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At least 595 records · Page 33Linked to original sources

PubMed1992

Developmental profile and tissue distribution of Drosophila alcohol dehydrogenase: an immunochemical analysis with monoclonal antibodies.

To analyze Drosophila alcohol dehydrogenase gene (Adh) expression and tissue distribution at various developmental stages, we devised several immunochemical techniques making use of monoclonal antibodies against Drosophila alcohol dehydrogenase (ADH), which had been obtained previously. We here report their application to analyze the expression of Adh in a wild-type strain of D. melanogaster. s-ELISA tests were performed to evaluate fluctuations in ADH content and specific activity during development in individual organs as well as in whole individuals. In all cases, ADH specific activity appeared to be quite constant, which implies that variations in enzyme activity reflect differences in protein content. Immunoblottings of crude homogenates revealed immunoreactive low relative molecular mass peptides in addition to the 27 KD monomeric band, showing a conserved banding pattern in different organs and developmental stages. Immunohistochemical assays on whole organs were used to analyze the general pattern of ADH distribution. Immunoperoxidase staining of cryosections proved to be of crucial relevance, as it yielded full details of the tissue localization of ADH within the ADH-positive organs. We have shown not only that ADH displays a specific distribution in some organs but also that the enzyme is restricted to certain cell types.

Alcohol Dehydrogenase↗

PubMedDate not supplied

[Sex differences in the effect of acylhydrazines on temperature and pain threshold and in pharmacokinetics and tissue distribution].

It was shown that acylhydrazines derivatives display high sex selectivity during the action on normal or elevated temperature and pain threshold. Tissue distribution and the pharmacokinetics of 125I- or 131-I-p-aminobenzhydrazide in the blood of males and females were different. It is assumed that essential differences in the structure of cell membranes of males and females underlie the sex differences in the pharmacological effects of acylhydrazines.

Aniline Compounds↗

PubMed1999

Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis and in pathological processes such as tumor growth, rheumatoid arthritis, and ocular neovascularization. A recombinant humanized monoclonal antibody (rhuMAb), rhuMAb VEGF, has been developed to inhibit the effects of VEGF in the treatment of solid tumors. Intravenous and s.c. pharmacokinetic studies were conducted in mice, rats, and cynomolgus monkeys. In addition, the tissue distribution of i.v. 125I-rhuMAb VEGF was investigated in rabbits. At a dose of approximately 10 mg/kg, the clearance of rhuMAb VEGF from the serum was 15.7 ml/day/kg in mice, 4.83 ml/day/kg in rats, and 5.59 ml/day/kg in cynomolgus monkeys, and the terminal half-life ranged from 6 to 12 days in all species. After s.c. administration, rhuMAb VEGF had a bioavailability of 69% in rats and 100% in mice and cynomolgus monkeys. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of rhuMAb VEGF using allometric scaling in humans. The predicted serum clearance of rhuMAb VEGF in humans was 2.4 ml/day/kg and the terminal half-life was 12 days. Two hours after i.v. bolus administration of 125I-rhuMAb VEGF in rabbits, trichloroacetic acid-precipitable radioactivity was noted primarily in the plasma, with lesser amounts in highly perfused tissues such as kidneys, testes, spleen, heart, and lungs. At 48 h after dosing, trichloroacetic acid-precipitable radioactivity was noted in plasma with minimal distribution to testes, bladder, heart, lungs, and kidneys. Tissue distribution and pharmacokinetic data indicate that rhuMAb VEGF is cleared slowly and distributes to specific sites in the body.

Animals↗

PubMed1985

The tissue distribution of diazinon and the inhibition of blood cholinesterase activities in rats and mice receiving a single intraperitoneal dose of diazinon.

The tissue distribution of diazinon and the inhibition of cholinesterase (ChE) activities in plasma, erythrocyte and brain were investigated using male rats and mice which received a single intraperitoneal (i.p.) dose of diazinon (20 or 100 mg/kg body wt) in olive oil. The blood diazinon level was estimated to reach a maximum at 1-2 h after the i.p. administration. It was demonstrated that the diazinon residue levels are the highest in the kidney, when comparing the distribution of diazinon among liver, kidney and brain in the animals after dosing. It was indicated that the ChE inhibition by diazinon exposure is greater in the plasma than in the erythrocytes for male mice, while its inhibition is greater in the erythrocytes for male rats. Brain ChE activity was also inhibited markedly in the mice after dosing.

