9 Ligands, Dicer RNase and miRNA/piRNA Proteins in Functional Adaptation to the Immune Escape and Xenophagy of Prostate Cancer Tissue.

The prototypic sensors for the induction of innate and adaptive immune responses are the Toll-like receptors (TLRs). Unusually high expression of TLRs in prostate carcinoma (PC), associated with less differentiated, more aggressive and more propagating forms of PC, changed the previous paradigm about the role of TLRs strictly in immune defense system. Our data reveal an entirely novel role of nucleic acids-sensing Toll-like receptors (NA-TLRs) in functional adaptation of malignant cells for supply and digestion of surrounding metabolic substrates from dead cells as specific mechanism of cancer cells survival, by corresponding ligands accelerated degradation and purine/pyrimidine salvage pathway. The spectrophotometric measurement protocols used for the determination of the activity of RNases and DNase II have been optimized in our laboratory as well as the enzyme-linked immunosorbent method for the determination of NF-κB p65 in prostate tissue samples. The protocols used to determine Dicer RNase, AGO2, TARBP2 and PIWIL4 were based on enzyme-linked immunosorbent assay. The amount of pre-existing acid-soluble oligonucleotides was measured and expressed as coefficient of absorbance. The activities of acid DNase II and RNase T2, and the activities of nucleases cleaving TLR3, TLR7/8 and TLR9 ligands (Poly I:C, poly U and unmethylated CpG), increased several times in PC, compared to the corresponding tumor adjacent and control tissue, exerting very high sensitivity and specificity of above 90%. Consequently higher levels of hypoxanthine and NF-κB p65 were reported in PC, whereas the opposite results were observed for miRNA biogenesis enzyme (Dicer RNase), miRNA processing protein (TARB2), miRNA-induced silencing complex protein (Argonaute-AGO) and PIWI-interacting RNAs silence transposon. Considering the crucial role of purine and pyrimidine nucleotides as energy carriers, subunits of nucleic acids and nucleotide cofactors, future explorations will be aimed to design novel anti-cancer immune strategies based on a specific acid endolysosomal nuclease inhibition.

Hypoxanthine Induces Neuroenergetic Impairment and Cell Death in Striatum of Young Adult Wistar Rats.

Hypoxanthine is the major purine involved in the salvage pathway of purines in the brain. High levels of hypoxanthine are characteristic of Lesch-Nyhan Disease. Since hypoxanthine is a purine closely related to ATP formation, the aim of this study was to investigate the effect of intrastriatal hypoxanthine administration on neuroenergetic parameters (pyruvate kinase, succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels) and mitochondrial function (mitochondrial mass and membrane potential) in striatum of rats. We also evaluated the effect of cell death parameters (necrosis and apoptosis). Wistar rats of 60days of life underwent stereotactic surgery and were divided into two groups: control (infusion of saline 0.9%) and hypoxanthine (10μM). Intrastriatal hypoxanthine administration did not alter pyruvate kinase activity, but increased succinate dehydrogenase and complex II activities and diminished cytochrome c oxidase activity and immunocontent. Hypoxanthine injection decreased the percentage of cells with mitochondrial membrane label and increased mitochondrial membrane potential labeling. There was a decrease in the number of live cells and an increase in the number of apoptotic cells by caused hypoxanthine. Our findings show that intrastriatal hypoxanthine administration altered neuroenergetic parameters, and caused mitochondrial dysfunction and cell death by apoptosis, suggesting that these processes may be associated, at least in part, with neurological symptoms found in patients with Lesch-Nyhan Disease.

Changes in plasma concentrations of hypoxanthine and xanthine in renal vein as an index of delayed kidney allograft function.

