A B S T R A C T The absorption of L-thyroxine (T4) and L-triiodothyronine (Ts) and the fractional rate of conversion of T4 to T3 were determined from the turnover rates of T4 and Ta in seven patients without endogenous thyroid function during separate treatment periods with these iodothyronines. Serum T3 concentration was measured by a radi-oimmunoassay procedure in which the iodothyronines are separated from the plasma proteins before incubation with anti-Ts antibody. Metabolic clearance rates were calculated by an integral (noncompartmental) approach since the use of single compartment kinetics led to a 40% overestimation of the metabolic clearance rate of T3. Based on the amount of hormone ingested and the observed hormonal turnover rates, the absorption of T4 and Ta (iodothyronine turnover/iodothyronine ingested) in man could be estimated. Absorption of T3 was complete in three subjects but decreased to 43% in a fourth who was suffering from mild congestive heart failure.Mean T4 absorption was 48.0±2.6% (SEM) for seven subjects. The mean fractional rate of T4 to Ta conversion determined during T4 replacement therapy (Ta turnover/ T4 turnover) was 42.6% (range 30.7-50.8%). Thus, approximately one-half of the T4 which was deiodinated was converted to T3 suggesting that monodeiodination is an obligatory step in the peripheral metabolism of T4. Calculations based on these results together with other available data suggest that under normal physiologic circumstances the major portion of the Ta pool is derived from monodeiodination of T4.

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IntroductionWithin the first weeks of human immunodeficiency virus (HIV) infection, virus replication reaches systemic circulation. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of disease progression, there is limited understanding of the conditions required to transform a small localized transmitted founder population into a large and heterogeneous systemic infection.MethodsCynomolgus and rhesus macaques were infected with simian immunodeficiency virus (SIV) and followed longitudinally. Plasma levels of SIV were monitored using qRT-PCR. Bacterial genomic DNA in plasma was characterized and quantified longitudinally using 16S ribosomal deep sequencing and qPCR. ELISA-based assays were used to monitor intestinal permeability (IFABP) and perturbation of bacteria-specific host factors (sCD14 and EndoCab). Flow cytometry was used to track peripheral blood lymphocyte populations. In vitro assays were performed by exposing freshly isolated peripheral blood mononuclear cells to bacterial lysate prepared from major translocators. Effects of bacterial lysate on CD4+ T cell activation and CD8+ T cell cytotoxicity were measured using flow cytometry. Statistical significance was calculated using ANOVA or Wilcoxon signed-rank testing.ResultsPrior to the peak of viremia, we observed a transient high-level influx of microbial genomic DNA into peripheral blood. This microbial translocation was accompanied by perturbation of bacteria-specific host factors in plasma, as well as expansion of the CD4+CCR5+ T cell compartment. Exposure of freshly isolated peripheral blood mononuclear cells to lysate prepared from major translocating taxa revealed differential taxa-specific effects on the CD4+CCR5+ T cell compartment and cytotoxic granule expression within CD8+ T cells.ConclusionsAltogether, our data identify the influx of microbial products into blood during hyperacute SIV infection as a candidate modifier of early interactions between the antiviral host response and nascent HIV infection. Over the next few months, we will explore the effect of inducing microbial translocation during SIV infection, with particular interest on microbial reactivity within the CD4+CCR5+ target cell compartment.

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