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At least 469 records · Page 26Linked to original sources

PubMed1984

The tissue distribution of thyroglobulin-responsive B and T cells in experimental autoimmune thyroiditis (EAT).

The tissue distribution of thyroglobulin antibody producing lymphocytes has been studied during the course of immunisation-induced experimental autoimmune thyroiditis in the rat. The iliac lymph nodes were initially the most important source of autoantibody but later in the disease the bone marrow and thyroid-draining lymph nodes were also involved. In addition small amounts of thyroglobulin antibody were made by thyroid-derived lymphocytes. A blastogenic response to thyroglobulin was found using lymphocytes from the iliac nodes initially and later from the spleen. These results demonstrate the widespread and sequential involvement of the lymphoid system in the autoimmune response to thyroglobulin.

Animals↗

PubMed1994

[Pharmacokinetics of paclitaxel in experimental animals. Part 2. Tissue distribution].

In S 180 bearing male mice, paclitaxel was rapidly distributed to various tissues within 10 minutes. The highest AUC was seen in the liver, and relatively high in the pancreas, kidney, thymus, intestine, stomach and lung. The concentration of paclitaxel in tumor tissue was not so high early time after administration, but was sustained for a long time with a half life of 12.3 hr. Elimination from the testis and thymus was also slow. The drug level in the brain was very low. In M 109 bearing female CDF1 mice, the distribution and elimination profile of paclitaxel was comparable to that in S 180 mice. The concentration of paclitaxel in the ovary, lung and uterus decreased slowly. In M 109 tumor, which was very sensitive to paclitaxel, the drug had a higher and long lasting distribution compared with S 180 tumor. In S 180 tumor bearing mice pretreated with CCl4, the paclitaxel level was found to be lower in the liver and higher in the other tissues including tumor, plasma, urine and bile than in non-treated mice.

Animals↗

PubMed1987

The absorption, tissue distribution and excretion of di-n-octyltin dichloride in rats.

In this study the absorption, tissue distribution and excretion of 14C-labeled di-n-octyltin dichloride ([14C]DOTC) in rats were investigated after oral and intravenous (i.v.) administration. Although after i.v. administration with 1.2 mg [14C]DOTC/kg body weight the tissue radioactivity was about 3-4 times higher than after oral administration with 6.3 mg [14C]DOTC/kg body weight, the relative tissue accumulation was found to be the same after the oral and i.v. dosage. The highest amount of radioactivity was found in liver and kidney, and to a lesser degree in adrenal, pituitary and thyroid glands. The lowest activity was recovered from blood and brain. No selective accumulation was observed in thymus, although it has been reported that thymus atrophy is the most sensitive parameter of DOTC toxicity in rats. For all tissues a time dependent decrease in radioactivity was found, except for kidney. The excretion of radioactivity in feces and urine was determined after a single i.v. or oral dose of 1.2 and 2 mg [14C]DOTC, respectively. After i.v. administration most of the radioactivity was excreted in the feces which was characterized by a biphasic excretion pattern. In orally treated rats more than 80% of the radioactivity was already excreted in the feces during the first day after administration. This indicated that only a small part of the DOTC was absorbed, which was calculated to be approximately 20% of the dose. Similar half-life values of 8.3 and 8.9 days were obtained from the fecal excretion of radioactivity after the i.v. and oral administration, respectively. The urinary excretion of radioactivity appeared to be independent of the body burden, since the daily amount of radioactivity excreted in urine was nearly the same independent of the route of administration as well as the time after administration.

Absorption↗

PubMed1991

Tissue distribution of type VIII collagen in human adult and fetal eyes.

