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Biomedical subjects

S H Hansen

Publications and source records attributed to S H Hansen.

At least 109 records · Page 6Linked to original sources
PubMed1989

Neurofilament-like pattern of reactivity in human foetal PNS and spinal cord following immunostaining with polyclonal anti-glial fibrillary acidic protein antibodies.

The intermediate filament protein, glial fibrillary acidic protein (GFAP), is widely used as a cell-specific marker molecule for immunocytochemical identification of astrocyte lineages in cell culture, in tissues during development, and in tissues undergoing pathological changes. This study demonstrates that a reaction pattern of two commercially available polyclonal anti-GFAP antibodies shows extensive similarity to the pattern of reactivity obtained with monoclonal antibodies to neurofilaments in the PNS and spinal cord of human embryos and foetuses, at 5 to 12 weeks of gestation. The polyclonal antibodies to GFAP labelled populations of neurons and their processes in the PNS and in the spinal cord. Monoclonal antibodies to GFAP only labelled glial cells in the spinal cord. Neurofilament adsorption of one of the anti-GFAP antisera abolished the neurofilament-like reaction pattern, while the structures also labelled with monoclonal antibodies to GFAP remained immunostained. The results presented may question previously published data obtained with these and possibly other polyclonal anti-GFAP antibodies.

Animals↗
PubMed1989

Internalized ricin and the plasma membrane glycoprotein MAM-6 colocalize in the trans-Golgi network of T47D human breast carcinoma cells.

We have analyzed the intracellular transport of endocytosed ricin in the human breast carcinoma cell line T47D. Cells were incubated with ricin (10 micrograms/ml) for 1 h at 37 degrees C. Marked reduction in the protein synthesis did not take place until the end of this period. To detect ricin immunocytochemically, a rabbit anti-ricin serum was used. Gel electrophoresis followed by immunoblotting revealed that the antiserum reacted specifically with ricin and detected both the ricin A-chain and the ricin B-chain. Immunofluorescence experiments showed endocytosed ricin in endosomal and lysosomal vacuoles throughout the cytoplasm, as well as in a typical perinuclear position corresponding to the Golgi region. Using the monoclonal mouse antibody 115D8 directed toward the high-molecular-weight membrane glycoprotein MAM-6 of human breast epithelial cells, we similarly obtained a swarms of small vesicles throughout the cytoplasm. To further analyze the apparent colocalization of ricin and MAM-6 in the perinuclear Golgi region, immunogold cytochemistry on ultracryosections was performed. MAM-6 was detected mainly in Golgi stacks and associated trans-Golgi network (TGN) profiles, in 0.1 to 0.2-micron secretory vesicles, and on the cell surface. Ricin was detected on the cell surface, in endosomes and lysosomes, and also in the TGN. Furthermore, by using immunogold double labeling, internalized ricin was found to colocalize with MAM-6 in the TGN.

Antibodies, Monoclonal↗
PubMed1989

Effects of mesalazine substitution on salicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis.

Some semen characteristics of eight male patients with clinically inactive ulcerative colitis were investigated. Semen analysis was carried out twice during salicylazosulfapyridine (SASP) treatment and repeated twice after at least 3 months' treatment with mesalazine. The motility variables all showed significant improvement during mesalazine treatment: the graded motility (p less than 0.05), motility in percentage (p less than 0.01), and the penetration in egg white (p less than 0.05). The semen plasma was analyzed for mesalazine and the metabolite Ac-mesalazine during both regimens. There was no difference in the semen plasma concentration of mesalazine during the two regimens, whereas Ac-mesalazine was significantly higher during mesalazine treatment than during SASP treatment, indicating that other SASP metabolites, most likely sulfapyridine, are the agent causing the abnormal sperm characteristics. We suggest that pure mesalazine preparations are a safer alternative in young men with chronic inflammatory bowel disease.

Adult↗
PubMed1989

New metabolites of the drug 5-aminosalicylic acid. I: N-beta-D-glucopyranosyl-5-aminosalicylic acid.

