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At least 631 records · Page 35Linked to original sources
PubMed1990

Liposomes as carriers of cisplatin into the central nervous system--experiments with 9L gliomas in rats.

The anticancer agent cis-diamminedichloroplatinum (cisplatin) has several disadvantages, including extreme nephrotoxicity, rapid binding to plasma proteins, and poor penetration of the central nervous system. In this study liposomes, which can cross the blood-brain barrier, were investigated for their potential in delivering therapeutic agents to brain tumors. Liposomes prepared from egg phosphatidylcholine and cholesterol in a 3:1 molar ratio were divided into 1-ml aliquots and either labeled with 14C or treated with horseradish peroxidase (HRP). The preparations were administered via the carotid artery to rats bearing 9L glioma. Radioactive uptake by brain tumor and normal tissues was measured with a liquid scintillation counter. The presence of HRP-containing liposomes in capillary endothelium and brain tumor cells was demonstrated by light and electron microscopic histochemical techniques. Thirty minutes after injection of 14C-labeled liposomes, radioactive uptake was higher in the spleen than in normal brain, brain tumor, liver, and kidney. Also uptake was greater in brain tumor and lower in kidney than that of cisplatin given alone. Light microscopy showed HRP-containing liposomes in brain tumor tissue 30 minutes after injection. On electron microscopy, liposomes were found to be regularly distributed in surface invaginations and vesicles of capillary endothelial cells. They were also observed within tumor cells. These results indicate that liposomes can penetrate the blood-brain barrier and hold promise as drug carriers in the treatment of brain tumors with cisplatin.

Animals↗
PubMed1989

[Study on air-powder abrasive system for prosthetic clinical application. 3. Bacterial adherence to the air-powder abraded metal surface].

The purpose of this study is to investigate the relation between the metal surface texture and bacterial adherence. The surface of Au-Ag-Pd alloy was treated with or without air-powder abrasion. Seven standard strains and two clinical isolates were used. The alloys were mixed with [6-3H]-thimidine labelled bacteria. The radioactivity was measured with a scintilation counter. Streptococcus sanguis and clinical isolated Bacteroides gingivalis were adhered in a larger amount to the air-powder abraded alloy surface than to nonabraded alloy surface. These results indicated that careful consideration is needed for application of air-powder abrasive system on metal crown with secondary caries and periodontal disease.

Bacterial Adhesion↗
PubMed1988

[Biochemical characterization of phenytoin-induced hyperplastic human gingival fibroblasts. Non-collagenous proteins biosynthesis].

Phenytoin (PHT), administered as an anticonvulsant, has a side effect gingiva overgrowth in approximately 50% of patients. The present study was attempted to explore the biochemical mechanism on non-collagenous protein biosynthesis as affected by PHT. Responder cells (RES A3, RES C2) of a patient with gingival overgrowth were obtained by the method of Kawase et al. Normal human gingival fibroblasts (Gin-1), purchased from ATCC, were also used. All cells were inoculated at 1 x 10(4) cells/cm2 (12 multi-well plate or 60 mm tissue culture dish), and then cultured for 4, 8 and 12 days with or without PHT (5 micrograms/ml). Prior to harvesting at the indicated times, cells were incubated with 14C-amino acids (1.25 microCi/ml) for 24 hours. The 14C-labeled proteins were isolated from the cell layers including extracellular matrix, following Kurkinen et al. with a minor change. Each 14C-labeled fraction was dissolved in 3 ml of Aquasol-2 and the radioactivity by a liquid scintillation counter. The DNA content of cell layers affected by PHT was increased on Gin-1, RES A3 and RES C2 at the post-confluence, resulting also in an increase in cell number. Two morphologically different phenotypes of responder cells were observed, differing in nuclear and cell sizes. At 12 days culture, RES A3, were stimulated by PHT, showed increased synthesis of both total extractable proteins (EP) and binding proteins (BP) labeled with 14C-amino acids. Therefore, at least two distinct phenotypic responder cells are present in the PHT-induced overgrowth gingiva, alter the synthesis of non-collagenous proteins.

