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Biomedical subjects

N Heinz

Publications and source records attributed to N Heinz.

At least 19 recordsLinked to original sources
PubMed2004

Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1beta: a possible explanation for the changes in matrix synthesis during osteoarthritis.

OBJECTIVE: To analyse the distribution patterns of tenascin and proteoglycans in normal and osteoarthritic cartilage, and to determine the effect of interleukin 1beta (IL1beta) on aggrecan and tenascin expression by human articular chondrocytes in vitro. METHODS: Normal and osteoarthritic cartilage and bone samples were obtained during total knee replacements or necropsies. After fixation and decalcification, paraffin embedded specimens were sectioned perpendicular to the surface. Specimens were graded according to Mankin and subdivided into those with normal, and mild, moderate, and severe osteoarthritic lesions. Serial sections were immunostained for tenascin. Tenascin expression by healthy and osteoarthritic chondrocytes was quantified by real time polymerase chain reaction (PCR). Furthermore, in cell culture experiments, human articular chondrocytes were treated with 0.1 or 10 ng/ml IL1beta. Real time PCR analyses of aggrecan and tenascin transcripts (normalised 18S rRNA) were conducted to determine the effect of IL1beta on later mRNA levels. RESULTS: Tenascin was immunodetected in normal and osteoarthritic cartilage. In osteoarthritic cartilage increased tenascin staining was found. Tenascin was found specifically in upper OA cartilage showing a strong reduction of proteoglycans. Greatly increased tenascin transcript levels were detected in osteoarthritic cartilage compared with healthy articular cartilage. IL1beta treatment of articular chondrocytes in vitro significantly increased tenascin transcripts (approximately 200% of control) and strongly reduced aggrecan mRNA levels (approximately 42% of control). CONCLUSIONS: During progression of osteoarthritis the switch in matrix synthesis occurs mainly in upper osteoarthritic cartilage. Furthermore, changes in synthesis patterns of osteoarthritic chondrocytes may be significantly influenced by IL1beta, probably diffusing from the joint cavity within the upper osteoarthritic cartilage.

Aggrecans↗
PubMed1995

Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon.

The amino acid imbalance hypothesis should explain the fatigue originating in the brain during sustained exercise or over-training as a branched-chain (BCAA)/aromatic amino acids (AAA) imbalance with increased brain tryptophan uptake and 5-hydroxytryptamine synthesis. The serum amino acid profile was determined in 9 ultra-triathletes before and after completing the 1993 Colmar ultra-triathlon to additionally analyse the extent of this amino acid imbalance during such an extreme prolonged contest lasting more than 23 hours. The summed serum concentration of 25 amino acids decreased by 18% from 3962 +/- 846 to 3255 +/- 694 umol.l-1 likely reflecting a catabolic state of the organism with a decrease in 18 individual amino acids by 9-56%, an increase in cystine (+38%), methionine (+24%), tyrosine (+10%), phenylalanine (+12%), free tryptophan (+74%), and constant glutamine, leucine and total tryptophan levels. Since plasma volume increased by approximately 7.6% with a 3.3 kg body mass decrease in the athletes during the ultra triathlon, a decrease in intra-cellular water with an extra-cellular fluid increase is hypothesized. This decrease in cellular hydration state is seen as a protein-catabolic signal.

Adult↗
PubMed1983

[Saluretic and diuretic effects of xipamide-triamterene combinations in varying dose ratios in rats].

The saluretic and diuretic properties of 4-chloro-5-sulfamoyl-2',6'-salicyloxylidide (xipamide) and 2,4,7-triamino-6-phenyl-pteridine (triamterene) were determined in rats following sole and combined application in various dosages and dose ratios. Xipamide dosages ranged from 0.01-30 mg/kg body weight. Xipamide, when given alone, revealed a significant dose-dependent increase in sodium excretion and urine volume compared to control animals even in the smallest dose to be tested (0.01 mg/kg). Triamterene as sole agent led to an increased sodium and water excretion when given in a natriuretic threshold dose of approximately 1.0 mg/kg. Potassium excretion was slightly enhanced following xipamide application and decreased significantly with triamterene treatment. The combined application of xipamide and triamterene in dose ratios of 1:1-1:4 (xipamide/triamterene) resulted in an increased sodium excretion which was almost additive following high triamterene dosages. Potassium elimination decreased significantly when threshold triamterene dosages were added. High triamterene dosages in all dose ratios of the combined application resulted in potassium levels which only could be registered following sole triamterene application.

