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Biomedical subjects

U Hoppe

Publications and source records attributed to U Hoppe.

68 records · Page 4Linked to original sources

Radioimmunoassay for leukotriene E4. Use for determination of total sulfidopeptide-leukotriene release from rat gastric mucosa.

A conjugate of leukotriene (LT) E4 and bovine serum albumin (BSA) was prepared by covalently linking the free amino group of the hapten to the protein using dimethyl pimelindiimidate (DMP) as coupling reagent. Anti-LTE4 antibodies were raised in rabbits immunized with the conjugate. Binding of [3H]LTE4 to the antibodies is inhibited by 50% with 0.63 ng LTE4, while the relative cross-reaction of LTC4 and LTD4 is 46.3% and 12.6%, respectively. Using the radioimmunoassay release of sulfidopeptide-LT (SP-LT) from rat gastric mucosa incubated in vitro was determined after quantitative enzymatic conversion of SP-LT to LTE4. It could be demonstrated that this method is suitable for determination of SP-LT in biological material.

Amino Acids, Sulfur↗

Leukotriene synthesis by human gastrointestinal tissues.

The prostaglandin and leukotriene synthesizing capacity of human gastrointestinal tissues obtained at surgery was investigated using radioimmunoassay for prostaglandin E2, leukotriene B4 and sulfidopeptide leukotrienes. The leukotriene immunoassay data were validated by high-pressure liquid chromatography (HPLC). During incubation at 37 degrees C, fragments of human gastric, jejuno-ileal and colonic mucosa released considerably larger amounts of prostaglandin E2 than of leukotriene B4 and sulfidopeptide leukotrienes. Gastrointestinal smooth muscle tissues released even larger amounts of prostaglandin E2, but smaller amounts of leukotrienes than the corresponding mucosal tissues. Adenocarcinoma tissue released larger amounts of leukotriene B4, sulfidopeptide leukotrienes and prostaglandin E2 than normal colonic mucosa. Ionophore A23187 (5 micrograms/ml) did not stimulate release of prostaglandin E2 from any of the tissues investigated, but enhanced release of leukotriene B4 and sulfidopeptide leukotrienes. HPLC analysis demonstrated that immunoreactive leukotriene B4 co-chromatographed almost exclusively with standard leukotriene B4, while immunoreactive sulfidopeptide leukotrienes consisted of a mixture of leukotrienes C4, D4 and E4. Leukotriene synthesis by human gastrointestinal tissues was inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual enzyme inhibitor BW755C (3-amino-1-(trifluoromethylphenyl)-2-pyrazoline hydrochloride). Synthesis of prostaglandin E2 was inhibited by the cyclooxygenase inhibitor indomethacin as well as by BW755C. Incubation of gastrointestinal tissues in the presence of glutathione decreased the amounts of leukotrienes D4 and E4, while release of leukotriene C4 was simultaneously increased. On the other hand, incubation of tritiated leukotriene C4 with incubation media from human gastric or colonic mucosa resulted in conversion of the substrate to [3H]leukotriene D4 and [3H]leukotriene E4. The results indicate the capacity of human gastrointestinal tissues to synthesize the 5-lipoxygenase-derived products of arachidonate metabolism, leukotriene B4 and sulfidopeptide leukotrienes, in addition to larger amounts of prostaglandin E2. Furthermore, considerable activities of the sulfidopeptide leukotriene-metabolizing enzymes gamma-glutamyl transpeptidase and dipeptidase were detected in human gastrointestinal tissues. These enzymes might play an important role in biological inactivation and/or change of biological profile of sulfidopeptide leukotrienes generated in the human gastrointestinal tract.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗

[Leukotriene synthesis by gastrointestinal tissue and its pharmacologic modification].

