European journal of pharmacology
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Reperfusion damage involves opening of the mitochondrial permeability transition pore (mPTP) and loss of ATP synthesis. Several cardioprotective pathways are activated by ischemic or pharmacological post-conditioning (PC). The mechanisms that are activated by PC in no co-morbidity murine models include: activation of rescue kinases, oxidative stress reduction, glycolytic flux regulation and preservation of ATP synthesis. ⋯ The cardioprotective effect of PC was abolished with both L-NAME (inhibitor of constitutive NO synthase) and ODQ (inhibitor of soluble guanylate cyclase), whereas the NO donor (DETA-NO) restored cardioprotection even in the presence of L-NAME or ODQ. We also found that mitochondrial structure and function was preserved in PC hearts. We conclude that PC exerts cardioprotection in hearts with previous infarct by maintaining mitochondrial structure and function through NO-dependent pathway.
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General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. ⋯ Propofol synergistically interacted (overall ≈40%) in preventing the remifentanil-induced BHR. Remifentanil induces BHR via stimulating capsaicin-sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor. The propofol/remifentanil combination may be safely administered in course of TCI-TIVA procedures also in heaves affected horses.
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The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. ⋯ Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone.
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We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or menhaden oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. ⋯ Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and menhaden oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
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Antidepressant drugs of the SSRI family are used as a third-line treatment for neuropathic pain. In contrast MAOi antidepressants, that also increase extracellular serotonin bioavailability have little or no effects on this condition. In addition to their action of the serotonin transporter, some SSRI have been shown to inhibit voltage gated sodium channels. ⋯ Paroxetine and fluoxetine also had a prominent effect on the frequency-dependent inhibition, with a greater effect on Nav1.7. In contrast to SSRIs, MAOi did not affect Na(+) channels currents. These results suggest that, in certain conditions, the analgesic effect of SSRIs may in part be due to their interactions with Na(+) channels.