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PubMed1991

Toxicity and tissue distribution of pentachlorophenol and permethrin in pipistrelle bats experimentally exposed to treated timber.

The dependence of bats in Britain on houses as roosts may result in them being exposed to pesticides used in remedial timber treatments. Pentachlorophenol (PCP) and permethrin are used as a fungicide and an insecticide for timber treatment, respectively. The present study investigated toxicity and distribution in body tissues of these two pesticides in pipistrelle bats. Four groups of nine to ten bats were kept in separate outdoor flight enclosures and were provided with roost boxes treated with either PCP only, permethrin, PCP/permethrin mixture or solvent only (control). At the start of the experiment, mean (+/-SE) PCP and permethrin concentrations on the surface of wooden blocks that had been treated in the same way as roost boxes were 69.32+/-6.76 mg g(-1) (n=6) and 3.3+/-1.6 mg g(-1) (n=3), respectively. All bats exposed to PCP and PCP/permethrin treated boxes died within 24 and 120 h, respectively; nine out of the ten controls survived the 32 day experimental period (P<0.001; both groups compared with control). Bats exposed to permethrin treated boxes survived as well as controls. Mean (+/-SE) carcass PCP concentration (excluding deposits on fur) of bats exposed to PCP and PCP/permethrin treated boxes was 13.11+/-2.52 microg g(-1)BW (n=20). PCP burdens on fur were positively correlated with total weight of PCP in the carcass (P<0.001). PCP was present in fat depots, liver, kidney and the remainder of the body which, despite containing low PCP concentrations, was the main PCP reservoir (66.4+/-5.0% of carcass PCP load; n=20). Total PCP in the carcass was significantly correlated with lipid weight (P<0.005). Permethrin was not detectable in body washes and tissues of bats exposed to PCP/permethrin mixture or permethrin.

Journal Article↗

PubMed1993

Adipose tissue distribution as assessed by magnetic resonance imaging and total body fat by magnetic resonance imaging, underwater weighing, and body-water dilution in healthy women.

A method for estimating total body fat (TBF) and the amount and distribution of adipose tissue in humans by using magnetic resonance imaging (MRI) is described. Thirty transaxial images of subjects were taken by a nuclear magnetic imager (0.02 T). Adipose tissue volume was calculated from adipose tissue area in each image and from the distances between images. The CV when estimating total volume of body adipose tissue was 1.5%. TBF of healthy Swedish women was estimated by the MRI method (n = 25), by underwater weighing (UWW) (n = 20), and by body-water dilution (BWD) (n = 23). When assessed by MRI and BWD, women contained 1.4 +/- 2.9% less and 4.7 +/- 4.0% more TBF, respectively, than when assessed by UWW. On average, 74.2% of total adipose tissue volume was situated subcutaneously. Subcutaneous fat:fat-free body weight and nonsubcutaneous fat:fat-free body weight were both significantly correlated with percent TBF but the women stored excess fat subcutaneously rather than nonsubcutaneously.

Adipose Tissue↗

PubMed1991

Three types of mouse peptidylarginine deiminase: characterization and tissue distribution.

Three types of mouse peptidylarginine deiminase were separated by DEAE-Sephacel ion-exchange column chromatography, and we propose designating them peptidylarginine deiminase type I, II, and III according to the order of elution. The type II enzyme was widely distributed in various tissues including the skeletal muscle, whereas the type I enzyme was localized in the epidermis and uterus, and the type III enzyme was detected in the epidermis and hair follicles. These enzymes were distinguished by their molecular weights and substrate specificity. The molecular weights were estimated to be approximately 54,000 (type I) and 100,000 (type II and III) by Sephacryl S-200 gel filtration column chromatography. On SDS-PAGE the type II and III enzymes gave Mr = 81,000 and Mr = 76,000, respectively. Among the substrates tested, the type I enzyme showed highest activity toward BZ-L-Arg-NH2, type II toward BZ-L-Arg-O-Et, and type III toward protamine. Western blot analysis showed that antibodies against the type II enzyme were immuno-crossreactive to the type III enzyme.

Animals↗

PubMed1990

Obesity and adipose tissue distribution as risk factors for the development of disease. A review.