1. A new unstable metabolite of 5-aminosalicylic acid (5-ASA) was found in plasma from healthy volunteers dosed with 5-ASA i.v. 2. The metabolite was prepared by incubation of 5-ASA with rat liver homogenate, and isolated using preparative h.p.l.c. 3. The metabolite was identified as N-beta-D-glucopyranosyl-5-aminosalicylic acid by n.m.r. spectroscopy and by FAB mass spectrometry. 4. N-beta-D-Glucopyranosyl-5-ASA was formed non-enzymically from 5-ASA and glucose in phosphate buffer pH 7.4, and was unstable under weakly acidic conditions, decomposition increasing with temperature, i.e. decomposition was complete after 30 min at pH 5.0 and 23 degrees C.

Adult↗
PubMed1989

Enzymic synthesis of two glucuronides of the hydroxyisoxazole GABA-agonist, THIP, and the in vivo glucuronidation of THIP in rat.

1. A method for preparative enzymic synthesis of two glucuronides of THIP (3-hydroxy-4,5,6,7-tetrahydro-isoxazolo[5,4-c]pyridine) is described. 2. Using FAB mass spectrometry, u.v. and 1H- and 13C-n.m.r. spectroscopy, the two glucuronides were identified as N- and O-glucuronides respectively. 3. An h.p.l.c. method for determination of THIP and the two intact glucuronides in urine has been developed. 4. The glucuronidation pattern of THIP in rats has been examined; THIP was excreted as a THIP-O-glucuronide but not as a THIP-N-glucuronide.

Animals↗
PubMed1989

Effect of insulin on growth and expression of smooth muscle isoactin in human breast gland myoepithelial cells in a chemically defined culture system.

Myoepithelial cells express both epithelial and stromal (smooth muscle) cell characters. Moreover, while separating the luminal (secretory) epithelial cells from the connective tissue in normal breast glands, myoepithelial cells apparently disappear in invasive carcinomas, or their phenotypic characteristics become down-regulated. In the present study we have used a chemically defined culture model system to study how expression of smooth muscle isoforms of actin in myoepithelial cells is influenced by insulin by using immunoblotting, immunofluorescence and electron microscopy. We show that in the absence of insulin, myoepithelial cells do not proliferate but exhibit a differentiated phenotype. Hence, they contain distinct bundles of actin filaments and also numerous caveolae at the cell surface. In contrast, with insulin in the medium, cell proliferation increases dramatically. Concomitantly the smooth muscle actin expression and the associated caveolae disappear within a week. However, other cytoskeletal proteins such as keratins and vimentin are expressed no matter whether insulin is absent or present.

Actins↗
PubMed1989

Release of granulocyte elastase and complement changes during hysterectomy.

Complement activation and release of granulocyte elastase has been previously reported during major vascular surgery and has been ascribed to plasma/cell interactions with foreign surfaces or to administration of blood or plasma. The effect of uncomplicated general anaesthesia and surgery, not requiring blood or plasma, on complement activation and signs of proteinase release was assessed by measuring C3d and elastase-alpha-1 PI, respectively, in nine patients undergoing elective hysterectomy. There was a minor decrease in plasma C3d during anaesthesia, surgery and in the post-operative period caused by the diluting effect of intravenous fluids. Elastase alpha-1 PI remained largely unchanged until the first post-operative day, when a significant increase was seen (p less than 0.05); on the second and third day significant elevated values were still observed. Release of granulocyte elastase seems to be a generalized response to surgical trauma and may be a part of the endocrine-metabolic stress response.

Adult↗
PubMed1988

Absorption of 5-aminosalicylic acid from colon and rectum.

In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant difference could be demonstrated between the two parts of the large bowel, but the absorption was considerably restricted compared with previous results obtained from the jejunum. The results confirm in a direct manner earlier observations on 5-ASA released from sulphasalazine.

Adult↗
PubMed1987

Separation of basic drug substances by reversed-phase high-performance liquid chromatography on dynamically modified silica and on bonded-phase materials.

