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Brain-uptake of azidothymidine in rats: Effect of insulin
smmune
BlOL PSYCHIATRI 1989;25:89A-93A
Kesponsi
IN RATS: 187 BRAIN-UPTAKE OF AZIDOTHYMIDINE EFFECT OF INSULIN Marion E. Wolf, Steven Ayre, Brian Skaletski, Aron D. Mosnalm North Chicago,
IL
Human immunodeficiency virus affects not only the immune function but is also neurotropic, emphasizing the need for antiviral agents able to cross the blood-brain barrier. Using the Oldendorf technique (6-8 week-old Sprague-Dawley male white rats, ipsilateral cerebral hemisphere) we have determined the brain-uptake index (BUI) for azidothymidine (AZT) as 5.4 + .08 (x t SD, N = 13, range 4.4-6.6; antipyrine used as diffusible standard). Administration of insulin (IV, 0.6 or 1.O units, but not 0.1, 0.2, or 0.3 units per rat, three or ten minutes before decapitation) resulted in a higher BUI for AZT in most individual animals, reaching statistically significant importance in at least one experimental group (1 .O unit, 10 minutes before BUI determination). While these are only preliminary results, and need independent confirmation, the possibility that insulin could alter the rate of brain penetration of AZT in humans presents an important therapeutic challenge.
188 HIV-RELATED NEUROLOGICAL FINDING IN DRUG USERS J. Weiner, L. Handelsman, A.J. Rowan, M. Aronson, T. Horvath Bronx, NY
A wide range of neurological deficits are attributed to HIV infection. Twenty-four drug users (7 HIV - ,9 asymptomatic HIV + ,8 AIDS) were examined by a neurologist (JW) using a standard mental status (MSE) and neurological exam and blinded to HIV serostatus. There were no differences between the HIV - and HIV + asymptomatic groups. However, the AIDS group compared to the other two groups combined demonstrated increased self-reported complaints about cognitive ability (Fisher’s exact test, p < .03 and increased presence of abnormalities on formal MSE (chi-square 16.6, p < .OOl). Self-reported complaints and MSE normalities were correlated (Spearman R = .77, p < .OOl). The sum of the domains of the neurological exam (excluding MSE) which were abnormal was greater in the AIDS group than the other two groups combined (Mann-Whitney test, Z-tailed, p < .02). These findings could not be attributed to intergroup differences in age, education, substance use, medical debility, prior neurological disease or behavioral disorder. Only one AIDS subject has advanced dementia. Therefore, the results support the usefulness and sensitivity of the standard MSE and neurological exam as a marker for the onset and progression of HIV dementia in drug users.
189 HIV INFECTION AND CORTICAL EVOKED POTENTIALS T.B. Horvath, A. Peterson, L. Handelsman, M. Aronson, S. Herman, J. Jacobson, J. Weiner, A.J. Rowan
(EPS)
Bronx, NY
Previous reports suggested a prolongation of Brainstem Auditory Evoked Response (BSAER) and Visual Evoked Potential (VEP) latencies both in AIDS dementia and in asymptomatic HIV infected individuals. We studied 24 substance abusing individuals
BlOL PSYCHIATRI 1989;25:89A-93A
Kesponsi
IN RATS: 187 BRAIN-UPTAKE OF AZIDOTHYMIDINE EFFECT OF INSULIN Marion E. Wolf, Steven Ayre, Brian Skaletski, Aron D. Mosnalm North Chicago,
IL
Human immunodeficiency virus affects not only the immune function but is also neurotropic, emphasizing the need for antiviral agents able to cross the blood-brain barrier. Using the Oldendorf technique (6-8 week-old Sprague-Dawley male white rats, ipsilateral cerebral hemisphere) we have determined the brain-uptake index (BUI) for azidothymidine (AZT) as 5.4 + .08 (x t SD, N = 13, range 4.4-6.6; antipyrine used as diffusible standard). Administration of insulin (IV, 0.6 or 1.O units, but not 0.1, 0.2, or 0.3 units per rat, three or ten minutes before decapitation) resulted in a higher BUI for AZT in most individual animals, reaching statistically significant importance in at least one experimental group (1 .O unit, 10 minutes before BUI determination). While these are only preliminary results, and need independent confirmation, the possibility that insulin could alter the rate of brain penetration of AZT in humans presents an important therapeutic challenge.
188 HIV-RELATED NEUROLOGICAL FINDING IN DRUG USERS J. Weiner, L. Handelsman, A.J. Rowan, M. Aronson, T. Horvath Bronx, NY
A wide range of neurological deficits are attributed to HIV infection. Twenty-four drug users (7 HIV - ,9 asymptomatic HIV + ,8 AIDS) were examined by a neurologist (JW) using a standard mental status (MSE) and neurological exam and blinded to HIV serostatus. There were no differences between the HIV - and HIV + asymptomatic groups. However, the AIDS group compared to the other two groups combined demonstrated increased self-reported complaints about cognitive ability (Fisher’s exact test, p < .03 and increased presence of abnormalities on formal MSE (chi-square 16.6, p < .OOl). Self-reported complaints and MSE normalities were correlated (Spearman R = .77, p < .OOl). The sum of the domains of the neurological exam (excluding MSE) which were abnormal was greater in the AIDS group than the other two groups combined (Mann-Whitney test, Z-tailed, p < .02). These findings could not be attributed to intergroup differences in age, education, substance use, medical debility, prior neurological disease or behavioral disorder. Only one AIDS subject has advanced dementia. Therefore, the results support the usefulness and sensitivity of the standard MSE and neurological exam as a marker for the onset and progression of HIV dementia in drug users.
189 HIV INFECTION AND CORTICAL EVOKED POTENTIALS T.B. Horvath, A. Peterson, L. Handelsman, M. Aronson, S. Herman, J. Jacobson, J. Weiner, A.J. Rowan
(EPS)
Bronx, NY
Previous reports suggested a prolongation of Brainstem Auditory Evoked Response (BSAER) and Visual Evoked Potential (VEP) latencies both in AIDS dementia and in asymptomatic HIV infected individuals. We studied 24 substance abusing individuals