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At least 649 records · Page 36Linked to original sources

PubMed1977

Tissue distribution of radioactivity in rats given tritiated analogues of hepatotoxic pyrrolizidine alkaloids.

1. [3H]Retronecine 7,9-bis-N-ethylcarbamate (RC) given intravenously (120 mg/kg) to male rats showed similar tissue distribution of radioactivity to that after an equally hepatotoxic dose (40 mg/kg) of [3H]synthanecine A bis-N-ethylcarbamate (SAC), but the 3H in most tissues after 3H-SAC was about double that after 3H-RC. 2. Concentrations of radioactivity were initially highest in liver and lung, but were higher in lung after 3H-RC than after 3H-SAC, reflecting the higher pneumotoxicity of the former. Concentrations of radioactive metabolites strongly attached to liver tissue were approx. the same 1 day after similarly hepatotoxic doses of either compound. 3. Excretion of radioactivity from 3H-RC was about double that from 3H-SAC in urine, and half that in faeces during the first day.

Animals↗

PubMed1989

Restricted tissue distribution of Mlsa determinants. Stimulation of Mlsa-reactive T cells by B cells but not by dendritic cells or macrophages.

Evidence was sought on the tissue distribution of Mlsa determinants, a class of cell-associated non-H-2 alloantigens that is highly immunogenic for unprimed T cells. Whereas normal CD4+ T cells and an Mlsa-reactive T hybridoma gave strong responses to Mlsa-positive stimulator populations containing Ig+ B cells, anti-Mlsa responses to B-depleted stimulators were almost undetectable. The B-depleted stimulators tested included Thy-1- spleen cells from mu-suppressed mice (mice treated with anti-mu antibody from birth) and J11d- preparations of spleen dendritic cells (DC) and peritoneal macrophages (M phi) from normal mice. Each of these populations was strongly immunogenic for allo-H-2-reactive T cells. The failure to detect Mlsa determinants on Ig- APC, i.e., M phi and DC, suggests that Mlsa determinants are not typical H-2-associated peptides. The data are more compatible with a model in which Mlsa determinants represent (or form part of) an integral cell membrane molecule expressed largely, and perhaps exclusively, on B cells. T cells might recognize these molecules only in native form, "processed" Mlsa determinants being nonimmunogenic. Consistent with this possibility, no evidence was found that Mlsa-negative B cells could absorb Mlsa determinants from Mlsa-positive B cells in a chimeric environment.

Animals↗

PubMed2003

Topical application of ALA and ALA hexyl ester on a subcutaneous murine mammary adenocarcinoma: tissue distribution.

Although 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has proven to be clinically beneficial for the treatment of certain cancers, including a variety of skin cancers, optimal tissue localisation still remains a problem. An approach to improve the bioavailability of protoporphyrin IX (PpIX) is the use of ALA derivatives instead of ALA. In this work, we employed a subcutaneous murine mammary adenocarcinoma to study the tissue distribution pattern of the ALA hexyl ester (He-ALA) in comparison with ALA after their topical application in different vehicles. He-ALA induced porphyrin synthesis in the skin overlying the tumour (SOT), but it did not reach the tumour tissue as efficiently. Only 5 h after He-ALA lotion application, tumour porphyrin levels surpassed control values. He-ALA delivered in cream induced a substantially lower porphyrin synthesis in SOT, reinforcing the importance of the vehicle in the use of topical PDT. Porphyrin levels in internal organs remained almost within control values when He-ALA was employed. The addition of DMSO to ALA formulation slightly increased tumour and SOT porphyrin biosynthesis, but it did not when added to He-ALA lotion.

Administration, Topical↗

PubMedDate not supplied

Tissue distribution of methylenedioxymethamphetamine.

Two cases of death involving methylenedioxymethamphetamine (MDMA) are reported; one case is a fatal acute overdose and the other is a drug-related death. The tissue distribution of MDMA is reported in both cases.

3,4-Methylenedioxyamphetamine↗

PubMed1999

Evaluation of the pharmacokinetic features and tissue distribution of the potent nonnucleoside inhibitor of HIV-1 reverse transcriptase, N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240) with an analytical HPLC method.