Recent studies have shown the predictive power of abdominal distribution of adipose tissue for the development of cardiovascular disease, stroke, diabetes as well as strong associations to the previously known risk factors for these endpoints. The reason for the accumulation of abdominal fat might be due to an imbalance between cortisol and sex steroid hormones. Cortisol receptor density seems to be particularly high in abdominal adipose tissue, leading to expression of lipoprotein lipase activity primarily here. Progesterone and testosterone seems to counteract this, the former perhaps through competition with the cortisol receptor. Accumulation of intraabdominal fat, particularly in the tissues drained by the portal circulation, probably leads to high free fatty acid concentrations in the portal vein, because of the high lipolytic sensitivity of these tissues. This in turn seems to inhibit hepatic clearance of portal insulin, leading to peripheral hyperinsulinemia, insulin resistance, perhaps hypertension as well as hyperlipidemia via drive by free fatty acids of lipoprotein synthesis in the liver. These are risk factors for diabetes, cardiovascular disease and stroke. It is of interest that subjects with abdominal adipose tissue have several factors leading to increased cortisol and low sex steroid hormone secretion, including stress, high alcohol consumption and smoking. This might provide some of the background to this syndrome.

Abdominal Muscles↗

PubMed1992

The primary structure and tissue distribution of cathepsin C.

A cDNA for rat cathepsin C (dipeptidylaminopeptidase I) was isolated. The encoded protein is composed of the signal peptide of 28 residues, the propeptide of 201 residues and the mature enzyme region of 233 residues. The amino acid sequence of the mature enzyme region has 39.5 to 30.5% identity to other papain family proteinases. Cathepsin C is, therefore, belongs to papain family, although its propeptide region is much longer than those of other cysteine proteinases and show no significant sequence similarity to any other cysteine proteinase. The mRNA and protein for cathepsin C are broadly distributed in rat tissues, but the relative proportions of cathepsin C and other cysteine proteinases are found to vary from tissue to tissue.

Amino Acid Sequence↗

PubMed1998

Recombinant caprine 3H-[N-acetylglucosamine-6-sulfatase] and human 3H-[N-acetylgalactosamine-4-sulfatase]: plasma clearance, tissue distribution, and cellular uptake in the rat.

The use of recombinant lysosomal enzymes for enzyme replacement therapy (ERT) is likely to be a necessary component of effective treatment regimens for lysosomal storage diseases (LSDs). The mechanism and rate of uptake into target cells, rate of disappearance of the enzyme from plasma, and its tissue distribution are important factors to assess the need for possible modifications to the enzyme, particularly for LSDs that affect the central nervous system (CNS). Two recombinant lysosomal enzymes, caprine N-acetylglucosamine-6-sulfatase (rc6S) and human N-acetylgalactosamine-4-sulfatase (rh4S), deficient in MPS IIID and MPS VI, respectively, were radiolabeled and purified. The major portion (>77%) of each recombinant enzyme contained the mannose-6-phosphate (M6P) recognition marker as demonstrated by their ability to bind to a M6P receptor affinity column. The uptake of 3H-rc6S and 3H-rh4S into cultured rat brain cells was also inhibited by the addition of 5 mM M6P to the culture medium. After iv administration of 0.4-0.5 mg/kg of 3H-rc6S and 1 mg/kg of 3H-rh4S to the rat, both enzymes were rapidly lost from the circulation in a biphasic fashion (t1/2 for 3H-rc6S = 1.25+/-0.15 min and 37.17+/-23.29 min; t1/2 for 3H-rh4S = 0.41 and 5.3 min). At this dose, about 6% of 3H-rc6S, but only 0.49% of 3H-rh4S, remained in the plasma 4 h after administration, whereas approx 30% of 3H-rc6S and more than 50% of 3H-rh4S was found in the liver. At doses of 1.6-2.0 mg/kg of 3H-rc6S and 1 mg/kg 3H-rh4S, but not at the lower dose of 3H-rc6S, trace levels of both 3H-rc6S and 3H-rh4S were detected in the brain. The low level of enzyme recovered from the brain suggests that modification of rc6S will be necessary to achieve sufficient enzyme uptake into the CNS for effective therapy of MPS IIID.

Animals↗

PubMed2001

Tissue distribution of GAP1(IP4BP) and GAP1(m): two inositol 1,3,4,5-tetrakisphosphate-binding proteins.

