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Biomedical subjects

F Matzkies

Publications and source records attributed to F Matzkies.

At least 19 recordsLinked to original sources
PubMed1997

Differential regulation of glomerular gelatinase B (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in obese Zucker rats.

The obese Zucker rat represents a model of obesity combined with insulin resistance and hyperlipidaemia, which over a period of several months develops spontaneous glomerulosclerosis. The present study addressed the question as to whether glomerular sclerosis was associated with alterations in the degradation of matrix components. In the early phase (up to 6 months) glomeruli from obese rats displayed increased total collagen content (+64%) and decreased gelatinolytic activity (-34%) as compared to lean control animals. This decline in glomerular gelatinolytic activity was due to a reduction in gelatinase B [matrix metalloproteinase (MMP)-9]. Glomerular MMP-9 mRNA was reduced 4.6 +/- 0.6-fold (n = 3; p < 0.05), MMP-9 protein was not detectable by Western blotting and MMP-9 activity was considerably suppressed in gelatin zymograms. MMP-2, in terms of mRNA expression and activity, was unchanged. Tissue inhibitor of metalloproteinases (TIMP)-1 mRNA expression, TIMP-1 protein (immunohistochemistry) and TIMP-1 activity (reverse zymography) were enhanced in glomeruli from obese rats, while TIMP-2 mRNA remained unchanged. Moreover, mRNA for the alpha 1 IV collagen chain was 2.1 +/- 0.8-fold higher in glomeruli isolated from obese animals (n = 3; p < 0.05). These findings indicate that matrix expansion in glomeruli from obese Zucker rats is due to both enhanced synthesis of matrix components as well as reduced degradation by matrix metalloproteinases. Apparently the latter effect is based on a reduction in MMP-9 and up-regulation of its inhibitor TIMP-1.

Albuminuria↗
PubMed1996

Tubular gelatinase A (MMP-2) and its tissue inhibitors in polycystic kidney disease in the Han:SPRD rat.

Thickening of the tubular basement membrane is one of the hallmarks of the polycystic kidney disease (PKD). The present study was conducted to investigate the potential role of the matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitors (TIMP-1 and TIMP-2) in the accumulation of matrix components in PKD. As a model of PKD, two-month-old heterozygous Han:SPRD rats, which are at an early stage of cystogenesis, were used. MMP-2, but not MMP-9 (gelatinase B) nor MMP-3 (stromelysin) could be detected in proximal tubules of the normal rat kidney. The presence of the inhibitors TIMP-1 and TIMP-2 was confirmed on the mRNA level. In tubules from PKD rats MMP-2 activity was lower (31 +/- 8 vs. 58 +/- 7 U/prep., N = 9, P < 0.05), mRNA of MMP-2 was reduced 4.2 +/- 0.6-fold (N = 4, P < 0.05) and enzyme protein was depressed 3.8 +/- 0.8-fold (N = 4, P < 0.05). By contrast, TIMP-1 mRNA was 9.0 +/- 1.1-fold and TIMP-2 mRNA 3.8 +/- 0.7-fold (N = 4, P < 0.05) elevated over controls. Cyst fluid from homozygous rats contained MMP-2 protein and activity. These findings indicate that tubular MMP-2 activity is reduced in PKD, due to down-regulation of MMP-2, up-regulation of TIMP-1 and TIMP-2, and luminal secretion of the enzyme. It is conceivable that these alterations relate to the enhanced matrix accumulation observed in the evolution of PKD.

Animals↗
PubMed1992

[Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].

Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.

Allopurinol↗
PubMed1992

Ultrasound studies of the effect of trospium chloride on gall-bladder kinetics.

In a randomized double-blind study the effects of increasing doses of trospium chloride (Spasmo-lyt, CAS 10405-02-4), 0.2, 0.5, 1.0, and 1.5 mg i.v., on gall-bladder contractility were compared among themselves and against placebo and n-butylscopolamine bromide (20 mg i.v.) by an intraindividual 5-fold crossover technique. Gall-bladder volumes after drug-induced contraction (fat stimulus with sodium iopodate) were measured by ultrasound scanning conducted by a single examiner. Serial measurements, carried out in 6 female subjects without any evidence of gall-bladder disease, demonstrated a dose-dependent trend of inhibition of gall-bladder motility produced by trospium chloride. In the maximal doses employed (1.0 and 1.5 mg i.v.) trospium chloride effected almost total inhibition of motility. The response to n-butylscopolamine bromide tested in a nonblind comparison, showed a dose-effect ratio of roughly 40:1 between trospium chloride and n-butylscopolamine bromide given intravenously. This work confirms that ultrasound measurement of gall-bladder volume is a suitable pharmacodynamic model for testing the dose-effect relationships of antispasmodic agents.

