Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study

<p>Abstract</p> <p>Background</p> <p>Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery.</p> <p>Methods</p> <p>Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193–273) and 208 min (145–300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons.</p> <p>Results</p> <p>Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied.</p> <p>Conclusion</p> <p>Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.</p

Imaging the Dopamine Uptake Site with Ex Vivo [ 18 F]GBR 13119 Binding Autoradiography in Rat Brain

We studied the binding of [ 18 F]GBR 13119 {1-[[(4-[ 18 F]fluorophenyl) (phenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine} to rat brain with autoradiography after intravenous injection. The rank order of binding was dorsal striatum > nucleus accumbens = olfactory tubercle > sub-stantia nigra = ventral tegmental area > other areas. Binding was blocked by prior injection of dopamine uptake blockers but not by injection of dopamine receptor antagonists or drugs that bind to the dialkylpiperazine site. Unilateral 6-hydroxy dopamine lesions of dopamine neurons caused a marked decrease in striatal and nigral binding on the side of the lesion. We conclude that intravenous injection of [ 18 F]GBR 13119 provides a useful marker of presynaptic dopamine uptake sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66209/1/j.1471-4159.1990.tb04178.x.pd

Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells

Epigenetic treatment concepts have long been ascribed as being tumour-selective. Over the last decade, it has become evident that epigenetic mechanisms are essential for a wide range of intracellular functions in healthy cells as well. Evaluation of possible side-effects and their underlying mechanisms in healthy human cells is necessary in order to improve not only patient safety, but also to support future drug development. Since epigenetic regulation directly interacts with genomic and chromosomal packaging density, increasing genomic instability may be a result subsequent to drug-induced epigenetic modifications. This review highlights past and current research efforts on the influence of epigenetic modification on genomic stability in healthy human cells

Nicotinamide Inhibits Alkylating Agent-Induced Apoptotic Neurodegeneration in the Developing Rat Brain

BACKGROUND: Exposure to the chemotherapeutic alkylating agent thiotepa during brain development leads to neurological complications arising from neurodegeneration and irreversible damage to the developing central nerve system (CNS). Administration of single dose of thiotepa in 7-d postnatal (P7) rat triggers activation of apoptotic cascade and widespread neuronal death. The present study was aimed to elucidate whether nicotinamide may prevent thiotepa-induced neurodegeneration in the developing rat brain. METHODOLOGY/PRINCIPAL FINDINGS: Neuronal cell death induced by thiotepa was associated with the induction of Bax, release of cytochrome-c from mitochondria into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1). Post-treatment of developing rats with nicotinamide suppressed thiotepa-induced upregulation of Bax, reduced cytochrome-c release into the cytosol and reduced expression of activated caspase-3 and cleavage of PARP-1. Cresyl violet staining showed numerous dead cells in the cortex hippocampus and thalamus; post-treatment with nicotinamide reduced the number of dead cells in these brain regions. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) and immunohistochemical analysis of caspase-3 show that thiotepa-induced cell death is apoptotic and that it is inhibited by nicotinamide treatment. CONCLUSION: Nicotinamide (Nic) treatment with thiotepa significantly improved neuronal survival and alleviated neuronal cell death in the developing rat. These data demonstrate that nicotinamide shows promise as a therapeutic and neuroprotective agent for the treatment of neurodegenerative disorders in newborns and infants

Healthy ageing and depletion of intracellular glutathione influences T cell membrane thioredoxin-1 levels and cytokine secretion

Background: During ageing an altered redox balance has been observed in both intracellular and extracellular compartments, primarily due to glutathione depletion and metabolic stress. Maintaining redox homeostasis is important for controlling proliferation and apoptosis in response to specific stimuli for a variety of cells. For T cells, the ability to generate specific response to antigen is dependent on the oxidation state of cell surface and cytoplasmic protein-thiols. Intracellular thiols are maintained in their reduced state by a network of redox regulating peptides, proteins and enzymes such as glutathione, thioredoxins and thioredoxin reductase. Here we have investigated whether any relationship exists between age and secreted or cell surface thioredoxin-1, intracellular glutathione concentration and T cell surface thioredoxin 1 (Trx-1) and how this is related to interleukin (IL)-2 production.Results: Healthy older adults have reduced lymphocyte surface expression and lower circulating plasma Trx-1 concentrations. Using buthionine sulfoximine to deplete intracellular glutathione in Jurkat T cells we show that cell surface Trx-1 is lowered, secretion of Trx-1 is decreased and the response to the lectin phytohaemagglutinin measured as IL-2 production is also affected. These effects are recapitulated by another glutathione depleting agent, diethylmaleate.Conclusion: Together these data suggest that a relationship exists between the intracellular redox compartment and Trx-1 proteins. Loss of lymphocyte surface Trx-1 may be a useful biomarker of healthy ageing. © 2013 Carilho Torrao et al.; licensee Chemistry Central Ltd