A sulphite-oxidase-deficient rat model: metabolic characterization.
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Biomedical subjects
Publications and source records attributed to G Chiang.
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Generator-produced Rb-82, a 75-sec positron emitter with potential for myocardial blood-flow imaging, was studied with various ion-exchange columns to evaluate the characteristics of alumina as an adsorber for the 25-day Sr-82 parent. Test columns of alumina, Bio Rex 70, and Chelex 100 were loaded with multimillicurie amounts of no-carrier-added Sr-82/Sr-85 (Sr-85 is a production contaminant). The breakthrough of Sr-82/Sr-85, and the yield of Rb-82, were determined for long-term elutions from each column with up to 4 liter of 2% NaCl solution at pH 8 to 9. The breakthrough of Sr-82/85 was 10(-6)-10(-5) from aluminal 10(-6)-10(-4) from Chelex 100 and Bio Rex 70. The effects of eluent flow rate and concentration, and of alumina volume, on the breakthrough and yield were also studied. An improved and automated Rb-82 generator was used for myocardial and brain blood-flow studies in experimental animals and in man; it was equipped with solenoid flow-control valves and five in. of lead shielding for the alumina columns, which were charged with 25-50 mCi Sr-82 (100-150 mCi Sr-85). The Rb-82 generator with alumina column provided up to 20-40 mCi of Rb-82 as often as every 5-10 min with less than 10(-5) breakthrough of Sr-82/85 over the 2- to 3-mo, useful life of the generator.
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We have previously described the inhibition of human immunodeficiency virus serotype 1 (HIV-1) using the antimalarial hydroxychloroquine (HCQ), a weak base that inhibits the posttranslational modification of glycoprotein 120 (gp 120) in T cells and monocytes. The mechanism of inhibition of gp 120 production was presumed to be the ability of HCQ to increase endosomal pH and therefore alter enzymes required for gp120 production. To further clarify this action, we have determined the effect of HCQ and its enantiomers on endosomal pH. Pretreatment of cells with HCQ and the levo- and dextro-enantiomers at concentrations demonstrated to suppress anti-HIV-1 activity increased endosomal pH to levels similar to increases seen with chloroquine and ammonium chloride, two other weak bases, and decreased gp 120 production. The dextro- and levo-enantiomers suppressed HIV-1 replication to a similar extent and were no more toxic than racemic HCQ. We next compared the anti-HIV-1 effect of HCQ with zidovudine (ZDV) in both newly and chronically HIV-1-infected T-cell and monocytic cell lines (63 and 63HIV). HCQ suppressed HIV-1 replication in a dose-dependent manner in both recently and chronically infected T-cell and monocytic cell lines. In contrast, ZDV pretreatment had potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. An additive effect of HCQ with ZDV was observed in the newly infected T and monocytic cells but not in the chronically infected cells. Although the anti-HIV-1 effect of HCQ was less than that of ZDV, HCQ may still be potentially useful either as an alternative HIV-1 treatment or in combination with other anti-HIV-1 agents, especially in patients who have rheumatic manifestations of HIV-1 infection.
Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in T cells and monocytes in vitro by inhibiting posttranscriptional modification of the virus. An initial randomized, placebo-controlled clinical trial conducted in 38 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3 demonstrated that the amount of recoverable virus declined significantly in the HCQ group compared with the placebo group over the 8-week study period. These preliminary observations were expanded into a second 16-week clinical trial comparing the efficacy of HCQ with that of zidovudine (ZDV) in 72 asymptomatic HIV-1-infected patients with CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d (n = 35) or ZDV 500 mg/d (n = 37) for 16 weeks. No adverse reactions to the study medications were observed in either the HCQ or ZDV group. Patients in both groups had reduced levels of recoverable HIV-1 RNA in the plasma, reduced levels of cultured virus, and reduced levels of serum p24 antigen after the 16-week study period. However, no difference was noted in absolute CD4+ counts between the two groups. Interleukin-6 and serum immunoglobulin G levels were significantly reduced in the HCQ group but not in the ZDV group. These findings support the results of the previous clinical trial. Thus HCQ may be potentially useful in the treatment of patients with HIV-1 infection.