The type VIII collagen tissue distribution in human adult (32-78 yr of age) and fetal (16-27 weeks of gestation) eyes was studied immunohistochemically using a monoclonal antibody to type VIII collagen. Type VIII collagen was distributed in a linear or fibrous fashion in adult eyes in Descemet's membrane of the cornea, the trabecular meshwork, the walls of Schlemm's canal, Bruch's membrane, the choroidal stroma, the sclera, the cribriform plates of the optic nerve, and the intima of the central retinal artery. The staining in the central retinal artery was similar to that of type IV collagen. No distinct positive staining was seen in other blood vessels. When fetal eyes were examined, significant differences in positive staining were found between adults and fetuses in the sclera. In fetal eyes, the posterior sclera was strongly stained; however, the positive staining gradually decreased, and in the equatorial area it disappeared. The cribriform plates of the lamina cribrosa and the presumptive Bruch's membrane in fetal eyes did not react with the antibody. The trabecular meshwork and Descemet's membrane, but no other part of anterior section of fetal eyes, reacted with the antibody.

Adult↗

PubMed1990

Placental transfer and tissue distribution of vitamin E in pregnant rabbits.

alpha-Tocopherol (vitamin E) is widely prescribed in neonatal intensive care units, in large doses and by different schedules, for the prevention of retrolental fibroplasia, intraventricular haemorrhage, bronchopulmonary dysplasia, and haemolytic anaemia. Since the efficacy of the drug in premature newborns seems related to early administration, the physicochemical characteristics of the drug itself and available formulations limit the major therapeutic aim of promptly raising levels of vitamin E in premature babies during the early hours of life. It has thus been suggested that vitamin E be given to the mother before delivery to produce higher drug concentrations in the newborn. To see whether this would work, the tissue distribution and transplacental transfer of vitamin E were studied in six pregnant rabbits at steady-state after an i.v. bolus + infusion to give a mean venous blood concentration of about 325 mumol l-1 of alpha-tocopherol acetate, corresponding to about 30 mumol l-1 of alpha-tocopherol. Endogenous levels were measured in six control pregnant rabbits. In treated animals alpha-tocopherol was increased in liver, spleen, placenta, lung, mammary gland, blood, and bile but not in brain, heart, fat, muscle or adrenals probably because distribution into these tissues is very slow. Vitamin E levels in the placenta of treated mothers were 15 times those of control rabbits, but the vitamin was not detectable in amniotic fluid and only very low levels were found in fetal blood. These findings do not indicate any advantage of giving mothers alpha-tocopherol acetate before delivery.

Animals↗

PubMed1994

Tissue distribution of ryanodine receptor isoforms and alleles determined by reverse transcription polymerase chain reaction.

The tissue distribution of mRNA for ryanodine receptor (ryr) isoforms in various porcine tissues has been determined using the reverse transcription-polymerase chain reaction (RT-PCR). First strand cDNA was synthesized from total tissue RNA with reverse transcriptase and random hexamer primers. PCR primers were selected to amplify an approximately 500-base pair segment from homologous regions near the 5' end of the skeletal (ryr1), cardiac (ryr2), or brain (ryr3) ryr cDNA sequences. The specific amplification of each of the ryr isoforms was confirmed by restriction enzyme mapping and DNA sequencing. A ryr1 RT-PCR product was identified in skeletal muscle and esophagus, a ryr2 RT-PCR product was identified in cardiac muscle, aorta and esophagus, and a ryr3 RT-PCR product was identified in skeletal and cardiac muscle, aorta, esophagus, adrenal gland, small intestine, and lung. All three ryr isoforms were identified throughout the brain, including the parietal, frontal, and temporal lobes of the cerebrum, thalamus/hypothalamus, cerebellum, and brain stem. The normal (Arg615) and mutant (Cys615) ryr1 alleles were expressed in the brains of normal and malignant hyperthermia susceptible pigs, respectively. These results thus demonstrate expression of two ryr isoforms in each type of striated muscle, and all ryr isoforms in a number of regions of the nervous system. The wide distribution of ryr1 in the brain provides a possible neurogenic etiology of malignant hyperthermia.

Alleles↗

PubMed2002

Bioaccumulation, elimination, and tissue distribution of chlorpyrifos by red hybrid Tilapia in fresh and brackish waters.