Two members of the GAP1 family, GAP1(IP4BP) and GAP1(m), have been shown to bind the putative second messenger Ins(1,3,4,5)P4 with high affinity and specificity, though other aspects of their behaviour suggest that in vivo, whereas GAP1(IP4BP) may function as an Ins(1,3,4,5)P4 receptor, GAP1(m) may be a receptor for the lipid second messenger PtdIns(3,4,5)P3. As a step towards clarifying their cellular roles, we describe here how we have raised and characterised antisera that are specific for the two proteins, and used these to undertake a comprehensive study of their tissue distribution. Both proteins are widely expressed, but there are several clear differences between them in the tissues that show the highest levels of expression.

Animals↗

PubMed2002

Cloning and tissue distribution of two Na+/H+ exchangers from the Malpighian tubules of Aedes aegypti.

A Na(+)/H(+) exchanger (NHE) on the apical membrane of mosquito Malpighian tubule (MT) cells is believed to participate in the blood-feeding mosquito's vital secretion of Na(+) and fluid. This study presents the molecular cloning, primary structure, and tissue distribution of two cDNAs encoding Aedes aegypti mosquito MT NHEs. The cDNA sequences were obtained from mosquito MT total RNA using reverse transcription-polymerase chain reaction (RT-PCR) and 5' and 3' rapid amplification of cDNA ends (RACE). The two sequences encode proteins of 678 and 1,179 amino acids with calculated molecular weights of 74,473 and 130,276, respectively. When comparing the 678 amino acid protein to the first 678 amino acids of the other protein, the two clones show 98% identity to each other. They also exhibit high identity to Drosophila melanogaster NHEs. Hydropathy analysis reveals that while both clones have 10-13 transmembrane segments, the 1,179 amino acid protein has an extensive carboxy terminus while the 678 amino acid protein has an extremely short carboxy terminus. RT-PCR analysis shows that both clones are expressed in the mosquito Malpighian tubules at the larval and pupal stages, in addition to the adult stage before and after blood-feeding. Expression of both clones was also detected in adult mosquito ovaries, midguts, and hindguts.

Aedes↗

PubMed1987

Tissue distribution and developmental expression of the messenger RNA encoding angiogenin.

New blood vessel growth occurs during normal fetal development and in diseases such as cancer and diabetes. The polypeptide angiogenin induces new blood vessel growth in two biological assays and may play a role in the vascular development of the fetus and in the neovascularization that accompanies diseases and wound healing. A complementary DNA probe for human angiogenin was used to examine the tissue distribution of angiogenin messenger RNA (mRNA) in the developing rat and in selected transformed cell lines. Angiogenin mRNA was detected predominantly in adult liver but was also detectable at low levels in other tissues. The expression of the angiogenin gene in rat liver was found to be developmentally regulated; mRNA levels were low in the developing fetus, increased in the neonate, and maximal in the adult. The amount of angiogenin mRNA in human HT-29 colon carcinoma and SK-HEP hepatoma cells was not greater than that in normal rat liver. These results demonstrate that angiogenin is predominantly expressed in adult liver, that the pattern of angiogenin gene expression is not temporally related to vascular development in the rat, and that the transformed cells studied do not contain more angiogenin mRNA than does normal liver. If angiogenin activity is controlled at the transcriptional level, the results of this study suggest that the primary function of angiogenin in vivo may be in processes other than the regulation of vascular growth.

Age Factors↗

PubMed1985

11C-labeling of indolealkylamine alkaloids and the comparative study of their tissue distributions.

Five indolealkylamines (N,N-dimethyltryptamine, N-methyltryptamine, bufotenine, O-methylbufotenine, N,N,N-trimethyltryptamine iodide) were labeled with 11C by use of 11CH3I. The labeled compounds were synthesized with a radiochemical yield of 2-50% (based on trapped 11CH3I) in 20-35 min with radiochemical purities of more than 92%. The tissue distributions of these labeled compounds were investigated in rats. In all cases, the accumulations in the liver, lung and small intestine were high. [11C]DMT and [11C]OMB also accumulated to a large extent in the brain, where their accumulation was retained. Brain uptake of three other radiopharmaceuticals was low. [11C]DMT is the radiopharmaceutical of choice for the study of the serotonin action mechanism in the brain, because it has the highest radiochemical yield and the highest brain uptake of these 11C-labeled compounds.

Animals↗

PubMed2004

Identification and tissue distribution of mRNAs encoding salmon-type calcitonins-IV and -V in the rainbow trout.