Benzilates↗
PubMed1990

[Maltose-dextran--a new combination solution for the induction of diuresis in man].

40 healthy men received an infusion solution of low molecular dextran with either 0%, 5%, 10% or 20% Maltose over a 60 min period. The combination of LMWD with 10% maltose solution showed a significant increase of urine excretion from 132 ml/h to 315 ml/h at the end of the infusion. The overall excretion rate in 3 h was 683 ml, 185 ml more than infused. The increase in urine excretion from 53.0 ml/h to 173.5 ml/h after the application of 5% maltose/dextran 40 solution was only due to a water diuresis. The maltose concentration was not high enough to induce a visible osmotic diuresis. The application of 20% maltose/dextran 40 solution showed a clear osmotic effect. Nevertheless, there was no significant increase in the urinary excretion rate compared to the LMWD solution without any maltose. The high oncotic and osmotic pressure of this combination activated mechanisms, which were opposed to the induced osmotic diuresis.

Adolescent↗
PubMed1989

[Pilot study of the action of Doqualast on dietary hyperuricemia in volunteers].

For eight days 8 healthy volunteers were treated with a formula diet and additional 1680 purine base per day. Beginning with day 5, doqualast was administered orally in a dosage of 200 mg t.i.d. Serum uric acid level was lowered by doqualast from 7.84 +/- 0.9 mg/dl to 5.09 +/- 0.8 mg/dl (p less than 0.01). Uric acid clearance increased from 7.6 +/- 2.5 ml/min to 11.5 +/- 2.4 ml/min (p less than 0.05). Excretion of uric acid in urine increased from 622 +/- 231 mg/d to 890 +/- 233 mg/d at the end of therapy. Total cholesterol in serum was lowered from 222 +/- 70 mg/dl to 159 +/- 48 mg/dl (p less than 0.05). The new uric acid lowering drug doqualast was well tolerated clinically. No adverse effects on biochemistry parameters were observed.

Adult↗
PubMed1987

[Nutritional behavior of non-insulin-dependent type II diabetes patients using the KALI 2.1.2 computer program].

Forty patients with non-insulin-dependent diabetes mellitus (NIDDM) were investigated regarding their individual diet history, including dietary pattern and dietary habits. The energy intake in men was 2,180 +/- 460 kcal/day. The carbohydrate content was 192 +/- 57 g/day (38 +/- 7%), protein 93 +/- 20 g/day (19 +/- 3%) and fat 96 +/- 26 g/day (43 +/- 7%). Nutritional intake of saturated fatty acids was 37 +/- 11 g/day, whereas the intake of polyenic acid was 14 +/- 5 g/day. Thus the p/s-quotient was 0.4 +/- 0.1. The cholesterol intake amounted to 396 +/- 165 mg/day. The dietary fibre content was 33 +/- 21 g/day. The caloric intake of women was 1,800 kcal/day. The daily amount of carbohydrate was 154 +/- 46 g/day (37 +/- 6%), of protein 82 +/- 21 g/day (20 +/- 4%), of fat 82 +/- 32 g/day (43 +/- 6%). Saturated fatty acids were 33 +/- 14 g/day, polyenic acid 11 +/- 5 g/day, the p/s-quotient 0.4 +/- 0.2. The cholesterol intake was calculated to be 341 +/- 118 mg/day. The supply of electrolytes, trace elements and vitamins was often marginal. We found that usually practiced diabetes diet is too fatty, rich in cholesterol and poor in carbohydrate and fibre. As a result of the high amount of fat, which comprises 43% of the total calories and the low p/s-quotient of 0.4, the diet must be considered atherogenic.

Blood Pressure↗
PubMed1987

[Effect of beverages containing lactate of fermented grains on metabolism in the human].

