Single ingestion of di-(2-propylheptyl) phthalate (DPHP) by male volunteers: DPHP in blood and its metabolites in blood and urine.

Di-(2-propylheptyl) phthalate (DPHP) is used as a plasticizer for polyvinyl chloride products. A tolerable daily intake of DPHP of 0.2 mg/kg body weight has been derived from rat data. Because toxicokinetic data of DPHP in humans were not available, it was the aim of the present work to monitor DPHP and selected metabolites in blood and urine of 6 male volunteers over time following ingestion of a single DPHP dose (0.7 mg/kg body weight). Concentration-time courses in blood were obtained up to 24 h for DPHP, mono-(2-propylheptyl) phthalate (MPHP), mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPHP), and mono-(2-propyl-6-oxoheptyl) phthalate (oxo-MPHP); amounts excreted in urine were determined up to 46 h for MPHP, OH-MPHP, oxo-MPHP, and mono-(2-propyl-6-carboxyhexyl) phthalate (cx-MPHP). All curves were characterized by an invasion and an elimination phase the kinetic parameters of which were determined together with the areas under the concentration-time curves in blood (AUCs). AUCs were: DPHP > MPHP > oxo-MPHP > OH-MPHP. The amounts excreted in urine were: oxo-MPHP > OH-MPHP> > cx-MPHP > MPHP. The AUCs of MPHP, oxo-MPHP, or OH-MPHP could be estimated well from the cumulative amounts of urinary OH-MPHP or oxo-MPHP excreted within 22 h after DPHP intake. Not considering possible differences in species-sensitivity towards unconjugated DPHP metabolites, it was concluded from a comparison of their AUCs in DPHP-exposed humans with corresponding earlier data in rats that there is no increased risk of adverse effects associated with the internal exposure of unconjugated DPHP metabolites in humans as compared to rats when receiving the same dose of DPHP per kg body weight.

Bis-(2-propylheptyl)phthalate (DPHP) metabolites emerging in 24h urine samples from the German Environmental Specimen Bank (1999-2012).

Bis-(2-propylheptyl)-phthalate (DPHP) has been introduced as a substitute for other high molecular weight phthalates primarily used in high temperature applications (e.g. cable wires, roofing membranes). The aim of this study was to investigate how the increased usage of DPHP is reflected in urine samples collected over the last 14 years and to evaluate the current extent of exposure. We analyzed 300 urine samples (24h voids) from the German Environmental Specimen Bank collected in the years 1999, 2003, 2006, 2009 and 2012, 60 samples per year, from 30 male and 30 female volunteers (age: 20-30 years) for three specific, secondary oxidized DPHP metabolites (with hydroxy, oxo and carboxy modifications of the alkyl side chain). We determined DPHP metabolites with a previously developed GC-HRMS method, enabling us to unambiguously distinguish DPHP metabolites from co-eluting, structurally isomeric di-iso-decyl phthalate (DIDP) metabolites. All samples were blinded before analysis. We detected no DPHP metabolites in urine samples from the years 1999, 2003 and 2006. Thereafter, detection rates increased from 3.3% in 2009 to 21.7% in 2012. Mono-oxo-propylheptylphthalate (oxo-MPHP) was the most abundant metabolite, with concentrations between

Volume estimation of multicellular colon carcinoma spheroids using Cavalieri's principle.

Multicellular tumour-spheroids are regarded as suitable models for cancer research, similar to avascular tumour parts. As a size parameter of the spheroids, usually their maximum diameter is used, estimated on a section presumed to be equatorial or near equatorial. Estimation of the volume of spheroids is of interest for the detection of subtle changes in different kinds of investigations. Since spheroids are often not truly spherical, and because model-based methods for volume determination may be biased, Cavalieri's principle, rediscovered recently for stereology, was used to determine the volume of the spheroids. Here we report the results of the volume estimation of colon carcinoma spheroids, together with an outline of the basic stereological principle and formulas used. The spheroids investigated had a volume between 1.4 and 92.3 mm3 (mean 33.9). The volume fraction of necrotic to viable tissue cells was between 0.6:1 and 2.2:1. The coefficient of error (CE) was remarkably low with 3.7% for the volumes. Both inter- and intraobserver-variability were extremely low with correlation coefficients (r2) of 99%. Thus, the high precision of the stereological method, combined with a low workload, make it ideally suitable for routine volume estimation.

Giant cell myocarditis: first report of disease recurrence in the transplanted heart.

A 51-year-old female underwent heart transplantation for endomyocardial biopsy-proved giant cell myocarditis complicated by rapidly progressive congestive heart failure unresponsive to immunosuppression. Preoperatively there was no evidence of an associated extracardiac granulomatous disease. Twenty-one months after heart transplantation, giant cell myocarditis recurred in the allograft associated with sustained ventricular arrhythmias. There remained an absence of concomitant extracardiac granulomatous diseases and infections. Increased corticosteroid therapy cleared myocardial inflammation but did not abolish ventricular arrhythmias, which required pharmacologic intervention and the insertion of an Intertach II antitachycardia pacemaker. Compared with a value of 0.56 obtained 1 year after heart transplantation, left ventricular ejection fraction decreased to 0.29 at the time of diagnosis of giant cell myocarditis and remained subnormal 6 months later. Because giant cell myocarditis can recur in the allograft, the candidacy of patients with this disease for heart transplantation must be carefully assessed.

