Prevention of benzene-induced myelotoxicity by nonsteroidal anti-inflammatory drugs.

Benzene affects hematopoietic progenitor cells leading to bone marrow depression and genotoxic effects such as micronucleus formation. Progenitor cell proliferation and differentiation are inhibited by prostaglandins produced by macrophages. Administration of benzene to DBA/2 or C57BL/6 mice caused a dose-dependent bone marrow depression and a significant increase in marrow prostaglandin E level and both were prevented by the coadministration of indomethacin and other inhibitors of the cyclooxygenase component of prostaglandin H synthase. Levels of benzene that decreased bone marrow cellularity also caused genotoxic effects measured as increased micronucleated polychromatic erythrocytes in peripheral blood, which was also prevented by the coadministration of indomethacin. These results suggest a possible role for prostaglandin synthase in benzene myelotoxicity; a mechanism by which this might occur is presented

Regulation of bone marrow cell growth in diffusion chambers: the effect of adding normal and leukemic (CML) polymorphonuclear granulocytes

Inhibition of granulopoiesis was studied using the diffusion chamber (DC) technique. When mature granulocytes from human blood or syngeneic mouse peritoneal fluid were added to mouse bone marrow cells cultured in DC, a significant depression of granulopoiesis took place, and a stimulation of macrophage formation was observed in 7-day cultures. Human granulocytes had a stronger inhinitory capacity than mouse granulocytes. The inhibition appeared to be tissue-specific and caused by a diffusible factor. A time study showed that the added granulocytes had no observable effect on the growth of proliferative granulocytes and CFU-C during the first days of culture. A rapid decrease of proliferative granulocytes after day 5 was preceded by a similar reduction of CFU-C 1 day earlier. The effect of CFU-S was more variable. In one strain of mice, there was a consistent increase in the granulocyte co-culture group, whereas in another strain a significant increase was observed only on day 2. Hislotologic examination showed that mature granulocytes changed the colony distribution, so that a significant relative decrease of granuloid colonies occurred. The nature of this delayed suppression of granulopoiesis is not evident from these data. A possible explanation is that factors released by mature granulocytes prevent recruitment of CFU-C and granulocyte precursors from the CFU-S compartment by blocking the granulopoietic pathway. Leukemic (CML) granulocytes isolated from blood were less able to inhibit granulopoiesis than normal granulocytes with mouse bone marrow as well as human bone marrow as target cells.</jats:p

Regulation of bone marrow cell growth in diffusion chambers: the effect of adding normal and leukemic (CML) polymorphonuclear granulocytes

Abstract Inhibition of granulopoiesis was studied using the diffusion chamber (DC) technique. When mature granulocytes from human blood or syngeneic mouse peritoneal fluid were added to mouse bone marrow cells cultured in DC, a significant depression of granulopoiesis took place, and a stimulation of macrophage formation was observed in 7-day cultures. Human granulocytes had a stronger inhinitory capacity than mouse granulocytes. The inhibition appeared to be tissue-specific and caused by a diffusible factor. A time study showed that the added granulocytes had no observable effect on the growth of proliferative granulocytes and CFU-C during the first days of culture. A rapid decrease of proliferative granulocytes after day 5 was preceded by a similar reduction of CFU-C 1 day earlier. The effect of CFU-S was more variable. In one strain of mice, there was a consistent increase in the granulocyte co-culture group, whereas in another strain a significant increase was observed only on day 2. Hislotologic examination showed that mature granulocytes changed the colony distribution, so that a significant relative decrease of granuloid colonies occurred. The nature of this delayed suppression of granulopoiesis is not evident from these data. A possible explanation is that factors released by mature granulocytes prevent recruitment of CFU-C and granulocyte precursors from the CFU-S compartment by blocking the granulopoietic pathway. Leukemic (CML) granulocytes isolated from blood were less able to inhibit granulopoiesis than normal granulocytes with mouse bone marrow as well as human bone marrow as target cells.</jats:p

The thermospheric auroral red line polarization: comparison between theory and observations

International audienc

Noninvasive imaging of angiotensin receptors after myocardial infarction.

ObjectivesThe purpose of this study was to evaluate the feasibility of noninvasive imaging of angiotensin II (AT) receptor upregulation in a mouse model of post-myocardial infarction (MI) heart failure (HF).BackgroundCirculating AT levels do not reflect the status of upregulation of renin-angiotensin axis in the myocardium, which plays a central role in ventricular remodeling and evolution of HF after MI. Appropriately labeled AT or AT receptor blocking agents should be able to specifically target AT receptors by molecular imaging techniques.MethodsAT receptor imaging was performed in 29 mice at various time points after permanent coronary artery ligation or in controls using a fluoresceinated angiotensin peptide analog (APA) and radiolabeled losartan. The APA was used in 19 animals for intravital fluorescence microscopy on a beating mouse heart. Tc-99m losartan was used for in vivo radionuclide imaging and quantitative assessment of AT receptor expression in 10 mice. After imaging, hearts were harvested for pathological characterization using confocal and 2-photon microscopy.ResultsNo or little APA uptake was observed in control animals or within infarct regions on days 0 and 1. Distinct uptake occurred in the infarct area at 1 to 12 weeks after MI; the uptake was at maximum at 3 weeks and reduced markedly at 12 weeks after MI. Ultrasonographic examination demonstrated left ventricular remodeling, and pathologic characterization revealed localization of the APA tracer with collagen-producing myofibroblasts. Tc-99m losartan uptake in the infarct region (0.524 +/- 0.212% injected dose/g) increased 2.4-fold as compared to uptake in the control animals (0.215 +/- 0.129%; p &lt; 0.05).ConclusionsThe present study demonstrates the feasibility of in vivo molecular imaging of AT receptors in the remodeling myocardium. Noninvasive imaging studies aimed at AT receptor expression could play a role in identification of subjects likely to develop heart failure. In addition, such a strategy could allow for optimization of anti-angiotensin therapy in patients after MI