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1.
Summary. Despite the wide interest in using modified amino acids as putative biomarkers of oxidative stress, many issues remain as
to their overall reliability for early detection and diagnosis of diseases. In contrast to conventional single biomarker studies,
comprehensive analysis of biomarkers offers an unbiased strategy for global assessment of modified amino acid metabolism due
to reactive oxygen and nitrogen species. This review examines recent analytical techniques amenable for analysis of modified
amino acids in biological samples reported during 2003–2007. Particular attention is devoted to the need for validated methods
applicable to high-throughput analysis of multiple amino acid biomarkers, as well as consideration of sample pretreatment
protocols on artifact formation for improved clinical relevance. 相似文献
2.
Zolotarev YA Dolotov OV Inozemtseva LS Dadayan AK Dorokhova EM Andreeva LA Alfeeva LY Grivennikov IA Myasoedov NF 《Amino acids》2006,30(4):403-408
Summary. Here a new approach of the elucidation of paths of proteolytic biodegradation of physiologically active peptides, based on
the use of a peptide with isotopic label at all amino acid residues and the enrichment of HPLC samples with unlabeled peptide
fragments in UV-detectable concentration, has been proposed. The method has been applied for the investigation of degradation
dynamics of the neuroactive heptapeptide MEHFPGP (Semax) in the presence of plasma membranes, and cultures of glial and neuronal
cells obtained from the rat basal forebrain. The splitting away of ME and GP, and formation of pentapeptides are the predominant
processes in the presence of all tested objects, whereas the difference in patterns of resulting peptide products for glial
and neuronal cells has been detected. In conclusion, the approach applied allows analyzing physiologically active peptide
concentrations in biological tissues and degradation pathways of peptides in the presence of targets of their action. 相似文献
3.
Interaction between the actions of taurine and angiotensin II 总被引:1,自引:0,他引:1
Summary. The amino acid, taurine, is an important nutrient found in very high concentration in excitable tissue. Cellular depletion
of taurine has been linked to developmental defects, retinal damage, immundeficiency, impaired cellular growth and the development
of a cardiomyopathy. These findings have encouraged the use of taurine in infant formula, nutritional supplements and energy
promoting drinks. Nonetheless, the use of taurine as a drug to treat specific diseases has been limited. One disease that
responds favorably to taurine therapy is congestive heart failure. In this review, we discuss three mechanisms that might
underlie the beneficial effect of taurine in heart failure. First, taurine promotes natriuresis and diuresis, presumably through
its osmoregulatory activity in the kidney, its modulation of atrial natriuretic factor secretion and its putative regulation
of vasopressin release. However, it remains to be determined whether taurine treatment promotes salt and water excretion in
humans with heart failure. Second, taurine mediates a modest positive inotropic effect by regulating [Na+]i and Na+/Ca2+ exchanger flux. Although this effect of taurine has not been examined in human tissue, it is significant that it bypasses
the major calcium transport defects found in the failing human heart. Third, taurine attenuates the actions of angiotensin
II on Ca2+ transport, protein synthesis and angiotensin II signaling. Through this mechanism taurine would be expected to minimize many
of the adverse actions of angiotensin II, including the induction of cardiac hypertrophy, volume overload and myocardial remodeling.
Since the ACE inhibitors are the mainstay in the treatment of congestive heart failure, this action of taurine is probably
very important.
Received November 10, 1998, Accepted May 19, 1999 相似文献
4.
Jaques Belik Gema E. González-Luis Francisco Perez-Vizcaino Eduardo Villamor 《Free radical biology & medicine》2010,48(2):177-188
Isoprostanes are prostaglandin-like bioactive molecules generated via nonenzymatic peroxidation of lipid membrane-derived arachidonic acid by free radicals and reactive oxygen species. Their cognate receptors, biological actions, and signaling pathways are poorly understood. Aside from being sensitive and specific biomarkers of oxidative stress, E- and F-ring isoprostanes have important biological functions and likely mediate many of the disease-related pathological changes for which they are used as indicators. The biochemical pathways involved in isoprostane formation, their pathogenetic relevance to adult disease states, and their biological function are addressed. Developmentally, plasma and tissue content data show that isoprostane levels are highest during fetal and early neonatal life, when compared with adults. As such, the available data suggesting that isoprostanes play an important biological role, as well as possibly actively participate in the regulation of pulmonary vascular tone and the transition from fetal to postnatal life, are here reviewed. Lastly, the association between isoprostanes and certain neonatal clinical conditions is addressed. Although its existence has been recognized for almost 20 years, little is known about the critical importance of isoprostanes during fetal life and immediate neonatal period. This review is an attempt to bridge this knowledge gap. 相似文献
5.