Four types of calcitonin are produced in salmonid fish, although their functional diversity is almost unknown. To explore the significance of these isoforms, we have characterized salmon-type calcitonin (sCT) mRNAs in the rainbow trout (Oncorhynchus mykiss), and examined their tissue distribution. In addition to the previously isolated sCT-I cDNAs, two new forms of sCT cDNA were cloned from the ultimobranchial gland, and one of them (sCT-IV cDNA) was predicted to encode an N-terminal peptide of 80 amino acid residues, a putative cleavage site Lys-Arg, sCT-IV, a cleavage and amidation sequence Gly-Lys-Lys-Arg, and a C-terminal peptide of 18 amino acids. The sCT-IV precursor was 78% identical with the rainbow trout sCT-I precursors. The other cloned cDNA encoded a precursor for a novel CT, sCT-V. The sCT-V peptide was different from sCT-IV by only one amino acid residue: Val at position 8 in the latter was replaced by Met. The sCT-V precursor had 80 and 90% identity with the sCT-I and -IV precursors respectively. No cDNA clones were obtained for sCTs-II or -III.Tissue distribution of sCT-I, -IV and -V mRNAs was examined by RT-PCR and specific cleavage with restriction enzymes. An amplified fragment from sCT-I mRNA was detected not only in the ultimobranchial gland, but also in the gills, testis and ovary. RT-PCR analysis coupled to restriction digestion further revealed that sCT-IV mRNA was expressed in both the testis and the ultimobranchial gland. The expression sites of sCT-IV mRNA were localized to the Leydig cells of the testis and to the parenchymal cells of the ultimobranchial gland, by in situ hybridization histochemistry. Although the amino acid sequence of sCT-V peptide was nearly the same as that of sCT-IV, the sCT-V gene showed a much wider pattern of expression: the band amplified by RT-PCR was detected in all the tissues examined except the kidney, gills and blood cells. The sCT-V mRNA was shown to be localized in the parenchymal cells of the ultimobranchial gland, but not in other tissues at the cellular level, suggesting very low expression of sCT-V mRNA in those tissues. Our results show different patterns of tissue expression of three types of sCT genes in the rainbow trout, suggesting that sCTs-I, -IV and -V might differ in their local actions.

Amino Acid Sequence↗

PubMed1994

Tissue distribution and elimination of indium in male Fischer 344 rats following oral and intratracheal administration of indium phosphide.

The use of indium phosphide (InP) in the semiconductor industry has raised concerns about potential occupational exposure. The tissue distribution and elimination of indium were investigated in adult male Fischer 344 rats following either a single or 14 consecutive daily oral doses, or following an intratracheal instillation of InP (10 mg/kg). The concentrations of indium ions in blood, urine, feces, and tissues were quantified either using direct acid digestion followed by electrothermal atomic absorption spectrophotometry (ET-AAS) or using an extraction method with methyltricapryl ammonium ions to remove indium from the matrix followed by ET-AAS. Indium was poorly absorbed from the gastrointestinal tract in both single and multiple oral dose studies. Upon its absorption, indium was relatively evenly distributed among the major organs such as liver, kidney, lung, spleen, and testes. By 96 h after oral dose treatment, less than 0.11% of the dose of indium was recovered from tissues in the single- or multiple-dose experiment. At 96 h, retention of indium in the body was about 0.36% of the dose (except for lung) following intratracheal instillation of InP. Following oral dose administration, the majority of indium was recovered from the gastrointestinal tract and its contents. The high recovery of indium (73% of the dose) in the feces after intratracheal instillation presumably reflects mucociliary clearance and/or biliary excretion of indium. Urinary indium accounted only for 0.08-0.23% of the dose during a 240-h collection period in both single- and multiple-dose studies. It seems that fecal excretion serves as the major route for indium elimination, and this results from poor absorption. Because of the poor absorption of indium following multiple oral doses or intratracheal instillation of InP, it seems unlikely that indium will accumulate in the body following InP exposure.

Administration, Oral↗

PubMed1995

A compilation of meropenem tissue distribution data.