The chromatographic behaviour in the reversed-phase mode of various drug substances, which are nitrogen-containing bases, has been investigated. Three different types of column materials were used, ordinary chemically bonded ODS-silica, deactivated ODS-silica specifically designed for the separation of bases and bare silica dynamically modified by adding long-chain quaternary ammonium compounds to the eluent. Various brands were tested for all three types of column materials. When using ODS-silica as the column material, considerable tailing of peaks and prolonged retention was observed. Also the deactivated columns exhibited tailing problems, but less pronounced. For both types of bonded-phase material it was possible to reduce the tailing considerably by the addition of an anti-tailing agent to the eluent. On bare silica used in the dynamic modification mode the tailing was almost negligible.

Chromatography, High Pressure Liquid↗
PubMed1987

Reversed-phase high-performance liquid chromatographic assay for the simultaneous determination of diflunisal and its glucuronides in serum and urine. Rearrangement of the 1-O-acylglucuronide.

A reversed-phase ion-pair high-performance liquid chromatographic assay for the simultaneous determination of diflunisal and its ester and ether glucuronide in urine and serum has been developed. The determination of the ester glucuronide in serum has not been previously reported. The genuine glucuronide conjugates isolated from urine were used as standards. The ester glucuronide is found to be unstable, especially in neutral and basic solutions, and special precautions therefore have to be taken during sampling and sample treatment. Nine rearrangement/degradation products of the ester glucuronide were detected.

Chromatography, High Pressure Liquid↗
PubMed1987

Toluene metabolism during exposure to varying concentrations combined with exercise.

The urinary excretion of hippuric acid (HA) and ortho-cresol (O-cr) in man was measured in two studies of 7-h exposure to toluene in a climate chamber, either constant concentration of 100 ppm or varying concentrations containing peaks of 300 ppm but with a time-weighted average of 100 ppm. In Study A, four males were exposed to clean air and to constant and varying concentrations of toluene in combination with rest and with 100 W exercise in 140 min. Exercise increased end exposure excretion rate of HA and O-cr by 47 and 114%, respectively. After exposure, all excess HA was excreted within 4 h, while O-cr was eliminated with a half life of about 3 h. Alveolar air concentration of toluene varied between 21 and 31 ppm during constant exposure and between 13 and 57 ppm during varying exposure, but no difference in mean alveolar toluene concentration or in metabolite excretion was seen between the exposure schedules. In Study B, 32 males and 39 females aged between 31 and 50 years were exposed once to either clean air, constant or varying concentrations of toluene. Background excretion rate of HA was 0.97 +/- 0.75 mg/min (1.25 +/- 1.05 g/g creatinine) and rose to 3.74 +/- 1.40 mg/min (3.90 +/- 1.85 g/g cr) during the last 3 h of exposure to 100 ppm toluene. The corresponding figures for O-cr were 0.05 +/- 0.05 micrograms/min (0.08 +/- 0.14 mg/g cr), and 2.04 +/- 0.84 micrograms/min (2.05 +/- 1.18 mg/g cr). The individual creatinine excretion rate was considerably influenced by sex, body weight and smoking habits, thus influencing the metabolite concentration standardised in relation to creatinine. It is concluded that both metabolites are estimates of toluene exposure. O-cr is more specific than HA, but the individual variation in excretion of both metabolites is large, and when implementing either of them as biological exposure indices, the influence of sex, body size, age as well as consumption of tobacco and alcohol has to be considered.

Adult↗
PubMed1987

Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro.

We have studied platelet aggregation and fibrinolytic activity in six patients with chronic inflammatory bowel disease treated with 5-aminosalicylic acid (mesalazine). There were no changes in these measurements during normal treatment, i.e. 1.5 g per day with a slow-release formulation, nor after an intravenous dose of 250 mg. Also in vitro tests were negative, in contrast to the inhibition seen with aspirin (acetylsalicylic acid). We conclude that treatment with mesalazine does not constitute a hazard to these patients in regard to prolonged bleeding time caused by an influence on platelet aggregation or fibrinolytic activity.

Adult↗
PubMed1987

Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.