Fibroblasts↗
PubMed2006

Tissue distribution and excretion of N-methyl-2-pyrrolidone in male and female rats.

OBJECTIVES: N-methyl-2-pyrrolidone (NMP) belongs to solvents widely used in the petrochemical industry a well as in the production of pesticides, veterinary drugs and paint removers. NMP is easily absorbed from the respiratory tract, digestive system and through the skin. It is a compound of slight acute toxicity that also displays moderate irritating activity. The aim of this study was to assess tissue distribution and excretion following a single intraperitoneal NMP administration. MATERIALS AND METHODS: Tissue distribution and excretion of NMP following administration of a single dose of 250 mg/kg body weight (350 kBq/rat) was investigated using 14C. Blood plasma (6 rats per time point) were sampled up to 72 h after administration and determination of radioactivity. Male and female rats (4 animals per time point) were decapitated at appropriate time intervals and examined tissues were removed for determination of radioactivity. Excretion of 14C in urine and feces were also measured. All radioactivity measurements were carried out using a Rackbetta 1209 (LKB, Sweden) liquid scintillation counter. RESULTS: The highest 14C activity in tissues and internal organs of female and male rats was observed 4 h after administration of the compound. The highest accumulation was detected in the muscles and fat tissue as well as in the liver and testicles. During 72 h following administration, approximately 80% of the dose was excreted in urine. Elimination of the compound in feces was far less significant: only about 5% of the dose was excreted at once. CONCLUSIONS: The results of the study indicate that there are no significant differences in 14C-NMP tissue distribution between male and female rats; NMP absorption from the peritoneal cavity to blood is rapid, disappearance from plasma is monophase and kidneys are the main route of excretion of NMP and/or its metabolites from the rat body after administration of a dose equal to 10% of LD50. The ability to accumulate NMP and/or its metabolites in testes and seminal vesicles may be the reason for fertility impairment in male rats observed after repeated exposure to this compound.

Animals↗
PubMed1999

Multiprobe RNase protection assay with internally labeled radioactive probes, generated by RT-PCR and nested PCR.

RNase Protection Assay (RPAs) is a highly sensitive and reproducible method of quantitating the levels of specific mRNA transcripts. The introduction of the commercially available Multiprobe RPAs allow comparing and quantifying the expression of up to different mRNA species in a single sample of 1-20 micrograms of total RNA. To generate probes which are not commercially available, we prepared highly specific probes by RT-PCR and nested PCR. Then, after ligation of a T7 promoter, another PCR was performed with a primer set consisting of a specific sense primer and antisense T7 primer. Only the antisense strand of the double stranded PCR-product contained the T7-promoter sequence on its 5' end, allowing in vitro transcription and internal labeling with [alpha-32]UTP. Probe concentration was determined in a scintillation counter and equal counts were introduced in the assay. In vitro transcription of the PCR generated probes resulted in radioactive probes with a very high specific activity, allowing simultaneous analysis of 70 different RNA samples. RPA could be performed under the same conditions as recommended for the commercially available probe sets, avoiding time consuming optimization of reaction conditions. Negative controls consisted of yeast RNA and sense RNA probes. Positive controls were single stranded templates, generated by asymmetric PCR. Dilution series revealed a high reproducibility and the potential of this technique to semi-quantitate mRNA in different RNA samples. In conclusion, probes may be generated by RT-PCR and nested PCR that will work with the commercially available Multiprobe RPAs. The high probe yield allows analysis of a great number of samples using the same set of probes with a high reproducibility.

Antigens, CD↗
PubMed1989

The influence of piracetam on digoxin up-take by different rabbit tissues in vitro.

