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It is well known that the response to painful stimuli varies between individuals and this could be consequence of individual differences to pain sensitivity that may be related to genetic factors. Catechol-O-methyltransferase (COMT) is one of the enzymes that metabolize catecholamine neurotransmitters. Differences in the activity of COMT influence the functions of these neurotransmitters. A single nucleotide polymorphism (Val158Met) of COMT leads to a three to four fold reduction in the activity of the enzyme and has been associated to modifications in the response to a pain stressor. Neuropathic pain is a progressive nervous system disease due to an alteration of the peripheral or central nervous system. To elucidate the possible role of COMT polymorphism in the susceptibility to neuropathic pain, we have performed a case-control study in a Spanish population. Analysis of the (Val158Met) COMT polymorphism was performed by PCR amplification and DNA digestion with restriction enzymes. Our study concludes that functional Val158Met polymorphism of COMT gene is not associated to increased susceptibility to neuropathic pain.

Compared with sevoflurane, propofol administration during suprarenal aortic clamping and unclamping led to modulation of markers of inflammation and decreased NFkappaB expression.

Purpose: A laboratory investigation was undertaken to assess the effects of propofol on renal function, through modulation of the systemic inflammatory response, in an in vivo experimental model of aortic surgery in comparison with sevoflurane.Methods: Twenty young male piglets were anesthetized with either propofol 4 mg·kg -1 ·hr -1 (n = 10) or sevoflurane 1.5% end-tidal concentration (n = 10). Animals were subjected to aorta-aortic bypass with suprarenal aortic clamping for 30 min. At specific intervals (basal -before the start of surgery; reperfusion 15 min after unclamping the aorta; at 24, 48 and 72 hr after surgery, and on the seventh day after surgery) the levels of the following were determined: plasma creatinine, renal myeloperoxidase, tumour necrosis factor-α, interleukin 1-ß, and interferon-γ; kidney superoxide anion and its detoxifying enzyme superoxidase dismutase, kidney malondialdehyde and the activity of inducible nitric oxide synthase. Seven days after surgery, the animals were anesthetized using the described techniques, and after blood withdrawal and kidney sampling they were sacrificed. Results:In comparison with sevoflurane, propofol was associated with a lower concentration of plasma creatinine (P < 0.05) together with lower concentrations of myeloperoxidase, tumour necrosis factor-α, interleukin 1-ß, interferon-γ, superoxide anion and superoxidase dismutase, malondialdehyde and inducible nitric oxide synthase (P < 0.05). Conclusion:In an experimental model of aortic reconstructive surgery, and compared with sevoflurane, propofol anesthesia is associated with less neutrophil infiltration, lower plasma proinflammatory cytokine levels, lower production of oxygen free radicals, less lipid peroxidation, and reduced inducible nitric oxide synthase activity. These observations suggest a possible renal protective effect of propofol in this surgical setting. Objectif

We have studied the pharmacokinetics and distribution of ketamine and its biotransformation products in dogs after extradural administration of ketamine at L4-5. The mean apparent uptake rate constants of ketamine for plasma and CSF were 4.17 (SD 1.84) and 5.15 (2.50) h-1, respectively. The concentrations of ketamine in CSF were greater than those found in plasma. The elimination half-life values of the parent drug for both biological fluids were similar (4.3 (2.96) h and 4.6 (3.31) h for plasma and CSF, respectively). The apparent formation rate constant of norketamine was greater than that of dehydronorketamine. However, the concentrations of the biotransformation products in CSF were smaller than those of the parent drug. These results are similar to the distribution of ketamine and its metabolites in different cerebral structures and tissues. The concentrations decreased in concert with the increase in polarity of the metabolites. A specific distribution for all compounds was observed. Ketamine showed a greater affinity for brainstem, while norketamine and dehydronorketamine were distributed mostly in cerebellum and kidney, respectively.

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