The aim of this study was to evaluate the plasma levels of hypoxanthine (HX) and xanthine in the renal vein blood samples for prediction of delayed graft function (DGF). Two blood samples were taken from 47 kidney recipients, intraoperatively. The first sample was obtained from a peripheral vein before vascular anastomosis and the second from the allograft renal vein, 15 minutes after the anastomosis. Purine metabolites including xanthine and HX were measured and their associations with operative time, anastomosis time, frequency of clamping, urine output, and DGF were evaluated. The mean levels of xanthine and HX were 0.12 +/- 0.10 mg/L and 0.37 +/- 0.17 mg/L in the first plasma samples, respectively. Thirty patients (63%) had no significant changes in neither of their purine metabolite levels and 17 (37%) had higher levels of HX, but not xanthine, in their second samples. Only anastomosis time had a significant relation with the level of the metabolites (P = .04). Three patients (10%) with no changes in the metabolites and 5 (29.4%) with higher HX levels had DGF (P = .12). The anastomosis time and frequency of vascular clamping were higher and the urine output after the anastomosis was lower in the patients with DGF. Cold ischemia in kidney transplantation causes a mild increase in the HX concentration indicative of short-term ischemia effects on the cell metabolism. But it cannot predict DGF. Anastomosis time, frequency of clamping, and urine output after the anastomosis are more sensitive indices.

Prediction of Graft Viability from Non-Heart-Beating Donor Pigs Using Hepatic Microdialysate Hypoxanthine Levels

Background. Non-heart-beating donors (NHBDs) are not yet acceptable in orthotopic liver transplantation (OLTX) because of the high frequency of primary graft nonfunction. In this study, we aimed to develop a new predictive method of graft viability in OLTX from NHBDs. Materials and methods. (1) Pigs were subjected to 15 min of hepatic ischemia and reperfusion (I/R). (2) Porcine OLTX was performed using grafts obtained from NHBDs subjected to in situ warm ischemia (0, 30, and 60 min). During both operations, hepatic hypoxanthine levels were measured by a microdialysis method. Results. In the I/R model, hypoxanthine accumulated during ischemia and decreased after reperfusion, whereas marked xanthine and uric acid production were observed after reperfusion. In the NHBDs model, all of the 0-min group, 6 of 13 pigs in the 30-min group, and 1 of 6 pigs in the 60-min group survived more than 7 days. Significant increases of hypoxanthine levels were seen dependent on warm ischemic time. In the 30-min group, hypoxanthine levels were significantly higher in the pigs that died than in those that survived, and correlated with aspartate aminotransferase, lactate dehydrogenase, and adenosine triphosphate levels of recipients. Histological examination revealed that graft injury was severe in the pigs with higher hypoxanthine levels. Conclusions. It is suggested that hepatic microdialysate hypoxanthine levels during warm ischemia in NHBDs were correlated with graft viability in the recipient. By using of this technique, prediction of the graft viability may be possible during donor operation.

Purine Content of Raw and Roasted Chicken Broiler Meat

ABSTRACTAdenine, guanine and hypoxanthine were determined in raw and roasted broiler parts. The levels of adenine and guanine increased slightly when the meat was cooked. These increases were attributed to moisture and fat losses by the tissues during roasting. The level of hypoxanthine remained constant or decreased in the tissues because some of the purine was removed with the cooking juices. The cooking juices were found to contain high levels of hypoxanthine and only trace amounts of adenine and guanine.

Mechanism of release of ferritin iron in vivo by xanthine oxidase.

Studies of the biochemical mechanism for the release of iron from hepatic ferritin stores have revealed the participation of the enzyme xanthine oxidase (1). During this reaction between the enzyme and ferritin iron some of the iron in the ferric state is reduced to the ferrous form and can be removed from the protein in the presence of iron-binding agents such as cr,a'-dipyridyl or the plasma iron-binding globulin, siderophilin. Evidence for the participation of this enzyme in the release of ferritin iron is based for the most part on in vitro studies using rat liver slices subjected to lowered oxygen tension. Such tissue slices accumulate ferrous-ferritin and high levels of hypoxanthine and xanthine, substrates for xanthine oxidase, as well as uric acid, their oxidation product. In addition, indirect evidence implicates this mechanism in the release of ferritin iron to the plasma in the intact animal; as a result of liver hypoxia following extensive blood loss, the plasma iron and uric acid of dogs is found to increase to a considerable extent. (2). The results of the present study serve to confirm the participation of xanthine oxidase in the in tivo liberation of tissue iron to the circulation.