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Biomedical subjects

R Götz

Publications and source records attributed to R Götz.

At least 73 records · Page 4Linked to original sources

Pressure-diameter curves of mesometrial arteries of guinea pigs demonstrate a non-muscular, oestrogen-inducible mechanism of lumen regulation.

Pressure-diameter curves were determined on mesometrial (uterine radial) arteries obtained from guinea pigs during different stages of ovarian cycle and pregnancy. In order to investigate changes in arterial diameter that are not caused by the vascular musculature, we studied excised arteries that were relaxed by papaverine (40 mg/l). The pressure-diameter curves were found to be shifted toward wider diameters when the arteries studied were obtained from pregnant, oestrous or oestrogen treated animals (oestradiol benzoate, 10 micrograms s.c.): the external diameter at 60 mm Hg transmural pressure on the 14th day of pregnancy exceeded the one during dioestrus by 50%. At term, there was a 7-fold increase. During oestrus and 24 h after oestrogen treatment the diameter was 30-40% wider than during dioestrus. Moreover, we found that the diameter measured on excised vessels in the presence of papaverine is the same as the one observed in situ. We conclude that the mesometrial arteries of guinea pigs possess a muscle-independent mechanism of lumen regulation. The mechanism operates in non-pregnant and pregnant animals. It may be induced by oestrogen and seems to be qualified for long-term lumen regulation during pregnancy. In contrast, dilation by smooth muscle relaxation appears to be of minor importance in mesometrial arteries.

Animals↗

Structure of complex flagellar filaments in Rhizobium meliloti.

The complex flagella of Rhizobium meliloti 2011 and MVII-1 were analyzed with regard to serology, fine structure, subunits, and amino acid composition. The serological identities of flagellar filaments of the two strains were demonstrated by double immunodiffusion with antiflagellin antiserum. The filaments had a diameter of 16 nm. Their morphology was dominated by the prominent undulations of an external three-start helix running at a 10-nm axial distance and at an angle of 32 degrees. Faint nearly axial striations indicated the presence of a tubular core of a different helical order. The complex filaments consisted of 40,000-dalton flagellin monomers. Typically, the amino acid composition was 3 to 4% higher in nonpolar residues and 5 to 7% lower in aspartic and glutamic acids (and their amides) than that of plain flagellar proteins. There were no immunochemical relationships among Pseudomonas rhodos, Rhizobium lupini, and R. meliloti complex flagella, suggesting that the latter represent a new class.

Amino Acids↗

[Liver damage caused by chronic cadmium poisoning].

A case report is given of a 46 year old person concerned professionally with melting gold, who exhibited bioptically and histologically verified lesions of the liver after chronic intoxication with cadmium. This patient was exposed throughout 8 years during his job activities to cadmium vapors. He exhibited during the time of investigation decreased renal function with tubular proteinuria as well as a polyneuropathy. In addition, hepatic lesions could be found, as small focal necrosis, fatty degeneration and fibrosis. Cadmium content of the liver was increased 13 times above normal.

Cadmium Poisoning↗

Oral keto analogs of branched-chain amino acids in hyperammonemia in patients with cirrhosis of the liver. A double-blind crossover study.

Previous uncontrolled studies indicated a positive effect of keto analogs of amino acids on plasma ammonia in patients with cirrhosis of the liver and on portal-systemic encephalopathy. In the present double-blind study the influence of keto analogs of the branched chain amino acids valine, leucine and isoleucine on plasma ammonia and encephalopathy was investigated in 12 patients with cirrhosis of the liver and surgical portal systemic shunts. In addition to the usual therapy with lactulose and protein restriction (40 g protein/day) all patients received 15.24 g keto analogs and placebo orally over 4 weeks in a crossover regimen. In contrast to uncontrolled studies, plasma ammonia, which was elevated in all patients before the beginning of the study, was not significantly changed. In addition plasma amino acids, electroencephalogram, number connection test, clinical state and laboratory tests were not influenced by the therapy with keto analogs.