Animals↗

PubMed1997

Comparative pharmacokinetics, tissue distribution, and tumor accumulation of phosphorothioate, phosphorodithioate, and methylphosphonate oligonucleotides in nude mice.

The goals of this study were to systematically compare the pharmacokinetics and tissue distribution of phosphorothioate (PS), methylphosphonate (MP), and phosphorodithioate (PS2) oligonucleotide analogs; 15-mers of sequence d-TAC GCC AAC AGC TCC (5'-3') complementary to the AUG region of K-ras were radiolabeled with carbon-14. Oligomers were administered as a single dose in the tail vein of nude mice harboring a K-ras-dependent human pancreatic tumor (CFPAC1). The kinetics of PS, PS2, and MP oligomer availability in the bloodstream was followed. Concentration versus time profiles for all oligomers were biphasic, indicative of a two-compartment model. A rapid distribution phase with t1/2 alpha values of 1 minute or less and an elimination phase with average t1/2 beta values of 24-35 minutes were observed. Volumes of distribution (Vd) were 3.2, 4.8, and 6.3 ml for PS2, MP, and PS, respectively, in comparison to 3.6 ml for sucrose, a fluid-phase marker. Relative tissue drug levels obtained at 1 and 24 hours after administration were kidney > liver > spleen > tumor > muscle. Total kidney and liver oligonucleotide accumulation was approximately 7%-15% of the initial dose, with tumor accumulating 2%-3%. Intact compound was recovered from all tissues, including tumor, as assessed by high-pressure reversed-phase HPLC coupled to radiometric detection. Integrity of the oligonucleotides ranged from 73% in blood to 43%-46% in kidney and liver. Kidney and liver appear to be the primary sites of metabolism. These results demonstrate widespread tissue availability of these compounds and suggest their development as potential antitumor agents.

Animals↗

PubMed1994

Widespread tissue distribution of multiple mitochondrial DNA deletions in familial mitochondrial myopathy.

We used Southern blot analysis and the polymerase chain reaction to analyze the tissue distribution of multiple mitochondrial DNA (mtDNA) deletions in a 45-year-old man with familial mitochondrial myopathy-Southern blots showed two major types of abnormal mtDNA with approximately 4- and 8-kilobase deletions in the skeletal and extraocular muscles. The amount of muscle mtDNA with deletions correlated approximately with the severity of muscle involvement. The polymerase chain reaction showed multiple mtDNA deletions even in clinically asymptomatic tissues, the pattern of which differed with the type of tissue. Nucleotide sequences of several mtDNAs with deletions showed that the deletions were flanked by direct repeats consisting of 3 to 12 nucleotides. Leukocytes from the patient's affected sister and his mother exhibited the same mtDNA deletion pattern. Most of the same deletions were present in leukocytes obtained from the patient's father.

Adolescent↗

PubMed1983

Tissue distribution of styrene, styrene glycol and more polar styrene metabolites in the mouse.

A primary objective of the present investigation was to determine the tissue distribution of styrene, styrene glycol, and more polar metabolites in mice at different times (0.5-5 h) after the intraperitoneal administration of styrene (3.3 mmol/kg). Another aim was to determine the dose dependence of the metabolite pattern of styrene in the different tissues. The dose range chosen was 1.1-4.9 mmol of styrene/kg administered intraperitoneally, and the time delay 2 h after dosing. The highest initial concentrations of unchanged styrene were found in adipose tissue, pancreas, liver, and brain. Styrene glycol reached its maximum concentration within 1 h in most tissues. The levels in the kidneys, lungs, pancreas, and liver far exceeded those in subcutaneous adipose tissue. Only in the liver and kidneys was a notable amount of styrene glycol conjugated. Polar metabolites occurred to a considerable extent in the liver, kidneys, lungs, and plasma. The concentration of unmetabolized styrene seemed to increase exponentially with the dose in subcutaneous adipose tissue, liver, kidneys, lungs, and brain. No tendency towards a decreased relative occurrence of styrene glycol was observed at higher doses. However, when the dose was increased, the more polar metabolites occurred at relatively lower levels in all tissues except brain.

