Whole‐cell patch‐clamp recordings were made from visually identified hippocampal interneurones in slices of rat brain tissue in vitro. Bath application of the bombesin‐like neuropeptides gastrin‐releasing peptide (GRP) or neuromedin B (NMB) produced a large membrane depolarization that was blocked by pre‐incubation with the subtype 2 bombesin (BB2) receptor antagonist [D‐Phe6,Des‐Met14]bombesin‐(6‐14)ethyl amide.
The inward current elicited by NMB or GRP was unaffected by K+ channel blockade with external Ba2+ or by replacement of potassium gluconate in the electrode solution with caesium acetate.
Replacement of external NaCl with Tris‐HCl significantly reduced the magnitude of the GRP‐induced current at ‐60 mV. In contrast, replacement of external NaCl with LiCl had no effect on the magnitude of this current.
Photorelease of caged GTPγS inside neurones irreversibly potentiated the GRP‐induced current at ‐60 mV. Similarly, bath application of the phospholipase C (PLC) inhibitor U‐73122 significantly reduced the size of the inward current induced by GRP.
Reverse transcription followed by the polymerase chain reaction using cytoplasm from single hippocampal interneurones demonstrated the expression of BB2 receptor mRNA together with glutamate decarboxylase (GAD67).
Although bath application of GRP or NMB had little or no effect on the resting membrane properties of CA1 pyramidal cells per se, these neuropeptides produced a dramatic increase in the number and amplitude of miniature inhibitory postsynaptic currents in these cells in a TTX‐sensitive manner.
Chronic pain resulting from metastatic bone cancer remains poorly understood and resistant to treatment. Here we have examined the effect of the novel COX-2 enzyme inhibitor lumiracoxib in a model of bone cancer pain in the rat. Lumiracoxib was administered orally twice daily from day 10 to day 20 after injection of MRMT-1 tumour cells into one tibia. Mechanical hyperalgesia, measured as the reduction in weight-bearing of the ipsilateral limb, and the development of static and dynamic allodynia were significantly inhibited by repeated lumaricoxib administration. A similar reduction in hyperalgesia and allodynia was noted after twice daily administration of another COX-2 inhibitor, valdecoxib, whilst a single acute administration of either drug on day 20, produced no anti-nociceptive activity. Bone mineral density measurements, radiological scores and histological analysis showed that chronic lumaricoxib treatment also significantly attenuated bone destruction induced by tumour cell injection. These data indicate that lumiracoxib and other COX-2 inhibitors have potential therapeutic benefit in the treatment of bone cancer pain.
The cause of the ICL in this patient is unknown. HPV is not known to be an immunosuppressive agent; it remains to be determined whether the HPV-associated lesions are the cause or the result of immunosuppression.
The prevalence of sensitization to formaldehyde releasers (FRs) differs according to geographic area and has changed over time. Several factors may influence prevalence, including different patch test systems or concentrations or the allergen selection in different baseline patch test series, habits of the populations, and regulations and legal concentration limits in cosmetics. 1,2 Quaterium-15 had been SANZ-SÁNCHEZ ET AL. 173
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