Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis.

To provide a further test of the dual binding site hypothesis proposed for acetylcholinesterase (AChE) inhibitor heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) A7A, short-tether (ethylene hexylene) homologs A2A-A6A were prepared. En route to these compounds, convenient and scaleable syntheses of useful pharmaceutical intermediate 9-chloro-1.2,3,4-tetrahydroacridine 3 and A7A were developed. AChE and butyrylcholinesterase (BChE) inhibition assays of A2A-A10A confirm that a seven methylene tether (A7A) optimizes AChE inhibition potency and AChE/BChE selectivity. Finally, these studies indicate that simultaneous binding of alkylene-linked 9-amino-1,2,3,4-tetrahydroacridine dimers to the catalytic and peripheral sites of AChE is possible with a tether length as short as 5 methylenes.

Rising HIV infection rates in Ho Chi Minh City herald emerging AIDS epidemic in Vietnam.

OBJECTIVE: To describe the epidemiology of HIV in Ho Chi Minh City in the context of current surveillance data from Vietnam. METHODS: Since the late 1980s, HIV surveillance data have been collected in Ho Chi Minh City from centers for the treatment of venereal disease and tuberculosis, centers for the rehabilitation of injecting drug users and sex workers, prenatal clinics, blood banks and other sites. RESULTS: The first case of HIV infection in Vietnam was identified in 1990 in Ho Chi Minh City. The cumulative number of reported HIV infections in this city at the end of 1996 was 2774, about half of the number of cases in the country; 86% of infections were among men, 86% among injecting drug users, 2.5% among patients with sexually transmitted diseases and 2.5% among sex workers. The first HIV infection among antenatal women was detected in 1994. The prevalence of HIV among injecting drug users rose dramatically from 1% in 1992 to 39% in 1996, compared with 1.2% among sex workers, 0.3% among blood donors and 1.3% among tuberculosis patients in 1996. The populations of injecting drug users and sex workers in Ho Chi Minh City are estimated to be 30000 and 80000, respectively, and rates of sexually transmitted diseases are 2-3 per 1000 persons per year. By the end of December 1996, 42 out of 53 provinces had reported HIV infections, and border areas near China and Cambodia began identifying large numbers of HIV-seropositive people. CONCLUSIONS: Ho Chi Minh City is at the forefront of a new HIV epidemic in Vietnam. This epidemic shows similarities to that in Thailand nearly a decade ago, with rapidly rising HIV rates among injecting drug users and infection already established among sex workers. Prevention efforts should include the targeting of injecting drug users and sex workers outside rehabilitation centers, the availability of sterile needles and condoms, the establishment of anonymous testing sites, the control of sexually transmitted diseases and the coordination of programs within southeast Asia.

PIP: An analysis of annual sentinel surveillance data from Viet Nam indicates that Ho Chi Minh City is at the forefront of a new HIV epidemic. Since 1990, data on HIV cases have been collected from prenatal clinics, blood banks, centers for the treatment of sexually transmitted diseases (STDs) and tuberculosis, and rehabilitation centers for injecting drug users and commercial sex workers. The first HIV case in Viet Nam was reported in 1990 in Ho Chi Minh City. By the end of 1996, a cumulative total of 4961 HIV cases had been documented in Viet Nam, 2774 of which were in Ho Chi Minh City. In Ho Chi Minh City, 86.5% of cumulative HIV infections involved men. The distribution of total HIV cases by group has been: injecting drug users, 86.0%; tuberculosis patients, 3.3%; sex workers, 2.5%; STD patients, 2.5%; and pregnant women, 0.6%. By 1996, 42 of Viet Nam's 53 provinces had reported HIV cases and infection rates are rising dramatically in border areas near China and Cambodia. The pattern documented in this analysis resembles that observed in Thailand a decade ago: rapidly rising HIV rates among injecting drug users and infection already established among sex workers, without dissemination to the general population. The necessary infrastructure and resources for control of the epidemic are far more limited in Viet Nam than Thailand, however. Recommended, to prevent the further spread of HIV in Viet Nam, are educational activities targeted at injecting drug users and sex workers outside of rehabilitation centers, the availability of condoms and sterile needles, establishment of anonymous testing sites, control of STDs, and the coordination of programs within southeast Asia.