Animals↗

PubMed1990

Receptors for human interferon alpha on bovine cells: specificity and tissue distribution.

Human interferon alpha 1 (HuIFN alpha 1) is known to protect bovine as well as human cells against viral infection. Hence, we investigated the specificity and tissue distribution of receptors for HuIFN alpha 1 on various cells. [35S]HuIFN alpha 1 bound specifically to homogenates of bovine tissues and particularly to bovine liver, but there was also specific binding to spleen, kidney, brain, adrenal gland, lung, thymus, skeletal muscle, heart, mammary gland and testis. There was no difference in the degree of binding of HuIFN alpha to foetal or adult liver. Competitive binding experiments showed that bovine interferon alpha C (BoIFN alpha C) competed with HuIFN alpha 1 for binding to a bovine liver plasma membrane preparation, indicating that these two IFNs bind to the same receptor. An 35S-labelled IFN alpha 1-receptor complex was isolated from bovine liver extracts by SDS/polyacrylamide gel electrophoresis, and shown to have a molecular weight of 153 kDa. Isolation of the bovine IFN alpha receptor would be a feasible approach to the characterization of the HuIFN alpha receptor.

Animals↗

PubMed1996

A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death.

Members of the bcl-2 gene family are essential regulators of cell survival in a wide range of biological processes. A1, a member of the family, is known to be expressed in certain adult tissues. However, the precise tissue distribution and function of A1 remains poorly understood. We show here that A1 is expressed in multiple tissues during murine embryonic development. In the embryo, A1 was detected first at embryonic day 11.5 in liver, brain, and limbs. At day 13.5 of gestation, A1 expression was observed in the central nervous system, liver, perichondrium, and digital zones of developing limbs in a pattern different from that of bcl-X. In the central nervous system of 15.5-day embryos, A1 was expressed at high levels in the ventricular zone and cortical plate of brain cortex. Significantly, the interdigital zones of limbs and the intermediate region of the developing brain cortex, two sites associated with extensive cell death, were devoid of A1 and bcl-X. The expression of A1 was retained in many adult tissues. To assess the ability of A1 to modulate cell death, stable transfectants expressing different amounts of A1 protein were generated in K562 cells. Expression of A1 was associated with retardation of apoptotic cell death induced by actinomycin D and cycloheximide as well as by okadaic acid. Confocal microscopy showed that the A1 protein was localized to the cytoplasm in a pattern similar to that of Bcl-2. These results demonstrate that the expression of A1 is wider than previously reported in adult tissues. Furthermore, its distribution in multiple tissues of the embryo suggests that A1 plays a role in the regulation of physiological cell death during embryonic development.

Animals↗

PubMed1992

Sex hormones and adipose tissue distribution in premenopausal cigarette smokers.

Androgen dominance is associated with android (abdominal) adiposity and increased health risk. Cigarette smoking has an anti-estrogenic effect in women and recent evidence has linked cigarette smoking with abdominally-localized adipose tissue. The relationship between cigarette smoking, endogenous sex steroid levels and adipose tissue distribution in women has not been examined. We assessed anthropometric indicators of fat distribution and serum levels of estradiol, testosterone and sex hormone-binding globulin (SHBG) in 56 women aged 20-35 years (27 cigarette smokers and 29 non-smokers). Free estradiol and testosterone were estimated. Endocrine and anthropometric variables were adjusted for overall fatness. Cigarette smokers had significantly higher mean serum levels of SHBG than non-smokers (63.38 nmol/l and 57.85 nmol/l, respectively; P less than 0.01); there were no differences in serum estradiol, testosterone or estimated free levels of these sex steroids. Cigarette smokers had a more android distribution of adipose tissue: significantly greater waist-to-hip ratio (WHR) (P less than 0.01), greater waist-to-thigh ratio (WTR) (P less than 0.02) and smaller thigh girth (P less than 0.05). Waist and umbilical girths were greater in cigarette smokers (P less than 0.0002), but there was no difference in the sum of central skinfold thicknesses (abdominal, iliac crest and supra-spinale). A significant interaction (P less than 0.05) of cigarette smoking with serum testosterone levels was observed in effects on WHR; the relative impact of serum testosterone upon abdominal adiposity was greater in cigarette smokers than in non-smokers. The results suggest that in premenopausal women, cigarette smoking promotes android adiposity by increasing abdominal fat deposition and decreasing femoral fat deposition via interactive effects with sex steroids. The results also suggest an effect of cigarette smoking on serum SHBG, independent of effects on androgen/estrogen balance.