Cross-sectional biomarker studies can provide a snapshot of the frequency and characteristics of exposure/disease in a population at a particular point in time and, as a result, valuable insights for delineating the multi-step association between exposure and disease occurrence. Three major issues should be considered when designing biomarker studies: selection of appropriate biomarkers, the assay (laboratory validity), and the population validity of the selected biomarkers. Factors related to biomarker selection include biological relevance, specificity, sensitivity, biological half-life, stability, and so on. The assay attributes include limit of detection, reproducibility/reliability, inter-laboratory variation, specificity, time, and cost. Factors related to the population validity include the frequency or prevalence of markers, greater inter-individual variation than intra-individual variation, intra-class correlation coefficients (ICC), association with potential confounders, invasiveness of specimen collection, and subject selection. Three studies are selected to demonstrate different features of cross-sectional biomarker studies: (1) characterizing the determinants of the biomarkers (study I: urinary PAH metabolites and environmental particulate exposure), (2) relationship of multiple biomarkers of exposure and effect (study II: relationship between urinary PAH metabolites and oxidative stress), and (3) evaluating gene-environmental interaction (study III: effect of genetic polymorphisms of GSTM1 on the association of green tea consumption and urinary 1-OHPG levels in shipbuilding workers). 相似文献
6.
Several attempts at building a satisfactory model of the glucose-insulin system are recorded in the literature. The minimal
model, which is the model currently mostly used in physiological research on the metabolism of glucose, was proposed in the
early eighties for the interpretation of the glucose and insulin plasma concentrations following the intravenous glucose tolerance
test. It is composed of two parts: the first consists of two differential equations and describes the glucose plasma concentration
time-course treating insulin plasma concentration as a known forcing function; the second consists of a single equation and
describes the time course of plasma insulin concentration treating glucose plasma concentration as a known forcing function.
The two parts are to be separately estimated on the available data. In order to study glucose-insulin homeostasis as a single
dynamical system, a unified model would be desirable. To this end, the simple coupling of the original two parts of the minimal
model is not appropriate, since it can be shown that, for commonly observed combinations of parameter values, the coupled
model would not admit an equilibrium and the concentration of active insulin in the “distant” compartment would be predicted
to increase without bounds. For comparison, a simple delay-differential model is introduced, is demonstrated to be globally
asymptotically stable around a unique equilibrium point corresponding to the pre-bolus conditions, and is shown to have positive
and bounded solutions for all times. The results of fitting the delay-differential model to experimental data from ten healthy
volunteers are also shown. It is concluded that a global unified model is both theoretically desirable and practically usable,
and that any such model ought to undergo formal analysis to establish its appropriateness and to exclude conflicts with accepted
physiological notions.
Received: 22 June 1998 / Revised version: 24 February 1999 相似文献
7.
Whiteaker JR Lin C Kennedy J Hou L Trute M Sokal I Yan P Schoenherr RM Zhao L Voytovich UJ Kelly-Spratt KS Krasnoselsky A Gafken PR Hogan JM Jones LA Wang P Amon L Chodosh LA Nelson PS McIntosh MW Kemp CJ Paulovich AG 《Nature biotechnology》2011,29(7):625-634
High-throughput technologies can now identify hundreds of candidate protein biomarkers for any disease with relative ease. However, because there are no assays for the majority of proteins and de novo immunoassay development is prohibitively expensive, few candidate biomarkers are tested in clinical studies. We tested whether the analytical performance of a biomarker identification pipeline based on targeted mass spectrometry would be sufficient for data-dependent prioritization of candidate biomarkers, de novo development of assays and multiplexed biomarker verification. We used a data-dependent triage process to prioritize a subset of putative plasma biomarkers from >1,000 candidates previously identified using a mouse model of breast cancer. Eighty-eight novel quantitative assays based on selected reaction monitoring mass spectrometry were developed, multiplexed and evaluated in 80 plasma samples. Thirty-six proteins were verified as being elevated in the plasma of tumor-bearing animals. The analytical performance of this pipeline suggests that it should support the use of an analogous approach with human samples. 相似文献
8.
