Effects of 6-Chloro-2',3'-Dideoxyguanosine (6-Cl-ddG) in Surface Lymph Nodes of Rhesus Monkeys (Macaca mulatta) Chronically Infected with Simian Immunodeficiency Virus (SIVmac239).

Abstract

ABSTRACT. We studied the effects of 6-chloro-2', 3'-dideoxyguanosine (6-Cl-ddG), an antiretroviral drug, in surface lymph nodes of rhesus monkeys (Macaca mulatta) chronically infected with simian immunodeficiency virus (SIV). The rhesus monkeys were treated with 25 mg/kg of 6-Cl-ddG every 8 hr for 2 weeks. We performed sequential biopsies of the surface lymph nodes three times: before, during, and after the drug treatment. The 6-Cl-ddG dramatically decreased the number of infectious virus (measured by limiting dilution assay) in lymph node mononuclear cells. This decrease was consistent with the decrease in the number of viral RNA-positive cells in lymph nodes (analyzed by in situ hybridization). Histopathological analysis revealed that hyperplastic lymphoid follicles were reduced in size, especially, enlarged areas of centroblasts in lymphoid follicles (the so-called dark areas of germinal centers) were declined. Our results demonstrated that 6-Cl-ddG decreased the viral burden concomitantly with reduced hyper-activation of germinal centers in lymphoid follicles of SIV-infected rhesus monkeys. -KEY WORDS: antiretroviral drug, 6-chloro-2', 3'-dideoxyguanosine, histopathological change, lymph node, simian immunodeficiency virus.

Evidence of active microglia in substantia nigra pars compacta of parkinsonian monkeys 1 year after MPTP exposure

“…Series of sections regularly spaced at intervals of 1,440 m were stained for calbindin D-28K (1:1,000; Chemicon Temecula) in order to delimit the subregions of the nucleus; tyrosine hydroxylase (TH) polyclonal antibody (1:500; Incstar) in order to quantify the loss of dopaminergic neurons and fibers in the MPTP-intoxicated monkeys; glial fibrillary acidic protein (GFAP; monoclonal antibody; 1:500; Chemicon) to analyze the putative astrogliosis in the SNpc of the parkinsonian monkeys; and human leukocyte antigen-DR (HLA-DR, ␣-chain, CR3/43 clone; 1:50 monoclonal antibody; Dako) in order to observe the microglial activation (Graeber et al, 1994). The specificity of HLA-DR antibody has already been demonstrated and it has been extensively used to detect activated microglia in monkey brain (Beilke et al, 1991;Otani et al, 1997;Sloane et al, 1999;Schwartz et al, 2002).…”