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PubMed1975

Absorption, excretion and tissue distribution of natural organic and inorganic zinc-65 in the rat.

The absorption and tissue distribution of organic and inorganic forms of 65-Zn were studied in the rat following single tracer oral doses. Rats dosed with 65-Zn grown into young corn and rye plants (organic form) absorbed and retained more 65-Zn in tissues than those given 65-Zn mixed with tissue paper (inorganic forms). A part of the beneficial effect was evident when 65-Zn was mixed with forage. The relatively high absorption values indicate that both forms were readily available, and thus incorporating zinc into young forage protein is not of major practical importance.

Animal Feed↗

PubMed1988

Effects of adrenalectomy and of adrenal hormones on the tissue distribution of 14 elements in the rat.

The effects of adrenalectomy (ADY) and of replacement therapy using a mineralocorticoid, deoxycorticosterone (DOC) and a glucocorticoid, dexamethasone (DEX) on the tissue distribution of elements in the rat, were studied under semichronic conditions. The elements Na, K, Ca, Mg, Fe, S, P, Rb, Sr, Mn, Cu, and Zn were determined in whole blood, plasma, brain, liver, kidney, heart, skeletal muscle, spleen, thymus, and bone. Additionally, Mo was determined in kidney and liver and Ba in bone. ADY modified concentrations of all elements tested. Small changes were observed for K, Mg, Ca, S, and P, whereas much larger changes were noted for Na, Rb, and Sr. Cu, Zn, and Fe were mainly modified in liver and kidney, organs involved in storage and/or elimination. The consequences of ADY were corrected fairly well by DEX for Mg, Mn, Ca, Cu, and Mo; by DOC for Na and K, and by the two corticoids for Zn, Fe, Sr, and Rb. This study revealed that corticoids, mainly glucocorticoids, play an important role in the plasma and tissue balance of elements. It is suggested that these results may have a pathological and clinical significance.

Adrenal Cortex Hormones↗

PubMed1991

Tissue distribution, intracellular localization, and in vitro expression of bovine macrophage scavenger receptors.

Macrophage scavenger receptors are trimeric membrane proteins implicated in the pathologic deposition of cholesterol in atherogenesis. The authors have studied the tissue distribution and intracellular localization of bovine scavenger receptors using monoclonal antibovine receptor antibody IgG-D2. The receptor proteins were detectable in macrophages of various organs and tissues, particularly Kupffer cells, alveolar macrophages, and macrophages in the spleen and lymph nodes. In the brain, perivascular macrophages were immunoreactive with IgG-D2. Fibroblasts, endothelial cells, smooth muscle cells, and dendritic cells such as epidermal Langerhans cells, interdigitating cells, or follicular dendritic cells, however, showed no immunoreactivity to IgG-D2. Immunoelectron microscopy showed localization of reaction products for these receptors on the cell surface, vesicles, and endosomes of macrophages. Transient expression of bovine scavenger receptors on cultured cells shows that scavenger receptors are mainly expressed in the endoplasmic reticulum, nuclear envelope, and Golgi apparatus of nonmacrophage cells and moved to the cell surface and endosomes of macrophagelike cells. These results indicate that efficient intracellular transport of scavenger receptors in macrophages is mediated by a macrophage-specific transport system.

Acetic Anhydrides↗

PubMed1998

Tissue distribution of the guinea-pig decay-accelerating factor.

MCA44 is a monoclonal antibody (mAb) to guinea-pig decay-accelerating factor (DAF) and, using this mAb, tissue distribution of guinea-pig DAF was studied by immunofluorescence. Guinea-pig DAF was found to be expressed not only on the vascular endothelium but also on different types of cells, such as the tubular epithelium of the kidney, epidermal cells of the skin and synovial lining cells. As there was no significant reduction in staining intensity with MCA44 following treatment with phosphatidylinositol-specific phospholipase C, many guinea-pig DAF molecules expressed in these tissues may be of the transmembrane form.

Animals↗

PubMed1998

Identification and tissue distribution of human cystathionine beta-synthase mRNA isoforms.

