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PubMed1987

Transdermal absorption of fentanyl and sufentanil in man.

We have studied the transdermal absorption of tritiated fentanyl (citrate and base) and sufentanil citrate. Approximately 50 micrograms of drug in water was applied to the forearm skin of volunteers (5 subjects for fentanyl citrate and base, 6 for sufentanil). When the water had evaporated the site was covered with an occlusive dressing. Total urine collections were carried out for 96 h in 12 h periods. At 24 h the dressing was removed and skin removed with serial applications of adhesive tape. The radioactivity in the urine and on the tape was measured in a scintillation counter. Urine recovery expressed as a percentage of the absorbed dose was 17.9 +/- 1.9% for fentanyl citrate, 20.5 +/- 5.6% for fentanyl base, and 22.5 +/- 2.5% for sufentanil. In one subject who ran 10 miles with a sufentanil patch in situ the recovery was 52.3%. The systemic availability of fentanyl by this route is approximately 30% of that found using the intravenous route.

Administration, Cutaneous↗

PubMed1984

Simultaneous measurement of adherence and chemiluminescence by polymorphonuclear leukocytes.

Oxygen radical release from adhering polymorphonuclear leukocytes (PMN) has been implicated as an important feature of many vascular diseases. We developed a technique by which adherence and production of O2 radicals by PMN can be measured simultaneously. The technique combines the conventional nylon fiber assay for measuring adherence of PMN with concurrent scintillation counter measurement of chemiluminescence (CL) to assess O2 radical production by PMN. We found that adherence of PMN to nylon fiber is associated with increases in CL. Moreover, increases in CL appear to be dependent on generation of O2 radicals from PMN since they are not seen with PMN from a patient with chronic granulomatous disease (CGD) or in the presence of O2 radical scavengers, superoxide dismutase, or catalase. Furthermore, agents which increase the adherence of PMN to nylon fiber are associated with increases in CL. Use of this approach may facilitate simultaneous evaluation of adherence and O2 radical generation by PMN.

Cell Adhesion↗

PubMed1975

The influence of varying oxygen tensions in inspired gas on 133Xenon muscle clearance and fatigue levels during sustained and dynamic conctractions.

Isometric and isotonic endurance levels of both elbow flexors and knee extensors were tested during inspired gas mixtures of ca. 10%, 21% or 100% oxygen in nitrogen. The four work loads were set a 25, 50, 60 and 70% of maximal volitional isometric strength (IS). The isotonic exercise routine was carried out using weight lifting techniques of 20 repetitions per min from 75 degrees to 105 degrees of elbow flexion and knee extensions respectively. Prior to, during, and after the endurance experiments 133Xe clearance was monitored by light weight scintillation counters. A depot of 0.1 to 0.2 ml of isotonic saline containing 50 to 150 muCi of the isotope was used as an intramuscular tracer. The exercise clearance values varied inversely to the test load during isometric exercise. Isotonic exercise for both elbow flexors and knee extensors showed increasing clearance values up to 60% IS. Above this level a decrease in total clearance was recorded. Oxygen tension had no statistical effect on the clearance values. However, the relatively large scatter of the 133Xe clearance method, and an inhomogenous perfusion of skeletal muscle may have masked any anticipated effect of the various O2 tensions. Variations due to the raised intramuscular pressure appeared to be much more dominant than the hypothezised variation due to the 3 set oxygen tensions.

Adult↗

PubMed1978

[Clinical and cell kinetic data on the combination of cytosine arabinoside with daunorubicin, isosfamide, thioguanine, and vincristine for remission induction and maintenance in patients with acute myelocytic leukaemia (author's transl)].

