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Biomedical subjects

H C Heinrich

Publications and source records attributed to H C Heinrich.

At least 19 recordsLinked to original sources
PubMed1992

Noninvasive liver-iron quantification by computed tomography in iron-overloaded rats.

RATIONALE AND OBJECTIVES: The benefit of computed tomography (CT) for the noninvasive determination of liver-iron concentration in human iron-overload diseases is a controversy in the literature. To study the sensitivity of CT for liver-iron quantification under experimental conditions, the authors measured single- and dual-energy CT numbers in vivo in the livers of iron-overloaded rats. METHODS: Thirty-five rats were subjected to an iron-rich diet for various periods, from 1 to 20 weeks, then scanned by single- and dual-energy CT. CT absorption was correlated to liver-iron content, which was determined by wet ashing and spectrophotometry. RESULTS: Whereas a good correlation (r = 0.99 at 96 kV; r = 0.95 at 125 kV) between CT numbers and liver-iron concentration was found, CT was insensitive to low concentrations of iron. Dual-energy CT scanning results showed greater scattering in liver-iron quantification compared with single-energy CT. CONCLUSIONS: In rats, the sensitivity of single- and dual-energy CT is too low to quantify liver iron in the diagnostically most relevant region of mild liver siderosis (1-3 mg iron/g wet weight [w.wt]).

Animals↗
PubMed1992

Iron overload of the liver by trimethylhexanoylferrocene in rats.

Iron-deficient female Wistar rats were fed a diet, which contained 0.5% trimethylhexanoylferrocene, over a 56-week period. This dietary iron loading resulted in a progressive siderosis and enlargement of the liver with a maximum iron content of 947.0 +/- 148.0 mg (vs. 0.07 +/- 0.04 mg in iron deficiency) and a maximum organ weight of 39.4 +/- 6.6 g (vs. 6.9 +/- 1.4 g in iron-deficient control rats). Up to 43 weeks, whole liver iron rose by increase in iron concentration (max. 28.0 +/- 6.1 mg/g wet weight, w.w.) as well as by enlargement of the organ. Afterwards whole liver iron increased solely by ongoing hepatomegaly. At the commencement of iron loading, stainable iron was almost exclusively stored by hepatocytes equally throughout all areas of the liver lobule. Later, the distribution of iron-loaded hepatocytes became strikingly periportal, and, in addition, Kupffer cells as well as sinus-lining endothelia began to store iron. Animals with a liver iron concentration of more than 10.4 +/- 0.75 mg/g w.w. showed no further increase in ferritin and haemosiderin within hepatocytes. Iron-burdened Kupffer cells/macrophages, however, accumulated permanently, hereby forming intrasinusoidal and portal siderotic nodules and areas. First signs of liver damage such as necrosis of single hepatocytes and mild fibrosis began at a liver iron concentration of 14.7 +/- 1.4 mg/g w.w. With advancement of iron loading, focal necrosis of hepatocytes and iron-burdened macrophages took place, and significant perisinusoidal as well as portal fibrosis developed. Cirrhosis, however, the final stage of impairment in iron overload of the liver in humans, could not be induced in this animal model up to now.

Animals↗
PubMed1992

Bismuth absorption from 205Bi-labelled pharmaceutical bismuth compounds used in the treatment of peptic ulcer disease.

The absorption of bismuth from five 205Bi-labelled pharmaceutically used bismuth compounds was studied in man. From single oral doses of all compounds under investigation only less than 0.1% bismuth was absorbed and excreted with the urine. A significantly higher absorption was observed from the colloidal bismuth subcitrate (0.042% of the dose) and the basic bismuth gallate (0.038%) than from the basic bismuth salicylate, nitrate, and aluminate (0.005-0.002%). No retention of bismuth in the whole body was found from the single dose experiment. The biologic fast-term half-lives of absorbed bismuth were calculated to be 0.12 and 1.5 days.

Adult↗
PubMed1991

Bioavailability of bismuth from 205Bi-labelled pharmaceutical oral Bi-preparations in rats.