Cystathionine beta-synthase (CBS) catalyzes the irreversible, serine-dependent conversion of homocysteine to cystathionine via a transsulfuration pathway. CBS deficiency not only is the leading cause of homocystinuria, an inherited genetic disorder, but may contribute to cardiovascular disease as well. We isolated three new isoforms of human CBS mRNA from a human liver cDNA library. We designate these CBS mRNAs as CBS 3, CBS 4, and CBS 5, and the CBS mRNAs reported previously by Kraus et al. (1993) (Hum. Mol. Genet. 2, 1933-1938) and Kruger and Cox (1994) (Proc. Natl. Acad. Sci. USA 91, 6614-6618) as CBS 1 and CBS 2, respectively. Sequence analyses show that the only difference among the five CBS mRNAs is at the beginning of the 5'-untranslated region. Tissue distribution studies reveal that liver and pancreas have the highest amounts of CBS mRNAs. CBS mRNA is present in all regions of the brain tested. We also report the differential distribution of CBS mRNA isoforms in tissues, showing that pancreas contains all five CBS isoforms and the liver has four CBS mRNA isoforms, CBS 1-4. The kidney contains only CBS 1 and CBS 2. In human fetal tissues, CBS 2 is present in the liver and kidney. PCR-based quantitative analyses of CBS mRNA isoforms in human liver demonstrate that CBS 1 and CBS 2 are the major species, with CBS 2 being more abundant, while CBS 3-5 are the minor species. Furthermore, results from our human liver cDNA screening and primer extension experiments show that each of the five CBS transcripts begins with a different exon, suggesting that CBS gene transcription might be regulated by more than one promoter.

Alternative Splicing↗

PubMed2000

Determining the state of the deceased during cardiopulmonary resuscitation from tissue distribution patterns of intubation-related lidocaine.

The objective of this study was to determine whether the concentrations of lidocaine, used for endotracheal intubation, in body fluids and tissues reflect the state of the circulation of the deceased during cardiopulmonary resuscitation. The tissue distribution of lidocaine was investigated in seven individuals (Cases 1-7) who underwent medical treatment with endotracheal intubation using Xylocaine jelly (a 2% lidocaine hydrochloride preparation), before being pronounced dead. Six patients (Cases 1-6) had cardiopulmonary arrest on arrival at hospital. In Cases 1-4, there was no restoration of heartbeat during cardiopulmonary resuscitation. However, systemic distribution of intubation-related lidocaine was observed and the kidney-to-liver ratios of lidocaine were less than 1. In Cases 5 and 6, the heartbeat resumed temporarily with cardiac massage, and a kidney-to-liver lidocaine ratio greater than 1 was observed. In Case 7, where the patient was comatose upon admission to hospital, the kidney-to-liver ratio of lidocaine was also greater than 1. These phenomena were substantiated in animal experiments. Our results indicate that the absorption of tracheal lidocaine during the artificial circulation resulting from cardiopulmonary resuscitation results in a kidney to liver ratio of less than 1, whereas absorption during natural circulation gives a ratio greater than 1. The kidney-to-liver ratio of intubation-related lidocaine may give useful information on the state of a patient during cardiopulmonary resuscitation.

Absorption↗

PubMed1985

Effect of butylated hydroxytoluene pretreatment on the excretion, tissue distribution and DNA binding of [14C]aflatoxin B1 in the rat.

The effect of butylated hydroxytoluene (BHT) pretreatment (0.5% in the diet for 10 days) on the excretion, tissue distribution and DNA binding of orally administered [14C]aflatoxin B1 (AFB1) was determined in male Fischer F344 rats. The amount of radioactivity excreted in the urine and faeces by 24 hr was higher in BHT-treated rats than in controls. Treatment with BHT enhanced the excretion of water-soluble metabolites in the urine and in the large intestines plus faeces at the earlier sampling times. The amount of radioactivity bound to hepatic nuclear DNA was six times less in the BHT-pretreated rats than in controls 6 hr after administration of the isotope. The half-lives of [14C]DNA in the rat liver were 30 and 46 hr for control and BHT-pretreated rats, respectively. These results indicate that BHT pretreatment may protect the animal from the carcinogenic effects of AFB1 by enhancing the detoxification and excretion of the mycotoxin.

