Nalfurafine prevents 5′-guanidinonaltrindole- and compound 48/80-induced spinal c-fos expression and attenuates 5′-guanidinonaltrindole-elicited scratching behavior in mice

The aims of the present study were to establish if nalfurafine, a kappa opioid agonist, inhibits compulsive scratching in mice elicited by the s.c. administration (behind the neck) of 5′-guanidinonaltrindole (GNTI), a kappa opioid antagonist; to assess if nalfurafine prevents c-fos expression provoked by GNTI or compound 48/80, two chemically diverse pruritogens; and to distinguish on the basis of neuroanatomy, those neurons in the brainstem activated by either GNTI-induced itch or formalin-induced pain (both compounds given s.c. to the right cheek). Pretreatment of mice with nalfurafine (0.001–0.03 mg/kg s.c.) attenuated GNTI (0.3 mg/kg)-evoked scratching dose-dependently. A standard antiscratch dose of nalfurafine (0.02 mg/kg) had no marked effect on the spontaneous locomotion of mice. Tolerance did not develop to the antiscratch activity of nalfurafine. Both GNTI and compound 48/80 provoked c-fos expression on the lateral side of the superficial layer of the dorsal horn of the cervical spinal cord and pretreating mice with nalfurafine inhibited c-fos expression induced by both pruritogens. In contrast to formalin, GNTI did not induce c-fos expression in the trigeminal nucleus suggesting that pain and itch sensations are projected differently along the sensory trigeminal pathway. Our data indicate that the kappa opioid system is involved, at least in part, in the pathogenesis of itch; and that nalfurafine attenuates excessive scratching and prevents scratch-induced neuronal activity at the spinal level. On the basis of our results, nalfurafine holds promise as a potentially useful antipruritic in human conditions involving itch.     

Endoscopy-assisted Periacetabular Osteotomy

Periacetabular osteotomy has been recommended for reconstructing symptomatic dysplastic hips in adolescents and young adults, but requires substantial incisions and exposure. To minimize large incisions, we asked whether periacetabular osteotomy could be performed with a mini-incision under direct endoscopic control. We used five fresh-frozen cadaver pelves and developed curved guides and osteotomes for the osteotomy. We were able to perform a periacetabular osteotomy under endoscopic and image intensifier control and to fix the osteotomy with two cannulated screws. We identified no damage to vital structures or intraarticular fracture in any of the five cadavers we subsequently dissected. We believe periacetabular osteotomy may be performed with a mini-incision under direct endoscopic control. Our preliminary observations suggest the approach might be explored in limited prospective clinical trials by experienced individuals. Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.     

Does passive smoke exposure trigger acute asthma attack in children?

The relationship between asthma and passive smoking has been well established. However, it is still not clear whether an acute asthma attack can be induced by acute smoke exposure. The specific aims of this study were: 1- To assess the degree of smoke exposure through urinary cotinine levels in asthmatic children during and 4 weeks after asthma attacks and, 2- To evaluate the reliability of parental questionnaires in asthmatic children by comparing the data obtained from cotinine measurements and parental reports. Thirty-two consecutive asthmatic children who were admitted to the emergency clinic were included in the study. Parents were asked to complete a questionnaire about their smoking habits and housing conditions. Urinary cotinine and creatinine levels were measured in children during and 4 weeks after the acute asthma attack. The mean age of the patients was 5.7 +/- 3.2 years. The mean attack rate was 3.5 +/- 3.8 per year. Thirty-eight percent of the patients were taking no preventive treatment. In 80 % of patients, urinary cotinine and creatinine ratios (CCR) were significantly above the non-exposed, non-smoker levels. However, CCR levels during acute asthma attacks were not higher than those measured 4 weeks after the acute attack (314.6 +/- 299.1 vs. 203.8 +/- 165.2 ng/mg respectively, p > 0.05). Although parental reports of passive smoke exposure was 71 %, CCR levels revealed that 81 % and 97 % of children were exposed to passive smoke during acute attacks and asymptomatic periods, respectively. In conclusion, although the proportion of children with acute asthma attacks who were exposed to passive smoking was high, the degree of passive smoke exposure was not higher during acute attacks. Parental questionnaires were found to be unreliable in reporting passive smoke exposure in asthmatic children during acute attacks.