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Biomedical subjects

G Kröning

Publications and source records attributed to G Kröning.

At least 19 recordsLinked to original sources

Antidotal effects of 2,3-dimercaptopropane-1-sulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the organotoxicity of dibutyltin dichloride (DBTC) in rats.

1. Dialkyltin compounds have been widely used in industry and agriculture, mainly as biocides, catalysts and plast stabilizer. In dependence on the length of the alkyl chains these organotins exert toxic effects on the immune system, the bile duct, liver and pancreas. It has been supposed that similar to organoarsenic the toxicity of the dialkyltin compounds is related to reactions with biological dithiol groups. Therefore, in the present study, the antidotal effects of 2,3-dimercapto-propane-1-sulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the organotoxic effects of dibutyltin dichloride (DBTC, single administration of 27 micromol kg(-1) b.w. i.v.) in rats were studied using different doses (100 and 500 micromol kg(-1) b.w.) and routes of administration (i.p. and p.o.) of both chelators. Several parameters of organotoxicity (thymus weight and cellularity, bile duct diameter, histological lesions of pancreas and liver, activities of amylase, lipase and alkaline phosphatase, bilirubin and hyaluronic acid in serum) were measured from 6 h to 8 weeks. 2. DMPS and DMSA diminished the DBTC induced bile duct, pancreas and liver lesions stronger than the thymus atrophy. Moreover, the development of a fibrosis of the pancreas and a cirrhosis of liver several weeks after single administration of DBTC to rats was inhibited by DMPS and DMSA. The antidotal effects on serum parameter were observed after both administration routes of the chelators. DMPS was more effective than DMSA in most measured parameters. The decrease in the biliary excretion of organotin by DMPS and DMSA seems to be the reason for the pronounced protective effects of DMPS and DMSA on bile duct, pancreas and liver. 3. For the treatment of poisonings with dibutyltin compounds, the administration of DMPS or DMSA can be recommended.

Alkaline Phosphatase↗

Increased plasma ACTH in rats exposed to the elevated plus-maze is independent of the pineal gland.

The involvement of the pineal gland in activation of the hypothalamic-pituitary-adrenocortical (HPA) axis evoked by a stressful stimulus (exposure to the elevated plus-maze) was investigated. Plasma ACTH levels were measured in pinealectomized and pineal-intact rats (sham-operated and non-operated) immediately after a 5 min placement into a plus-maze. A statistically significant elevation in plasma ACTH was measured within all groups; however, no statistical differences between pinealectomized and pineal-intact rats were observed. Similarly, comparison of the plasma ACTH basal values obtained from animals only kept in their home cages did not reveal any statistical differences between pinealectomized and pineal-intact rats. From these results it can be concluded that the pineal gland is not involved in anxiety-related behavior and ACTH response.

Adrenocorticotropic Hormone↗

Fluorometric determination of total retinyl esters in triglyceride-rich lipoproteins.

A time-consuming sample preparation and measuring procedure is required for the quantitation of retinyl palmitate by HPLC. We developed a fluorometric method for the determination of total retinyl esters in chylomicrons, chylomicron remnants, and VLDL. This method is precise, sensitive, rapid, simple, and particularly useful for large-scale studies of postprandial lipid metabolism. Because the turbidity of postprandial lipemic samples interferes with the fluorescence measurement, all samples were incubated for 10 min with a clearing buffer containing esterase and detergents. This buffer eliminates the turbidity and hydrolyzes all retinyl esters to retinol. The fluorescence signal (excitation wavelength, 330 nm; emission wavelength, 490 nm) was linear from 0.1 mg/L up to 4 mg/L retinyl palmitate, and the CVs were 3.6% within-run and 5.1% within-series. A first application studied postprandial lipoproteins, which were first separated by ultracentrifugation and then subjected to size exclusion chromatography. Fluorescence analysis revealed that the chylomicron density fraction contains large amounts of chylomicron remnants.

Buffers↗

Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions.

Dibutyltin dichloride (DBTC; 6 mg/kg body weight, i.v.) induced acute interstitial pancreatitis in rats. The course of the pancreatitis was examined within 28 days by light and electron microscopy as well as by pathobiochemistry (amylase, lipase, alkaline phosphatase, and bilirubin in serum; tin concentration in biliopancreatic juice, tissue, and concretions). The pathogenesis of the DBTC-induced pancreatitis in rats was studied by different experimental designs (in intact animals, after bile duct ligation, after surgical bypass of the bile duct). DBTC caused toxic necrosis of the biliopancreatic duct epithelium, which is then shed into the duct and forms obstructing plugs in the distal common bile duct. Interstitial pancreatitis occurred during the first 4 days, accompanied by significantly increased activities of serum alpha-amylase and lipase. After 7 days extensive infiltration of the pancreatic interstitium with mononuclear cells was observed. Twenty-eight days after administration of DBTC one-third of the rats showed periductal and interstitial fibrosis as well as an active inflammatory process in the pancreas. The findings suggest a twofold pathogenesis of the DBTC-induced pancreatitis: first, the cytotoxic effects on the biliopancreatic duct epithelium lead to epithelial necrosis with obstruction of the duct, subsequent cholestasis, and interstitial pancreatitis; and second, the hematogenic DBTC effects cause direct injury of pancreatic cells (mitochondrial damage, autophagy, cell necrosis) followed by interstitial edema and inflammation. Both processes lead to this special type of DBTC-induced acute pancreatitis with a tendency to a chronic course, when the obstruction of the duct and cholestasis persist.