Aflatoxin B1↗

PubMed2001

Tissue distribution and genetic typing of porcine circoviruses in pigs with naturally occurring congenital tremors.

Congenital tremors (CT) type A2 is associated with porcine circovirus (PCV) and deficient and abnormal myelin. The aim of this study was to determine the tissue distribution and genetic type of PCV in 1-2-day-old pigs with naturally occurring CT type A2 using in situ hybridization, polymerase chain reaction (PCR), and indirect fluorescent antibody tests on frozen tissue sections. CT-affected and clinically normal pigs were selected from 4 farms in the midwestern USA that were undergoing outbreaks of CT type A2. All CT and most normal pigs were infected with PCV. PCV was widely distributed in tissues of infected pigs and was most common in tissues of the central nervous system and liver. In all infected pigs, there were more PCV-infected cells in brain and spinal cord than in nonneural tissues. CT pigs had many more PCV-infected cells in the brain and spinal cord than did clinically normal pigs because of a more diffuse distribution and a larger proportion of infected cells. The cells most commonly infected with PCV in brain and spinal cord were large neurons. In nonneural tissues, macrophages were the most frequent cell type infected. PCR analysis demonstrated only PCV type 2 and not PCV type 1 in all PCV-infected pigs on all 4 farms.

Animals↗

PubMed1988

Tissue distribution of 125I-labelled bovine superoxide dismutase (SOD) in the rat.

Bovine copper/zinc superoxide dismutase (SOD) was labelled with 125I using the chloramine-T method. The tissue distribution of 125I-SOD (dose of SOD 5 mg/kg) was studied with whole-body and microautoradiography at various times after an intravenous injection. The distribution of 125I-SOD showed a remarkable organ specificity in that the localization of the enzyme to the kidneys and the urinary tract completely dominated the autoradiograms. The time pattern of localization of 125I-SOD also gives a clear picture of the renal handling of the enzyme in that, as a consequence of the renal elimination, the enzyme rapidly disappears from the circulation with an elimination half time of about 6 min. Up to 20 min. after the injection, there were high concentrations of 125I-SOD in the renal pelvis, ureter and urinary bladder showing that in addition to renal uptake there was an initial substantial urinary excretion of the enzyme. From the microautoradiography it is clear that the grains were exclusively localized over proximal tubular cells and tended to be concentrated at the luminal rather than the peritubular side of tubule. This would be compatible with renal uptake secondary to glomerular filtration of 125I-SOD, which is what one would expect from the renal handling of a protein with a molecular weight around 31,000 and an isoelectric point around pH 5.4. Pretreatment with a large dose of SOD (88 mg/kg) tended to competitively decrease the renal uptake of labelled SOD after 5 min. and apparently further increase its renal excretion. However, a noticeable renal uptake of 125I-SOD was still apparent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in a freshwater snail (Bellamya aeruginosa) from a large shallow, eutrophic lake of the subtropical China.

Tissue distributions and seasonal dynamics of the hepatotoxic microcystins-LR and -RR in a freshwater snail (Bellamya aeruginosa) were studied monthly in a large shallow, eutrophic lake of the subtropical China during June-November, 2003. Microcystins (MCs) were quantitatively determined by High-Performance Liquid Chromatography (HPLC) with a qualitative analysis by a Finnigan LC-MS system. On the average of the study period, hepatopancreas was the highest in MC contents (mean 4.14 and range 1.06-7.42 microg g(-1)DW), followed by digestive tracts (mean 1.69 and range 0.8-4.54 microg g(-1)DW) and gonad (mean 0.715 and range 0-2.62 microg g(-1)DW), whereas foot was the least (mean 0.01 and range 0-0.06 microg g(-1)DW). There was a positive correlation in MC contents between digestive tracts and hepatopancreas. A constantly higher MC content in hepatopancreas than in digestive tracts indicates a substantial bioaccumulation of MCs in the hepatopancreas of the snail. The average ratio of MC-LR/MC-RR showed a steady increase from digestive tracts (0.44) to hepatopancreas (0.63) and to gonad (0.96), suggesting that MC-LR was more resistant to degradation in the snail. Since most MCs were present in the hepatopancreas, digestive tracts and gonad with only a very small amount in the edible foot, the risk to human health may not be significant if these toxic parts are removed prior to snail consumption. However, the possible transference of toxins along food chains should not be a negligible concern.