Animals↗
PubMed1982

[Pharmacokinetics of xipamide and triamterene in healthy probands].

Simultaneous detection of 4-chloro-5-sulfamoyl-2',6'-salicyl-oxylidide (Xipamide) and 2,4,7-triamino-6-phenyl-pteridine (Triamterene) in urine specimen of healthy volunteers was achieved by means of a new high performance liquid chromatography (HPLC) method. Pharmacokinetics of both substances in combination (Neotri, dose ratio xipamide: triamterene = 1:3) did not significantly differ from those of the sole substances. Peak urine elimination of unaltered xipamide was 2.5 +/- 0.7 mg/h when given alone and 2.0 +/- 0.7 mg/h in the presence of triamterene. The data for the triamterene excretion were 0.7 +/- 0.1 mg/h and 1.0 +/- 0.3 mg/h, respectively within 1-3 h post application. Assuming a two-compartment pharmacokinetic model the terminal elimination half-lives of unchanged xipamide were 5.3 +/- 1.9 h (monosubstance) and 4.0 +/- 0.6 h (combination). The corresponding data for unchanged triamterene were 6.4 +/- 1.3 h (monosubstance) and 5.5 +/- 1.8 h (combination).

Adult↗
PubMed1981

[Studies on determining the mutagenicity risk of triethylenetetramine (author's transl)].

Triethylenetetramine (TETA) is the only available effective drug for the treatment of patients with Wilson's disease and with simultaneous intolerance to D-penicillamine. In the Ames-test, however both TETA and the structurally similar tetramine BE 6184 are mutagenic. The naturally occurring spermine, a closely related tetramine differing only in one additional methylene group in every carbon chain, shows no mutagenicity. TETA does not exhibit any mutagenic potency in the micronucleus-test.

Animals↗
PubMed1981

[Relationship between digoxin plasma concentrations and frequency of digoxin intoxication (author's transl)].

Using appropriate transformations the relationship between the frequency of digoxin intoxication and the corresponding digoxin plasma levels can be shown to be linear. Therefore the relative frequencies have to be transformed into probits and the digoxin plasma levels have to be replaced by their logarithms. With intoxication frequencies from published data the IC50, i.e., the plasma level leading to an intoxication in 50% of cases, is 2.9 ng/ml. At 1.0 ng/ml the intoxication frequency is estimated below 1%, at 4.0 ng/ml the estimated frequency is just below 80%. In the intoxication diagnosis of a single patient the plasma level is of only poor significance.

Biotransformation↗
PubMed1981

[Digitoxin plasma concentrations during oral treatment (author's transl)].

In 198 patients, among them 153 with a creatinine clearance of less than 20 ml/min, the relationship between the digitoxin plasma level and retrospective data on daily digitoxin dose, age, body weight and renal function has been evaluated. A multiple regression analysis yielded only a very weak correlation (100 r2 = 13.2%, n = 186), with the digitoxin dose having by far the highest partial coefficient of determination (100 r2 = 11.5%). The partial correlation for the renal function was too small as to be relevant (100 r2 = 0.6%). Owing to the weakness of correlation it is impossible to predict the digitoxin plasma level on the basis of standard clinical data. A single dose in the range of 0.07 to 0.1 mg/day seems to be an appropriate treatment for most patients. Corresponding to a median dose of 0.082 mg digitoxin daily during steady state a median plasma level of 14.6 ng/ml has been calculated.

Age Factors↗
PubMed1980

[On the pharmacology of the alpha-receptor blocker BE 2254 (HEAT) (author's transl)].

The alpha-adrenolytic activity of BE 2254 was investigated in in vitro as well as in vivo assays. On the isolated rat anococcygeus muscle, 2-[beta-(4-hydroxyphenyl)-ethyl-amino-methyl]tetralone(1) (BE 2254) shows a high affinity for postsynaptic alpha-adrenoceptors (pA2 = 8.9), in contrast to its much weaker potency (pA2 = 6.7) in inhibiting clonidine on the electrically driven rat vas deferens, thus suggesting a relative preference for postsynaptic alpha-adrenoceptors. BE 2254 effects on other catecholamine receptors are either negligible or not detectable. The hypotensive action of BE 2254 is shown to be solely due to alpha-blockade. All alpha-adrenolytic actions studied were of competitive nature.

