Proinflammatory cytokines interleukin 1 and tumor necrosis factor induce cytokines that are chemotactic for neutrophils, T cells and monocytes.
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Biological Factors↗
Biomedical subjects
C Larsen
Publications and source records attributed to C Larsen.
Ultrasound guided needle biopsy of skeletal muscle in neuromuscular disease.
Guided by ultrasonography percutaneous needle biopsy of skeletal muscle was performed in 24 patients, using the one hand held Biopty system and a 2 mm Tru-Cut needle. The specimens were graded with regard to diagnostic quality and utility and almost all specimens (96%) were of highest quality. The use of ultrasonography was helpful in selecting a suitable area for the biopsy and vascular structures could be avoided. The procedure was well tolerated and easy to perform, and no complications were recorded.
Adult↗
Gastrointestinal tuberculosis in patients with pulmonary tuberculosis.
Proven or suspected intestinal tuberculosis was diagnosed in 23 (46 per cent) of 50 patients with smear-positive, cavitating pulmonary tuberculosis. The diagnosis was regarded as proven in 14 patients and suspected in the remaining nine. The frequency of proven gastrointestinal disease increased with the severity of the pulmonary tuberculosis. Small intestinal disease was encountered in only two patients. Small mucosal lesions in the caecum were the most commonly detected pathological features. Colonoscopy was of particular value in establishing the diagnosis, which could not be predicted from the patients' abdominal signs or gastrointestinal symptoms.
Adolescent↗
[Nursing care. Open care plans--why and how!].
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Humans↗
High-performance size-exclusion chromatographic procedure for the determination of fluoresceinyl isothiocyanate dextrans of various molecular masses in biological media.
A high-performance size-exclusion chromatographic procedure, using Nucleosil Diol, for the quantitative analysis of fluoresceinyl isothiocyanate dextrans of various molecular masses (10,000-150,000) in biological media was developed. The influence of the molecular mass and the degree of substitution of the conjugates on the chromatographic behaviour are discussed. In addition to quantitation, the molecular mass of the conjugates with degree of substitution below 1.6 could be estimated from the chromatograms. Linear standard calibration curves were obtained at concentrations down to 0.050 micrograms ml-1 in rabbit plasma and urine and homogenates of rabbit liver, lymph node and muscle when the derivative (degree of substitution 0.85) was monitored by fluorescence detection (lambda ex = 493 nm, lambda em = 520 mm). The fluoresceinyl isothiocyanate dextrans were found to be stable for more than three days at 37 degrees in all biological media under investigation. A pH-rate profile for the alkaline hydrolysis of fluoresceinyl isothiocyanate dextrans was constructed. The applicability of the method to pharmacokinetic studies was demonstrated by recording the plasma concentration-time profile of a fluoresceinyl isothiocyanate dextran T-70 conjugate following intravenous injection to a rabbit. In relation to future pharmacokinetic investigations on dextran conjugates, the results reported indicate that labelling of the parent dextran with fluoresceinyl isothiocyanate and monitoring of the fluoresceinyl isothiocyanate dextran conjugate throughout the organism using the described method is a promising development.
Animals↗
[Usefulness of ultrasonic scanning in the diagnosis of infantile hypertrophic pyloric stenosis].
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Humans↗
Tetramine: occurrence in marine organisms and pharmacology.
The occurrence of tetramethylammonium ion (TMA) in marine organisms is reviewed. The pharmacological action of TMA is also discussed, with special emphasis on the sign and symptoms experienced by oral poisonings. It is concluded that the major manifestations of TMA poisonings may be attributed to interactions with the autonomous nervous system. Fatal intoxications are due to neuromuscular blockade.
Animals↗
The toxin tetramine from the "edible" whelk Neptunea antiqua.
The chemical nature of extracts of the marine gastropod Neptunea antiqua collected in the North Sea has been investigated. Amino acid analysis and spectroscopical studies (FAB MS, 1H NMR, 13C NMR and IR) on fractions purified by Biogel P-2 and Amberlite IR 120 column chromatography allowed the identification of 19 components. It was established that the water-soluble toxin responsible for poisonings, following ingestion of this snail, is tetramine (the tetramethylammonium ion present as an unknown salt). Contrary to what occurs in other Neptunea species (N. arthritica and N. intersculpta), tetramine was found not only in the salivary gland, but also in the remaining part of the animal, albeit in smaller concentration. In the isolated guinea-pig ileum assay, synergistic effects with other main components present (betaine, homarine) could not be demonstrated. Choline esters, believed to act synergistically in other Neptunea species, were not detected in Neptunea antiqua.
