Effect of an l-Carnitine–Containing Peritoneal Dialysate on Insulin Sensitivity in Patients Treated With CAPD: A 4-Month, Prospective, Multicenter Randomized Trial

Bonomini, Mario; Liberato, Lorenzo Di; Rosso, Goffredo Del; Stingone, A; Marinangeli, Giancarlo; Consoli, Agostino; Bertoli, Silvio; Vecchi, A. De; Bosi, Emanuele; Russo, Roberto; Corciulo, Roberto; Gesualdo, Loreto; Giorgino, Francesco; Cerasoli, Paolo; Castelnuovo, Augusto Di; Monaco, M.P.; Shockley, Ty R.; Rossi, Cláudia; Arduini, Arduino

doi:10.1053/j.ajkd.2013.04.007

Cited by 44 publications

(33 citation statements)

References 43 publications

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“…Low and high blood spot QCs were run in replicate in each plate, before and after the real samples. The DIMS analysis for the evaluation of metabolite profile in DBS samples was performed using a Liquid Chromatography-tandem Mass Spectrometry (LC/MS/MS) system consisting of an Alliance HT 2795 HPLC Separation Module coupled to a Quattro Ultima Pt ESI tandem quadrupole mass spectrometer (Waters Corporation, USA) (Sirolli et al, 2012; Bonomini et al, 2013; Rizza et al, 2014). The instrument was operated in positive electrospray ionization mode, using MassLynx V4.0 Software (Waters) with auto data processing by NeoLynx (Waters Corporation, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The mass spectrometer ionization source settings were optimized for maximum ion yields for every analyte. The capillary voltage was set to 3.25 kV, the source and desolvation temperature were 120°C and 350°C respectively, and the collision cell gas pressure was 3–3.5 e-3 mbar Argon (Sirolli et al, 2012; Bonomini et al, 2013; Rizza et al, 2014). …”

Section: Methodsmentioning

confidence: 99%

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n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

Cutuli

Bartolo

Caporali

et al. 2014

Front. Aging Neurosci.

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As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA) exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations) found in n-3 PUFA supplemented mice also pointed toward an effective neuroprotection. On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

Cutuli

Bartolo

Caporali

et al. 2014

Front. Aging Neurosci.

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“…For both agents, favorable profiles of systemic effects have been previously reported, such as improved metabolism and immune competence [ 68 ]. In a recent phase II trial in nondiabetic PD patients, carnitine-enriched PD fluids improved glucose metabolism [ 69 ]. Addition of alanyl-glutamine has resulted in restoration of cellular stress responses, attenuation of peritoneal inflammation, and protection of the peritoneal membrane in experimental systems [ 54 , 60 ] and is being tested in a phase II trial (EudraCT Number: 2013-000400-42).…”

Section: Future Solutionsmentioning

confidence: 99%

Is there such a thing as biocompatible peritoneal dialysis fluid?

Schmitt

Aufricht

2016

Pediatr Nephrol

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Introduction of the so-called biocompatible peritoneal dialysis (PD) fluids was based on a large body of experimental evidence and various clinical trials suggesting important clinical benefits. Of these, until now, only preservation of residual renal function—likely due to lower glucose degradation product load and, in case of icodextrin, improved fluid and blood pressure control—have consistently been proven, whereas the impact on important clinical endpoints such as infectious complications, preservation of PD membrane transport function, and patient outcome, are still debated. In view of the high morbidity and mortality rates of PD patients, novel approaches are warranted and comprise the search for alternative osmotic agents and enrichment of PD fluids with specific pharmacologic agents, such as alanyl-glutamine, potentially counteracting local but also systemic sequelae of uremia and PD.

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“…In this context, our recent studies support the use of l -carnitine, which is involved in the mitochondrial oxidation of long-chain fatty acids,20 as a suitable osmotic agent in PD 21. The presence of l -carnitine in the solution was safe and well tolerated,21,22 and proved to be more biocompatible than glucose in several experimental models 21,23. In addition, a PDS containing l -carnitine significantly increased insulin sensitivity in a 4-month randomized controlled study in nondiabetic CAPD patients 22…”

Section: Introductionmentioning

confidence: 71%

Effect of peritoneal dialysis fluid containing osmo-metabolic agents on human endothelial cells

Bonomini¹,

Silvestre²,

Tomo³

et al. 2016

DDDT

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BackgroundThe use of glucose as the only osmotic agent in peritoneal dialysis (PD) solutions (PDSs) is believed to exert local (peritoneal) and systemic detrimental actions, particularly in diabetic PD patients. To improve peritoneal biocompatibility, we have developed more biocompatible PDSs containing xylitol and carnitine along with significantly less amounts of glucose and have tested them in cultured Human Vein Endothelial Cells (HUVECs) obtained from the umbilical cords of healthy (C) and gestational diabetic (GD) mothers.MethodsPrimary C- and GD-HUVECs were treated for 72 hours with our PDSs (xylitol 0.7% and 1.5%, whereas carnitine and glucose were fixed at 0.02% and 0.5%, respectively) and two glucose-based PDSs (glucose 1.36% or 2.27%). We examined their effects on endothelial cell proliferation (cell count), viability (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay), intracellular nitro-oxidative stress (peroxynitrite levels), Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 membrane exposure (flow cytometry), and HUVEC-monocyte interactions (U937 adhesion assay).ResultsCompared to glucose-based PDSs, our in vitro studies demonstrated that the tested PDSs did not change the proliferative potential both in C- and GD-HUVECs. Moreover, our PDSs significantly improved endothelial cell viability, compared to glucose-based PDSs and basal condition. Notably, glucose-based PDSs significantly increased the intracellular peroxynitrite levels, Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 membrane exposure, and endothelial cell–monocyte interactions in both C- and GD-HUVECs, as compared with our experimental PDSs.ConclusionPresent results show that in control and diabetic human endothelial cell models, xylitol–carnitine-based PDSs do not cause cytotoxicity, nitro-oxidative stress, and inflammation as caused by hypertonic glucose-based PDSs. Since xylitol and carnitine are also known to favorably affect glucose homeostasis, these findings suggest that our PDSs may represent a desirable hypertonic solution even for diabetic patients in PD.

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Effect of an l-Carnitine–Containing Peritoneal Dialysate on Insulin Sensitivity in Patients Treated With CAPD: A 4-Month, Prospective, Multicenter Randomized Trial

Cited by 44 publications

References 43 publications

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

Is there such a thing as biocompatible peritoneal dialysis fluid?

Effect of peritoneal dialysis fluid containing osmo-metabolic agents on human endothelial cells

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