31 adult patients (study A) with acute myelocytic leukaemia were treated for remission induction with cytosine arabinoside (ARA-C, 100 mg/m2/day) by a 7 (5) day continuous infusion. 3 (2) doses of daunorubicin (DNR, 45 mg/m2 i.v.) were added at daily intervals. For maintenance 5 day ARA-C was given monthly in sequential combination with DNR, thioguanine (TG), or ifosfamide (IFOS). 16 (52%) patients achieved complete remission (C.R.) after 1.8 (1-3) courses and 6.7 (3-10) weeks from treatment start. The median survival for responders and non-responders was 11.5 months, early death rate within 6 weeks was 3 (10%). Median remission duration was 13.5 months. Among 11 patients surving for 7-22 months 7 patients are in first remission for 5.5-20.5 months. DNR, IFOS and TG were given before the 3rd day of ARA-C infusion. In a previous group of 34 leukaemic patients and in 44 therapy courses DNA histograms of bone marrow cells using pulse cytophotometry showed marked accumulation in S-phase for 75% of courses. Also (G2 + M)-cells in the DNA distribution and thymidine pulse labelling indices were markedly increased in most cases, whereas thymidine uptake by scintillation counter was diminished and mitotic indices had not changed significantly. In now 15 patients (study B) the induction regimen was intensified by adding vincristine (VCR, 2 mg i.v.) and 3 doses of IFOS (600 mg/m2 i.v.). Preliminary results are 50% C.R. after 1,7 (1-2) courses and 6.8 (5-10) weeks from initiation of therapy. 2 patients died in the first 6 weeks.

Adolescent↗

PubMed1978

A quantitative method for measurement of lysosomal acid phosphatase latency in cultured rat heart cells with 210Pb.

A method is described for measuring the latency of lysosomal acid phosphatase in cultured rat heart endotheloid cells. 210Pb was added to a medium used to demonstrate acid phosphatase activity by the Gomori lead method, and the amount of lead deposited was measured with a liquid scintillation counter. Deposition rates were measured after enzyme activation pretreatments with acetate buffer (pH 5.0) at various osmolalities, and after formaldehyde fixation. Formaldehyde, alloxan, or fluoride in the Gomori medium were evaluated for their differential effects on lysosomal and non-lysosomal acid phosphatase. The method was found to provide a sensitive, rapid and quantitative evaluation of acid phosphatase latency and should be useful for studying the integrity of lysosomes within cells.

Acetates↗

PubMed1979

Measurements at the piE3 single beam correlated to dosimetry and therapy-planning for the pion applicator at SIN.

Using ionization chambers, aluminium activation, TLD and scintillation counters 3-dimensional total dose-distributions, stardose-distributions and pion stop-distributions have been measured in a single pion beam for various momenta and momentum spreads. It is demonstrated how these data will be used as an input into the therapy-planning program. The techniques developed are suited to check dynamical treatment with 60 pion beams.

Elementary Particles↗

PubMed1978

The use of Cerenkov radiation in the measurement of 115mCd in blood and other tissues.

A new method for the activity measurement of 115mCd in biological samples was proposed. After tissues mineralization with 60% perchloric acid and 30% hydrogen peroxide (I) or with 0.5 M ethanolic sodium hydroxide (II) the solutions were measured in automatic liquid scintillation counter SL-30 by CERENKOV technique. The channels ratio method was successfully applied for standardization. The recoveries of 115mCd varied in the ranges: 93.6-102% and 82.7-99.3% for method I and II, respectively.

Animals↗

PubMed1983

Isoelectric focusing of steroid hormone receptors in slabs of polyacrylamide gel.

Isoelectric focusing in 1-2 mm thick slabs of polyacrylamide gel is a versatile and specific method for quantitation and characterization of estrogen, mineralocorticoid, progestin, and glucocorticoid receptors. This method has been used for routine measurements of estrogen receptor in human breast cancer in Stockholm since 1976. It is also used for quantitation of estrogen receptor in fine needle biopsies from breast cancer tissue. Isoelectric focusing in gel slabs allows rapid separation (1.5 hr) of receptors from other non-receptor proteins that bind steroid hormones, such as transcortin and sex hormone-binding globulin. The tritium-labeled steroid-receptor complex is localized by slicing the gel followed by radioactivity analysis in a liquid scintillation counter. The isoelectric point of the tritium peak is determined with a surface electrode. The isoelectric point serves as a qualitative control. Thus, only one analysis is needed for each receptor quantitation, provided that a saturating concentration of tritiated ligand is used for receptor binding. This means that a minimal amount of tissue is needed for one receptor analysis with isoelectric focusing.

Acrylic Resins↗

PubMed1979

In vitro sensitivity test of stomach cancer tissues by the use of metal grid method.

Ninety-nine specimens obtained from 53 patients with stomach cancer were cultured for about 3 days by means of the stainless steel grid method. In vitro effects of antitumor drugs on the cancer cells were evaluated autoradiographically or biochemically using a liquid scintillation counter to measure the uptake of 3H-thymidine. The radioactivity of the labeled tumor cells of both control fragments and fragments affected by drugs varied greatly among individual tumors. Therefore, the in vitro efficacy of antitumor drugs was represented as a comparison with that of control fragments. Positive correlation between in vitro tests and the clinical effects of antitumor drugs was observed in the specimens of 18 cases.