Tissues of the gastrointestinal tract synthesize leukotriene (LT) B4 and the sulfidopeptide-leukotrienes LTC4, LTD4 and LTE4 from endogenous substrate. Formation of leukotrienes was demonstrated using radioimmunoassay, high pressure liquid chromatography (HPLC) and bioassay. Under basal conditions the gastrointestinal tissues released minor amounts of leukotrienes only. Formation of lipoxygenase-derived products of arachidonic acid metabolism was, however, significantly increased in the presence of various stimuli. Thus, significant amounts of LTB4 and of sulfidopeptide-leukotrienes were released from colonic and gastric mucosa of guinea-pigs sensitized against ovalbumin when incubations were carried out in the presence of antigen. Antigen-induced leukotriene formation was not found in the muscularis propria and subserosal of ovalbumin-sensitized guinea-pigs. Release of cyclooxygenase-derived metabolites of arachidonic acid, on the other hand, was most abundant in the subserosal layer of the guinea-pig colon and was not influenced by the immunological reaction. Inhibitors of cyclooxygenase, such as indomethacin, reduced gastrointestinal formation of prostaglandins, but not of leukotrienes. Inhibitors of 5-lipoxygenase, however, significantly decreased leukotriene formation. Synthesis of LTB4 and of sulfidopeptide-leukotrienes was also found in human colonic mucosal tissue, using the divalent cation-ionophore A23187 as stimulating agent. HPLC analysis demonstrated that the sulfidopeptide-leukotrienes released were composed of a mixture of LTC4, LTD4 and LTE4. In addition, human colonic mucosal tissue contained high activities of enzymes that rapidly convert LTC4 to LTE4. As in most biological systems LTE4 is less active than LTC4 and LTD4 degrading enzymes might represent a local inactivating mechanism. Mucosal tissue of patients with Crohn's disease synthesized considerably more LTB4 and sulfidopeptide-leukotrienes than non-inflamed mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa.

Ethanol-induced gastric mucosal damage is characterized by microcirculatory changes such as stasis and plasma leakage. Sluggish blood flow and stasis have also been observed after administration of exogenous leukotriene (LT) C4. The effect of ethanol on the release of LTC4 from rat gastric mucosa was therefore investigated. It was found that intragastric instillation of ethanol increases gastric mucosal release of LTC4 in a dose- and time-dependent manner parallel to the production of gastric lesions. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the anti-ulcer drug carbenoxolone (CX) inhibited mucosal release of LTC4 and simultaneously protected against gastric damage caused by ethanol. It is concluded that increased formation of LTC4 and/or other 5-lipoxygenase-derived products of arachidonate metabolism may be involved in ethanol-induced gastric damage. Furthermore, inhibition of the 5-lipoxygenase pathway may be an important mechanism of action of gastric protective drugs.

Animals↗

[The diagnosis of hepatic metastases (author's transl)].

The report deals with 404 patients suffering from hepatic metastases. Average age is 62,2 years. The primary tumour was situated in the stomach in 43,8%, followed by extrahepatic bile ducts or the gallbladder, rectum, pancreas and colon. Hepatomegaly is the most frequent symptom. 72,2% of all patients had a positive liver-scan, 78% a pathological bromsulfalein test.

Adult↗

Late-onset sensorineural hearing loss in Coffin-Lowry syndrome.

The Coffin-Lowry syndrome (CLS) is a rare clinical entity where patients present with a characteristic facies, mental retardation and bone abnormalities. So far about 60 cases have been reported. Sensorineural hearing loss is not a characteristic symptom and a late-onset hearing loss has not been reported so far. We report on 4 brothers with CLS, aged 9-17 years, of whom 3 suffered from a severe sensorineural hearing loss with an onset during late childhood and adolescence after a normal hearing during early childhood. CT scans revealed no cochlear abnormalities. The boys were successfully equipped with hearing aids. It is suggested that in all CLS patients the hearing ability should be examined during early infancy and retested regularly in cases with normal hearing as these cases indicate that in CLS a late-onset hearing loss is possible during late childhood and adolescence.

Abnormalities, Multiple↗

Severe hearing loss in Pallister-Killian syndrome.

