From October 23 to October 27, 1989, an outbreak of gastroenteritis occurred aboard a cruise ship in the Caribbean. The 818 passengers and 518 crew members were surveyed for gastrointestinal symptoms; 72 (14%) of 512 passengers and 12 (3%) of 388 crew members who answered the survey reported having a diarrheal illness. Multiple-antibiotic-resistant Shigella flexneri 4a was isolated from 19 ill passengers and two ill crew members. Thirteen people were hospitalized, and prolonged duration of illness was associated with taking an antibiotic to which the isolated strain of Shigella was resistant. A case-control study of food items implicated German potato salad as the vehicle of transmission. It was prepared and probably infected by a food handler from a country where multiple-antibiotic-resistant Shigella is common. Spread may have been facilitated by the limited availability of toilet facilities for the galley crew. This outbreak demonstrates how antibiotic-resistant strains can be introduced into the United States, where they can pose treatment problems. The continuing problem of foodborne gastrointestinal disease in settings such as cruise ships underscores the need for basic hygienic control for food handlers and food preparation areas. In addition, the availability of adequate working conditions for crew members, including appropriately furnished toilet facilities, may be important issues that must be addressed in order to decrease the frequency of diarrhea outbreaks aboard cruise ships.

No abstract

Agomelatine (S-20098), an analog of melatonin, has shown promise as a chronobiotic in animal models of sleep phase disorders and is being developed for clinical use. Previous research has shown that the pharmacological profile of melatonin-like drugs overlaps that of gamma-amino butyric acid (GABA) agonists. Given the potential of drugs within the latter class for recreational abuse in humans, evaluation of this potential for melatonin analogs that target similar therapeutic indications is important. In the present study, agomelatine was tested in animal models of the subjective and reinforcing effects of CNS depressant drugs; i.e., diazepam discrimination in rats and IV methohexital self-administration in rhesus monkeys, respectively. Neither agomelatine nor melatonin substituted for diazepam in rats trained to discriminate 2.5 mg/kg diazepam from vehicle. Further, agomelatine was not self-administered by rhesus monkeys. These results suggest that agomelatine would not produce diazepam-like intoxication in humans, nor would it likely be subject to abuse.

No abstract

Zonisamide (Zonegran ® ) is a broad-spectrum antiepileptic agent that shares some pharmacological properties with other anticonvulsants, including phenytoin, carbamazepine, and valproic acid, but is differentiated from these agents by the ability to significantly block T-type calcium channels. Zonisamide interacts with the γ-amino-butyric acid (GABA) receptor in an allosteric manner, and thus does not modulate GABA receptor effects. However, given the potential of drugs within the latter class for drug abuse in humans, an evaluation of zonisamide for abuse potential is an important component of its potential sideeffect profile. In the present study, zonisamide was tested in animal models of the subjective and reinforcing effects of central nervous system (CNS) depressant drugs, e.g., diazepam discrimination in rats and intravenous self-administration in rhesus monkeys, respectively. In addition, zonisamide was evaluated for physical dependence liability in a chronic infusion model using rats. Zonisamide did not substitute for diazepam in rats trained to discriminate 2.5-mg/kg diazepam from vehicle nor was it self-administered by rhesus monkeys experienced in methohexital-reinforced responding. Continuous infusion of zonisamide (400 or 600 mg/kg/day) did not prevent the loss of body weight associated with discontinued pentobarbital infusion. These doses of zonisamide did produce some incomplete attenuation of observable signs of pentobarbital withdrawal, likely due to direct sedative or depressant effects of these high doses. These results suggest that zonisamide would not produce diazepam-like intoxication in humans nor would it likely be subject to abuse when made more widely available. Further, when administered chronically, zonisamide would not be expected to produce physical dependence of the CNS depressant type. Taken together, these results support the prediction that zonisamide would have low abuse liability. Drug Dev. Res. 54:66-74, 2001.