Integrated pipeline for mass spectrometry-based discovery and confirmation of biomarkers demonstrated in a mouse model of breast cancer 总被引:2,自引:0,他引:2
Whiteaker JR Zhang H Zhao L Wang P Kelly-Spratt KS Ivey RG Piening BD Feng LC Kasarda E Gurley KE Eng JK Chodosh LA Kemp CJ McIntosh MW Paulovich AG 《Journal of proteome research》2007,6(10):3962-3975
Despite their potential to impact diagnosis and treatment of cancer, few protein biomarkers are in clinical use. Biomarker discovery is plagued with difficulties ranging from technological (inability to globally interrogate proteomes) to biological (genetic and environmental differences among patients and their tumors). We urgently need paradigms for biomarker discovery. To minimize biological variation and facilitate testing of proteomic approaches, we employed a mouse model of breast cancer. Specifically, we performed LC-MS/MS of tumor and normal mammary tissue from a conditional HER2/Neu-driven mouse model of breast cancer, identifying 6758 peptides representing >700 proteins. We developed a novel statistical approach (SASPECT) for prioritizing proteins differentially represented in LC-MS/MS datasets and identified proteins over- or under-represented in tumors. Using a combination of antibody-based approaches and multiple reaction monitoring-mass spectrometry (MRM-MS), we confirmed the overproduction of multiple proteins at the tissue level, identified fibulin-2 as a plasma biomarker, and extensively characterized osteopontin as a plasma biomarker capable of early disease detection in the mouse. Our results show that a staged pipeline employing shotgun-based comparative proteomics for biomarker discovery and multiple reaction monitoring for confirmation of biomarker candidates is capable of finding novel tissue and plasma biomarkers in a mouse model of breast cancer. Furthermore, the approach can be extended to find biomarkers relevant to human disease. 相似文献
9.
Xiaobo Lin Susan B. Racette Lina Ma Michael Wallendorf Catherine Anderson Spearie Richard E. Ostlund Jr 《PloS one》2015,10(2)
BackgroundDietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI.ConclusionThe ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease. 相似文献
10.
The use of proteomics to profile biological fluids and identify therein biomarkers for cancer and other diseases was initially received with considerable excitement. However, results have fallen short of the expectations. Traditionally, protein biomarkers have been identified by measurement of relative expression changes between case and control samples from which differentially expressed proteins are then considered to represent biomarker candidates.We argue that current individual proteomics-based biomarker discovery studies lack the statistical strength for the identification of high-confidence biomarkers. Instead, multi-group efforts are necessary to facilitate the generation of sufficient sample sizes. This is contingent on the ability to collate and cross-compare data from different studies, which will require the use of a common metric or standards.Though profound, the technical challenges for absolute protein quantification can be overcome. The use of matrix specific, shared standards for absolute quantitation presents an opportunity to facilitate the much needed, but currently impossible, comparisons of different studies. In addition to community-wide approaches to standardize pre-analytical biomarker research studies, it is also important to establish means to integrate experimental data from different studies in order to assess the usefulness of proposed biomarkers with sufficient statistical certainty. 相似文献
11.
Basu S 《Free radical research》2004,38(2):105-122
Isoprostanes, are a novel group of prostaglandin-like compounds that are biosynthesised from esterified polyunsaturated fatty acid (PUFA) through a non-enzymatic free radical-catalysed reaction. Several of these compounds possess potent biological activity, as evidenced mainly through their pulmonary and renal vasoconstrictive effects, and have short half-lives. It has been shown that isoprostanes act as full or partial agonists through thromboxane receptors. Both human and experimental studies have indicated associations of isoprostanes and severe inflammatory conditions, ischemia-reperfusion, diabetes and atherosclerosis. Reports have shown that F2-isoprostanes are authentic biomarkers of lipid peroxidation and can be used as potential in vivo indicators of oxidant stress in various clinical conditions, as well as in evaluations of antioxidants or drugs for their free radical-scavenging properties.