Animals↗

PubMed1975

The objective and timing of drug disposition studies, appendix I. Species differences in the tissue distribution of metazimid, an imidazolone derivative.

A marked species difference has been observed in the tissue distribution of metazimid in the rat vs the dog after repeated doses. Differences in toxicity between these species are consistent with tissue levels but not plasma levels. No species differences in patterns of drug metabolism could be found in association with the marked difference in tissue cumulation.

Animals↗

PubMed2000

Tissue distribution and interindividual variation in human UDP-glucuronosyltransferase activity: relationship between UGT1A1 promoter genotype and variability in a liver bank.

The variability in a liver bank and tissue distribution of three probe UDP-glucuronosyltransferase (UGT) activities were determined as a means to predict interindividual differences in expression and the contribution of extrahepatic metabolism to presystemic and systemic clearance. Formation rates of acetaminophen-O-glucuronide (APAPG), morphine-3-glucuronide (M3G), and oestradiol-3-glucuronide (E3G) as probes for UGT1A6, 2B7, and 1A1, respectively, were determined in human kidney, liver, and lung microsomes, and in microsomes from intestinal mucosa corresponding to duodenum, jejunum and ileum. While formation of E3G and APAPG were detectable in human kidney microsomes, M3G formation rates from kidney microsomes approached the levels seen in liver, indicating significant expression of UGT2B7. Interestingly, rates of E3G formation in human intestine exceeded the hepatic rates by several fold, while APAPG and M3G formation rates were low. The intestinal apparent Km value for E3G formation was essentially identical to that seen in liver, consistent with intestinal UGT1A1 expression. No UGT activities were observed in lung. Variability in APAPG and M3G activity across a bank of 20 human livers was modest (< or = 7-fold), compared to E3G formation, which varied approximately 30-fold. The E3G formation rates were found to segregate by UGT1A1 promoter genotype, with wild-type (TA)6 rates significantly greater than homozygous mutant (TA)7 individuals. Kinetic analyses were performed to demonstrate that the promoter mutation altered apparent Vmax without significantly affecting apparent Km. These results suggest that glucuronidation, and specifically UGT1A1 activity, can profoundly contribute to intestinal first pass metabolism and interindividual variability due to the expression of common allelic variants.

Acetaminophen↗

PubMed1998

Tubular localization and tissue distribution of peptide transporters in rat kidney.

PURPOSE: To define the tubular localization and tissue distribution of PEPT1 (low-affinity, high-capacity transporter) and PEPT2 (high-affinity, low-capacity transporter) in rat kidney. METHODS: mRNA expression of PEPT1 and PEPT2 was assessed with reverse transcription-polymerase chain reaction (RT-PCR) methods using cDNA prepared from microdissected nephron segments in rat. Tissue localization of rat renal PEPT1 and PEPT2 mRNA was further assessed by in situ hybridization with radiolabeled probes. RESULTS: RT-PCR analysis of microdissected segments from rat nephron showed that both PEPT1 and PEPT2 are confined to a proximal tubule. While PEPT1 is specific for early regions of the proximal tubule (pars convoluta), PEPT2 is overwhelmingly but not exclusively expressed in latter regions of the proximal tubule (pars recta). All other segments along the nephron were negative for PEPT1 or PEPT2 mRNA transcripts. These finding were supported by in situ hybridization results in which PEPT1 was selectively expressed in kidney cortex and PEPT2 in the outer stripe of outer medulla. CONCLUSIONS: Contrary to current opinion, the data suggest that peptides are handles in a sequential manner in proximal regions of the nephron, first by the low-affinity, high-capacity transport system and second by the high-affinity, low-capacity transport system.

Animals↗

PubMed1998

Effect of the Mdr1a P-glycoprotein gene disruption on the tissue distribution of SDZ PSC 833, a multidrug resistance-reversing agent, in mice.