PURPOSE: The purpose of the present study was to examine the pharmacokinetic features and tissue distribution of N-[2-(2-fluorophenethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-240), a novel non-nucleoside inhibitor of HIV reverse transcriptase with potent anti-viral activity against AZT-sensitive as well as multidrug-resistant HIV-1 strains. METHODS: A sensitive and accurate high performance liquid chromatography (HPLC)-based quantitative detection method was established to measure concentrations of HI-240 in pharmacokinetic studies. The plasma concentration-time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameter values. RESULTS: HI-240 had an elimination half-life of 78.3 +/- 2.0 min after i.v. administration and 196.8 +/- 3.1 min after i.p. administration. The systemic clearance of HI-240 was 2194 +/- 61 ml/h/kg after i.v. administration and 9339 +/- 1160 ml/h/kg after i.p. administration. Following i.v. injection, HI-240 rapidly distributed to and accumulated in multiple tissues with particularly high accumulation in adipose tissue, adrenal gland, and uterus+ovary. The concentration of HI-240 in brain tissue was comparable to that in the plasma, indicating that HI-240 easily crosses the blood-brain-barrier. Following i.p. injection, HI-240 was rapidly absorbed with a t1/2ka and a tmax values of less than 10 min. Following oral administration, HI-240 was absorbed with a t1/2ka of 4.2 +/- 1.1 min and a tmax of 95.1 +/- 25.1 min. The intraperitoneal bioavailability was estimated at 23.5%, while the oral bioavailability was only 1%. CONCLUSIONS: The HPLC-based accurate and precise analytical detection method and pilot pharmacokinetic studies described herein provide the basis for advanced preclinical pharmacodynamic studies of HI-240. The ability of HI-240 to distribute rapidly and extensively into extravascular compartments and easily cross the blood-brain barrier represent significant pharmacokinetic advantages over AZT.

Administration, Oral↗

PubMed1991

Tissue distribution of selective warfarin binding sites in the rat.

Liver microsomes contain a specific warfarin binding site that is related to the target enzyme vitamin KO reductase [Thijssen HHW and Baars LGM, Biochem Pharmacol 38: 1115-1120, 1989]. In this study the distribution of the warfarin binder in the rat was investigated. Rats were given tracer doses of [14C]warfarin and tissue distribution was estimated after a time period. The selectivity of the distribution was verified by the ability of unlabeled warfarin to displace in vivo the tissue accumulated [14C]warfarin. The relation to the target enzyme vitamin KO reductase was verified by comparing the results with distribution behavior in the Scottish warfarin-resistant rat strain. The results show that in addition to liver various non-hepatic tissues accumulate warfarin. Among the tissues having a high accumulation ratio and a high rate of exchange by unlabeled warfarin are liver, pancreas, kidney, and salivary gland. Also arteria (aorta), bone, lung and spleen show exchangable [14C]warfarin accumulation. In HS rats the [14C]warfarin distribution was affected similarly for all tissues; lower levels of accumulation and higher rates of exchange by unlabeled warfarin. The tissue-bound warfarin was recovered predominantly in the microsomal fraction. Its release could only be accomplished in the presence of dithiothreitol and appeared to be stereoselective. The in vivo distribution pattern correlated with the number of warfarin binding sites in the tissue microsomes. The microsomal vitamin KO reductase activity did not always correlate to the binding capacity. The distribution was not affected by vitamin K deficiency. Warfarin-treated rats showed vitamin K epoxide accumulation in most of the organs having the warfarin binder.

Animals↗

PubMed1975

Dynamics of tissue distribution of radiopotassium as affected by simulated differences in regional extraction.

Simulation of tissue uptake and release of radiopotassium with a digital computer shows that tissue distribution of this diffusible indicator of regional blood flow will be essentially static during recirculation of the isotope despite large differences in regional extractions. Thus, the widely accepted view that static distribution results from homogeneous extractions may be invalid.

Computers↗

PubMed1980

Influence of dietary cystine on intestinal absorption and tissue distribution of methionine in the chick.

Studies were conducted on intestinal absorption and tissue distribution of methionine by chicks fed a crystalline amino acid diet containing .2% DL-methionine and .2 or .4% L-cystine or L-cysteine. Chicks fed the higher level of cystine or cysteine had previously been shown to exhibit depressed growth as opposed to chicks fed the lower level of these amino acids. In two experiments, 35S radioactivity of whole plasma and the protein and supernatant fractions were compared among chicks fed the different treatments at 30 or 60 min after oral intubation of L-[35S]-methionine into the crops. When the data were analyzed factorially, a significant level effect was noted for whole plasma and the protein and supernatant fractions, all of which were higher for chicks fed .2% L-cystine than those fed .4% L-cystine. Results with chicks fed the two levels of L-cysteine generally agreed with those of chicks fed L-cystine, although the differences were not as great. The labeled methionine was also added to diets containing .2 or .4% L-cystine of meal-fed chicks. Higher levels of radioactivity were observed in the liver but not in muscle or plasma of chicks fed the lower level of cystine at 7 hr after oral consumption of the isotope. No significant differences in liver, muscle, or plasma radioactivity were noted in a fourth experiment between chicks fed .2 or .4% L-cystine at 24 hr after intraperitoneal injection of L-[35S]-methionine. In vitro studies showed no differences in methionine accumulation by isolated intestinal segments incubated with three levels of cystine.