The action of increasing piracetam concentration on the digoxin up-take by various rabbit tissues was investigated in vitro. 125J-digoxin was used and radioactivity was counted in a gamma scintillation counter. Piracetam 100 micrograms/ml has a small increasing action on digoxin up-take by parenchymatous rabbit tissues. This action may be due to the beneficial effect of the substance on tissue microcirculation and cell metabolism. This action is equilibrated or reversed by piracetam 200 micrograms/ml and 400 micrograms/ml. It is suggested that piracetam displays digoxin from its binding-sites but these concentrations are above those ones used for clinical purposes.

Animals↗
PubMed1987

Gastric emptying in patients with flatulent dyspepsia, with and without gallbladder disease.

It has been suggested that the symptoms of flatulent dyspepsia are caused by a functional disturbance of the upper gastrointestinal tract. The aim of this study was to investigate delayed gastric emptying as the basis of symptoms in patients with and without gallbladder disease and after cholecystectomy. There were 13 dyspeptic patients with gallbladder disease, 12 with normal gallbladders, and 13 post-cholecystectomy patients. Gastric emptying was measured by means of a 99mTc-labelled scrambled egg meal and external scintillation counter. The rate of emptying in the symptomatic groups was compared with that in 24 asymptomatic normal control subjects and 12 non-dyspeptic patients with gallbladder disease. Delayed gastric emptying tended to occur in patients with gallbladder disease with and without dyspepsia and was not specifically associated with symptoms.

Adult↗
PubMed1996

Biodistribution of cocaine during perinatal period in rats.

Differences in cocaine-induced central nervous system toxicity in pregnant and postpartum rats have been observed. For example, a 20 mg/kg, intraperitoneal dosage of cocaine that was tolerated during pregnancy caused tonic-clonic convulsions and death during the postpartum period. In the present study, biodistribution of cocaine during different perinatal periods was investigated to understand the differences in toxicity. Nonpregnant, 22-day pregnant, and postpartum rats were injected with 3H cocaine (12 mg/20 mu ci/kg, i.v.). Rats were sacrificed under ether anesthesia at predetermined time intervals. Brain, serum, fetal brain and placenta (from pregnant rats) samples were isolated, solubilized, and counted in a scintillation counter for radioactivity. Peak levels of cocaine were observed at 15 and 60 minutes after injection in maternal serum and brain, respectively, in 22-day pregnant rats. However, peak levels of cocaine were observed at 30 minutes after the injection in placental and fetal brain tissues from 22-day pregnant rats. Cocaine level of brain was elevated in all postpartum rats compared to nonpregnant and pregnant rats. These results indicated that higher levels of cocaine is distributed to brain after delivery compared to the nonpregnant and pregnant rats which may explain increased CNS toxicity during postnatal period.

Animals↗
PubMed1996

An intravitreal device providing sustained release of cyclosporine and dexamethasone.

PURPOSE: A device that releases cyclosporine and dexamethasone into the eye for extended periods of time might be beneficial in diseases such as proliferative vitreoretinopathy and uveitis. In this study we examine the pharmacokinetics and toxicity of cyclosporine and dexamethasone combined in an intravitreal sustained-release device and the toxicity of a similar device containing only dexamethasone in rabbits. METHODS: Rabbits were divided into three groups for (1) evaluation of the drug tissue levels and device release kinetics following implantation of a device containing 100 micrograms of cyclosporine labeled with 2 microCi of 3H-cyclosporine and 2 mg of dexamethasone; (2) evaluation of the toxicity of this intravitreal device; and (3) evaluation of the toxicity of a similar device containing 2 mg of dexamethasone only. Cyclosporine was measured using a scintillation counter and dexamethasone was measured by high pressure liquid chromatography (HPLC). Toxicity was evaluated by electroretinography, clinical examination, and light microscopy. RESULTS: Vitreous concentrations of cyclosporine (+/- standard deviation) averaged 0.06 (+/- 0.02) microgram/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (+/- 0.9) micrograms/ml. Devices containing cyclosporine and dexamethasone released each drug at rates similar to devices containing cyclosporine or dexamethasone alone. Devices containing both cyclosporine and dexamethasone caused reversible depressions in the b-wave amplitude of photopic and scotopic electroretinograms (ERG's). There was no evidence of toxicity associated with the devices containing dexamethasone only. There was no drug-related toxicity evident on clinical or histopathologic examination of eyes with devices containing the combination of cyclosporine and dexamethasone or dexamethasone alone. CONCLUSIONS: We conclude that the device maintains potentially therapeutic levels of both cyclosporine and dexamethasone in the vitreous. Reversible electroretinographic abnormalities are attributable to cyclosporine. A sustained-release device containing cyclosporine and dexamethasone may be useful for reducing inflammation in diseases such as proliferative vitreoretinopathy and uveitis.

