guanidinosuccinic-acid and Inflammation

Specific guanidino compounds have been described as uraemic toxins and their concentrations are increased in renal failure due to dimished glomerular filtration, whereas the guanidino compound creatine is used as a performance-enhancing substance in athletes. The present study investigates the effects of creatine supplementation on plasma guanidino compounds in a chronic haemodialysis population.. Twenty male haemodialysis patients were included in a placebo-controlled cross-over trial. Patients were treated with creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical parameters were determined, as well as the prognostic inflammatory and nutritional index (PINI).. Upon creatine supplementation, guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased three-fold and argininic acid concentrations doubled. Guanidinosuccinate concentrations did not change, but correlated inversely with CRP (r = -0.736; P = 0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma urea concentration (r = 0.54; P = 0.02).. Creatine supplementation in haemodialysis patients significantly altered the concentration of specific guanidino compounds. Guanidinosuccinate correlated positively with plasma urea and negatively with inflammation markers.

Topics: Administration, Oral; Aged; Arginine; Biomarkers; C-Reactive Protein; Creatine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Follow-Up Studies; Glycine; Guanidines; Humans; Inflammation; Male; Nephelometry and Turbidimetry; Prognosis; Renal Dialysis; Renal Insufficiency; Severity of Illness Index; Succinates; Treatment Outcome; Urea

Abdominal aortic aneurysm (AAA) is a permanent and localized aortic dilation, defined as aortic diameter ≥3 cm. It is an asymptomatic but potentially fatal condition because progressive enlargement of the abdominal aorta is spontaneously evolving towards rupture.Biomarkers may help to explain pathological processes of AAA expansion, and allow us to find novel therapeutic strategies or to determine the efficiency of current therapies. Metabolomics seems to be a good approach to find biomarkers of AAA. In this study, plasma samples of patients with large AAA, small AAA, and controls were fingerprinted with LC-QTOF-MS. Statistical analysis was used to compare metabolic fingerprints and select metabolites that showed a significant change. Results presented here reveal that LC-QTOF-MS based fingerprinting of plasma from AAA patients is a very good technique to distinguish small AAA, large AAA, and controls. With the use of validated PLS-DA models it was possible to classify patients according to the disease stage and predict properly the stage of additional AAA patients. Identified metabolites indicate a role for sphingolipids, lysophospholipids, cholesterol metabolites, and acylcarnitines in the development and progression of AAA. Moreover, guanidinosuccinic acid, which mimics nitric oxide in terms of its vasodilatory action, was found as a strong marker of large AAA.

Topics: Aorta; Aortic Aneurysm, Abdominal; Biomarkers; Chromatography, High Pressure Liquid; Chromatography, Liquid; Female; Guanidines; Humans; Inflammation; Lysophospholipids; Male; Mass Spectrometry; Metabolomics; Models, Statistical; Quality Control; Spectrometry, Mass, Electrospray Ionization; Succinates

Alveolar macrophages acquire 1 alpha-hydroxylase activity in inflammation, and thereby metabolize 25 hydroxyvitamin D3 (25 D3) to the active metabolite, 1 alpha,25-dihydroxyvitamin D3 (1,25 D3, calcitriol). Calcitriol is a potent differentiation agent that modulates mononuclear phagocyte activation and effector functions. The mediators that induce macrophage 1 alpha-hydroxylase activity are not well delineated. Furthermore, it is unclear whether calcitriol is a product only of terminally differentiated macrophages or whether less mature mononuclear phagocytes can produce it as well. The ability of newly recruited monocytes to produce calcitriol as an autocrine differentiation agent is particularly important in inflammation, as it may substantially expand the functional repertoire of these cells. To assess the effects of cytokines on 1 alpha-hydroxylase activity, blood monocytes were cultured in the presence and absence of human recombinant tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukins 1 and 2 and then incubated with 25 D3 substrate. The conditioned media were assayed for calcitriol by high-performance liquid chromatography and competitive receptor binding assay. No detectable calcitriol was produced by unstimulated monocytes. However, all the cytokines markedly increased monocyte calcitriol production (range 133-151 pg/mg protein; in all cases P < .001). We then determined whether calcitriol production was suppressed by preincubation with either dexamethasone or the putative uremia toxin guanidinosuccinic acid (GSA). Dexamethasone pretreatment significantly inhibited subsequent cytokine-induced calcitriol production by monocytes, as did GSA (average 69 and 63% of control, respectively).

Topics: Calcitriol; Cells, Cultured; Cholestanetriol 26-Monooxygenase; Cytokines; Dexamethasone; Enzyme Induction; Granuloma; Guanidines; Humans; Inflammation; Kidney; Monocytes; Phagocytes; Steroid Hydroxylases; Succinates