Bioaccumulation, degradation, elimination and tissue partitioning of chlorpyrifos (Dursban 25E) was studied under static conditions for 3-4 days, in fresh (FW) and brackish (BW) waters by two methods: in the renewal method, fish were transferred every 24 h to FW or BW aquaria containing 0.05 mg l(-1) of the insecticide; in the spiking method, the original concentration of 0.005 mg l(-1) was spiked every 8 h. Samples of fish and water were collected at regular intervals and residues determined gas chromatographically. In the renewal experiments with 0.05 mg l(-1), bioconcentration reached its peak within 8 h of exposure in FW (1.25 mg l(-1)) and within 1 h in BW (0.95 mg g(-1)); in spiking experiments with 0.005 mg l(-1), these peaks were attained in 48 h in FW (3.8 mg g(-1)) and 8-24 h in BW (1.67 mg g(-1)). Thereafter, the concentrations declined. The concentrations of an unidentified metabolite were generally but not always correlated with that of the parent compound. Upon exposure of contaminated fish to uncontaminated waters, 72% was eliminated within the first 12 h and 4% later in 60 h in FW, and only 23% in 1 h and another 21% in the following 60 h in BW. Concentration of the metabolite was very high during the elimination. In the renewal experiment with 0.05 mg l(-1) of chlorpyrifos, tissue distribution was much higher in FW than in BW, while the reverse was true in spiking experiments with 0.005 mg l(-1) of the chemical. Testis, heart and brain had the highest levels of residues, followed by ovaries and other tissues.

Animals↗

PubMed1985

Tissue distribution, developmental profiles and effect of denervation of enolase isozymes in rat muscles.

The tissue distribution of muscle-type alpha beta and beta beta enolases in rats were determined with the sandwich-type enzyme immunoassay method which utilized the purified antibodies specific to the alpha and to the beta subunit of enolase, and beta-D-galactosidase from Escherichia coli as label. All the tissues examined contained detectable levels of both alpha beta and beta beta enolases. The beta beta enolase was found at high levels in the skeletal muscle tissues (tongue, esophagus, diaphragm and leg muscles) and in the cartilages (xipoid process and auricular cartilage). The alpha beta enolase was distributed at a relatively high concentration in the heart and in the above-mentioned tissues. The beta beta enolase in the leg muscles, diaphragm and tongue was present on the day of birth at a concentration higher than that of the alpha alpha and alpha beta enolases, and its concentration further increased in a manner apparently related to the functional state of each tissue. Denervation of the leg muscles by cutting the sciatic nerve in adult rats resulted in a drastic change in the isozymes profile. The concentration of beta beta enolase in the tibialis anterior gastrocnemius lateralis and extensor digitorum longus (about 800 pmol/mg protein) decreased to about a half in a few weeks after denervation. In contrast, the concentrations of alpha alpha (2 pmol/mg) and alpha beta (80 pmol/mg) usually showed a slight increase by the treatment (alpha alpha, 7 pmol/mg; alpha beta, 100 pmol/mg after 2 weeks). As compared with these three muscles, the soleus had normally a low enolase level and the effect of denervation was less drastic. These results seem to suggest that the concentration of beta beta enolase is closely correlated with the functional state of the muscle tissue.

Animals↗

PubMed1987

Tissue distribution of mRNAs encoding the alpha isoforms and beta subunit of rat Na+,K+-ATPase.

The tissue distribution of the multiple forms of rat Na+,K+-ATPase was examined at the molecular level with cDNA probes specific for the alpha, alpha (+), alpha III and beta subunit mRNAs. Northern and slot blot analyses demonstrate that these mRNAs are produced in a tissue-specific manner. RNAs encoding the alpha (+) isoform are detected in kidney, brain, heart, adipose, muscle, stomach and lung, whereas alpha III RNA is detected in brain, stomach and lung. Both alpha and beta mRNAs are present in all the tissues studied, although at very different levels. Examination of heart tissue in greater detail demonstrates that the levels of mRNA encoding the alpha subunit are greater in the atria than in the ventricles, while the converse is true for alpha (+).