Adrenergic alpha-Antagonists↗
PubMed1980

[Drug release in vitro from digoxin formulations with high bioavailability (author's transl)].

The drug release of four brands of digoxin tablets (A, B, C, D) with known bioavailability was examined using three liberation systems. The paddle method (1) could only ascertain a uniformly good release of all brands. A flow-cell (II) and a special method testing the supersaturation (III) indicated significant differences in drug release. Both II and III pointed to the brand having the best bioavailability. Beyond it no satisfactory correlation was found between the values of bioavailability and drug release.

Biological Availability↗
PubMed1980

[Urinary copper excretion from rats following administration of aliphatic and alicyclic polyamines (author's transl)].

The cupriuretic effectivity of tetradentate chelating agents was measured in rats and compared with that of D-penicillamine. The applied chelators are aliphatic and alicyclic tetramines and tetramine-analogous substances with two nitrogen-atoms substituted by oxygen. Urine copper excretion was measured during 24 h (and 6 and the following 18 h, respectively) after single and repeated doses over a period of 5 days. The aliphatic tetramines, triethylenetetramine (TETA, TRIEN) and BE 6184, were the most active substances. Simultaneous application of TETA and D-penicillamine does not induce a summation or potentiation of the copper elimination. After s.c. application TETA seems to be three times more effective than orally. The potency of aliphatic and alicyclic tetramines is discussed on the basis of in vitro data.

Animals↗
PubMed1979

Relationship between dose and plasma level of digoxin and patient characteristics.

The correlation between the daily dose of digoxin, its plasma level and clinical characteristics of 213 patients receiving beta-acetyldigoxin treatment has been evaluated. After logarithmic transformation of lognormally distributed variables multiple linear regression analysis was performed. Eight predictor variables were chosen: sex, age, height, weight, glycoside dose, creatinine and potassium level in serum and dose of spironolactone. The resulting correlation coefficient was 0.46, i.e. only 100 x r2 = 21.4% of the variance of the steady state digoxin plasma level could be interpreted with the aid of these variables. For only 4 of the 8 variables (age, glycoside dose, serum level of creatinine, and spironolactone dose) were partial coefficients of regression and of correlation significantly different from zero. Almost 80% of the variance could not be accounted for. This finding is in accordance with conclusions in the literature.

Adult↗
PubMed1979

[Clinical study on digoxin tablets with high bioavailability (author's transl)].

The relationship between different maintenance doses and the steady-state digoxin blood concentration was studied in 160 patients with heart failure. All patients received digoxin tablets of the same brand (Digacin). The bioavailability of this brand is 82% compared with an i.v. standard. During the treatment with daily doses of 0.2 mg and 0.3 mg average serum digoxin levels of 1.09 +/- 0.45 ng/ml and 1.33 +/- 0.53 ng/ml were measured in patients with normal renal function. The daily dose of 0.4 mg digoxin was in correlation to an average serum level of 1.75 +/- 0.81 ng/ml. 81% and 86% of all patients with normal renal function taking 0.2 or 0.3 mg digoxin every day were found to have levels in the range of 0.7 to 2.0 ng/ml. The influence of sex, age, height, body weight, maintenance dose, serum creatinine and serum potassium on the variance of the digoxin plasma levels was computed by multiple linear regression. The multiple correlation coefficient was r = 0.666, the coefficient of determination (100 r2) being 44.4%. Therefore 44.4% of the total variance could be explained by these variables. Individual variables accounted for the following percentages of the total variance: serum creatinine 29.1%; maintenance dose 14.5%; age 4.3%; and reciprocal of body weight 3.9%.

Aging↗
PubMed1978

Correlation between inhibition of (Na+, K+)-membrane-ATPase and positive inotropic activity of cardenolides in isolated papillary muscles of guinea pig.