The involvement of mdr1a P-glycoprotein (P-gP) on the tissue distribution of the multidrug resistance-reversing agent SDZ PSC 833 was assessed by use of mdr1a (-/-) mice. The mdr1a (-/-) and wild-type mdr1a (+/+) mice received a 4-h constantrate i.v. infusion (2 micrograms/min) of [14C]SDZ PSC 833. Mice were sacrificed at 0, 0.5, 1, 2 and 4 h during infusion and at 0.5, 1, 3, 8 and 24 h after stopping the infusion. Blood and tissues were analyzed on total (14C) and parental SDZ PSC 833 concentrations. Mdr1a (-/-) mice exhibited increased SDZ PSC 833 accumulation in cerebrum, cerebellum and somewhat in testes and small intestine compared with the wild-type mice. The difference between mdr1a (-/-) and (+/+) brain (cerebrum and cerebellum) penetration depended on SDZ PSC 833 blood concentrations, because this cyclosporin analog apparently governs its own brain penetration by inhibiting the P-glycoprotein pump in mdr1a (+/+) mice. Thus the mdr1a (-/-)/(+/+) ratio of brain concentrations tended to decrease and increase at high and low blood concentrations, respectively. These findings clearly demonstrate the interaction of SDZ PSC 833 with the P-glycoprotein present at the blood-brain barrier. The SDZ PSC 833 distribution in other mdr1a P-glycoprotein-expressed tissues, as well as its metabolism and elimination, was not affected by the mdr1a gene disruption. This suggests that factors other than mdr1a P-gP are involved in the disposition of this multidrug resistance-reversing agent.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Tissue distribution of human IgG Fc receptors CD16, CD32 and CD64: an immunohistochemical study.

The tissue distribution of human IgG Fc receptors (Fc gamma Rs) classified in three clusters of differentiation (CD16, using 5 antibodies, CD32, using 2 antibodies; and CD64, using 3 antibodies) was evaluated by immunohistochemistry on lymphoid (lymph node, spleen, thymus, tonsil) and non-lymphoid (heart, jejunum, kidney, liver, lung, muscle, stomach, and skin) tissues. Macrophage-like cells, including Kupffer cells, expressed all three classes of Fc gamma R. Part of the cells coexpressed HLA-DR. Interdigitating dendritic cells that were present in high density in interfollicular areas of a lymph node showing dermatopathic lymphadenopathy were immunoreactive for CD32, but not for CD16 or CD64 antibodies. In lymphoid tissue, mantle zones of secondary follicles were labeled by CD32 and some CD16 antibodies. The immunolabelling of mantle zones was not present after washing the sections at low pH, which suggests that the molecules detected were passively absorbed on the cell surface (i.e. soluble Fc gamma R). The immunolabelling of tonsil sections by various CD16 antibodies showed three patterns. The first (anti-Leu-11b) revealed labelling of solitary macrophage-like cells. The second (BW209/2 and 3G8) revealed, in addition, labelling of germinal centres. The third (CLBgran1 and CLBgran11) revealed labelling of solitary cells and follicle mantles. This labelling on tissue sections was also seen in the analysis of follicular dendritic cells isolated from tonsil. The cells were faintly immunoreactive for 3G8, as well as for CD16 mAb CLBgran1, and both CD32 mAbs. In all tissues investigated there was immunoreactivity for Fc gamma Rs in varying intensity on endothelial cells of blood vessels.

Antibodies, Monoclonal↗

PubMed1988

Tissue distribution of an endogenous ligand to the Na, K ATPase molecule.

A variety of evidence indicates the presence of a circulating ligand to the Na, K ATPase molecule that is involved in the regulation of extracellular sodium metabolism. To examine the potential role of endogenous ligands to the Na, K ATPase molecule in the regulation of intracellular sodium metabolism, the tissue distribution of digitalis-like activity was quantitated in several brain regions and peripheral organs. The digitalis-like activity of desalted and delipidated extracts of tissue was widely distributed and produced a displacement of tritiated ouabain that was parallel to the displacement produced by cold ouabain. These results suggest that tissue contains an endogenous ligand to the Na, K ATPase molecule and that this ligand may regulate intracellular sodium metabolism in an autocoid-like manner.