The bioavailability of 205Bi from various 205Bi-labelled pharmaceutical oral bismuth preparations was studied in rats. The intestinal absorption, calculated from 205Bi whole body retention and accumulated 205Bi urinary excretion, was small in general, but significantly higher (0.26-0.33% of dose) from oral bismuth citrates (basic bismuth citrate, colloidal bismuth subcitrate) as compared to basic bismuth nitrate, salicylate, gallate, and bismuth aluminate (0.04-0.11% of dose). After oral administration, the retained bismuth was mainly accumulated in the kidney, followed by bone, red blood cells and the lung. The whole body retention, faecal and urinary excretions of 205Bi were described by a three-compartment model. Biological 205Bi half-lives of 10, 36 and 295 h were derived in rats.

Administration, Oral↗
PubMed1991

Inhibition of intestinal absorption and decorporation of radiocaesium in humans by hexacyanoferrates(II).

The effect of hexacyanoferrate(II) preparations, KFe[Fe(CN)6], (KFeHCF) anol Fe4[Fe(CN)6]3, (FeHCF) on intestinal radiocaesium absorption was studied in two male volunteers. The 134Cs absorption was decreased from 100 to 3-10% when 500-1000 mg KFeHCF or FeHCF were administered 10 min before the 134Cs-labelled test meal. However, when HCF was administered simultaneously with the test meal, the 134Cs absorption was decreased to only 38-63%. The biological half-time of previously absorbed 134Cs was reduced from 106 (73) to 44 (46) days by daily administration of 3 times 0.5 g KFeHCF. The 134Cs dose conversion factors lie below the values recommended by IRCP 30, indicating that the IRCP model represents a cautious description of the Cs biokinetics in our study.

Adult↗
PubMed1990

Ferrioxamine and its hexadentate iron-chelating metabolites in human post-desferal urine studied by high-performance liquid chromatography and fast atom bombardment mass spectrometry.

Three iron-containing fractions were detected by high-performance liquid chromatography (HPLC) on a reverse-phase column in the 24-h urine of two patients with hereditary hemochromatosis following the injection of deferoxamine mesylate (Desferal). These fractions have virtually identical absorption spectra in the visible range, with a broad maximum around 430 nm. Molecular weight determination of these fractions was performed by fast atom bombardment mass spectrometry (FAB-MS), which gave intense ion signals for the protonated molecular ions of the intact iron chelates, namely, at m/z 614 for ferrioxamine (FOA; Mr 613), at m/z 629 for metabolite I (FOA-MI; Mr 628), and at m/z 601 for metabolite II (FOA-MII; Mr 600). The molecular weight of FOA-MI is compatible with deamination of the terminal amino function and oxidation of the adjacent carbon atom to a carboxyl group; the molecular weight of FOA-MII is compatible with loss of a C2H4 unit from FOA-MI by beta oxidation. Quantification of iron in post-Desferal urine samples either by atomic absorption spectrometry (AAS) or by HPLC leads to results which are identical within experimental error. In ten subsequent 12-h urine samples of a patient under therapy (subcutaneous infusion of Desferal), the following distribution of urinary iron was found: FOA-MI, 58.4 +/- 4.7% (arithmetic mean +/- SD); FOA, 33.2 +/- 4.9%; FOA-MII, 8.4 +/- 1.7%. Addition of 2 mM ethylenediaminetetraacetic acid (EDTA) to the chromatographic solvents was used as a stability test for FOA and its two metabolites MI and MII.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1990

Bioavailability of iron and cyanide from oral potassium ferric hexacyanoferrate(II) in humans.

After oral administration of 500 mg KFe[Fe(CN)6] labelled with 59Fe either in the ferric or ferrous position and with 14C in the cyanide group only 0.22% of the FeII and less than 0.04% of the FeIII were absorbed in three male volunteers. Only 2 mg non-complex bound 14C-labelled cyanide (0.03 mg CN-/kg body wt) were absorbed from 500 mg [14C]KFeHCF, which is about a factor of 20-100 below the lethal dose in humans (0.5-3.5 mg CN-/kg body wt). Therefore, iron(III) hexacyanoferrates(II) can be considered as safe antidotes, i.e. for inhibiting the intestinal absorption of radiocaesium or for accelerating the excretion of already absorbed 134/137Cs in the case of a severe nuclear accident.

Biological Availability↗
PubMed1990

Efficacy of different hexacyanoferrates(II) in inhibiting the intestinal absorption of radiocaesium in rats.

