Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jan 2013
Effects of betamethasone on neuropathic pain in a rat spare nerve injury model.
The aim of the present study was to examine the effect of glucocorticoids on neuropathic pain using a rat spare nerve injury (SNI) model. Eighty rats were treated divided into the following groups: (i) a sham-operated group; (ii) a group subjected to SNI (S); (iii) a group subjected to SNI and administered 4 μg betamethasone intrathecally (D1); and (iv) a group subjected to SNI and administered 1 mg betamethasone at the site of nerve injury (D2). The mechanical withdrawal threshold (MWT) and thermal withdrawal duration (TWD) were measured 1 day before and the 1, 3, 7 and 14 days after SNI. ⋯ Levels of TNF-α and IL-1β were significantly lower in the D1 and D2 groups compared with the S group at all time points after surgery (P < 0.05). Betamethasone suppressed astrocyte activation and increases in TNF-α and IL-1β levels in a rat model of neuropathic pain. Local injection of betamethasone resulted in smaller increases in spinal GR expression and more pronounced improvement in pain behaviour compared with intrathecal injection.
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Clin. Exp. Pharmacol. Physiol. · Oct 2012
Effects of fatty acids on cardioprotection by pre-ischaemic inhibition of the malate-aspartate shuttle.
1. The malate-aspartate shuttle (MAS) is the main pathway for balancing extra- and intramitochondrial glucose metabolism. Pre-ischaemic shutdown of the MAS by aminooxyacetate (AOA) mimics ischaemic preconditioning (IPC) in rat glucose-perfused hearts. ⋯ Postischaemic glucose oxidation was suppressed by FA and did not differ significantly between the different groups. 4. In conclusion, the reduction in IS induced by pre-ischaemic MAS shutdown is not compromised by physiological FA concentrations. Transient MAS shutdown may be involved in IPC, but is not sufficient on its own as the underlying mechanism for IPC.
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Clin. Exp. Pharmacol. Physiol. · Oct 2012
Adenosine A(2A) receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2 Hz train-of-four or 50 Hz tetanic stimuli.
1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. ⋯ ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade.
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Clin. Exp. Pharmacol. Physiol. · Aug 2012
ReviewNewcastle disease virus: a promising agent for tumour immunotherapy.
Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus (NDV) represents an attractive new tool for tumour immunotherapy. ⋯ Apoptosis following NDV infection may contribute to the observed oncolytic effects; however, NDV could also stimulate both innate and adaptive antitumour immune responses. For many years, different approaches have been investigated (or are in the process of being developed) regarding the use of NDV for the treatment of malignancies. Recent advances using reverse genetics have provided a means of generating recombinant NDV strains with improved oncolytic and immune regulatory properties.
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Clin. Exp. Pharmacol. Physiol. · Aug 2012
FT23, an orally active antifibrotic compound, attenuates structural and functional abnormalities in an experimental model of diabetic cardiomyopathy.
Diabetic cardiomyopathy is characterized by early diastolic dysfunction and structural changes, such as interstitial fibrosis and cardiac hypertrophy. Using the Ren-2 rat model, we sought to investigate the effect of FT23 on the structural and functional changes associated with diabetic cardiomyopathy. Heterozygous Ren-2 rats were rendered diabetic with streptozotocin by tail vein injection. ⋯ Diastolic dysfunction, as measured by mitral valve (MV) E/A ratio and MV deceleration time, was also significantly attenuated by FT23. Picrosirius red-stained heart sections revealed that cardiac fibrosis in the diabetic rats was reduced by FT23 compared with that in vehicle-treated rats, with a concomitant reduction in collagen I immunostaining and infiltration of macrophages, as demonstrated by ED1 immunostaining. The results of the present study suggest that FT23 inhibits the activity of TGF-β and attenuates structural and functional manifestations of diastolic dysfunction observed in a model of diabetic cardiomyopathy.