Antineoplastic Agents↗

PubMed1980

A single-step method for determination of the specific radioactivity of lipids.

The use of a liquid scintillation counter to measure both the mass and the radioactivity content of charred 14C-labeled lipid bands from thin layer chromatoplates has been evaluated. Following lipid mass determination from a measurement of the external standard channels ratio, a suitable choice of counting parameters enabled a reproducible and efficient 14C count to be obtained over virtually the whole range of lipid concentrations tested. Although the charring procedure resulted in some loss of radioactivity, the efficiency of counting remained high enough for accurate dpm measurements.

Carbon Radioisotopes↗

PubMed1996

The role of antioxidants in the prevention of t-butyl hydroperoxide-induced chemiluminescence.

An experimental system which assesses the antioxidant potential of ascorbic acid, glutathione, uric acid, and taurine was developed. The system comprised hemoglobin, luminol, t-butyl hydroperoxide, and different concentrations of antioxidants in TRIS-HCl buffer (pH 7.4). Control assays were performed by excluding antioxidants. Chemiluminescence was detected using a liquid scintillation counter in single photon mode. All antioxidants, when applied in the appropriate concentrations, decreased the maximum chemiluminescence values. The minimum concentrations which decreased the chemiluminescence values were defined for each of the antioxidants.

Antioxidants↗

PubMed1996

The effects of detergents on t-butyl hydroperoxide-induced chemiluminescence.

We examined the effects of Triton X-100, digitonin, sodium dodecyl sulfate, taurocholic acid, and cetylpyridinium chloride on hemoglobin-catalyzed and t-butyl hydroperoxide-induced chemiluminescence. The experimental system contained hemoglobin, luminol, t-butyl hydroperoxide, and different concentrations of detergents (5-100 mg/dl) in TRIS-HCl buffer. Control assays were performed by excluding detergents. Chemiluminescence was detected using a liquid scintillation counter in single photon mode. All concentrations chosen for each detergent reduced the maximum chemiluminescence value and retarded the time that maximum chemiluminescence occurred. The most prominent reduction in maximum chemiluminescence was observed with 50 and 100 mg/dl digitonin. The smallest reduction was observed with 5 mg/dl sodium dodecyl sulfate, without retardation of the time that maximum chemiluminescence occurred. Our aim was to use detergents in membrane-containing experimental systems and hence to identify the detergent with the least effect on chemiluminescence. Our results suggest that sodium dodecyl sulfate is the most suitable detergent for chemiluminescence studies in membrane systems.

Catalysis↗

PubMed1999

Determination of iodide amounts in urine and water by isotope dilution analysis.

Urinary iodide and iodine in drinking water were determined in 318 healthy children aged 0 to 18 yr living in Izmir and environmental rural and urban areas in the western part of Turkey. The method is based on substochiometric isotope dilution analysis. Iodide was precipitated by substoichiometric amounts of AgNO3. Iodide-131 was used as a tracer. Electrophoresis was performed to separate Ag131I from excess 131I-. The Ag131I zone was cut off the electrophoresis paper and counted with a NaI(Tl) scintillation counter. Count rates were plotted versus added KI concentrations. The unknown iodide amount was found by using these linear plots. Iodide concentration ranges were within 1.8-100.45 micrograms/L in the analyzed drinking water samples. The mean value was 44.14 +/- 17.33 micrograms/L and the median was 58.08 micrograms/L. Urinary iodide concentration ranges were 0.22-142.22 micrograms/L. The median of the distribution was 37.71 micrograms/L and the mean was 40.30 +/- 24.05 micrograms/L. The results show that the examined area suffers moderate iodine deficiency.

Adolescent↗

PubMed2002

The single-plasma-sample method for determining the glomerular filtration rate with Tc-99m-diethylenetriamine pentaacetic acid in childhood and adolescence: is it age-dependent?