Animals↗

PubMed1986

Pharmacokinetics and tissue distribution of liposome-encapsulated cis-bis-N-decyl-iminodiacetato-1,2-diaminocyclohexane-platinum (II).

The pharmacokinetics and tissue distribution of a lipophilic analogue of cisplatin, cis-bis-N-decyl-iminodiacetato-1,2-diaminocyclohexane platinum (II) (N-decyl-IDP), were studied after the i.v. administration of the free drug in suspension in phosphate-buffered saline (F-N-decyl-IDP) and encapsulated in multilamellar liposomes comprising dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol at a molar ratio of 7:3 (L-N-decyl-IDP). The encapsulation efficiency and stability at 14 days of L-N-decyl-IDP were greater than 95%. The blood clearance of both forms of the drug fit a two-compartment model. The peak blood level of elemental platinum for L-N-decyl-IDP was fourfold higher than for the free drug (24.2 versus 6.1 micrograms/ml). In consequence, a fourfold difference in the volumes of distribution was observed (176 ml/kg for L-N-decyl-IDP versus 608 ml/kg for F-N-decyl-IDP). Liposome encapsulation reduced the drug clearance by threefold; therefore, the CXT of L-N-decyl-IDP was threefold higher than that of F-N-decyl-IDP (1308 micrograms platinum/ml per min versus 395 micrograms platinum/ml per min). Tissue platinum levels were significantly increased by liposome encapsulation in the lung (33 versus 3.6 micrograms/g), spleen (38.3 micrograms/g versus none detected), and liver (16.2 versus 11.7 micrograms/g), and unchanged in the kidneys. Although only F-N-decyl-IDP resulted in detectable levels of platinum in the small bowel (70.5 micrograms/g), the stool excretion was similar for both forms of the drug. The organ distribution changes secondary to liposome encapsulation may result in an increased antitumor activity of N-decyl-IDP in tumors involving the lung, spleen, and liver, and avoidance of gastrointestinal toxicity.

Animals↗

PubMed1986

Tissue distribution of 14C-labeled residues of aminocarb in brown bullhead (Ictalurus nebulosus Le Sueur) following acute exposure.

Young brown bullhead (Ictalurus nebulosus) were exposed to aminocarb (4-dimethylamino-3-methylphenyl N-methylcarbamate) at lethal and sublethal concentrations and the tissue distribution of total unspecified residues was examined. The concentration of residues in each tissue increased with the concentration of exposure. The liver and stomach/intestine accumulated the largest concentrations of residues of all the tissues studied except for the abdominal fat deposit, which could not be evaluated at all exposure concentrations. These two tissues also displayed a steady increase in the proportion of the total body burden of aminocarb residues during 4 days of exposure to 0.092 mg aminocarb/liter. The proportion of residues in the carcass at this level of exposure decreased steadily over this same period, but was more similar to that found during exposure at the two lethal concentrations (92.7 and 159.3 mg/liter) as opposed to that found at the intermediate, nonlethal exposure level of 41.1 mg/liter. For all tissues examined, the concentration of residues at the end of 4 days of exposure to 0.092 mg/liter was significantly lower than the peak concentration reached during the exposure period, and clearance of residues was found to be relatively rapid.

Animals↗

PubMed1994

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a noncalcemic analogue of 1 alpha, 25-dihydroxyvitamin D3, in rats.

