Pharmacology
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The physiological effects of a novel MRI contrast agent, Gd(ABE-DTTA), were investigated in dogs, monitoring parameters in blood samples. Each animal (n = 8 in the short-term, n = 4 in the long-term group) underwent isoflurane anesthesia followed by the generation of myocardial infarction and received a contrast agent at the MRI effective dose. Blood samples were collected 24 and 48 h, and 7, 14, 28, 35, 49 and 56 days after contrast agent administration. ⋯ ALT enzyme activity increased in the short-term group 24 and 48 h after agent administration as expected from the effect of isoflurane anesthesia. Between days 7 and 56 no elevation in ALT was observed. In dogs no substantial short- or long-term effect was observed on the investigated, physiological parameters after Gd(ABE-DTTA) administration at the MRI effective dose.
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Paracetamol is often used as an analgesic following hepatic resection. During liver resection, vascular clamping is carried out to reduce blood loss. Previous studies have described transient postoperative rises in serum aminotransferase levels and decreases in prothrombin time and factor V levels. We have examined paracetamol metabolism after liver resection. ⋯ This study showed a reduction of paracetamol metabolism in the liver resection group with significantly increased paracetamol levels. However, the maximum mean plasma concentration reached was not clinically or toxicologically significant. For these reasons, we cannot suggest that paracetamol should or should not be avoided in patients undergoing liver resection.
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The contributions of adenosine receptor subtypes to antinociception produced by adenosine were determined at the spinal level. There are 4 types of adenosine receptors, namely A1, A(2A), A(2B) and A3. The authors investigated the properties of the subtypes of spinal adenosine receptors in terms of nociceptive modulation. ⋯ Intrathecal adenosine inhibited phase 2 flinching response without affecting phase 1 response. CPT, CSC, alloxazine and MRS 1220 antagonized the antinociceptive action of adenosine during phase 2 of the formalin test. These results suggest that spinal adenosine A1, A(2A), A(2B) and A3 receptors may play an important role in the antinociception of adenosine in the formalin-induced facilitated state.
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We examined the properties of the drug interaction between morphine and 5-HT(3) receptor antagonist at the spinal level. The nociceptive state was induced by subcutaneously injecting formalin solution (5%, 50 microl) into the hindpaw of the rats. Intrathecal morphine and m-CPBG (5-HT(3) receptor agonist) dose-dependently decreased the flinching response during phase 1 and phase 2 in the formalin test. ⋯ Intrathecal naloxone had little effect on attenuation of the antinociception of intrathecal m-CPBG. Taken together, no reciprocal interaction was noted between 5-HT(3) receptor and opioid receptors at the spinal level. Thus, the 5-HT(3) receptor antagonist may be useful to manage opioid-induced emesis at the spinal level.
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Comparative Study
Synergic antinociceptive interaction between tramadol and gabapentin after local, spinal and systemic administration.
The possible interaction between tramadol and gabapentin on formalin-induced nociception in the rat was assessed. Tramadol, gabapentin or a fixed-dose ratio combination of gabapentin and tramadol were administered peripherally, spinally and orally to rats, and the antinociceptive effect was determined in the 1% formalin test. Isobolographic analyses were used to define the nature of the interactions between drugs. ⋯ Although efficacy was not improved, local peripheral administration resulted in the highest increase in potency, being about tenfold. Spinal and systemic administration increased potency threefold. Data indicate that low doses of the tramadol-gabapentin combination can interact synergistically to reverse formalin-induced nociception and may represent a therapeutic advantage for clinical treatment of inflammatory pain.