Higher levels of F2-isoprostanes have been found in the normal human pregnancy compared to non-pregnancy, but their physiological role has not been well studied so far. Since bioactive F2-isoprostanes are continuously formed in various tissues and large amounts of these potent compounds are found unmetabolised in their free acid form in the urine in normal basal conditions with a wide inter-individual variation, their role in the regulation of normal physiological functions could be of further biological interest, but has yet to be disclosed. Their potent biological activity has attracted great attention among scientists, since these compounds are found in humans and animals in both physiological and pathological conditions and can be used as reliable biomarkers of lipid peroxidation. 相似文献
Higher levels of F2-isoprostanes have been found in the normal human pregnancy compared to non-pregnancy, but their physiological role has not been well studied so far. Since bioactive F2-isoprostanes are continuously formed in various tissues and large amounts of these potent compounds are found unmetabolised in their free acid form in the urine in normal basal conditions with a wide inter-individual variation, their role in the regulation of normal physiological functions could be of further biological interest, but has yet to be disclosed. Their potent biological activity has attracted great attention among scientists, since these compounds are found in humans and animals in both physiological and pathological conditions and can be used as reliable biomarkers of lipid peroxidation. 相似文献
12.
Xi He Jiaojiao Liu Bo Liu Jingshan Shi 《Experimental biology and medicine (Maywood, N.J.)》2021,246(4):436
One of the key characteristics of aging is a progressive loss of physiological integrity, which weakens bodily functions and increases the risk of death. A robust biomarker is important for the assessment of biological age, the rate of aging, and a person''s health status. DNA methylation clocks, novel biomarkers of aging, are composed of a group of cytosine-phosphate-guanine dinucleotides, the DNA methylation status of which can be used to accurately measure subjective age. These clocks are considered accurate biomarkers of chronological age for humans and other vertebrates. Numerous studies have demonstrated these clocks to quantify the rate of biological aging and the effects of longevity and anti-aging interventions. In this review, we describe the purpose and use of DNA methylation clocks in aging research. 相似文献
13.
Summary. This study examines the relationship between traditional risk factors of coronary artery disease and indicators involved
in the metabolism of l-arginine (plasma and urine l-arginine, plasma l-citrulline, serum creatinine and urine orotic acid). Our study population consisted of 40 healthy male volunteers aged between
35 and 55 years. We found an inverse association between serum creatinine and blood pressure, between plasma l-citrulline and blood pressure, as well as between urine l-arginine and blood pressure. We also found a positive association between plasma LDL-cholesterol and urine l-arginine and a negative correlation between plasma l-arginine and LDL-cholesterol. Orotic acid measured from urine was not associated with any of the indicators of l-arginine metabolism. Our results indicate that l-arginine metabolism is of profound significance for cardiovascular health. However, our study does not answer questions relating
to causality. Further studies are needed to clarify the causal relationship between cardiovascular risk factors, especially
elevated blood pressure and high LDL-cholesterol, and indicators of l-arginine metabolism.
Received January 18, 1999 相似文献
14.
15.
Biomarkers of DHA status 总被引:1,自引:1,他引:0
Connye N. Kuratko Norman Salem Jr. 《Prostaglandins, leukotrienes, and essential fatty acids》2009,81(2-3):111
Docosahexaenoic acid (DHA, 22:6n-3) is a long chain omega-3 fatty acid that is the primary n-3 fatty acid found in the central nervous system where it plays both a structural and functional role in cells. Because the tissues of interest are generally inaccessible for fatty acid analysis in humans and because precise DHA intake is difficult to determine, surrogate biomarkers are important for defining DHA status. Analysis of total lipid extracts or phospholipids from plasma or erythrocytes by gas chromatography meet the criteria for a useful biomarker of DHA status. Furthermore, both plasma and erythrocyte DHA levels have been correlated with brain, cardiac, and other tissue levels. Use of these biomarkers of DHA status will enable future clinical trials and observational studies to define more precisely the DHA levels required for either disease prevention or other functional benefits. 相似文献
16.
17.