The influence of intestinal transit time on the release of 5-aminosalicylic acid (5-ASA) from a peroral, slow-release preparation (Pentasa) was studied at steady state in seven healthy volunteers. Daily dose was 1500 mg Pentasa, normal transit time (NTT) was 24 h (16-26 h) and accelerated transit time (ATT), caused by a laxative, was 5 h (4-9 h). Median total recovery (24 h, 5-ASA + acetyl-5-ASA) was 87% (61-129%) (NTT) and 81% (56-100%) (ATT), respectively, (P greater than 0.10). The total faecal excretion of 5-ASA (per cent of dose) increased from 16%, (9-21%) (NTT) to 29%, (16-38%) (ATT) (P less than 0.02). Free 5-ASA rose from 12% (4-19%) to 17% (10-25%), the retained part (in granules) from 4% (2-5%) to 12% (4-24%). Urinary excretion decreased correspondingly from 32% (19-59%) to 21% (11-38%), predominantly as Ac-5-ASA (P less than 0.05). Mean plasma Ac-5-ASA concentration decreased from 1.42 micrograms ml-1 to 0.86 microgram ml-1 (P less than 0.05). An almost complete release of 5-ASA from Pentasa takes place during NTT. At ATT conditions about 88% is released, indicating Pentasa to be an acceptable source of 5-ASA in diarrhoeal states.

Adult↗
PubMed1987

Salazosulfapyridine and metabolites in fetal and maternal body fluids with special reference to 5-aminosalicylic acid.

In 7 pregnant women, treated prophylactically with salazosulfapyridine (SASP) 3 g/day, amniotic fluid (16th week, n = 4, maternal and cord plasma (n = 5) and breast milk (n = 3) were analysed for SASP and the metabolites sulfapyridine (SP), acetyl sulfapyridine (Ac-SP), 5-aminosalicylic acid (5-ASA) and acetyl 5-aminosalicylic acid (Ac-5-ASA). Amniotic fluid contained concentrations of SASP, SP and Ac-SP and partly also Ac-5-ASA comparable to those previously found by others, whereas 5-ASA concentrations were very low. The ratios of maternal to cord plasma for all SASP metabolites were about 1:1-1:2, except for 5-ASA, cord plasma being extremely low. In breast milk, only traces of 5-ASA were detected, while Ac-5-ASA was above the plasma level. Only negligible amounts of 5-ASA are thus transferred to the fetus/newborn, which is of significance for the future use of the new non-sulfa-containing 5-ASA preparations during and after pregnancy.

Adult↗
PubMed1986

5-Aminosalicylic acid in patients with an ileo-rectal anastomosis. A comparison of the fate of sulfasalazine and Pentasa.

The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24-hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5-ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed.

Aminosalicylic Acids↗
PubMed1986

Assay of tolfenamic acid and its metabolites by liquid chromatography on dynamically modified silica: application in pharmacokinetics.

An LC method able to separate all known metabolites of tolfenamic acid was developed. It was applied to characterize the metabolic profiles after single and multiple peroral doses of tolfenamic acid to volunteers. Up to 80% of the dose, mostly conjugated metabolites, could be recovered in the urine by this method. Two of the metabolites showed plasma half-lives of several days and peculiar conjugation properties.

Journal Article↗
PubMed1986

Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis.

Fifteen adult and 19 pediatric outpatients with ulcerative colitis were studied to determine the steady-state kinetics of 5-aminosalicylic acid (5-ASA) released from salazosulfapyridine (SASP). Results of excretion in adults (mean 24-h recovery of 5-ASA, 21% in urine and 57% in feces) were compatible with those of healthy volunteers. Since mean SASP dose/kg body weight (about 50 mg/kg) and compliance (reflected in sulfapyridine recovery) were equal in adults and pediatric patients, the results of the patient groups could be compared. Near-complete azo reduction of SASP occurs in children. Absorption and excretion of 5-ASA and metabolism to acetyl-5-ASA did not differ statistically between pediatric and adult patients. However, the fecal excretion of the drug and its metabolites was significantly lower in young patients, although fecal concentrations were the same. The present results demonstrate that SASP is an excellent sustained-release drug for the delivery of 5-ASA to the lower part of the bowel system and provide a reference for comparison of 5-ASA kinetics after treatment with newer 5-ASA preparations.

Adolescent↗