Coronary angiography during acute myocardial infarction in dogs: comparison of the hemodynamic effects of ionic and nonionic contrast media.

We compared the hemodynamic effects during coronary angiography of three nonionic contrast media, iopamidol, iohexol, and ioversol, with each other as well as with the standard ionic contrast medium containing 66% diatrizoate meglumine and 10% diatrizoate sodium (Hypaque-76) in the presence of a left anterior descending coronary artery occlusion in dogs. In 13 opened-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure (MAP), left ventricular diastolic pressure (LVDP) and rate of rise in left ventricular pressure (LV dp/dt) during left main coronary artery injections of 10 ml each of Hypaque-76, iopamidol, iohexol, and loversal 1 hour after left anterior descending coronary artery occlusion. The changes in LVSP and MAP were, respectively, -29 +/- 12 mm Hg and -21 +/- 11 mm Hg with Hypaque-76, 3 +/- 6.6 mm Hg and -0.2 +/- 3.6 mm Hg with iopamidol, 4.8 +/- 8.6 mm Hg and 0.5 +/- 4 mm Hg with iohexol, and -0.8 +/- 6 mm Hg and -1.5 +/- 33 mm Hg with ioversal (p less than 0.001). The change in LVDP was 5.4 +/- 4.4 mm Hg with Hypaque-76 but -1.5 +/- 3.1 mm Hg with iopamidol, -1.7 +/- 2.4 mm Hg with iohexol, and -0.5 +/- 2.5 mm Hg with ioversol (p less than 0.001). The LV dp/dt decreased 682 +/- 318 mm Hg/sec with Hypaque-76, but increased 412 +/- 297 mm Hg/sec with iopamidol, 350 +/- 214 mm Hg/sec with iohexol, and 293 +/- 191 mm Hg/sec with ioversol (p less than 0.001). Thus, each nonionic agent produced significantly fewer hemodynamic abnormalities than Hypaque-76. There was no significant difference between any of the nonionic agents on any hemodynamic parameter. These agents may be preferable in patients with acute myocardial infarction or significantly impaired myocardial function.

Differential hemodynamic effects of Hypaque-76 and Renografin-76 during coronary angiography: the role of calcium-binding additives.

Hypaque-76 (H76) and Renografin-76 (R76) are nearly identical ionic contrast media, except that R76 binds more calcium than H76 because of the presence of sodium citrate and EDTA in R76. To determine whether the calcium-binding additives in ionic contrast media contribute to the hemodynamic effects of contrast media during coronary angiography, left coronary angiography was performed in anesthetized dogs. In nine closed-chest dogs, 10 cc of H76 and R76 were injected in each dog in a blinded, randomized fashion. The effect of H76 and R76 on left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVDP), on mean aortic pressure (MAP), and on left ventricular (LV) dp/dt was recorded. Compared with H76, R76 produced a greater decrease in the LVSP (77 +/- 25 mmHg vs 48 +/- 17 mmHg P less than .05), MAP (72 +/- 24 mmHg vs 38 +/- 18 mmHg P less than .01), and LV dp/dt (747 +/- 87 mmHg/sec vs 460 +/- 81 mmHg/sec P less than .01). In nine additional open-chest dogs, left coronary angiography was performed 1 hour after occlusion of the proximal LAD coronary artery. Seven cc R76 produced a 35 +/- 15 mmHg decrease in LVSP, compared with 20 +/- 9 mmHg with H76 (P less than .01). The LV dp/dt decreased 720 +/- 387 mmHg/sec with R76, compared with 462 +/- 222 mmHg/sec with H76 (P less than 0.05). Thus, R76 produces significantly greater hemodynamic abnormalities than H76. Contrast media lacking calcium-binding agents may be preferable for coronary angiography.

Canopy transpiration and water fluxes in the xylem of the trunk of Larix and Picea trees - a comparison of xylem flow, porometer and cuvette measurements.

Leaf gas exchange, transpiration, water potential and xylem water flow measurements were used in order to investigate the daily water balance of intact, naturally growing, adult Larix and Picea trees without major injury. The total daily water use of the tree was very similar when measured as xylem water flow at breast height or at the trunk top below the shade branches, or as canopy transpiration by a porometer or gas exchange chamber at different crown positions. The average canopy transpiration is about 12% lower than the transpiration of a single twig in the sun crown of Larix and Picea. Despite the similarity in daily total water flows there are larger differences in the actual daily course. Transpiration started 2 to 3 h earlier than the xylem water flow and decreased at noon before the maximum xylem water flow was reached, and stopped in the evening 2 to 3 h earlier than the water flow though the stem. The daily course of the xylem water flow was very similar at the trunk base and top below the lowest branches with shade needles. The difference in water efflux from the crown via transpiration and the water influx from the trunk is caused by the use of stored water. The specific capacitance of the crown wood was estimated to be 4.7 x 10-8 and 6.3 x 10-8 kg kg-1 Pa-1 and the total amount of available water storage was 17.8 and 8.7 kg, which is 24% and 14% of the total daily transpiration in Larix and Picea respectively. Very little water was used from the main tree trunk. With increasing transpiration and use of stored water from wood in the crown, the water potential in the foliage decreases. Plant water status recovers with the decrease of transpiration and the refilling of the water storage sites. The liquid flow conductance in the trunk was 0.45 x 10-9 and 0.36 x 10-9 mol m-2s-1 Pa-1 in Larix and Picea respectively. The role of stomata and their control by environmental and internal plant factors is discussed.