Abdomen↗

PubMed1996

A comparative study of tissue distribution and photodynamic therapy selectivity of chlorin e6, Photofrin II and ALA-induced protoporphyrin IX in a colon carcinoma model.

An in vivo study of tissue distribution kinetics and photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA), chlorin e6 (Chl) and Photofrin (PII) was performed to evaluate the selectivity of porphyrin accumulation and tissue damage effects in a tumour model compared with normal tissue. C26 colon carcinoma of mice transplanted to the foot was used as a model for selectivity assessment. Fluorescence measurements of porphyrin accumulation in the foot bearing the tumour and in the normal foot were performed by the laser-induced fluorescence (LIF) system. A new high-intensity pulsed light delivery system (HIPLS) was used for simultaneous irradiation of both feet by light in the range of 600-800 nm, with light doses from 120 to 300 J cm-2 (0.6 J cm-2 per pulse, 1 Hz). Photoirradiation was carried out 1 h after injection of ALA, 3 h after injection of Chl and 24 h after injection of PII. A ratio of porphyrin accumulation in tumour vs normal tissue was used as an index of accumulation selectivity for each agent. PDT selectivity was determined from the regression analysis of normal and tumour tissue responses to PDT as a function of the applied light dose. A normal tissue damage index was defined at various values (50, 80 and 100%) of antitumour effect. The results of the LIF measurements revealed different patterns of fluorescence intensity in tumour and normal tissues for ALA-induced protoporphyrin IX (ALA-PpIX), Chl and PII. The results of PDT demonstrated the differences in both anti-tumour efficiency and normal tissue damage for the agents used. The selectivity of porphyrin accumulation in the tumour at the time of photoirradiation, as obtained by the LIF measurements, was in the order ALA-PpIX > Chl > PII. PDT selectivity at an equal value of anti-tumour effect was in the order Chl > ALA-PpIX > PII. Histological examination revealed certain differences in structural changes of normal skin after PDT with the agents tested. The results of PDT selectivity assessment with respect to differences in mechanisms of action for ALA, Chl and PII are discussed.

Aminolevulinic Acid↗

PubMed1987

Immunodominance in the T cell response to multiple non-H-2 histocompatibility antigens. IV. Partial tissue distribution and mapping of immunodominant antigens.

The immunization of C57BL/6 responder mice with spleen cells from H-2-matched BALB.B donors, which differ by multiple non-H-2 histocompatibility (H) antigens, results in the generation of cytotoxic T lymphocytes (CTL) that are specific for only a limited number of immunodominant antigens. Previous analysis of the genes encoding these dominant antigens has not mapped these genes to any of the non-H-2 H loci defined by congenic strains. It would have been expected that the histogenetic techniques employed for congenic strain selection would have preferentially identified the "strongest" H antigens. Therefore, we have investigated the possibility that immunodominant antigens do not belong to the class of non-H-2 H antigens encoded by genes mapping to H loci defined and mapped by congenic strains. The first experiments were aimed at identifying antigens that were expressed by independently derived inbred strains and were cross-reactive with the immunodominant cytotoxic T cell target (CTT-1) antigen of BALB.B. Strong cross-reaction with the C3H.SW (H-2b) strain was observed; the C3H gene encoding this antigen was mapped with BXH recombinant inbred strains. Contrary to the mapping of the CTT-1 gene to chromosome 1 in BALB.B, the C3H gene was shown to map to either chromosome 4 or chromosome 7. This result indicates that identical, or at least extensively cross-reactive, non-H-2 antigens may be encoded by genes mapping to independently segregating loci in different inbred strains. The tissue distribution of immunodominant antigens was approached by determining the reactivity of CTL specific for these antigens with either lymphoid-derived or fibroblast-derived targets. These CTL effectively lysed lymphoblast and lymphoid tumor targets but did not lyse an SV40-transformed fibroblast line that was shown to be efficiently lysed by CTL specific for non-H-2 H antigens defined by congenic strains. Therefore, it was concluded that immunodominant antigens detected by B6 anti-BALB.B CTL have a restricted tissue distribution in comparison to non-H-2 H antigens defined by congenic strains. The implications of these results for our understanding of the origin and heterogeneity of non-H-2 cell-surface antigen recognized by effector T cells are discussed.