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin (22-oxacalcitriol; OCT), a noncalcemic analogue of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], in rats were investigated. The binding affinity of OCT to plasma vitamin D binding protein (DBP) is extremely low and OCT mainly circulates in the blood as an intact form nonspecifically bound to lipoproteins especially to chylomicrons and low density lipoprotein (LDL). OCT intravenously injected into normal rats rats rapidly disappeared from the blood, and rapidly appeared in the bile as glucuronides of intact OCT and 1 alpha, 3 beta,20(S)-trihydroxy-9,10-secopregna-5,7,10(19)-triene (23,24,25,26, 27-pentanorOCT; pentanorOCT) as an OCT metabolite. When OCT or 1,25(OH)2D3 was injected into normal rats, significant amounts of OCT and 1,25(OH)2D3 were quickly detected in the thyroid and parathyroid glands, thymus, adrenals, liver, plasma, small intestine, kidneys, and calvaria. The detected amounts of OCT in the parathyroid glands, thymus, adrenals, liver, small intestine, and kidneys were significantly higher than the respective values for 1,25(OH)2D3 2 and/or 10 min after injection, while those of OCT in the plasma and calvaria were significantly lower than those of 1,25(OH)2D3. The in vivo rapid turn-over, nonspecific transportation, and incorporation of detectable amounts into the tissues are typical characteristics of OCT which may account for its specific activities.

Animals↗

PubMed1984

Absorption and tissue distribution of lead in thiamin-replete and thiamin-deficient rats.

Previous experimental results revealed that thiamin (vitamin B1) reduced lead (Pb) toxicity in calves and decreased tissue lead content in lead-treated calves and rodents. The objective of this experiment was to study the uptake and tissue distribution of lead in rats deprived of thiamin or given excess thiamin and to determine the effect of thiamin on lead absorption. Rats were divided into four groups and fed a thiamin-deficient or thiamin-supplemented diet. The thiamin-replete group also received daily injections of thiamin hydrochloride. Experimental diets were fed for 5 weeks, after which the rats were administered 10 muCi of 203Pb acetate (25 micrograms lead) and killed 6, 24, 48 or 72 hours later. Lead content and concentration of tissues increased twofold in the thiamin-replete group at 24 hours after dosing, but returned to control values 24 hours later. Tissue lead concentration of the thiamin-depleted group was slightly depressed at 24 hours after dosing, but this trend was reversed at the end of the experiment. Tissue lead concentrations in the pair-fed control group were three to seven times greater than in the other treatment groups 6 hours after dosing. The results indicate that thiamin facilitated absorption and increased the amount of lead initially taken up by tissue. Thiamin may also promote more rapid release of lead from tissues.

Animals↗

PubMed2003

Assessment of the tissue distribution of transplanted human endothelial progenitor cells by radioactive labeling.

BACKGROUND: Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs. METHODS AND RESULTS: Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [111In]indium oxine. EPCs (106) were injected in athymic nude rats 24 hours after myocardial infarction (n=8) or sham operation (n=8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, approximately 70% of the radioactivity was localized in the spleen and liver, with only approximately 1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02+/-0.19 in sham-operated animals to 2.03+/-0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69+/-1.54 in sham-operated animals to 4.70+/-1.55 (P<0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone. CONCLUSIONS: Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy.

Animals↗

PubMed1988

Tissue distribution of gallium following administration of the gallium-maltol complex in the rat: a model for an aluminium-maltol complex of neurotoxicological interest.

The intestinal absorption and subsequent tissue distribution of aluminium-maltol, a potentially neurotoxic complex found in foods, was investigated using gallium as a marker for aluminium. Gallium or gallium-maltol labelled with 67Ga was administered orally to rats. The amount of gallium in 'blood-free' tissues was measured by correcting for gallium in residual blood and an estimate of intestinal absorption was then made by summing the values for all tissues examined. In both the test (gallium-maltol dosed) and control (gallium only dosed) experiments absorption of gallium was significantly increased in the fasted state when compared with that of the fed animals. In fasted but not in fed animals, administration of gallium-maltol doubled the amount of gallium absorbed when compared with administration of gallium alone.

Aluminum↗

PubMedDate not supplied

Tissue distribution of the low molecular weight heparin, tinzaparin, following administration to rats by the oral route.