The inhibitory effect of various oral doses of different hexacyanoferrate(II) compounds (HCF) and the influence of the time interval of HCF-administration on intestinal 134Cs-absorption was studied in rats. Optimum inhibition was obtained by administration of HCF together with or 2 min before oral 134Cs loading. Using appropriate low amounts (0.1-0.5 mg) of the different HCF compounds, the inhibitory effect increased in the sequence KZnHCF less than KCuHCF less than FeHCF less than KCoHCF = KNiHCF less than NH4FeHCF = KFeHCF. Oral administration of 5 mg (0.5 mg) of KFeHCF, together with 134CsCl loading, reduces 134Cs-absorption from 41% (control) to 0.8% (2.8%). Zinc-, copper-, cobalt, and nickel hexacyanoferrates(II), despite showing a high caesium sorption capacity in vitro, were less effective in rats and are not suited for in vivo application, also because they may produce toxic side effects. As a consequence, the orally administered colloidal-soluble iron(III) hexacyanoferrates(II) (NH4Fe[Fe(CN)6] and KFe[Fe(CN)6]) have to be considered as the most valuable countermeasure against radiocaesium absorption for humans and domestic animals in the case of a severe nuclear accident in the future. Manganese oxide, a non-hexacyanoferrate(II) compound with known in vitro caesium binding capacity, showed no inhibitory effect on radiocaesium absorption in rats.

Animals↗
PubMed1990

Bioavailability of iron and cyanide from 59Fe- and 14C-labelled hexacyanoferrates(II) in rats.

"Soluble" (KFe(III)[Fe(II)(CN)6]) and "insoluble Prussian blue" (Fe(III)4[Fe(II)(CN)6]3 labelled with 59Fe either in the ferric (Fe(III)) or ferro (Fe(II)) position and 14C in the cyanide group were synthesized and administered intraperitoneally or orally to adult female rats with normal body iron stores. Following i.p. injection of KFe[Fe(CN)6], the colloidal complex is disintegrated into ferric iron and hexacyanoferrate(II) anion almost completely. About 96% of the ferric iron was retained in the body. Nearly 90% of both ferrous iron and cyanide were excreted with the urine within 7 days after i.p. injection, indicating that most of the undissociated hexacyanoferrate(II) anion ([Fe(CN)6]4-) was excreted through the kidney. Only 9% of the ferrous iron from [Fe(CN)6]4- was found mainly in carcass, liver and gut. As the 59Fe/14C-ratios in organs were found close to 1.0, the dissociation of the hexacyanoferrate(II) anion can only be small in vivo. No detectable 14CO2-activity (less than 0.01%) was monitored in the breath of rats after i.p. injection of the 14C-labelled KFe[Fe(CN)6], also indicating that no significant amounts of cyanide were released after parenteral administration. After oral administration of the soluble and insoluble Prussian blue, 0.3-0.7% of the ferric iron was absorbed and retained mainly in carcass, liver and blood. Only 0.06-0.18% of the ferrous iron was absorbed and mostly excreted with the urine (0.05-0.15%), so that only 0.01-0.03% of the oral ferrous 59Fe was retained in the body after 7-10 days. Very small fractions of 14C-label from the 14CN-group of the soluble and insoluble hexacyanoferrate(II) were observed in the exhaled air (0.04-0.08% of the oral dose). From the 14CO2-exhalation, the 14C-urine excretion and the distribution of iron in blood and organs it can be concluded that the hexacyanoferrate(II) moiety disintegrated only to a small extent in the intestinal tract after oral administration. From a dose of 36 mg hexacyanoferrate(II)/kg, an amount of free (non-complex bound) cyanide can be calculated which is in maximum two orders of magnitude below the LD100-level. Thus, the very low bioavailability of iron and cyanide from hexacyanoferrate(II) compounds after oral application is demonstrated in rats. In the case of a severe nuclear accident, appropriate doses of "soluble" and "insoluble" Prussian blue can be used as safe and effective antidote against radiocaesium contamination.

Animals↗
PubMed1988

Prevention of enteral radiocesium absorption by hexacyanoferrates(II) in piglets.

The efficacy of different hexacyanoferrates(II) in preventing the enteral absorption of 134Cs was studied in piglets. As compared to the controls, oral application of 134Cs together with KFe[Fe(CN)6], NH4Fe[Fe(CN)6], or Fe4[Fe(CN)6]3 resulted in a strong reduction of the 134 Cs-uptake by more than 97%. The decrease in enteral absorption depends on the dose of administered hexacyanoferrate(II), whereas differences between the compounds under study were small. The biological half-life of 134Cs in non-hexacyanoferrate(II) treated piglets was 21.6 +/- 3.3 days (mean +/- SD).