Concentrations of 17 cardenolides, cardenolide glucuronides and sulfates producing half-maximal inhibition of (Na+, K+)-membrane-ATPase from different organs and animal species were determined in vitro. In addition the concentrations that increased the contractility of guinea pig isolated papillary muscles to a particular level were investigated. Comparisons between ATPase-inhibiting and positive inotropic cardiac activities showed extensive parallelism: the correlation coefficients after log/log transformation were between 0.92 and 0.97. The same close correlations are found if dissociation constants of cardenolide receptor complexes and concentrations causing 86Rb-uptake inhibition in human erythrocytes are examined. The concentrations necessary for inhibition of (Na+, K+)-membrane-ATPase of the guinea pig heart and the concentrations required to achieve a defined positive inotropic effect in guinea pig papillary muscle showed a log/log correlation coefficient of 0.97 (P less than 0.001). In both tests the potencies covered more than three orders of magnitude. The results support Repke's hypothesis on the digitalis receptor.

Animals↗
PubMed1978

Comparison of the pharmacokinetics of digoxin and dihydrodigoxin in cats in single-dose studies.

Pharmacokinetics of 3H-dihydrodigoxin and 3H-digoxin after single intravenous and intraduodenal administration in cats are compared. Data could be described by an open two compartment body model. The beta half-life in plasma of dihydrodigoxin after initial rapid distribution is 4.6h compared to 10.4 h after digoxin administration. The volume of tissue distribution of dihydrodigoxin is 7 times smaller than that of digoxin (0.311 versus 2.051). The "specific uptake" of dihydrodigoxin into myocardium and some other tissues is very low. Over 5.5h the cumulative biliary and urinary elimination of dihydrodigoxin is definitely higher (45.7% versus 14.4%). An unexpected peak in TLC plates after dihydrodigoxin administration in blood, bile and urine was identified to be the sodium salt of the opened lactone structure: dihydrodigoxin acid.

Animals↗
PubMed1978

[Enhanced bioavailability of digoxin from silica matrix formulations (author's transl)].

The bioavailability of digoxin from 3 silica matrix formulations was assessed in single-dose crossover studies in 12 healthy human volunteers: digoxin/silica matrix tablets (I, Digacin), digoxin/silica matrix in capsule form (II) and digoxin/silica matrix dragées, protected against gastrict juice by film coating (III). Urinary glycoside excretion for 6 days after 0.5 mg doses were measured by radioimmunoasay. Referring to an intravenous injection the bioavailability of digoxin from Digacin tablets is 82%, from the encapsulated matrix 69%, and from the dragées 54%. In comparison with corresponding results from other investigators Digacin tablets havet the same high bioavailability as digoxin solutions. In vitro liberations of digoxin from the silica matrix formulations (94% in 90 s) is significantly better than from conventional tablets produces from a digoxin-lactose trituration (61% in 90 s).

Adult↗
PubMed1978

[Partition coefficients and Rm-values of cardenolides (author's transl)].

Partition coefficients (P) of 48 cardenolides were determined in octanol/water. Furthermore Rm-values of most of these substances were measured in different thin-layer chromatography systems (TLC) and related to P. Regression analysis revealed that the best linear fit of the data was obtained when Rm-values from reversed-phase TLC on octanol impregnated silica-gel layer as stationary phase and methanol/water as mobile phase were correlated with log P (r = 0.91). A better correlation between these two sets of data was obtained by restricting the calculations to groups of cardenolides with similar structural features (r = 0.96-0.98). The present results are showing that Rm-values from reversed-phase TLC--a rapid and reproducible method with many advantages over the tedious measurement of P--can be used to predict P.

Cardenolides↗
PubMed1978

[Lipophilicity and enteral absorption of cardenolides (author's transl)].

Intestinal absorption of 15 cardenolides has been examined in cats. The 3H-labelled substances were injected intraluminally into ligated duodenal loops of anaesthetized animals. 3H-Concentrations were followed in the portal circulation and in the bile. 1 h after drug administration the duodenal sac was removed, and the residual in the lumen then was washed out and assayed radiochemically. The decrease of radioactivity during 1 h was calculated as extent of absorption (QR). Cardenolide absorption was compared with the corresponding in vitro parameters of lipophilicity like octanol/water partition coefficients and Rm values from reversed phase thin-layer chromatography. The Spearman rank sum correlation test revealed coefficients of 0.95 to 0.97. The result lends support to the use of the easily available Rm values as a good tool to predict intestinal absorption of various cardenolides.

Animals↗