Administration, Oral↗

Procollagen-type III-peptide serum concentrations in chronic persistent and chronic active hepatitis and in cirrhosis of the liver and their diagnostic value.

Until now the determination of fibrotic processes in liver disease was restricted to histological examination of liver tissue. Recently a RIA was developed to determine the procollagen-type III-peptide concentrations in biological fluids. We used this RIA to measure the serum procollagen-type III-peptide concentrations in patients with chronic liver disease. Additionally in 24 patients with chronic persistent and chronic active hepatitis the collagen content in liver biopsies was determined histomorphometrically. The serum procollagen-type III-peptide concentrations in healthy controls (n = 40) were 6.4 +/- 0.6 ng/ml, in chronic persistent hepatitis (n = 47) 8.7 +/- 0.5 ng/ml, in chronic active hepatitis (n = 53) 20.8 +/- 2.9 ng/ml, and in alcoholic cirrhosis of the liver (n = 22) 47.7 +/- 6.1 ng/ml. Thus the patients with chronic active hepatitis and cirrhosis of the liver showed significantly elevated serum procollagen-type III-peptide levels. In chronic hepatitis a highly significant correlation (p less than 0.001) could be demonstrated between collagen content in liver tissue and serum procollagen-type III-peptide concentrations. The determination of serum procollagen-type III-peptide concentrations may prove a new useful parameter in biochemical evaluation of liver disease.

Biopsy↗

Kinetics of cholesterol gallstone dissolution by glycocheno-, glyco-ursodeoxycholic acid, and mixtures of both in vitro.

Cheno- and ursodeoxycholic acid feeding are both efficient in conservative gallstone therapy. Urso decreases biliary cholesterol excretion even more than cheno. Glyco-urso becomes dose dependent the predominant bile acid conjugate in bile under urso feeding. We therefore studied the kinetics of cholesterol gallstone dissolution in aqueous solutions of 100 mM glyco-cheno, 100 mM glyco-urso, and mixtures of both consisting of 40 mM glyco-urso plus 60 mM glyco-cheno and 80 mM glyco-urso plus 20 mM glyco-cheno in vitro. The daily dissolution rates of cholesterol achieved by these solutions were for 100 mM glyco-cheno 0.87 +/- 0.1 mg (mean +/- SEM), for 40 mM glyco-urso plus 60 mM glyco-cheno 0.28 +/- 0.003 mg, for 80 mM glyco-urso plus 20 mM glyco-cheno 0.07 +/- 0.002 mg, and for 100 mM glyco-urso 0.07 +/- 0.03 mg. Correspondingly were the weight decreases of the gallstones by 100 mM glyco-cheno 1.2 +/- 0.1 mg/day, by 40 mM glyco-urso plus 60 mM glyco-cheno 0.3 +/- 0.01 mg/day, by 80 mM glyco-urso plus 20 mM glyco-cheno 0.11 +/- 0.02 mg/day, and by 100 mM glyco-urso 0.1 +/- 0.02 mg/day. Complete gallstone dissolution occurred during the observation time of 4 months only by 100 mM glyco-cheno in 12.8 +/- 3.3 weeks. Thus glyco-urso dissolves only little cholesterol and decreases the speed of cholesterol gallstone dissolution. It is concluded that high doses of urso in gallstone therapy which lead to great amounts of glyco-urso in bile may diminish gallstone dissolution rates.

Chenodeoxycholic Acid↗

Effects of pentachlorophenol and 2,4,6-trichlorophenol on the disposition of sulfobromophthalein and respiration of isolated liver cells.

The effect of pentachlorophenol (PCP) and 2,4,6-tricholorphenol (2,4,6-T) on the disposition of the hepatodiagnostic dye, sulfobromophthalein (BSP) has been studied in isolated liver cells. PCP (4-6 microM) as well as 2,4,6-T (50-100 microM) interferes with the disposition of BSP. The main effect apparently occurs at the secretion step as both drugs severely impair the release of the glutathione conjugate of BSP into the medium. As a consequence, BSP and its conjugate accumulate in the cell. High doses of PCP did not increase the release of lactate dehydrogenase from the hepatocytes. Concentrations of the two phenols which interfere with the secretion of BSP also completely uncouple the oxidative phosphorylation of hepatocellular mitochondria. The dysfunction of liver cells described here may therefore be explained by the effect of PCP and 2,4,6-T on the energy production of the cells. The higher toxicity of PCP as compared to 2,4,6-T observed in our system corresponds well with the higher LD50 of the latter compound.