Animals↗
Quantitative determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in biological media by means of high-performance size exclusion chromatography with fluorescence detection.
A high-performance size exclusion chromatographic procedure using a Nucleosil Diol column and fluorescence detection has been developed for the determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in aqueous buffer solutions and biological media in the presence of the parent drug. The effect of several variables on the chromatographic behaviour of the compounds is discussed. Linear standard calibration curves were constructed for all the dextran derivatives incubated in whole blood and urine (human and rabbit), rabbit liver homogenate and human synovial fluid. In whole blood, the detection limit (lambda ex = 330 nm, lambda em = 360 nm) for a dextran T-70 pro-drug with a degree of substitution (DS) of 10.6 was found to be 2 micrograms ml-1 after applying a 20-micrograms sample to the column. The assay has been used in stability studies and determination of plasma concentration-time profiles after intravenous administration to rabbits of dextran-naproxen ester pro-drugs.
Animals↗
Macromolecular prodrugs. XVI. Colon-targeted delivery--comparison of the rate of release of naproxen from dextran ester prodrugs in homogenates of various segments of the pig gastrointestinal (GI) tract.
We have determined initial rates of naproxen formation from dextran-naproxen ester prodrugs incubated in homogenates of various segments of the pig GI tract. Drug liberation proceeded 15-17 times faster in cecum and colon homogenates than in aqueous pH 7.4 buffer or homogenates of the small intestine. The degree of conjugate substitution did not affect the liberation rates, whereas enhanced drug activation was observed with decreasing molecular size of the carrier dextran. During incubation in colon homogenates the average molecular weight of the dextran prodrugs decreased. The mechanism of drug activation from the prodrugs may therefore involve an initial depolymerization step of the dextran chains by dextranases secreted from bacteria in the pig colon. The generated small fragments then serve as substrates for esterases and other hydrolases.
Animals↗
Macromolecular prodrugs. XV. Colon-targeted delivery--bioavailability of naproxen from orally administered dextran-naproxen ester prodrugs varying in molecular size in the pig.
The bioavailability of naproxen after oral administration of aqueous solutions of various dextran-naproxen ester prodrugs in pigs was determined. The dextran prodrugs employed ranged in molecular weight from 10,000 to 500,000. As calculated relative to an equivalent oral dose of parent naproxen, the absorption fractions of all the derivatives were close to 100%. Only small interindividual variation of naproxen bioavailability was observed. The naproxen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of naproxen appearance in the blood (2-3 hr). Compared to administration of the prodrugs alone, coadministration of excess of the parent dextran further delayed the absorption of naproxen from the GI tract. The results of the present study demonstrate the potential of dextran prodrugs for colon site-specific delivery of drugs containing a carboxylic acid functional group.
Administration, Oral↗
Multicystic transformation of the kidneys in dialysis patients.
In a dialysis population patients who had been treated merely with haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) were examined with ultrasound. The occurrence of multicystic transformation of the kidney was 4/15 in HD patients and 8/25 in CAPD patients with no significant difference between the two groups. There was a significant association between the occurrence of multicystic transformation and the patient age while there was no significant association to the duration of dialysis or the duration of the uraemic state. No tumour or any other complication to cystic transformation was found. In 582 persons without renal disease examined as controls we found 44 with cystic change. This material does not support the recommendation of regular ultrasound examination of our dialysis patients. However, until these results can be confirmed by prospective studies we must recommend screening of all maintenance dialysis patients after a longer duration of dialysis.
Adult↗
Natural occurrence of the mycotoxin fusarochromanone, a metabolite of Fusarium equiseti, in cereal feed associated with tibial dyschondroplasia.
The mycotoxin fusarochromanone, a metabolite of Fusarium fungi, is able to induce tibial dyschondroplasia (TD) in chickens under experimental conditions. On the basis of health surveillance data on TD, two broiler farms with TD prevalence rates of up to 56% were identified. In the corresponding pelleted feed samples, fusarochromanone was detected in all 12 samples analyzed by column purification and TLC, with concentrations 4 to 59 micrograms/kg. No Fusarium fungi were available from the feed because of the pelleting process, but seven Fusarium equiseti strains previously isolated from Danish cereals were checked for fusarochromanone production, and all produced fusarochromanone at 57 to 1,435 mg/kg. Thus, the potential for fusarochromanone production by F. equiseti is considerable. The identification of fusarochromanone from feed and F. equiseti was confirmed by mass, infrared, and nuclear magnetic resonance spectral analyses. This is the first report of fusarochromanone as a naturally occurring contaminant.
