Dysbaric osteonecrosis among professional divers: a literature review.

AIM: Dysbaric osteonecrosis (DON) continues to be a significant occupational hazard that has significant medical and social consequences for professional divers. This review aims to evaluate the prevalence and risk factors of DON among professional divers and to summarize the scientific knowledge regarding distribution of the lesions as well as disease prognosis and treatment. METHOD: A literature review using the Medline database. RESULTS: The prevalence of DON varies between 0 and 70.6% in professional divers, and its prevalence is highest in Turkey, Hawaii, Korea and Japan but is dependent on activity and medical monitoring. The risk of DON is very low for military divers who strictly obey the decompression rules and who undergo periodic medical examination. DON pre- dominately occurs in the proximal part of the femur and humerus. In a majority of cases, DON will progress despite the absence of further dysbaric exposure. CONCLUSION: The pathophysiology of the disease is incompletely understood and other etiological factors are perhaps being overlooked.

Preclinical evaluation of the abuse potential of Pitolisant, a histamine H3 receptor inverse agonist/antagonist compared with Modafinil.

BACKGROUND AND PURPOSE: Pitolisant, a histamine H3 receptor inverse agonist/antagonist is currently under Phase III clinical trials for treatment of excessive daytime sleepiness namely in narcoleptic patients. Its drug abuse potential was investigated using in vivo models in rodents and monkeys and compared with those of Modafinil, a psychostimulant currently used in the same indications. EXPERIMENTAL APPROACH: Effects of Pitolisant on dopamine release in the nucleus accumbens, on spontaneous and cocaine-induced locomotion, locomotor sensitization were monitored. It was also tested in three standard drug abuse tests i.e. conditioned place preference in rats, self-administration in monkeys and cocaine discrimination in mice as well as in a physical dependence model. KEY RESULTS: Pitolisant did not elicit any significant changes in dopaminergic indices in rat nucleus accumbens whereas Modafinil increased dopamine release. In rodents, Pitolisant was without any effect on locomotion and reduced the cocaine-induced hyperlocomotion. In addition, no locomotor sensitization and no conditioned hyperlocomotion were evidenced with this compound in rats whereas significant effects were elicited by Modafinil. Finally, Pitolisant was devoid of any significant effects in the three standard drug abuse tests (including self-administration in monkeys) and in the physical dependence model. CONCLUSIONS AND IMPLICATIONS: No potential drug abuse liability for Pitolisant was evidenced in various in vivo rodent and primate models, whereas the same does not seem so clear in the case of Modafinil.