Animals↗

Uptake of sulfobromophthalein-glutathione conjugate by isolated hepatocytes.

Uptake of sulfobromophthalein-glutathione conjugate (BSP-GS) was studied using isolated hepatocytes and was compared with previous results with the parent BSP (Schwenk et al., Eur. J. Biochem. 64: 189-197, 1976). Adsorption of BSP-GS to the liver cell membrane has two sites with different affinities and binding capacities. Uptake of the conjugate is decreased by two metabolic inhibitors and appears to be saturable up to 12.5 microM with an apparent Km of 4 microM (7 for BSP) and a Vmax of 0.16 nmol x mg protein-1 x min-1 (2.6 for BSP). Similar to the parent BSP at higher concentrations a second mechanism of uptake is observed indicated by the nonlinear Hanes plot. SP-GS transport is competitively inhibited by BSP with a Ki of about 1 microM, and, similar to BSP, replacement of sodium ions in the medium had little effect on the rates of uptake. These results suggest a common transport mechanism for BSP and its glutathione conjugate. Furthermore, the effect of organic anions, bases, and steroids on uptake of BSP-GS has been tested.

Animals↗

Effects of biliary bile acid composition on biliary cholesterol saturation in gallstone patients treated with chenodeoxycholic acid and/or ursodeoxycholic acid.

Chenodeoxycholic acid (cheno) and ursodeoxycholic acid (urso) dissolve cholesterol gallstones in humans. In the present study conjugation of biliary bile acids with glycine and taurine and their effects on biliary cholesterol saturation were investigated during treatment with cheno, urso, and cheno-urso. Ten patients were included in this study, and every patient served as his own control. Each of the treatment periods lasted for 3 mo. During treatment with cheno or urso, daily doses of 11.9-15.6 mg/kg were administered, while during treatment with cheno-urso each bile acid was administered at one-half the dose. In the control period biliary bile acids consisted of 31.8 +/- 2.8% glycocheno, 10.9 +/- 1.2% taurocheno, 1.0 +/- 0.1% glycourso, and 0.3 +/- 0.1% taurourso. During the three treatment periods dihydroxy bile acids in bile and glycine conjugation of these dihydroxy bile acids increased significantly (P < 0.05). During treatment with urso the amounts of glycourso in bile were positively correlated to the dose of urso administered (P < 0.05). No correlation existed between urso dose and the amounts of taurourso in bile. Biliary cholesterol was 9.0 +/- 1.0 mol% in the control period and decreased during treatment with cheno, urso, and chenourso to 5.2 +/- 0.5, 3.7 +/- 0.3, and 3.8 +/- 0.3 mol%, respectively. Cholesterol saturation index corrected for the biliary content of glycourso and taurourso was 1.2 +/- 0.1 in the control period and decreased during treatment with cheno, urso, and cheno-urso to 0.8 +/- 0.1, 1.0 +/- 0.1 and 0.7 +/- 0.1, respectively. Thus urso treatment led to the lowest biliary content of cholesterol, but cheno-urso treatment led to significantly lower cholesterol saturation indices than urso treatment (P < 0.05).

Aged↗

[The pharmacokinetics of papaverine and its bioavailability from a sustained-action preparation].

The serum levels of intravenously and orally given papaverine were determined in healthy, fasting beagles. The bioavailability of the drug was assessed in the same animals following single administration of the sustained-action preparation Panergon (papaverine-hydrochloride). Based on a one-compartment model, the time of invasion, the half-life of elimination, the volume of distribution and the absorption rate of papaverine were calcualted. A comparison of the areas under the concentration curves shows the complete bioavailability of the papaverine contained in Panergon.

Administration, Oral↗