UNLABELLED: The aim of this study is to assess the accuracy of the pre-existing single-plasma-sample method (SPSM) to measure the glomerular filtration rate (GFR) with Tc-99m-diethylenetriamine pentaacetic acid (Tc-99m-DTPA) in children and adolescents. In addition, the age-independent SPSM is evaluated with two algorithms (Bubeck and Russell) applied for Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) SPSM. PATIENTS AND METHODS: The study was performed on 14 patients (12 men and 2 women; age range 3 to 19 yr) with renal diseases. Tc-99m-DTPA (5 MBq/kg) was injected intravenously and thereafter blood samples were taken at 5, 15, 60, 90, 120, 150 and 180 min via the indwelling tube. Radioactivity in the injection syringe and plasma was measured by means of a double-well single-plastic scintillation counter. The "true" GFR as a reference was determined by two methods: 1) 2-exponential curve fitting 7 samples (GFR7) and 2) 1-exponential curve fitting 3 samples between 90 and 150 min (GFR3) in a slow clearance phase. The GFR7 and GFR3 were searched for to the clearance (GFR1) estimated from a plasma concentration at various sample times by means of 3 equations designed for children (Groth & Aasted, Ham-I and -II) and 3 for adults (Christensen & Groth, Jacobsson, Itoh). RESULTS: All the SPSM showed close correlations (r > 0.95) with the reference methods. Among them, Jacobsson's equation at sample time = 120 min tended to be the most accurate (r = 0.9826, RMSE = 7.8 ml/min)). On the other hand, Ham-I's equation at sample time = 120 min was the most accurate, when it was referred to GFR3 in correction for overestimation (r = 0.9951, RMSE = 4.60 ml/min). The Bubeck and Russells' algorithms showed that the regression equation between the GFR7 and the estimates was different in 2 groups of adults (49 cases) and children/adolescents. CONCLUSION: Our study indicates that Jacobsson's and Christensen & Groth's equations designed for adults are also applicable in determining the GFR with Tc-99m-DTPA in children and adolescents. The algorithms applied for age-independent SPSM with Tc-99m-MAG3 appears to be applicable to SPSM with Tc-99m-DTPA in children, adolescents and adults, but the single age-independent equation with Tc-99m-DTPA will need further investigations.

Adolescent↗

PubMed2001

Comparison of 99mTc-tetrofosmin uptakes on planar images with those in excised rats organs.

UNLABELLED: The radioactivity in the organs adjacent to the heart causes interference with the quantitative assessment of myocardial uptake of tracer on scintigraphy. In order to investigate how much the functions of these organs affect myocardial uptake seen in imaging, we compared the myocardial uptake measured by means of a gamma camera with the actual activity in the excised organs. METHODS: Thirty-three rats were imaged at 5, 10, 15, 30, 45, 60, 90 and 120 min after the administration of 99mTc-tetrofosmin, and % injected dose per pixel (%ID/pixel) for each organ was assessed on planar images (PI measurement). Percent injected dose per gram of tissue (%ID/g) in the heart as well as lungs, liver, gastrointestines and blood was measured by means of a well scintillation counter (WC measurement). Comparison between PI and WC measurements was performed with % uptake, the PI-to-WC ratio and heart-to-organ ratios. RESULTS: Our WC measurement showed an increase in cardiac uptake until 30 min (1.67 +/- 0.31%) postinjection and subsequent gradual decrease, whereas PI measurement showed maximum activity of 1.81 +/- 0.52% at 15 min postinjection. There was a prominent difference between the two measurements, particularly at 10 min, with a PI/WC ratio of about 1.6 times. Our WC measurement showed maximum pulmonary uptake at 15 min (0.87 +/- 0.31%) and a gradual decrease over 15 min, whereas PI measurement showed maximum uptake at 10 min (1.14 +/- 0.38%). There was hardly any variation in activity observed later than at 10 min. Our WC measurement showed hardly any variance in hepatic activity from 5 min (0.77 +/- 0.19%) to 30 min (0.69 +/- 0.27%) with a subsequent gradual decrease. The percent uptake in PI measurement was generally greater than that in WC measurement, and high values were found at 10 min and 15 min with PI/WC ratios of about 3.3 times and 2.3 times, respectively. CONCLUSION: Percent uptakes in PI measurement were greater than those in WC measurement. The difference between the two measurements was prominent in the early phases. The cardiac uptake in PI measurement was significantly greater than that in WC measurement at 10 min. It was considered that this discrepancy between the two measurements was caused by the Compton scatter from the organs adjacent to the heart.

Animals↗

PubMed1998

Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs.