Animals↗
PubMed1989

The spatial distribution of parenterally administered monoclonal antibodies against CEA in a human colorectal tumour xenograft.

A recently developed experimental model consisting of athymic rats carrying human colonic tumours from the cell line LS 174 T in both hind legs was used. 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies were injected either intra-arterially after a bolus injection of mannitol, or intra-peritoneally with or without mannitol. On the fourth day the rats were killed and pieces from the tumours and various organs were measured in a well scintillation counter. Tumour pieces were then submitted to autoradiography and immunohistochemistry for examination of the antibody distribution at the cellular level. In all examined tumours injected with anti-CEA antibodies, most of the antibodies were located in the periphery close to fibrovascular septa. It appears, in addition to the specificity of the antibody for the CEA, that the tumour vascular permeability and anatomy are of utmost importance for tumour targeting in this experimental model with the particular antibody used.

Adenocarcinoma↗
PubMed1977

The intra-articular residual rate of 131I-fibrinogen and microautoradiographs of the synovial tissue in rheumatoid arthritis.

In this study, 131I-labeled human plasma fibrinogen (200 muCi) was injected intravenously into 21 patients with rheumatoid arthritis and 10 control patients without rheumatic diseases. The residual rates of radioiodinated fibrinogen in the knee joints were calculated by measuring with a scintillation counter the microautoradiographs of the synovial tissue obtained by punch biopsy from the knee joints. The residual rates in the knee joints without as well as with objective symptoms of RA were higher than in control patients. Radio-iodinated fibrinogen was demonstrated on the synovial villous surface, on the area of inflammatory cellular infiltration and stromal necrosis, and on the perivascular region of the synovial tissue from the knee joints of patients with RA, not only with, but also without clinical objective symptoms and histopathologic findings of fibrinoid necrosis, vascular superficial fibrinoid coating and fibrinoid degeneration of vascular wall. It is suggested that fibrinogen plays a role even in the early synovial tissue lesions of knee joints affected by RA.

Adolescent↗
PubMed1989

Sensitive detection of two IgG Fc receptors of mouse macrophages by chemiluminescence analysis.

Luminol-enhanced chemiluminescence assay was used to detect the surface expression and the consequent activation of receptors (FcRI and FcRII) of murine macrophages (M phi s). When murine IgG2a was used for the specific detection of FcRI and IgG2b for FcRII, a newly established procedure enabled us to detect the activation of each receptor with as few as 3 X 10(5) M phi s. Briefly, TNP-SRBC coated with monoclonal IgG2a or IgG2b antibodies directed to TNP (sensitized SRBC) were used as reagent, in the presence of 1 X 10(-5) M luminol, and the emission was measured with a liquid scintillation counter. When results obtained by chemiluminescence counting were compared to the results obtained by the rosette formation by adding the same SRBC reagent to peritoneal M phi s obtained after ip injection of Listeria, fortified chemiluminescence counting allowed us to obtain a more definite answer about the activation of each receptor. Under the conditions established, the specific activation of FcRI was obtained by the addition of rIFN alpha A/D to the resident M phi s in vitro and the specific activation of spleen M phi FcRII by iv injection of IAP (Immunosuppressive acidic protein) into mice. These two results supported the independence of the two receptors detected by the assay.

