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[Affinity of the elements in group VI of the periodic table to tumors and organs].

In order to investigate the tumor affinity radioisotopes, chromium (51Cr), molybdenum (99Mo), tungsten (181W), selenium (75Se) and tellurium (127mTe)--the elements of group VI in the periodic table--were examined, using the rats which were subcutaneously transplanted with Yoshida sarcoma. Seven preprarations, sodium chromate (Na251CrO4), chromium chloride (51CrCl3), normal ammonium molybdate ((NH4)299MoO7), sodium tungstate (Na2181WO4), sodium selenate (Na275SeO4), sodium selenite (Na275SeO3) and tellurous acid (H2127mTeO3) were injected intravenously to each group of tumor bearing rats. These rats were sacrificed at various periods after injection of each preparation: 3 hours, 24 hours and 48 hours in all preparations. The radioactivities of the tumor, blood, muscle, liver, kidney and spleen were measured by a well-type scintillation counter, and retention values (in every tissue including the tumor) were calculated in percent of administered dose per g-tissue weight. All of seven preparations did not have any affinity for malignant tumor. Na251CrO4 and H2127mTeO3 had some affinity for the kidneys, and Na275SeO3 had some affinity for the liver. Na2181WO4 and (NH4)299MoO4 disappeared very rapidly from the blood and soft tissue, and about seventy-five percent of radioactivity was excreted in urine within first 3 hours.

Animals↗

Red cell volume determination using a stable isotope of chromium.

OBJECTIVE: To validate and improve a method of red cell volume determination by use of a stable isotope of chromium. METHODS: Twelve subjects were sequentially injected with red blood cells labeled with a stable isotope of chromium (53Cr) and red blood cells labeled with radioisotopic chromium (51Cr). Measurement of 53Cr dilution was by gas chromatography/mass spectrometry. Measurement of 51Cr dilution was by gamma counter. RESULTS: Comparison of the two methods led to results that differed on average by 34.5 +/- 45.0 mL (1.8 +/- 2.2%), 0.3 to 3.2%, 95% confidence interval. CONCLUSION: Measurement of red cell volume by use of a stable isotope of chromium is accurate, with potential applications including measurement in pregnant women and children or other groups in whom exposure to radioisotopes is undesirable.

Blood Volume↗

Intravascular granulocyte kinetics in developing calves.

Intravascular granulocyte kinetic values of normal developing calves were determined, using the chromium radioisotope 51Cr as the cell label. A total of 15 kinetic trials were conducted in the calves at 8 to 365 days of age. The clearance of labeled granylocytes from the circulation was an exponential function. The kinetic data from the oldest group of calves (7 experiments on 5 calves, 180 days of age and older) were remarkably similar to those reported for persons. Mean total blood granulocyte pool was 6.34 times 10-8 granulocytes/kg of body weight, of which 45.6% was in the circulating granulocyte pool. Mean clearance half-life (T1/2) was 8.9 hours, and mean granulocyte turnover rate was 12.44 times 10-8 granulocytes/kg of body weight/day. In the oldest calf group, there was significant correlation between the blood granulocyte count and the total blood granulocyte pool size. There was also significant correlation between the total blood granulocyte pool size and the clearance half-life. The youngest group of calves (4 experiments on 4 calves, 8 to 16 days of age) had significantly larger total blood granulocyte pool and shorter intravascular half-life than did the oldest group. These factors combined to yield a markedly greater granulocyte turnover rate of 39.91 times 10-8 granulocytes/kg of body weight/day in the youngest group of calves. Calves of an intermediate age group (70 to 127 days) had kinetic which were intermediate between those of the youngest and oldest groups of calves.

Age Factors↗

The multiple-indicator dilution technique for characterization of normal and retrograde flow in once-through rat liver perfusions.

The technique of normal and retrograde rat liver perfusion has been widely used to probe zonal differences in drug-metabolizing activities. The validity of this approach mandates the same tissue spaces being accessed by substrates during both normal and retrograde perfusions. Using the multiple-indicator dilution technique, we presently examine the extent to which retrograde perfusion alters the spaces accessible to noneliminated references. A bolus dose of 51Cr-labeled red blood cells, 125I-albumin, 14C-sucrose and 3H2O was injected into the portal (normal) or hepatic (retrograde) vein of rat livers perfused at 10 ml per min per liver. The outflow perfusate was serially collected over 220 sec to characterize the transit times and the distribution spaces of the labels. During retrograde perfusion, red blood cells, albumin and sucrose profiles peaked later and lower than during normal perfusion, whereas the water curves were similar. The transit times of red blood cells, albumin and sucrose were longer (p less than 0.005), whereas those for water did not change. Consequently, retrograde flow resulted in significantly larger sinusoidal blood volumes (45%), albumin Disse space (42%) and sucrose Disse space (25%) than during normal flow, whereas the distribution spaces for total and intracellular water remained unaltered. The distension of the vascular tree was confirmed by electron microscopy, by which occasional isolated foci of widened intercellular recesses and spaces of Disse were observed. Cellular ultrastructure was otherwise unchanged, and there was no difference found between normal and retrograde perfusion for bile flow rates, AST release, perfusion pressure, oxygen consumption and metabolic removal of ethanol, a substrate with flow-limited distribution, which equilibrates rapidly with cell water (hepatic extraction ratios were virtually identical: normal vs. retrograde, 0.50 vs. 0.48 at 6 to 7.4 mM input concentration). These findings suggest that the functional and metabolic capacities of the liver remain unperturbed during retrograde perfusion, rendering the technique suitable for the investigation of zonal differences in drug-metabolizing enzymes.