Summary. Secondary amino acid disturbances from circulatory responses during hypoxia may cause problems in interpreting plasma amino
acid profiles of sick babies investigated for possible inherited defects. Systematic studies to characterise them are difficult
in man. We investigated the effects of hypoxia on plasma amino acids by studying 9 late gestation fetal sheep in utero during 11 one hour episodes of moderately severe isocapnic hypoxia. In 6 experiments, maternal plasma amino acids were also
monitored. Fourteen fetal plasma amino acids increased significantly, with the largest proportionate changes in alanine, valine,
leucine, isoleucine, phenylalanine, tyrosine, ornithine and lysine. Maternal amino acids did not increase. Probable explanations
were reflex peripheral vasoconstriction in skeletal muscle beds and decreased hepatic blood flow. The findings extend our
knowledge of the fetal response to hypoxic stress, demonstrate the importance of skeletal muscle in branched-chain amino acid
metabolism, and should help with interpretation of postnatal plasma amino acid disturbances.
Received January 29, 1999, Accepted February 22, 1999 相似文献
18.
Bonsi P Cuomo D Picconi B Sciamanna G Tscherter A Tolu M Bernardi G Calabresi P Pisani A 《Amino acids》2007,33(2):189-195
Summary. Polyamine metabolic genes are downstream targets of several genes commonly mutated in colon adenomas and cancers. Inhibitors
of ornithine decarboxylase, such as difluoromethylornithine (DFMO), and agents that stimulate polyamine acetylation and export,
such as non-steroidal anti-inflammatory drugs (NSAIDS), act at least additively to arrest growth in human cell models and
suppress intestinal carcinogenesis in mice. These preclinical studies provided the rationale for colon cancer prevention trials
in humans. A Phase IIb clinical study comparing the combination of DFMO and the NSAID sulindac versus placebo was conducted.
Endpoints were colorectal tissue polyamine and prostaglandin E2 contents and overall toxicity to participants. Participants
in the Phase IIb study served as a vanguard for a randomized, placebo-controlled prospective Phase III trial of the combination
of DFMO and sulindac with the primary study endpoint the prevention of colon polyps. Seventy percent of participants will
have completed the three years of treatment in December 2006. 相似文献
19.
Samar Basu 《Free radical research》2013,47(2):105-122
Isoprostanes, are a novel group of prostaglandin-like compounds that are biosynthesised from esterified polyunsaturated fatty acid (PUFA) through a non-enzymatic free radical-catalysed reaction. Several of these compounds possess potent biological activity, as evidenced mainly through their pulmonary and renal vasoconstrictive effects, and have short half-lives. It has been shown that isoprostanes act as full or partial agonists through thromboxane receptors. Both human and experimental studies have indicated associations of isoprostanes and severe inflammatory conditions, ischemia-reperfusion, diabetes and atherosclerosis. Reports have shown that F2-isoprostanes are authentic biomarkers of lipid peroxidation and can be used as potential in vivo indicators of oxidant stress in various clinical conditions, as well as in evaluations of antioxidants or drugs for their free radical-scavenging properties.Higher levels of F2-isoprostanes have been found in the normal human pregnancy compared to non-pregnancy, but their physiological role has not been well studied so far. Since bioactive F2-isoprostanes are continuously formed in various tissues and large amounts of these potent compounds are found unmetabolised in their free acid form in the urine in normal basal conditions with a wide inter-individual variation, their role in the regulation of normal physiological functions could be of further biological interest, but has yet to be disclosed. Their potent biological activity has attracted great attention among scientists, since these compounds are found in humans and animals in both physiological and pathological conditions and can be used as reliable biomarkers of lipid peroxidation. 相似文献
20.
Summary. So-called energy drinks with very high amounts of taurine (up to 4000 mg/l are usually granted by certificates of exemption)
are increasingly offered on the market. To control the currently valid maximum limits of taurine in energy drinks, a simple
and rapid analytical method is required to use it routinely in food monitoring. In this article, we describe a fast and efficient
analytical method (FTIR-spectroscopy) that is able to reliably characterize and quantify taurine in energy drinks. The determination
of taurine in energy drinks by FTIR was compared with amino acid analyzer (ion chromatography with ninhydrin-postcolumn derivatization).
During analysis of 80 energy drinks, a median concentration of 3180 mg/l was found in alcohol-free products, 314 mg/l in energy
drinks with spirits, 151 mg/l in beer-containing drinks and 305 mg/l in beverages with wine. Risk analysis of these products
is difficult due to the lack of valid toxicological information about taurine and its interferences with other ingredients
of energy drinks (for example caffeine and alcohol). So far, the high taurine concentrations of energy drinks in comparison
to the rest of the diet are scientifically doubtful, as the advertised physiological effects and the value of supplemented
taurine are unproven. 相似文献