Animals↗

PubMedDate not supplied

Tissue distribution and hypotensive effect of prazosin in the conscious rat.

We investigated the hypotensive effect and tissue distribution of prazosin (1 mg/kg i.v.) in conscious rats. This dose caused an immediate fall in blood pressure, associated with a nonsignificant increase in heart rate. Blood pressure then gradually rose to control over a 2-h period. Prazosin was measured in plasma and tissue samples by high-pressure liquid chromatography. Highest concentrations of drug were found in liver and kidney and the lowest in brain. The rate of decline of prazosin from plasma was similar to its decline from the tissues, indicating a rapid equilibrium. This rate of disappearance was also similar to the decay of the hypotensive response and suggests that prazosin in plasma may be in equilibrium with prazosin at its site of action.

Animals↗

PubMed2003

Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment.

Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. However, how persisting virus impacts various CD8 T-cell effector functions and influences other aspects of CD8 T-cell dynamics, such as immunodominance and tissue distribution, remains largely unknown. Using different strains of lymphocytic choriomeningitis virus (LCMV), we compared responses to the same CD8 T-cell epitopes during acute or chronic infection. Persistent infection led to a disruption of the normal immunodominance hierarchy of CD8 T-cell responses seen following acute infection and dramatically altered the tissue distribution of LCMV-specific CD8 T cells in lymphoid and nonlymphoid tissues. Most importantly, CD8 T-cell functional impairment occurred in a hierarchical fashion in chronically infected mice. Production of interleukin 2 and the ability to lyse target cells in vitro were the first functions compromised, followed by the ability to make tumor necrosis factor alpha, while gamma interferon production was most resistant to functional exhaustion. Antigen appeared to be the driving force for this loss of function, since a strong correlation existed between the viral load and the level of exhaustion. Further, epitopes presented at higher levels in vivo resulted in physical deletion, while those presented at lower levels induced functional exhaustion. A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells. These results have implications for the study of human chronic infections, where similar T-cell deletion and functional dysregulation has been observed.

Animals↗

PubMed1982

Effect of chronic immobilization stress on tissue distribution of vitamin A in rats fed a diet with adequate vitamin A.

The effect of consecutive daily immobilized stress on the metabolism of vitamin A was studied in rats by following changes in tissue distribution of the vitamin for 14 days. Male rats, fed a diet with adequate vitamin A, were subjected to 4 hours of daily immobilization for 1, 3, 7, 10 or 14 days. Ponderal growth was completely abolished, and serum vitamin A fell markedly. The amount of vitamin A in liver, testes and kidney decreased after the first period of restraint. On the other hand, the amount of vitamin A in adrenal glands increased gradually and reached a maximum (+62.3%) on the 7th day. In conclusion, this experiment showed that daily intermittent immobilization provoked a marked change in distribution of vitamin A in tissues.

Animals↗

PubMed2005

[The tissue distribution in mice and pharmacokinetics in rabbits of oridonin-solid lipid nanoparticles].

AIM: To investigate the tissue distribution and pharmacokinetics of oridonin-solid lipid nanoparticles in animals. METHODS: HPLC method was established to determine the concentration of oridonin in serum of rabbits and in different tissues of mice. The results after tail iv administration of oridonin and oridonin solid lipid nanoparticles were compared. RESULTS: The relative tissue content of oridonin of solid lipid nanoparticles in the liver, spleen, lung, heart and kidney were 4.25%, 3.44%, 1.19%, 0.52% and 0.60%, respectively. The concentration-time curves of oridonin and oridonin solid lipid nanoparticles were both fitted to the three-compartment model. T(1/2)pi = 0.087 h, T(1/2)alpha = 1.65 h, T(1/2)beta = 32.36 h, V(C) = 0.66 mL.kg(-1). CONCLUSION: Solid lipid nanoparticles could increase the hepatic and lienic targeting efficiency of oridonin in mice and improve its bioavailability. Solid lipid nanoparticles were helpful for oridonin to reach a long circulation time and were hopeful to be its novel drug carrier.