Albumins↗

Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver.

The hepatocytic entry of acetaminophen sulfate conjugate was examined in the rat liver, perfused with red cells with and without albumin, by use of the multiple-indicator dilution technique. [3H]acetaminophen sulfate was injected into the portal vein in a bolus of blood containing 51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or 125I-labeled albumin (a high-molecular-weight interstitial reference, included when albumin was present), and the time courses of their outflow into the hepatic venous blood were observed. The [3H]acetaminophen sulfate, which binds partially to albumin, emerged between albumin and sucrose in the presence of albumin, processed the upslope of the sucrose curve and showed a late low-in-magnitude tailing; the precession disappeared in the absence of albumin. Biliary excretion of [3H]acetaminophen sulfate was less than 1% of the dose. Quantitative evaluation with a barrier-limited, space-distributed variable transit time model (including rapidly equilibrating albumin binding) accounted for the albumin effect on [3H]acetaminophen sulfate behavior and demonstrated a low liver cell permeability for the acetaminophen sulfate and a small interstitial binding space for its nonalbumin-bound fraction in excess of that for sucrose, which in the absence of albumin was of similar dimensions.

Acetaminophen↗

Sensitivity of bile acid breath test in the diagnosis of bacterial overgrowth in the small intestine with and without the stagnant (blind) loop syndrome.

The bile acid breath test was studied to examine its sensitivity for establishing the diagnosis of bacterial overgrowth in comparison to that of the Schilling test and small-intestinal cultures in 12 patients with a stagnant (blind) loop syndrome, as well as in 38 patients who had other conditions with suspected bacterial contamination of the small intestine. The presence of bile acid malabsorption was excluded in all 50 patients by studies of fecal excretion of radioactively labeled bile acids. The bile acid breath test was positive in 100% (12/12) of the patients with a stagnant (blind) loop syndrome, whereas 92% (11/12) had a positive Schilling test and 75% (9/12) a positive small-intestinal culture. The abnormal tests improved only in 2 of 4 patients treated with tetracycline. In the group of 38 patients without demonstrable dilated or blind loops of small bowel who were suspected of having bacterial contamination of small bowel, the bile acid breath test was positive in 53% (20/38), the Schilling test in 39% (15/38), and the small-intestinal culture in 45% (17/38). The difference in the incidence of positive results between the tests in the two patient groups was statistically not significant. The findings of these studies have the following diagnostic implications: (1) Bile acid breath test, Schilling test, and cultures of aspirates from the upper small bowel are of comparable sensitivity in the detection of bacterial overgrowth in the small intestine. (2) A negative bile acid breath test makes the diagnosis of a stagnant (blind) loop syndrome very unlikely.

Bacteria↗

Drug residue formation from ronidazole, a 5-nitro-imidazole. IV. The role of the microflora.

When radioactive 1-methyl-5-nitroimidazole-2-methanol carbamate, ronidazole, labeled at the 4,5-ring positions was administered orally to germ-free and conventional rats, a much larger fraction of the radioactivity was excreted in the feces of the conventional animals. Determination of the total radioactive residues present in the carcass, blood, plasma, liver, fat and kidney 5 days after dosing indicated that the carcass of the germ-free animals contained a greater quantity of residue than that of conventional rats. On the other hand, the blood of the conventional animals contained a much higher level of radioactivity than that of the germ-free animals. These results show that while the microflora influence the distribution of the drug their presence is not obligating for the formation of persistent tissue residues in rats dosed with ronidazole.

Adipose Tissue↗

Extracellular space, blood volume, and the early dumping syndrome after total gastrectomy.

Extracellular space and blood volume were measured using 82Br dilution and 51Cr-tagged erythrocytes in 24 tumor-free patients after total gastrectomy. Eleven of the patients suffered from early dumping. Age, blood volume, and extracellular space were significantly smaller in dumpers (P less than 0.05). The dumping score could be predicted by a multiple regression model considering blood volume per lean body mass and extracellular space (r = 0.637; P = 0.0039). Rapid (t1/2 less than 360 seconds) emptying of the gastric substitute, assessed using a 99Tc-labeled solid test meal, was significantly associated with dumping in addition to extracellular space and blood volume (r = 0.876; P = 0.0018). Both rapid emptying and a narrow extracellular space seem to contribute to the early dumping syndrome.

Blood Volume↗

Labelling of lymphocytes with various radiosotopes for in vivo tracer studies; a review.

Several methods are available for labelling lymphoid cells with radioactive markers e.g. 3H, 14C, 125I, 131I, 35S, 75Se, based on general metabolic processes, involving DNA, RNA and protein synthesis in these cells. Together with methods for labelling lymphoid cells with 51Cr and 99mTc, radioisotopes which are captured in cells but not incorporated in its metabolites, these will be reviewed in the present paper. Attention will be given to possible applications of the use of radiosotope labels.

Amino Acids↗