Animals↗
PubMed1988

Radionuclide study of platelets and prosthetic interactions: external versus specimen quantitation.

UNLABELLED: Twenty-nine New Zealand white rabbits were allocated to undergo insertion of either polytetrafluoroethylene (PTFE) (n = 22) or microporous silicone rubber (SR) (n = 7), 3-mm diameter, 10-mm long aortic grafts. Animals with PTFE grafts received aspirin (ASA) 10 mg/kg/d and dipyridamole (DPM) 10 mg/kg/d (n = 11) or placebo (n = 11). Autologous In-111-oxine-labeled platelets were reinfused on reestablishment of blood flow through the graft. Using gamma camera images, an external graft platelet accumulation index (E-GPAI) was calculated as the In-111 activity in the graft area to the reference aorta at 24, 48, and 72 hours post implantation. Mean E-GPAI +/- SEM values for the ASA/DPM (n = 4) and control groups (n = 7) were 1.13 +/- 0.16 and 1.34 +/- 0.05 (NS) at 24 hours, 1.20 +/- 0.16 and 1.33 +/- 0.07 (NS) at 48 hours, and 1.38 +/- 0.07 and 1.35 +/- 0.10 (NS) at 72 hours, respectively. A similar internal graft platelet accumulation index (I-GPAI) was constructed based on In-111 activity in excised grafts and reference aorta measured in a scintillation counter. Mean I-GPAI +/- SEM values for the PTFE ASA/DPM (n = 9) and control groups (n = 8) at 48 hours post implantation were 43.1 +/- 2.7 and 216.8 +/- 73.9 (P = 0.05), respectively. I-GPAI values for the SR grafts were 192.5 +/- 43.1. CONCLUSION: The E-GPAI was not sensitive enough to demonstrate the effect of antiplatelet medication on platelet accumulation on the PTFE grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interaction of serum components with poly(methylmethacrylate) nanoparticles and the resulting body distribution after intravenous injection in rats.

Radiolabelled poly(methylmethacrylate) (PMMA) nanoparticles were coated with rat serum albumin (RSA), serum and inactivated serum, to examine the influence of these blood components on the body distribution of a model colloidal drug carrier. The particles were incubated overnight at 37 degrees C either in a 1% solution of RSA in phosphate buffered saline (PBS) or in serum obtained from the rats. A suspension of nanoparticles in PBS was used as a control. Serum complement inactivation was achieved by storage at 56 degrees C for 30 min. The suspensions were then injected intravenously via the tail vein of Wistar rats. The animals were sacrificed at five different time points (30 min, 2 h, 6 h, 24 h, and 7 d after injection) and two samples of each organ and two blood samples were weighed into scintillation vials. The radioactivity of each sample was then measured in a Beckman scintillation counter. Coating with RSA led to no significant change in the body distribution of the particles, whereas incubation in serum, especially with complement inactivation prior to injection, very significantly reduced the uptake of particles into the organs of the reticuloendothelial system (RES), e.g., liver, spleen, and bone marrow. At the same time, much higher concentrations of nanoparticles were observed in the serum and in non-RES organs and peripheral tissues (kidneys, muscles, and intestine). This effect was most pronounced after 30 min, but was still observable after 7 d.

Animals↗
PubMed1975

Heterogeneity of bile pigments formed by the breakdown of haemoglobin in the isolated male-dog kidney.

Normothermic perfused isolated male-dog kidneys formed radioactive bile pigments by the breakdown of radioactive haemoglobin prepared from [2-14C]glycin. After column chromatographic separation and preparation of dipyrrolic azopigments, 86.3 +/- 2.2% of the bile pigments seemed to be conjugated bilirubin. Thin-layer chromatographic separation of the azopigments of ethyl anthranilate revealed a good correlation between photometric scanning, radiochromatographic scanning and the radioactivity of the azopigments scraped off the thin-layer glass plates and counted in a liquid scintillation counter. Although the same heterogenity of the azopigments was observed as in dog bile, the isolated male-dog kidney formed significantly less alpha2- and significantly more gamma-fractions.