Animals↗

PubMed1999

Tissue distribution of dextran sulfate sodium (DSS) in the acute phase of murine DSS-induced colitis.

In the present study, we examined histochemically the tissue distribution of dextran sulfate sodium (DSS) in the acute phase of murine colitis induced by administering DSS in the drinking water. DSS was mainly observed in the Kupffer cells of the liver, in the macrophages of the mesenteric lymph node (MLN) and in the lamina propria of the large intestine after administration of DSS. We followed the time course of DSS distribution and found that DSS, which was considered as a large and negatively charged molecule that can not easily cross membranes, was distributed in the liver, the MLN, and the large intestine 1 day after the start of administration of DSS.

Animals↗

PubMed1998

Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats.

Ammonium chloride (NH4Cl) increases lysosomal pH and thereby abolishes intralysosomal accumulation of drugs. Its effect on the tissue distribution of biperiden and trihexyphenidyl in rats has been investigated. The tissue-plasma concentration ratios (Kp) of these drugs in various tissues were determined by infusion studies at steady-state in the presence or absence of NH4Cl. Treatment with NH4Cl reduced the Kp values for both drugs, causing the largest reduction in Kp in the lung (52.1 to 11.8 for biperiden and 59.5 to 18.9 for trihexyphenidyl; ratios of decrease 0.77 and 0.68, respectively), followed by the heart and kidneys, with relatively small reductions in the brain, gut, muscle and fat. Subcellular fractionation studies in the lung indicated that the subcellular fraction-plasma concentration ratio of each drug at the steady state (K(p,sf)) was reduced by treatment with NH4Cl, with the largest decrease in the post-nuclear fraction (ratio of decrease 0.82 for biperiden and 0.74 for trihexyphenidyl), followed by the nucleus, microsomes and supernatant, in that order. A strong correlation was found between the ratio of decrease in K(p,sf) after NH4Cl treatment and the specific activity of acid phosphatases, a marker of lysosomes, in each fraction (biperiden, r = 0.948; trihexyphenidyl, r = 0.945). These results suggest that acidic organelles contribute significantly to the distribution kinetics of anticholinergic drugs.

Adipose Tissue↗

PubMed1992

Stereoselective disposition and tissue distribution of carvedilol enantiomers in rats.

After intravenous bolus injection of rac-carvedilol at 2 mg/kg to the rat, the (+)-(R)- and (-)-(S)-enantiomer levels in the blood and tissues (liver, kidney, heart, muscle, spleen, and aorta) were measured by stereospecific HPLC assay. As compared with the (+)-(R), the (-)-(S) had a larger Vdss (3.32 vs. 2.21 liter/kg), MRT (33.4 vs. 25.6 min), and CLtot (96.1 vs. 83.8 ml/min/kg). AUC comparison after iv and po administration showed systemic bioavailability of the (-)-(S) to be about half that of its antipode, explained by the fact that the free fraction of the (-)-(S) in blood was 1.65-fold greater than that of the (+)-(R). Tissue-to-blood partition coefficient values for the (-)-(S) were 1.6- to 2.1-fold greater than those for the (+)-(R) in all tissues, showing that the (-)-(S) accumulates more extensively in the tissues. These results were consistent with the greater Vdss for the (-)-(S) estimated from systemic blood data. The stereoselective tissue distribution of carvedilol enantiomers results from an enantiomeric difference in plasma protein binding rather than in tissue binding.

Animals↗

PubMed1994

Zopiclone poisoning: tissue distribution and potential for postmortem diffusion.