PURPOSE: Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphatidylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-ChE drugs. METHODS: Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (1) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), an M3 muscarinic receptor antagonist, on neostigmine- or pyridostigmine-induced contraction of rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses. PI response. The tracheal slices were incubated in K-H solution containing LiCl and 3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist. 3[H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. RESULTS: Carbachol (0.1 microM), neostigmine (1 microM), pyridostigmine (10 microM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmine-induced contraction. Neostigmine- or pyridostigmine-induced IP1, accumulation was inhibited by 4-DAMP. CONCLUSIONS: The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.

Animals↗

PubMed1995

Phosphatidylinositol responses are involved in the vascular effects of thiamylal and fentanyl.

Although thiobarbiturates potentiate, and fentanyl attenuates peripheral vasoconstriction, the intracellular mechanism involved in this phenomenon is not clear. Because smooth muscle contraction induced by alpha 1-adrenoceptor agonists is mediated by the phosphatidylinositol (PI) response, this study was carried out to clarify if thiamylal and fentanyl affect the norepinephrine-induced PI response in rat aortic slices. Rat aortic slices were incubated in Krebs-Henseleit solution containing 5 mM LiCl, [3H]myo-inositol, and varying concentrations of thiamylal or fentanyl. The Pl response was stimulated by 0.9 microM (ED50) norepinephrine (NE). The [3H]inositol monophosphate (IP1) was separated from [3H]myo-inositol by column chromatography and counted with a liquid scintillation counter. The basal IP1 accumulation was not affected by thiamylal and fentanyl. Norepinephrine-induced IP1 accumulation was potentiated by thiamylal at concentrations of 10 microM and 100 microM. Norepinephrine-induced IP1 accumulation was attenuated by 1 microM and 10 microM fentanyl. The results suggest that thiamylal stimulates the NE-induced PI response, which potentiates the vasoconstriction, and fentanyl attenuates NE-induced PI response, which would attenuate the vasoconstriction.

Anesthetics, Intravenous↗

PubMed2006

Detection of maleate-induced Fanconi syndrome by decreasing accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine in the proximal tubule segment-1 region of renal cortex in mice: a trial of separate evaluation of reabsorption.

OBJECTIVE: Fanconi syndrome is a renal dysfunction characterized by various combinations of renal tubular transport dysfunction involving amino acids, glucose, protein and other substances. Most reabsorption of amino acids occurs in proximal renal tubule segment 1 (S1). The present study evaluated the possibility of early detection of drug-induced Fanconi syndrome, based on decreased renal accumulation of 125I-3-iodo-alpha-methyl-L-tyrosine (125I-IMT), an amino acid transport marker, in the S1 region of renal cortex. The present experimental model used maleate (MAL)-induced Fanconi syndrome in mice. Results were compared between 125I-IMT and 3 other clinical renal radiopharmaceuticals: 99mTc-2,3-dimercaptosuccinic acid (99mTc-DMSA); 99mTc-mercaptoacetylglycylglycylglycine (99mTc-MAG3); and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). METHODS: Male ddY mice (age, 6 weeks; body weight, 25 g) were used to create a Fanconi model of renal dysfunction. A single dose of maleate disodium salt was administered by intraperitoneal injection (6 mmol/kg). Hematoxylin and eosin (HE) staining of the renal cortex, renal autoradiography and measurement of renal radioactivity of labeled compounds were performed at 30, 60, 90 and 120 min after MAL injection. At 5 min after injection of labeled compounds (18.5 kBq for accumulation experiment, 670 kBq for autoradiography), animals were sacrificed by ether overdose and kidneys were removed. For the accumulation experiment, radioactivity was measured using a well-type scintillation counter. For autoradiography, 20-microm sections of frozen kidney were used with Bio-Imaging Analyzer. RESULTS: At 30 min after MAL injection, HE staining showed pyknosis in some proximal tubule cells. At that time, accumulations of 125I-IMT and 99mTc-DMSA in the S1 region were approximately 67% and 55% of control levels (p < 0.005). MAL increased accumulation of 99mTc-DTPA in the S1 region, but had no effect on accumulation of 99mTc-MAG3 in the S 1 region. CONCLUSIONS: Decreased accumulation of 123I-IMT in the S1 region appears to represent a useful marker for detection of MAL-induced Fanconi syndrome. In future, we plan to assess the efficacy of using 125I-IMT to monitor renal dysfunction induced by nephrotoxic clinical drugs.

Absorption↗