Meropenem body fluid and tissue concentration data from both published studies and samples obtained during efficacy evaluation have been compiled and presented according to a consistent format to facilitate comparison. The concentration data have been compared with the mode MIC data available for the pathogens isolated during the clinical evaluation of meropenem. These data support the widespread and rapid penetration of meropenem into the interstitial fluid of those tissues not protected by a tight epithelial barrier. Furthermore, they suggest that the proposed dosages of meropenem 500 mg or 1 g tds would provide an adequate duration of cover at tissue sites for the treatment of a range of commonly occurring pathogens. A higher dosage of 40 mg/kg or 2 g in adults given tds would be recommended for meningitis based on the penetration of meropenem into CSF. Overall, the tissue and body fluid data presented confirm the expectation, based on the plasma concentrations and theoretical arguments, that meropenem is rapidly and readily distributed into the interstitial fluid, thereby producing concentrations in tissues likely to be clinically effective. This is consistent with the available clinical data on the therapeutic efficacy of meropenem.

Carbapenems↗

PubMed1997

Tissue distribution of transplanted fetal liver cells in the human fetal recipient.

OBJECTIVE: Our purpose was to study the tissue distribution and concentrations of transplanted fetal liver cells in the human fetus. STUDY DESIGN: Radiolabeled indium 111 fetal liver cells were injected in vivo under ultrasonographic guidance into 10 normal fetuses (13 to 17 weeks of gestation) before a prostaglandin abortion. Six fetuses were injected intraperitoneally and four intracardially. Another two fetuses serving as controls were injected with indium-labeled maternal plasma. The fetuses were all alive, at least until 6 hours before expulsion. After expulsion the fetuses were dissected, and radioactivity was measured in various fetal tissues. Results for each tissue were expressed as percentages of the total injected dose. RESULTS: Significantly greater uptake of fetal liver cells in the liver, spleen, thymus, kidney, lung, and placenta was obtained with intracardiac than with intraperitoneal injection. Skeletal uptake did not differ in relation to mode of administration. With intracardiac injection uptake was greater in such parenchymal organs as the liver, spleen, and thymus (4.9%, 4.0%, and 3.9%, respectively). Uptake in the rib, clavicle, humerus, and sternum was 2.7%, 1.8%, 2.1%, and 1.1%, respectively. Placental uptake was 0.1%. The intracardiac route yielded a higher concentration of cells in different fetal organs than did injection of only radiolabeled maternal plasma, suggesting an active uptake of cells in different fetal hematopoietic organs. CONCLUSION: The mode of administration of fetal liver cells seems to be a major determinant of donor cell concentration in the transplanted human fetus and may be a significant determinant of the rate of successful engraftment.

Cell Movement↗

PubMedDate not supplied

Pharmacokinetics and tissue distribution of human urinary tumor necrosis factor binding protein in mice.

Iodinated natural human urinary tumor necrosis factor binding protein I (125I-uTBP) was iv injected into BALB/c mice, and its pharmacokinetics and tissue distribution were assessed during a short-term (0-1 hr) and for a long-term (0-24 hr) period. The blood 125I-uTBP concentration displayed a biphasic pattern that was adequately described by a biexponential function with estimated half-lives of 0.1 and 3.8 hr. The apparent volume of distribution (Vc) of the central compartment was 3 ml, which approximated the mouse blood volume. The clearance (CL) derived either from a model-dependent or a model-independent method of analysis was 2.5 and 2.9 ml/hr, respectively. One hr after the iv administration of 125I-uTBP, the radioactivity accumulated in the major organs and tissues. The highest concentrations in terms of pg per organ were seen in the skin and in the liver. When expressed as pg 125I-uTBP per mg organ, the distribution was the highest in the gallbladder, bladder, kidneys, and lungs. At 24 hr, the distribution of 125I-uTBP represented about 10% of the amount measured at 1 hr. The rank order of accumulation of the radiolabeled uTBP in the major organs, expressed as pg per organ at 24 hr was skin greater than liver greater than kidneys greater than lungs greater than gut greater than spleen greater than gallbladder.

Animals↗

PubMed1989

[Tissue distribution, inductive effect on liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran in Golden Syrian hamsters].