Animals↗
PubMed1988

Iron absorption in man calculated from erythrocyte incorporation of the stable isotope iron-54 determined by fast atom bombardment mass spectrometry.

The methodology of precise isotope abundance determinations of erythrocyte iron by fast atom bombardment mass spectrometry and signal averaging is established. For the determination of the 54Fe/56Fe ratio a relative precision of 0.5% and an absolute precision of 0.03% is achieved. After oral loading with 54Fe-enriched samples in the range between 5 and 25 mg per subject, the 14-day erythrocyte incorporation of 54Fe has been determined in five individuals, namely, two adults, two children, and one infant. In the two adults, the oral dose of 54Fe was simultaneously labeled with a trace amount of carrier-free 59Fe. In these double-isotope loading tests, a good agreement was observed between the absorption data determined on the basis of whole body retention of 59Fe and on the basis of the 54Fe erythrocyte incorporation. The stable isotope methodology applied allows measurement of the iron absorption using highly enriched 54Fe at a dose of 25 mg for an adult or at a dose of 5 mg for infants of about 1 year of age.

Adult↗
PubMed1988

Intestinal absorption of iron from 59Fe-labelled hexacyanoferrates(II) in piglets.

The intestinal absorption of 59Fe and 14C from hexacyanoferrates(II) was studied in piglets. KFeIII[FeII (CN)6] (I) and FeIII4[FeII(CN)6]3 (II) were labelled with 59Fe both in the Fe(III)-position (outside the complex anion, a) or in the Fe(II)-position (hexacyanoferrate anion, b). Labelling of the Fe(III)-position resulted in a 59Fe-absorption of 1.47% (Ia) and 1.34% (IIa), as judged by the 59Fe whole-body-retention measurement 14 days after oral administration. Even smaller amounts, 0.20% from Ib or 0.15% from IIb of the 59Fe-dose were absorbed and retained from the hexacyanoferrates(II) labelled in the Fe(II)-position. No 14CO2 was detected in the expired air of piglets after oral application of Fe4[59Fe(14CN)6]3, indicating that the amount of incorporated free cyanide ions can only be extremely small or even nil.

Administration, Oral↗
PubMed1987

Intestinal absorption of 59Fe from neutron-activated commercial oral iron(III)-citrate and iron(III)-hydroxide-polymaltose complexes in man.

Commercial oral iron preparations (drops) containing trivalent iron either as a citrate (C) or hydroxide-polymaltose complex (HP) were labelled with 59Fe in the thermal neutron flux of a research reactor. No measurable differences were observed between the original commercial preparation and the neutron-activated samples. In an intraindividual comparison oral doses of 100 mg 59Fe were administered as an aqueous 59Fe(II)-ascorbate solution (= reference), C (-59Fe) and HP (-59Fe) to starved subjects with normal and depleted iron stores. Two weeks later the whole body retention of absorbed 59Fe was measured and used for the calculation of 59Fe-absorption. Subjects with normal Fe-stores absorbed means a +/- SEM +/- SD = 8.53 +/- 0.29 +/- 1.2% of the 59Fe from the aqueous 59Fe(II)-ascorbate solution, 1.58 +/- 0.12 +/- 0.49 of the C-59Fe and 0.81 +/- 0.06 +/- 0.27% of the HP-59Fe. Subjects with depleted Fe-stores absorbed means a +/- SD = 17 +/- 3% of the 59Fe from the aqueous 59Fe(II)-ascorbate solution and only 2.4 +/- 1% from the HP-59Fe. The relative bioavailabilities were reduced from 100% (reference = Fe(II)-ascorbate) to 19% for the C-Fe and to 9.5% for the HP-Fe in subjects with normal Fe-stores. In subjects with depleted iron stores the relative bioavailability was decreased from 100 to 14% for the HP-Fe. Oral iron preparations with a relative bioavailability less than 10% or less than 30% are considered to be therapeutically ineffective or insufficient, respectively.

Biological Availability↗
PubMed1986

Metabolic conversion of L-[U-14C]phenylalanine to respiratory 14CO2 in healthy subjects, phenylketonuria heterozygotes and classic phenylketonurics.