Heparins are antithrombotic drugs given by intravenous and subcutaneous routes. However, we have observed that heparins have antithrombotic activity in a rat model when administered orally despite low plasma levels, with low molecular weight heparins (LMWHs) being effective at lower single doses than unfractionated heparins (UFH). Since LMWHs may have other pharmaceutical uses and little is known regarding the pharmacokinetics of oral LMWHs, our objectives were to determine the distribution of the LMWH tinzaparin (Logiparin) following oral dosing. To study distribution at different doses, 0.025-15 mg/kg tinzaparin was given by stomach tube to rats. Gut and non-gut tissues were sampled 4 h later. In a time course study, plasma and tissue samples were collected at eight time points within 24 h after oral administration (60 mg/kg, 4 rats/time interval). Accumulated urine and faeces were collected over 4 and 24 h using metabolic cages. Gut tissue and washes, faeces, urine and non-gut tissue were extracted and analysed for heparin by agarose gel electrophoresis with toluidine blue staining. Activated partial thromboplastin time (APTT) and anti-Xa activity, by Heptest and chromogenic assay, estimated plasma tinzaparin concentrations. Stomach and lung tinzaparin concentrations demonstrated a dose-effect. Peak concentrations in tissue and washes of stomach, duodenum, jejunum, ileum and colon were at 6-30, 15-30, 30 min, 2 and 4 h, respectively. Amounts found at peak times in combined tissue and washes accounted for 46% and 0.5% in stomach (15 min) and colon (4 h), respectively. Tinzaparin was recovered from liver, lung, endothelial samples, and urine at 24 h, but not in faeces. Non-significant increases were seen in APTT and the Heptest, however, anti-Xa activity was significantly greater than control at all times examined, peaking at 2 h. No bleeding was observed. Results are consistent with oral absorption of tinzaparin with wide tissue distribution, likely on endothelium with little in plasma, as previously observed for UFH. Oral administration of LMWHs should be further studied.

Administration, Oral↗

PubMed2005

Tissue distribution of quercetin in rats and pigs.

Quercetin is a dietary polyphenolic compound with potentially beneficial effects on health. Claims that quercetin has biological effects are based mainly on in vitro studies with quercetin aglycone. However, quercetin is rapidly metabolized, and we have little knowledge of its availability to tissues. To assess the long-term tissue distribution of quercetin, 2 groups of rats were given a 0.1 or 1% quercetin diet [approximately 50 or 500 mg/kg body weight (wt)] for 11 wk. In addition, a 3-d study was done with pigs fed a diet containing 500 mg quercetin/kg body wt. Tissue concentrations of quercetin and quercetin metabolites were analyzed with an optimized extraction method. Quercetin and quercetin metabolites were widely distributed in rat tissues, with the highest concentrations in lungs (3.98 and 15.3 nmol/g tissue for the 0.1 and 1% quercetin diet, respectively) and the lowest in brain, white fat, and spleen. In the short-term pig study, liver (5.87 nmol/g tissue) and kidney (2.51 nmol/g tissue) contained high concentrations of quercetin and quercetin metabolites, whereas brain, heart, and spleen had low concentrations. These studies have for the first time identified target tissues of quercetin, which may help to understand its mechanisms of action in vivo.

Animals↗

PubMedDate not supplied

Experimental studies on thallium toxicity in rats. II--The influence of several antidotal treatments on the tissue distribution and elimination of thallium, after subacute intoxication.

The influence of several antidotal treatments--e.g. Prussian Blue + Furosemide, Furosemide, activated Charcoal, Potassium Chloride and Potassium Iodide--on the tissue distribution and elimination of thallium after subacute intoxication is studied. From these experiments, the fate of electrolytes (Na+, K+, Cl-) may be evaluated. It was established that the efficacy of an antidotal treatment in thallium intoxication may be judged not only by the determination of its ability to interfere in the reabsorption and redistribution of thallium. Prussian Blue was the only antidotal that did not cause such a dangerous redistribution.

Animals↗

PubMed1997

Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists.

We describe the cloning, characterization, and tissue distribution of the two human peroxisome proliferator activated receptor isoforms hPPARgamma2 and hPPARgamma1. In cotransfection assays the two isoforms were activated to approximately the same extent by known PPARgamma activators. Human PPARgamma binds to DNA as a heterodimer with the retinoid X receptor (RXR). This heterodimer was activated by both RXR agonists and antagonists and the addition of PPARgamma ligands with retinoids resulted in greater than additive activation. Such heterodimer-selective modulators may have a role in the treatment of PPARgamma/RXR-modulated diseases like diabetes. Northern blot analysis indicated the presence of PPARgamma in skeletal muscle, and a sensitive RNase protection assay confirmed the presence of only PPARgamma1 in muscle that was not solely due to fat contamination. However, both PPARgamma1 and PPARgamma2 RNA were detected in fat, and the ratio of PPARgamma1 to PPARgamma2 RNA varied in different individuals. The presence of tissue-specific distribution of isoforms and the variable ratio of PPARgamma1 to PPARgamma2 raised the possibility that isoform expression may be modulated in disease states like non-insulin-dependent diabetes mellitus. Interestingly, a third protected band was detected with fat RNA indicating the possible existence of a third human PPARgamma isoform.

Amino Acid Sequence↗