Animals↗

PubMed2001

Enhanced systemic tissue distribution after dermal versus intravenous 3,3',4,4'-tetrachlorobiphenyl exposure: limited utility of radiolabel blood area under the curve and excretion data in dermal absorption calculations and tissue exposure assessment.

As a dioxin-like polychlorinated biphenyl (PCB), 3,3',4,4'-tetrachlorobiphenyl (TCB) is receiving increasing research and regulatory interest due to its high toxicity and persistence in the environment. (14)C-TCB was administered at an identical dose of 300 microg via the intravenous (iv) or dermal route to swine to examine the exposure route dependency of the relationship between tissue exposure and blood area under the curve (AUC) and the relationship between dermal absorption and excretion of radiolabel. After iv and dermal exposure, blood, urine, and feces samples were collected during the 11-day in vivo studies. At the end of the experiments, full mass balance studies were conducted to characterize tissue distribution of label. On average, over 70% of the applied dermal and iv doses were recovered. As expected, more than a 10-fold increase in blood AUC (0.49 vs 0.031, h x % dose/ml), plasma AUC (0.40 vs 0.038, h x % dose/ml), urine excretion (29 vs 2.3% of the applied dose), and fecal (30 vs 3.0% of the applied dose) excretion was determined after iv exposure compared to dermal exposure. However, we unexpectedly found that the tissue residue following iv exposure (8.0% of the applied dose) was only half that following dermal exposure (16% of the applied dose). Significantly larger (20- to 30-fold) ratios of blood AUC:tissue residue and excretion:tissue residue were observed after iv exposure compared to dermal exposure. This may indicate a route-related concentration-dependent blood-to-tissue partition process of pooled label, unique skin metabolism, or saturable hepatic metabolism of TCB. Thus, a long-term, low-input exposure pattern similar to this dermal exposure could be more harmful to systemic tissues than a short-term, high-dose exposure similar to this iv exposure. One should be aware that greater absorption, higher blood concentrations, greater blood and plasma AUCs, and greater excretion of label do not necessarily result in a greater overall tissue exposure and that some conventional approaches using label determination in blood and excreta without full mass balance studies may underestimate dermal absorption of chemicals similar to TCB.

Administration, Cutaneous↗

PubMed1983

Developmental pattern, tissue distribution, and subcellular distribution of cysteine: alpha-ketoglutarate aminotransferase and 3-mercaptopyruvate sulfurtransferase activities in the rat.

The tissue distribution, the subcellular distribution in liver, and the developmental patterns of cysteine:alpha-ketoglutarate aminotransferase (CAT) and 3-mercaptopyruvate sulfurtransferase (MPST) activities were determined in rats of the Sprague-Dawley strain. CAT activity was highest in heart and liver, whereas MPST activity was highest in liver and kidney. CAT activity was located primarily in the mitochondrial fraction with a low level of activity in all other fractions. MPST activity was located in both the mitochondrial and cytosolic fractions. The specific activity of CAT and MPST generally increased in rat liver, heart, and kidney during the developmental period from 18 days of gestation to 26 days after birth. Peak CAT-specific activity occurred at about 4 days of age and peak MPST activity occurred at about 21 days of age; peak activity of both CAT and MPST exceeded the adult specific activities. The distribution and developmental pattern of hydrogen sulfide production from cysteine, catalyzed by the coupled activities of CAT and MPST, was similar to those of CAT activity.

Animals↗

PubMed2002

Lack of association between adipose tissue distribution and IGF-1 and IGFBP-3 in men and women.

Insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), and obesity, and in particular visceral obesity, are putative cancer risk factors. Little is known, however, about the relationship between IGFs and obesity. We investigated the relationship between adipose tissue distribution and IGF-1 and IGFBP-3. Single-slice abdominal computed tomography scanning through the L4-L5 interspace was used to measure visceral adipose tissue (VAT) and subcutaneous adipose tissue (SQAT) in 432 community-based subjects (267 men, 165 women; ages, 55-77), participating in a cancer screening trial. Insulin, IGF-1, IGFBP-3, and the ratio of IGF-1:IGFBP-3, measured by radioimmunoassay, were compared with age, body mass index, absolute and relative VAT and SQAT, and total abdominal fat. We found that men had a higher mean IGF-1 (129.5 versus 108.9 ng/ml; P < 0.0001) and more VAT (201.5 cm(3) versus 166.6 cm(3); P < 0.0001) than women. In men and women, there was no correlation between IGF-1, IGFBP-3, or the ratio of IGF-1:IGFBP-3 with body mass index, total fat, VAT or SQAT, or fasting insulin. In contrast, fasting insulin was highly correlated to all measures of obesity (P = 0.0001). We conclude that obesity, adipose tissue distribution, and in particular VAT are not correlated with IGF-1, IGFBP-3, or the molar ratio of IGF-1:IGFBP-3. The lack of association between obesity and the IGF-1 axis suggests that the IGF-1 axis is not a likely mediator between VAT and disease.

Adipose Tissue↗

PubMed1987

Effect of disulfiram on milk transfer and tissue distribution of lead in the neonatal rat.

The effect of disulfiram (tetraethylthiuram disulphide) on uptake and tissue distribution of 203Pb was studied in neonatal rats exposed to lead via dams' milk. In the dams, treatment with disulfiram greatly increased the 203Pb concentration in brain and liver and decreased 203Pb concentration in plasma and erythrocytes, as compared to controls given only 203Pb. However, in the pups of disulfiram-treated dams total uptake of 203Pb was reduced by 50% and the concentration of 203Pb in brain and liver was significantly reduced. Consistent with these findings, the level of 203Pb in the maternal milk was lower in the disulfiram-treated dams compared to controls. It is suggested, that the lower lactational transfer and uptake of lead in the neonatal rat after treatment of the dams with disulfiram is due to retention and strong binding of lead to tissue components in the dams after formation of a lead-dithiocarbamate complex.

Animals↗

PubMed1992

Tissue distribution and antifungal effect of liposomal itraconazole in experimental cryptococcosis and pulmonary aspergillosis.

We studied the tissue distribution and in vivo antifungal effect of itraconazole, incorporated into pure dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes and administered intravenously. Eighty percent of the itraconazole was associated with DPPC. Drug levels in lung, brain, and liver, obtained after intravenous administration of tritiated itraconazole, were higher when the drug was administered intravenously as liposomal than when it was dissolved in cyclodextrin. Administration of the liposomal formulation also led to higher and sustained levels of intact itraconazole in serum. Efficacy was assessed in DBA/2 mice infected intravenously with 3 x 10(6) Cryptococcus neoformans, an inoculum responsible for early fatal pneumonia, or 3 x 10(5) C. neoformans, leading to delayed meningitis. In pneumonia, 20 mg/kg of liposomal itraconazole was more effective on survival than the same dose given intravenously in cyclodextrin or twice the dose administered orally dissolved in polyethylene glycol 200. In meningitis, liposomal itraconazole was also more efficient than the drug dissolved in cyclodextrin. These results were confirmed by colony counts in the brain and lung of infected mice. In immunosuppressed OF1 mice infected after inhalation of Aspergillus fumigatus spores, liposomal itraconazole (20 mg/kg x 3) was the only effective treatment. We conclude that intravenous liposomal delivery of itraconazole enhances both concentrations in infected tissues and the in vivo efficacy of the drug. Such passive targeting of antifungal agents other than amphotericin B might be helpful in the treatment of severe systemic mycoses, especially in the case of lung or brain involvement.

Animals↗