Animals↗

PubMed2006

Pharmacokinetic, tissue distribution, and excretion of puerarin and puerarin-phospholipid complex in rats.

Puerarin is a potential therapeutic agent for cardiovascular diseases. But its poor oral bioavailability restricts its clinical application. In present study, as an evaluation of a formulation to improve the bioavailability of the drug, puerarin and its phospholipid complex were given to rats by intragastrically (i.g.) administration to compare pharmacokinetic, tissue distribution, and excretion. Serum samples were obtained at designated times after a single oral dose of 400 mg/kg puerarin or its complex. Tissue samples (heart, liver, spleen, kidney, lung, and brain), urine, and feces were collected and analyzed by a sensitive and specific high performance liquid chromatography (HPLC) method after i.g. administration of puerarin or its phospholipid complex. Compartmental and non-compartmental analyses were applied to the serum concentration versus time data. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic software package. An open two-compartment, first-order model was selected for pharmacokinetic modeling. The results showed that after i.g. administration of 400 mg/kg puerarin and its phospholipid complex (equivalent to 400 mg/kg of puerarin), the pharmacokinetic parameters of the two formulations were different. The serum concentrations reached peaks at 0.894+/-0.521 h and 0.435+/-0.261 h, respectively, indicating the complex was more readily absorbed in serum than puerarin. The maximum concentrations for puerarin and its complex were 1.367+/-0.586 mg.L(-1) and 2.202+/-1.28 mg.L(-1) and AUC were 5.779+/-1.662 mg.h. L(-1) and 8.456+/-0.44 mg.h L(-1), respectively, indicating a higher bioavailability for the complex. The widely distribution characteristics of puerarin and its complex in tissues post-i.g. administration was identical and in a descending order as follows: lung, kidney, liver, heart, spleen, and brain. However, the amount was different. Puerarin distribution was higher in heart, lung, and brain after administering the complex. The cumulative 72 h urinary excretion of puerarin after i.g. administration of puerarin and its complex accounted for 1.05%, 1.11% of the administered dose, respectively. The cumulative feces excretion of puerarin was 32.3% and 25.5%. To sum up, oral administration of puerarin phospholipid complex modified the pharmacokinetics and tissue distribution of puerarin and it could be an effective oral formulation for puerarin.

Administration, Oral↗

PubMed2004

Pharmacokinetics and tissue distribution of platinum in rats following single and multiple oral doses of LA-12 [(OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV)].

The pharmacokinetics of total and free plasma platinum (Pt) and Pt tissue distribution were investigated in rats after oral administration of (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) (LA-12). Plasma and ultrafiltrate were sampled until 48 h and tissue samples were taken at 24 and 48 h after single doses of 38.6 or 540 mg LA-12/kg, and after once-a-day dosing of 4.3 or 38.6 mg kg(-1) LA-12 over 14 consecutive days. Total plasma Pt concentrations increased less than proportionally to the 14-fold increase in the single dose. The mean C(max) values of 1.5 and 6.3 mg L(-1) were observed at 0.5 and 1 h, respectively, and the mean AUC values achieved were 29 and 144 mg h L(-1). The highest tissue Pt concentrations were found in the liver and kidneys. Platinum was undetectable in the brain while in other tissues (muscle, skin, heart, lungs), the concentrations were lower (after single dose) or similar (after multiple doses) when compared to the plasma C(max) values. Plasma Pt concentrations after once-a-day dosing of 38.6 mg kg(-1) were two- to three-fold less than that after a single dose while Pt concentrations in various tissues rose two- to four-fold. Accumulation of Pt was even higher in the kidneys (seven-fold) and spleen (nine-fold). After once-a-day dosing, tissue Pt levels increased proportionally with the dose within the range from 4.3 to 38.6 mg kg(-1). At the same time, the increase in total plasma Pt concentrations was 40% less than proportional. Concentrations of Pt in the plasma ultrafiltrate decreased rapidly with the initial half-life of 1 h.

Administration, Oral↗