Animals↗
PubMed2003

Effect of immunoglobulin G from cows immunized with ferric citrate receptor (FecA) on iron uptake by Escherichia coli.

The effects of immunoglobulin (Ig) G from cows immunized with the ferric citrate receptor (FecA) on iron uptake by Escherichia coli were investigated. Receptor FecA was purified from E. coli UT5600/pSV66. Cows were immunized with 400 microg purified FecA three times at 21 d intervals during late lactation and the nonlactating period. Immunoglobulin G was purified by protein G affinity chromatography from colostral whey from cows immunized with FecA and from unimmunized control cows. The purified IgG from FecA immunized cows had higher IgG titers against FecA compared with control IgG. Fifteen E. coli isolated from intramammary infections and E. coli UT5600/pSV66 were grown in an iron-depleted medium containing 1 mM citrate to induce FecA. The bacterial cells were mixed with 0, 2, and 4 mg/ml purified IgG, and 55Fe was added to the assay. After 5, 10, and 15 min incubations at 37 degrees C, samples were passed through 0.45-pm pore size filters. Filters were washed with saline three times, and the radioactivity of 55Fe taken up by the bacterial cells on the filters was measured by a liquid scintillation counter. The measurements were expressed as numbers of 55Fe atoms per colony-forming unit and transformed to log10. The assay was repeated three times for each isolate in a partially balanced incomplete block design. The presence of IgG decreased 55Fe uptake by E. coli mastitis isolates and E. coli UT5600/pSV66. Anti-FecA IgG reduced 55Fe uptake by E. coli greater than IgG from unimmunized cows.

Animals↗
PubMed2004

Iron uptake by Escherichia coli cultured with antibodies from cows immunized with high-affinity ferric receptors.

The synergistic effects of immunoglobulin G (IgG) from cows vaccinated with ferric citrate receptor (FecA) and IgG from cows vaccinated with ferric enterobactin receptor (FepA) were measured in an in vitro iron uptake assay. Serum was isolated and pooled within treatment from five cows each vaccinated with FepA or FecA or not vaccinated. Immunoglobulin G was isolated by ammonium sulfate precipitation and protein G affinity chromatography. Six Escherichia coli isolates from bovine intramammary infections were cultured in an iron-depleted medium to induce high-affinity iron acquisition systems and, in iron-depleted conditions, to specifically induce the expression of FecA. The bacterial cells were mixed with either 3 or 6 mg/mL of purified IgG and 55Fe. The radioactivity of 55Fe taken up by the bacterial cells was measured by a liquid scintillation counter after 5-, 10-, and 15-min incubations at 37 degrees C. The combination of anti-FecA IgG and anti-FepA IgG reduced 55Fe uptake compared with either anti-FecA or anti-FepA alone. Iron uptake was reduced more by anti-FecA IgG than by anti-FepA IgG when the ferric citrate system was induced. Reduction of iron uptake did not differ between anti-FepA alone and anti-FecA alone when citrate was absent from the medium.

Animals↗
PubMed1975

Rapid determination of (carbon-14) glucose specific radioactivity for in vivo glucose kinetics.

Specific radioactivity of blood glucose was determined by use of a Dowex-1 anion-exchange column after (carbon-14) glucose was infused for in vivo kinetics. The first 20-ml eluate of protein-free blood filtrate from the column was discarded; then 10 ml was collected, lyophilized, and counted in a liquid-scintillation counter. Glucose concentration was determined and specific radioactivity calculated. Kinetic results were comparable to those obtained with the more laborious glucose-pentaacetate procedure.

Acetates↗