The hamsters have been known to be the least sensitive mammalian species to the acute toxicity of highly toxic polyhalogenated hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. In the present study, the tissue distribution, inductive effect of liver enzymes and acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) in male Golden Syrian hamsters were examined. The highest content (about 48% of dose) of PenCDF was found in the liver 5 days after a single i.p. dose of 1.0 mg/kg. The amount ranging about 5 to 10% of dose was also distributed to mesentery, skin and muscle. In liver, the distribution of PenCDF was just parallel to that of cytochrome P-450 (P-450), marker enzymes of liver endoplasmic reticulum, suggesting that PenCDF binds to P-450. The mode of inductive effects of PenCDF in hamsters was 3-methylcholanthrene-type as reported previously in rats. However, the typical enzymes such as benzo(a)pyrene 3-hydroxylase and DT-diaphorase were induced to a relatively less extent than did in rats. In hamsters pretreated with PenCDF at a dose of 0.5 mg/kg, the potent atrophy of thymus and the 3-fold increase of liver lipid peroxide were observed, whereas the body weight gain was not suppressed at all. These results suggest that the induction of liver enzymes and the atrophy of thymus might not be the direct cause of PenCDF-induced lethality in hamsters.

Animals↗

PubMed2004

Sensitive immunoassays for human and rat GMFB and GMFG, tissue distribution and age-related changes.

We developed sensitive and specific two-site enzyme immunoassays (EIA) for glia maturation factor beta (GMFB) and gamma (GMFG) using specific antibodies raised in rabbits. These assay systems enabled us to identify GMFB and GMFG (GMFs) in both human and rat samples and they were used to investigate the tissue distribution and serum concentrations of human and rat GMFs. In the case of rat, relatively high levels of GMFB were found in the central nervous system, except for the spinal cord, and in thymus and colon. Higher levels of GMFG were found in the thymus, spleen and colon. The distribution of GMFs in human was similar to that in rat. In the rat, the maximum serum concentration of GMFG was at 4 weeks of age. The decrease in its level was rapid for the first 30 days of life in both sexes. On the other hand, the concentration of GMFB in serum did not change significantly with age. Similarly, in human, the concentration of GMFG in serum was highest in the 21-30-year-old group and began to decrease rapidly in the 30-year-old group. In contrast, the concentration of GMFB did not change significantly during this period. No significant sex differences in the serum levels of GMFs were observed in human and rat. The present EIA systems are sufficiently sensitive for studying GMFs in human and rat organs.

Adult↗

PubMed2000

Tissue distribution and antitumor activity of topotecan delivered by intracerebral clysis in a rat glioma model.

OBJECTIVE: Intracerebral clysis is a drug delivery technique that depends on convection-enhanced microinfusion to achieve therapeutic drug levels within the brain. In this study, brain tumor-bearing rats were treated with topotecan delivered systemically and by the intracerebral clysis method. Our objective was to determine the efficacy and tissue distribution of topotecan delivered by intracerebral clysis. METHODS: The C6/Wistar rat glioma model was used after a thymidine incorporation assay determined topotecan sensitivity of C6 cells in vitro. Long-term survival of animals provided objective measurements of efficacy; records of animal weight during treatment and neurological status served to approximate toxicity. Topotecan tissue penetration was measured in samples of ex vivo tumor and surrounding brain tissue with high-pressure liquid chromatography. RESULTS: Dose escalation demonstrated significant sensitivity of C6 glioma cells to topotecan (median lethal dose, 0.19 micromol/L). Eleven of 12 rats bearing established intracerebral C6 glioma and receiving topotecan by intracerebral clysis survived beyond the end point of 120 days; no untreated control or systemically treated animal survived beyond 26 days (n = 18; P < 0.005). Histopathological assessment of animals demonstrated significant tumor masses in the brains of intraperitoneally treated animals and untreated control animals. In contrast, no residual tumor was found in the brains of intracerebral clysis groups. Animal weights during treatment were markedly reduced by intraperitoneal dosing (n = 6) but not by low-dose intracerebral clysis (32 microg/kg/d for 5 d; n = 6). None of the low-dose intracerebral clysis-treated animals demonstrated neurological toxicity, and one high-dose intracerebral clysis-treated animal (160 microg/kg/d for 2 d; n = 6) died during follow-up. Topotecan was detected well beyond the boundaries of the tumor and even in the contralateral hemisphere in animals treated with intracerebral clysis. CONCLUSION: Topotecan delivered by the intracerebral clysis method is effective for treatment of brain tumors in the rat glioma model. These studies provide compelling justification for further preclinical testing to formally evaluate toxicity and efficacy with variable dosing schedules.

Animals↗