Acute Disease↗

Prospective study on the influence of radiochemotherapy on pituitary function in children with acute leukaemia and NHL.

To assess effects of chemo- and radiotherapy on the endocrine system 31 children with acute leukaemia and NHL (3 AML, 24 ALL, 4 NHL) were investigated. Children were treated according to modified BFM protocols. 25 patients were before, 5 during and one after puberty (2 to 16 y.). Before treatment, during induction therapy, during cranial irradiation, 4-6 weeks later and during maintenance therapy the following hormone values were estimated: TSH and prolactin basal and 30 min. after TRH (5 micrograms/kg i.v.), LH and FSH basal. Final investigations included total T4 and T3. In conclusion, chemo- und radiotherapy lead to transient elevations of TSH and prolactin in a few patients, but without proof for permanent disorders. Due to the fact all 3 patients with hyperprolactinaemia showed high prolactin levels (700 to 770 mU/l) already before treatment it is unlikely therapy was the main cause of these observed alterations. Although basal LH and FSH values were in normal ranges for age the increasing values after cranial irradiation in prepubertal children may reflect a possible initiation of early maturation, reported by others. Furthermore a retrospective growth study was performed in children treated with 2 different protocols. Protocol LSA2L2 used in the past before 1981 resulted in a permanent reduction of the height. In contrast, the mean SDS for height in children treated with protocol VII declined only during the intensive period of treatment. A catch-up growth occured already during maintenance therapy. Prophylactic cranial irradiation with 18 Gy in our patients under protocol LSA2L2 did not affect growth during the first 5 years after diagnosis.

Acute Disease↗

[A complex program for microcomputer-supported immunoassay analysis].

The increasing availability of analytical methods based on saturation analysis call for efficient assay calculation. A comprehensive computer program was developed, allowing the calculation of different kinds of assays. Due to the user friendly structure it can be used also by inexperienced laboratory staff without difficulties. Its large adaptability can be a usefull support to optimize various kinds of assays.

Immunoassay↗

[Effects of dithiocarbamates on the mitotic activity of thymocytes].

The effects of dithiocarbamates on the mitotic activity of thymocytes were studied in vitro and in vivo. The mitotic activity was determined by counting of the metaphases blocked by colchicine. Using thymocytes of mice the mitotic activity in short-time cultures was inhibited (50%) by the following concentrations of the substances under study (EC50-values in mol/l): tetraethylthiuramdisulfide; (1; disulfiram) 4.2.10(-9); diethyldithiocarbamate (2) 3.2.10(-8), Cu-2, 2.6.10(-8), Zn-dimethyldithiocarbamate (3; Ziram) 1.9.10(-8), Zn-ethylene-bis-dithiocarbamate (4; Zineb) 2.3.10(-6). Using rat and guinea-pig thymocytes the ED50- values for 1 and 2 were found in the same concentration range as compared with thymocytes of mice. There was no impact on the vitality of cells by the mitosis inhibiting concentrations. In vivo the mitotic activity of thymocytes in mice was decreased only after application of high doses (500 mg/kg i.p.) of 2. After depletion of reduced glutathione (GSH) by the pretreatment of mice with diethylmaleate the effects of 2 were increased in vivo. In vitro GSH (10(-4) mol/l) decreased the mitosis inhibiting activity of 2 in mice thymocytes and the inhibition of the SH-enzyme ecto-ATPase in rat thymocytes. It is supposed that the inhibition of mitosis is due to the reaction of dithiocarbamates with SH-groups of microtubules and other functionally important proteines. The formation of tiyl radicals from dithiocarbamates may play a certain role in redox processes which can be influenced by GSH.

Adenosine Triphosphatases↗

[Synthesis and pharmacological properties of alkyl esters of various DL-omega-phenylamino acids].

The synthesis of some branched-chain and n-alkyl ester hydrochlorides of DL-2-phenylglycine, DL-3-phenyl-3-aminopropionic acid, DL-4-phenyl-4-aminobutyric acid, DL-phenylalanine and DL-4-phenyl-2-aminobutyric acid is described. For 28 alkyl esters of these DL-amino acids, the pharmacological data about the antagonism against spasms induced by barium chloride, histamine and acetylcholine in the guinea-pig ileum in vitro, as well as about the acute toxicity of intraperitoneally administered doses in the mouse, are reported. Empirical structure-activity relationships established for 36 compounds of this group of substances are discussed. It was found that the maxima of the four actions mentioned depended upon the length of the carbon chain in the molecule. In contrast, no clear-cut branching effect was observed. With reference to toxicity, DL-4-phenyl-2-aminobutyric acid n-octyl ester hydrochloride has been found to be the most favourable spasmolytic agent among the compounds under investigation.

Amino Acids↗