Zopiclone is the first cyclopyrrolone hypnotic and is chemically unrelated to any existing drug. The authors studied the tissue distribution and postmortem redistribution of zopiclone in a fatal suicidal overdose. A 29-year-old female weighing 64 kg had cardiac blood ethanol 153 mg% and zopiclone blood concentrations in the range 0.9-2.0 microgram/ml in 10 distinct sampling sites. After 40 h at room temperature the range was 0.9-1.8 micrograms/ml in 15 samples. Portal venous blood and urine concentrations were 3.0 and 10.5 micrograms/ml, respectively. Tissue concentrations (microgram/g) were spleen 5.8, peri-renal fat 5.0, psoas muscle 3.3, brainstem 2.8, gastrocnemius muscle 1.9, myocardium 1.6, and kidney 1.7. Eight liver samples had concentrations in the range 0.5-4.9 micrograms/g, with highest concentrations in the left lobe and adjacent to the gallbladder, probably reflecting postmortem diffusion from gastric residue (700 ml, 55.1 micrograms/ml) and bile (14.1 micrograms/ml). Of six lung samples, paired upper and middle samples had concentrations in the range 2.1-2.3 micrograms/g, the right postero-basal 1.3 micrograms/g and the left postero-basal 3.4 micrograms/g. Drug concentration in putrefactive pleural fluid was also higher on the left (2.1 micrograms/ml) than the right (1.4 micrograms/ml), probably reflecting postmortem diffusion from gastric residue. The authors conclude that zopiclone showed little preferential concentration in solid organs and consequently has relatively stable postmortem blood concentrations, with little drug redistribution artefacts. Postmortem diffusion from gastric drug residue elevates drug levels in the left lobe of the liver and left lung lower lobe.

Adipose Tissue↗

PubMed2000

Pharmacokinetics and tissue distribution of amoxicillin in healthy and Salmonella Typhimurium-inoculated pigs.

OBJECTIVE: To determine pharmacokinetics and tissue distribution of amoxicillin in healthy and Salmonella Typhimurium-inoculated pigs. ANIMALS: 12 healthy pigs and 12 S Typhimurium-inoculated pigs. PROCEDURE: Concentration of amoxicillin in tissue was measured by use of high-performance liquid chromatography 4, 8, 12, and 24 hours after IM administration. Pharmacokinetic values of amoxicillin in plasma were assessed by use of a 1-compartment model with first-order absorption. RESULTS: Inoculation caused diarrhea and increased rectal temperature and WBC count. Absorption half-life was shorter in inoculated pigs (0.26 hours) than in healthy pigs (0.71 hours), and inoculated pigs had longer elimination half-life. Distribution ratios in healthy pigs ranged from 0.31 to 0.56 and in inoculated pigs ranged from 0.14 to 0.48. Ratios for distribution to intestinal mucosa ranged from 0.34 to 1.16 in healthy pigs and from 0.22 to 0.36 in inoculated pigs. CONCLUSIONS AND CLINICAL RELEVANCE: Salmonella Typhimurium inoculation altered absorption of amoxicillin from the injection site and prolonged elimination half-life. However, distribution of amoxicillin to intestinal tract tissue was only affected to a minor degree.

Amoxicillin↗

PubMed1988

Studies on the tissue distribution of the puromycin-sensitive enkephalin-degrading aminopeptidases.

An antiserum generated to the soluble form of the rat brain puromycin-sensitive enkephalin-degrading aminopeptidase was used to determine the tissue distribution of the soluble and membrane-associated forms of this enzyme. All tissues examined contained significant levels of the soluble enzyme form, with this enzyme accounting for greater than 90% of the arylamidase activity in brain, heart, and skeletal muscle. Native gel electrophoresis coupled with activity staining as well as inhibition studies were used to confirm the presence of this enzyme in various tissues. Serum was found not to contain this particular aminopeptidase. In contrast to the results obtained with the soluble enzyme form, brain was the only tissue found to contain the membrane-associated enzyme form. Although all tissues contained membrane-associated aminopeptidase activity only the brain enzyme could be maintained in solution in the absence of detergent. In addition, the brain membrane-associated enzyme could be distinguished from the membrane-associated aminopeptidase activity in other tissues on the basis of its sensitivity to inhibition by puromycin.

Aminopeptidases↗