Amino Acids↗
Preliminary studies on the in vivo fate of FITC-dextrans and naproxen-dextran ester prodrugs administered i.v. to rabbits.
The plasma half life and the urinary recovery after i.v. administration to rabbits (35 mg/kg) of FITC-dextrans and naproxen-dextran ester prodrugs of molecular weights 40,000 and 70,000 were determined by employing a HP(SEC) procedure with fluorescence detection. The conjugates disappeared from the blood stream roughly according to first-order kinetics at a rate only slightly influenced by the molecular weight and faster than the parent carrier dextrans. 15-30% of the dose of the derivatives was eliminated through the kidneys as compared to 44% (T-40) and 17% (T-70) of the parent dextrans. Liver uptake of the compounds was assumed to be the main additional elimination pathway as 46% of an i.v. dose of FITC dextran T-70 was found in the liver four hours after the injection, whereas only minor amounts were detected in the spleen, lungs and the kidneys. The molecular weight distribution of the conjugates in the circulation shifted continuously in the high molecular weight direction. The role of the liver in plasma clearance of the conjugates and the influence of the molecular weight and electric charge on the in vivo fate of the dextran derivatives are discussed.
Animals↗
On the design of urokinase-labile prodrugs II. Structure-activity relationships in the urokinase catalyzed hydrolysis of H-GluGlyArg-anilides and -benzylamide.
Six H-GluGlyArg-anilides with different ortho or para substituents in the aniline group, and H-GluGlyArg-benzylamide were synthesized. KM and kcat for the urokinase-catalyzed hydrolysis of the compounds were determined at 37 degrees C and pH 7.40. In the initial rate measurements, HPLC was used for product quantitation. KM varied between 0.20 mM and 8.9 mM, whereas kcat varied between 0.8s-1 and 16.5s-1 for the investigated substrates. A Hammett plot and a "Charton plot" of the rate data are presented. kcat were, to a minor extent, dependent on the pKa of the leaving group, whereas steric effects had a more marked influence on the overall rate constant. A o-benzyl substituent in the aniline-leaving group exerts less sterical hindrance to the enzymatic hydrolysis than expected from the Charton plot. The significance of the results in relation to the development of urokinase labile dextran prodrugs in discussed.
Drug Design↗
[Dialogue in nursing--worth a discussion].
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Communication↗
Diagnostic positive and negative ion fast atom bombardment mass spectrometry of low-molecular-weight ammonium compounds of marine origin.
Five ammonium compounds--betaine, taurine, homarine, trigonelline and tetramethylammonium chloride--were investigated by positive and negative ion fast atom bombardment (FAB) mass spectrometry. Observation of the parent cation [M + H]+ together with series of clusters (e.g. [nM + H]+, n = 2-5) and fragmentation patterns in the positive FAB mode may be used diagnostically as a fingerprint of the compound. The shifts in mass and relative intensity by addition of trichloroacetic acid and metal salts offer corroborating information of the identity of a compound in a mixture. The FAB negative ion spectra were characterized by clusters incorporating the anion (e.g. [M + Cl]-) but are generally less informative than the spectra obtained in the positive mode.
Alkaloids↗
Interactions of aflatoxin and the antioxidant butylated hydroxytoluene in two-week-old chicks.
Two-week dietary administration of 2500 ppb aflatoxin was sufficient to cause a decrease in bursal weights and a reduction in the number of splenic leukocytes in chicks. No significant effects on weight gain or feed efficiency were evident. The chicks also had elevated heterophil-to-lymphocyte ratios, suggesting a heightened reaction to stress. This effect could be blocked by dietary administration of the antioxidant butylated hydroxytoluene (BHT) at a concentration eight-fold over that normally present to preserve control feed. The BHT treatment increased the activities of the enzymes glutathione-S-transferase, aniline hydroxylase and O-demethylase, which metabolize aflatoxins in the liver.
Administration, Oral↗