Recent data have shown that plasma levels of lipopolysaccharide (LPS) are a quantitative indicator of microbial translocation in HIV infected individuals.
To assess the impact of residual viral ...replication on plasma LPS in HAART-treated HIV+ subjects with <50copies/ml HIV-1 RNA and to evaluate LPS changes during repeated HAART interruptions not exceeding 2-month duration.
LPS was measured in 44 HIV+ subjects at T0 (during HAART) and at day 15 of the first and fourth HAART interruption. Ten uninfected, healthy donors were studied as well. Residual plasma HIV-1 RNA was measured at T0 by an ultra-ultrasensitive method with limit of detection of 2.5copies HIV-1 RNA/ml. Subjects with less than 2.5copies/ml (fully suppressed - FS) were compared to those with 2.5-50copies/ml (partially suppressed - PS).
At T0, plasma LPS levels were comparable in FS and uninfected subjects, whereas in PS they were higher than in uninfected subjects (p=0.049). After 4 HAART interruptions, they did not change significantly. However, LPS values were lower in FS than in PS (p=0.020). An inverse correlation was found between CD4 and LPS levels (p=0.044) in PS group only.
A reduced degree of microbial translocation was seen in subjects with a more complete suppression of viral replication. Repeated HAART interruptions had no significant impact on plasma LPS levels.
Several studies have shown the importance of evaluating Recent Thymic Emigrants (RTEs) by quantification of T cell receptor-rearrangement excision circles (TRECs), as a measure of
de novo T cell ...generation during human immunodeficiency virus-1 (HIV-1) infection. To determine whether acute viral infection may have an impact on TRECs, cynomolgus monkeys (
Macaca fascicularis) were infected intrarectally with simian human immunodeficiency virus (SHIV) 89.6P
cy11 and the number of signal-joint (sj) TRECs was determined in purified CD4
+ and CD8
+ populations for up to 28 weeks post-infection. Four weeks after infection, TRECs levels significantly decreased in both CD3
+CD4
+ and in CD3
+CD8
+ T lymphocytes of infected monkeys, whereas they remained unchanged in uninfected animals. This reduction was followed by a progressive TRECs number recovery in CD3
+CD4
+ T lymphocytes that positively correlated with changes in the levels of circulating CD3
+CD4
+ T cells. In the CD3
+CD8
+ T cell subset, TRECs number remained significantly low and inversely correlated with the increase in the percentages of CD3
+CD8
+ T cells. These data suggest that SHIV89.6P
cy11 intrarectal infection of cynomolgus monkeys differently affects TRECs content in CD3
+CD4
+ and CD3
+CD8
+ T cell subsets.
A preliminary study was conducted on adult male crab-eating monkeys (Macaca fascicularis) orally exposed to bis(tri-n-butyltin)oxide (TBTO) at doses of 0 and 160 micrograms/kg/day, 6 days/wk, for 22 ...wk. No treatment-related signs of toxicity or changes in body weight gain were detected during the course of the study. The haematological analyses performed every 2 wk indicated a decrease in total leucocyte count in the treated animals with significant values in wk 8, 10 and 22 of treatment. No differences from controls were noted in clinical chemistry and total tin concentration in blood. These preliminary data on the toxicity of TBTO in the primate model are intended to be an initial contribution towards a better evaluation of the potential toxicological hazard of TBTO to humans.
The effect of in utero TBTO exposure on blood composition in neonates, pups during weaning, and dams in the same period were investigated in mice. The dams were gavaged at dose levels 0, 5, 10, and ...20 mg TBTO/kg body weight on gestational days 6-15. At birth, litters were culled to eight pups, and blood analysis was performed on excess pups. On d 7, 14, and 21 the entire litters were sacrificed and blood (WBC, RBC, HGB, HCT, MCV, MCH, MCHC, and differential leukocyte count) of dams and pups was analyzed. Blood analysis of neonates revealed enhanced WBC count and altered red-cell parameters. Increase in WBC persisted until postnatal day (pnd) 21, while red-cell parameters regained normal values on pnd 7. No significant differences were found in thymus and spleen weights in the treated groups. Dams presented no alteration in blood composition or of spleen or thymus weights. The results of this investigation revealed that in utero exposure to TBTO induces a nonspecific alteration of hematological parameters in mice, but further studies are necessary to understand whether our results are either dependent on maternal status or a direct effect of TBTO on embryonic tissue.
Extrachromosomal forms of human immunodeficiency virus (HIV)-1 can be detected in peripheral blood mononuclear cell (PBMC) from HIV-infected patients in the absence of detectable viral replication ...and are thought to be a sign of active but cryptic virus replication. No information, however, are available on whether these forms are also present in animal models for acquired immunodeficiency syndrome (AIDS) and on their relation with other methods of detection of virus replication. To this aim, a polymerase chain reaction (PCR) approach was used to detect and analyze unintegrated circular 2-LTR-containing forms in PBMC of simian human immunodeficiency virus (SHIV)89.6P infected cynomolgus monkeys with RNA levels ranging between 1.8 × 10
6 and less than 50 copies/ml of plasma. 2-LTR forms were detected in 96.5% of monkeys' samples above 50 copies/ml of plasma, whereas they were present in 75.8% of monkeys' samples below 50 copies/ml of plasma. Persistence of unintegrated viral DNA in monkeys with undetectable plasma RNA could indicate either stability in non-dividing cells or ongoing low levels of viral replication in dividing cells.
The present paper is part of a research program which aims at a quantitative analysis of the effects of light and gibberellic acid (GA3) on growth of the first foliage leaf in durum wheat (Triticum ...durum Desf.). Since leaf growth is the combined result of the increase in cell number (cell division) and cell enlargement, the influence of light and GA3 treatment on cell division in the basal meristem of the first leaf in two cultivars, Cappelli and Creso, was investigated. Creso is a short-strawed cultivar carrying the Gai 1 gene which influences both plant height and insensitivity to applied GA3. Cell division, as measured by mitotic index, was similar in darkness, continuous red light and dichromatic irradiation (far-red plus red), while lower mitotic rates were observed under continuous far-red light: this indicates that the response of cell division is modulated by a high-irradiance reaction of phytochrome in both cultivars. The two cultivars showed different responses to blue light. In Cappelli, blue light and dichromatic irradiation (blue plus red) gave lower mitotic indices than the dark control, indicating the action of a specific blue-light-absorbing photoreceptor, whereas in Creso the response kinetics to all light regimes which included blue light were more complex. On the basis also of the results obtained with GA3 application in Cappelli, it appears that (i) the hormonal treatment is able to change the pattern of mitotic index only in the presence of the action of a blue-light receptor and (ii) the different responses of the two cultivars could be the result of different endogenous hormonal levels. The importance of the observations in relation to the data for first-leaf longitudinal growth reported in a previous paper (Baroncelli et al. 1984, Planta 160, 298—304) is discussed.
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