Inhibition of the replication of native and 3'-azido-2',3'-dideoxythymidine (AZT)-resistant simian immunodeficiency virus (SIV) by 3-nitrosobenzamide.

The 3-nitrosobenzamide (NOBA) drug abolishes SIV replication sharply at 20 microM concentration when CEM x 174 cells are preincubated for 1 h with the drug prior to viral infection. Treatment of CEM x 174 cells with 20 microM NOBA resulted in the inhibition of the synthesis of the DNA sequence coding for the gag gene, as determined by the PCR technique. Cell viability was directly proportional to the antiviral action of NOBA. Replication of AZT-resistant SIV 23740 in MMU 23740 cells in vitro was suppressed by NOBA in a concentration-dependent manner without significant effects on cell viability. Reverse transcriptase activity of SIVmac239 was unaffected by NOBA up to 800 microM concentration. Preincubation of two SIV strains with NOBA completely abolished their infectivity in human PHA-PBL cells. Replication of two strains of SIV in PHA-PBL cells was also inhibited by NOBA.

Evaluation of narcotic and narcotic antagonist interactions in primates.

Multiple and single drug interactions were studied in morphine-dependent monkeys whose dependency was maintained by self-infusion. Naloxone, naltrexone, and cyclazocine precipitated abstinence syndrome which the animals generally controlled with increased morphine intake. Methadone and L-alpha-acetylmethadol (LAAM) initially reduced, then increased, the morphine intake. Multiple interactions were studied using ethanol, seconal, diazepam, amphetamine, and diphenylhydantoin.

Detection of simian immunodeficiency virus RNA from infected rhesus macaques by the polymerase chain reaction.

A rapid method for the detection of simian immunodeficiency virus (SIV) RNA from peripheral blood mononuclear cells (PBMC) of experimentally infected rhesus macaques by the polymerase chain reaction (PCR) is reported. The PCR was carried out with a complementary DNA (cDNA) template using 3 pairs of primers that were designed to anneal to homologous sequences in conserved regions of 3 molecular clones of SIVmac. The specificity of the primers was confirmed by performing the PCR with template DNA from the 3 molecular clones. SIV-specific RNA was detected from 30 and 50 infected PBMC/6.25 x 10(5) PBMC of two animals.

Opioid dependency and T-helper cell functions in rhesus monkey.

Administration of morphine sulfate to rhesus monkeys may activate the quiescent lymphocyte for proliferation, induce a transient increase in the T cell proliferative response to mitogens, and cause an enhanced interleukin-2 release from the mitogen-stimulated lymphocytes. However, longitudinal studies of the animals dependent upon morphine or L-a-acetyl-methadol, a long-acting opioid, revealed an overall immunosuppression of T helper functions. In vitro studies using morphine and its antagonist naloxone suggested that the immunosuppression was not a result of a direct interaction between the opioids and conventional opiate receptors which might have been present on the lymphocytes. The studies also showed the importance of measuring [3H]thymidine incorporation rather than its uptake into cells to assess T cell activation.

Evidence for neurotransmitter abnormalities related to seizure activity in the epileptic baboon.

The experimental evidence that indicates that alterations in neurotransmitter activity exacerbate or diminish seizure responses to intermittent light stimulation in the Papio papio model of epilepsy is reviewed. Studies of the effects of drugs known to modify the synthesis, storage release, or activity of known or putative neurotransmitters are included. Catecholamines, to a lesser extent the indolamine, serotonin, and the inhibitory transmitter gamma-aminobutyric acid all alter seizures as do less well understood intrinsic hormones and pentapeptides. The anticonvulsant profile of the model is briefly reviewed. It is concluded that there is as yet no concrete evidence of an intrinsic deficit in any of the neurotransmitters to which the genetic photosensitivity of this model can be attributed.