Pallister-Killian syndrome is a rare disorder characterised by a specific combination of anatomic anomalies, mental retardation and lack of speech acquisition due to tetrasomy 12p. Hearing loss does not seem to be characteristic for this syndrome, although it was reported in several cases. We present the case of a girl first seen in our department at the age of 6 months. A severe sensory hearing loss was confirmed by subjective and objective audiometry. The child was successfully equipped with hearing aids. In the literature almost all children with Pallister-Killian syndrome are described as not developing verbal speech. Surprisingly their hearing abilities were not examined systematically. We advise audiological testing of children with Pallister-Killian syndrome.

Abnormalities, Multiple↗

Composition of the surface lipids from the European mole (Talpa europaea).

The surface lipids of the European mole consist of squalene, monoester waxes, triglycerides and cholesterol. As shown by GC/MS analysis, the fatty acid moieties of both monoester waxes and triglycerides belong to saturated unbranched (omega-1)- and (omega-2)-methyl-substituted and unsaturated homologous series. Double bonds are located at the 7/8- and 9/10-position. Apart from the cis- also trans-isomers were found. The alcohol moieties of the monoester waxes consisted of saturated unbranched, (omega-1)- and (omega-2)-methyl-substituted homologous series exclusively.

Animals↗

Serum levels of mepivacaine-HCl during continuous axillary brachial plexus block.

In order to find out whether repeated doses of plain mepivacaine are appropriate for long-lasting microvascular surgery, a catheter-induced axillary plexus block was performed in 17 patients by using 400 mg of mepivacaine-HC1 every two hours. All patients underwent replantation surgery of one or more amputated fingers. Duration of operation varied from 8 to 24 hours. In all cases, there was adequate analgesia and muscle relaxation for the surgical procedure. Serum levels of mepivacaine were determined before, and 15 and 60 minute after the initial injection. With each following injection of mepivacaine, blood samples were taken at the same time schedule. Within the first eight hours, after four 400 mg doses of mepivacaine were given, all serum levels remained below the level of 5 to 6 micrograms/ml, which is said to be the lower level for mild cerebral toxic reactions in venous blood (blood/plasma distribution 0.92 +/- 0.04). After this time, when more than 1600 mg of mepivacaine had been administered, two patients exceeded the level of 6 micrograms/ml. The highest serum concentration observed in any of the patients was 7.0 micrograms/ml. This was 15 minutes after the 12th injection of 400 mg of mepivacaine and an overall dosage of 4800 mg. None of the patients showed evident signs of central nervous system or cardiovascular toxicity.

Adult↗

Validation of the red blood cell test system as in vitro assay for the rapid screening of irritation potential of surfactants.

An in vitro red blood cell assay (RBC assay) is presented that allows one to estimate irritation potentials of tensides and detergents. The estimation is based on the differentiation between cell membrane lysis and cell protein denaturation. Both effects are measured photometrically by use of the inherent native dye oxyhemoglobin (HbO2). Besides hemolysis (H50) as a test parameter, the denaturation index DI is introduced, which is defined to be equal to 100% at a concentration of 30 mol sodium dodecylsulfate (SDS) per mole HbO2 as internal standard. The HbO2 release (H50), its denaturation (DI), and the ratio of both parameters (L/D ratio) are used to characterize the in vitro effects of surfactants. All data, including the L/D ratio are compared with in vivo data on eye irritancies, evaluated according to OECD Guideline #405 for testing chemicals, and with other published results from in vivo experiments. The good correlation of the L/D ratio of a broad range of 100 marketable shampoos with their corresponding Draize data (r = .806, p less than .0001) allows one to predict eye irritation potentials from another 20 commercially available shampoos in a blind trial with highly significant rank correlations to their in vivo irritancies (rs = .911, p less than .0001). Nearly similar good correlations were obtained by comparing ranks of in vivo and in vitro data of 16 anionic surfactants. All correlations found were significant (rs greater than .80 and p less than .0001). The RBC assay is an inexpensive, rapid, irritancy screening test that provides reliable results with good reproducibility. The test helps to reduce or even avoid animal testing in this application.

Animals↗