Ten healthy volunteers, 12 classic phenylketonuria (PKU) heterozygotes, and 5 classic phenylketonurics have been loaded orally with a mixture of 5 microCi of L-[U-14C]phenylalanine plus 25 mg/kg of L-[2H5]phenylalanine. For 3 h thereafter, carbon-14 activity in expired air and total carbon dioxide were measured continuously and the levels of L-phenylalanine and L-tyrosine in plasma were determined in six blood samples. After 3 h, 15.1 +/- 2.1% of the applied dose of radioactivity was recovered in the expired air of the healthy subjects, compared to 10.1 +/- 2.2% for PKU heterozygotes and 0.32 +/- 0.18% for classic phenylketonurics. The integrated activity expired provides a discrimination between normals and PKU heterozygotes with a classification error of about 13% compared to an error of about 9% based on the fasting L-phenylalanine over L-tyrosine ratio. A combination of these two parameters in a two-dimensional discriminatory analysis reduces the classification error to less than 1%. An intraindividual correlation between the absolute activity expired and the formation of L-[2H4]tyrosine formed is shown, confirming that ring hydroxylation of L-phenylalanine to L-tyrosine is mandatory in the catabolism of L-phenylalanine to carbon dioxide.

Breath Tests↗
PubMed1986

The NIH-shift in the in vivo hydroxylation of ring-deuterated L-phenylalanine in man.

Oral loading with L-[ring-2H5]phenylalanine has been performed at a dose of 25 mg/kg for detection of heterozygotes for classic phenylketonuria. Using three differently labeled batches of ring-deuterated L-phenylalanine, quantitative analysis of deuterium-labeled L-phenylalanine and L-tyrosine in plasma revealed different label distributions. Three different reaction mechanisms for the 4-hydroxylation of L-phenylalanine to L-tyrosine were used as the basis for model calculations of the transformation of the L-phenylalanine label distribution into that of L-tyrosine. The best agreement between observed and calculated distributions was found for the mechanism involving a migration of the 4-substituent into the 3- or 5-position (NIH-shift), followed by a random loss of the 4-/3- or the 4-/5-substituent from this intermediate structure.

Adult↗
PubMed1986

Impaired phenylalanine-tyrosine conversion in patients with iron-deficiency anemia studied by a L-(2H5)phenylalanine-loading test.

Ten patients with manifest iron deficiency and without documented relationship to phenylketonuria patients were orally loaded with 25 mg/kg of L-(2H5)phenylalanine. Before loading, the fasting phenylalanine-tyrosine plasma ratio was determined and after loading, the concentrations of labeled and nonlabeled phenylalanine and tyrosine were determined in five consecutive plasma samples. With respect to the fasting phenylalanine-tyrosine ratio and to the post-load ratios of labeled phenylalanine over labeled tyrosine, the iron-deficient patients showed data intermediate between those of normals and heterozygotes for phenylketonuria. Compared to a 100% in vivo activity of phenylalanine hydroxylase in normals and a circa 37% activity in heterozygotes for classic phenylketonuria, iron-deficient patients with an average hemoglobin of 8.6 +/- 1 g/dl showed an activity of circa 56%. After normalization of their iron status, four patients were subjected again to the L-(2H5)phenylalanine-loading test. For three of these individuals, test results shifted into the range of normal.

Adult↗
PubMed1985

Oral versus intravenous L-phenylalanine loading compared by simultaneous application of L-[2H5] and L-[15N]phenylalanine.

Oral loading with 1.5 g of L-[15N]phenylalanine was performed simultaneously with an intravenous infusion of 1.5 g of L-[2H5]phenylalanine in two healthy volunteers with normal phenylalanine-hydroxylase activity. For both volunteers peak levels of oral L-[15N]phenylalanine were about 20 micrograms/ml compared to peak levels of around 50 micrograms/ml for intravenous L-[2H5]phenylalanine. Throughout the four hours following application, the plasma levels of the intravenously administered phenylalanine were higher than the plasma levels of the phenylalanine administered orally. In contrast, similar plasma levels of L-[15N]tyrosine and of L-[2H4]tyrosine formed in vivo by hydroxylation of the corresponding stable isotope labelled L-phenylalanine precursors were observed during the test, indicating that about equal fractions of both the oral and of the intravenous L-phenylalanine are converted into L-tyrosine.

Administration, Oral↗