Nine healthy women received a new type of beverage over a period of 14 days. The daily dose was 1400 ml containing 14 g lactate. Acceptance was good. Blood cholesterol dropped from 193 +/- 21 mg/dl to 165 +/- 16 mg/dl (p less than 0.01). Blood potassium increased from 3.7 +/- 0.8 mmol/l to 4.3 +/- 0.2 mmol/l (p less than 0.01). Magnesium and calcium, however, showed a significant augmentation. No metabolic side effects were observed.

Beverages↗
PubMed1986

[Nutritional behavior of insulin-dependent diabetes patients studied with the KALI 2.1.2 computer program].

We investigated the levels of intake of essential nutrients in 51 patients with insulin dependent diabetes mellitus. The mean daily intake in males was 223 +/- 55 g carbohydrates, 111 +/- 22 g fat and 112 +/- 27 g protein. In females the mean daily intake was 166 +/- 36 g carbohydrates, 78 +/- 23 g fat and 97 +/- 25 g protein. the percentage of calories from carbohydrates, fat and protein was for males 36:40:18 and for females 37:39:21 respectively. The daily intake of dietary fiber was 32.5 +/- 8.0 g in men and 28.3 +/- 6.4 g in women. The mean linoleic acid intake was 12 +/- 5 g/day in men and 9 +/- 4 g in women. A marginal deficiency of linoleic acid was found in 15% of men and in 25% of women. The P/S ratio of the diet was 0.35. The consumption of vitamins, minerals and trace elements differed considerably from the recommended dietary allowances.

Adult↗
PubMed1985

[Effect of a new tube-feeding formula on metabolism, urinary electrolytes and gastrointestinal tract of healthy adults with and without a supplement of ballast material from soy bran].

Over a period of three weeks eight apparently healthy subjects received a new formula diet. From the second week on 30 grams of dietary fibers were administrated. This dietary fiber was produced from soya-bran and the eight subjects accepted this diet very well. No change of blood chemistry was measured. The stool weight without this dietary fiber amounted to 57 +/- + 15 g/day, where as by giving the fibre stoolweight rose up to 86 + 4 g/day. Transit time without fiber was 83 +/- 29 h and with fiber it dropped to 74 +/- 11 h (n.s.). The renal excretion of potassium, sodium, magnesium and calcium remained constant.

Blood↗
PubMed1985

[Lack of effect of alcohol on uric acid metabolism].

Six healthy men received a purine-free formula diet. Uric acid was measured from day to day in blood and urine. After an adaptation period of five days, six apparently healthy volunteers received ethanol in a dosage of 1.22 g/kg bw for the next five days. The subjects drank the ethanol between 7 p.m. and 9 p.m. In the beginning the uric acid concentration in blood was 5.3 +/- 1.1 mg/dl. After five days of testing the uric acid concentration was 5.6 +/- 1.2 mg/dl (n.s.). No alterations of uric acid elimination during day (7 a.m. and 7 p.m.) and night (7 p.m. and 7 a.m.) was observed. Uric acid clearance remained constant. The total uric acid elimination rate was 568 +/- 133 mg/d during the adaptation period. After ethanol consumption the uric acid elimination was 682 +/- 66 mg/d (n.s.). The tested ethanol consumption of 100 g/d thus resulted in no significant alterations.

Ethanol↗
PubMed1985

[The pharmacokinetics and bioequivalence of various dosage forms of ambroxol].

An intraindividual comparative single-dose study was carried out under carefully controlled conditions on 12 healthy volunteers in order to establish the bioavailability of trans-4-(2-amino-3,5-dibromobenzyl)-amino-cyclohexanol (ambroxol) the active principle of newly developed tablets and drops, in comparison to a commercial i.v. preparation. In an additional single-dose, cross-over study on 12 healthy volunteers the bioequivalence of ambroxol was investigated after administration of a newly developed vs. a commercial dose-equivalent, sustained-release dosage form. Following off-line derivatisation using formaldehyde to the corresponding tetrahydroquinazoline compound, ambroxol was assayed from plasma by high-performance liquid chromatography. A 2-compartment model was taken as a basis for the calculation of the plasma concentration curves and the pharmacokinetic parameters following intravenous injection of the drug. After i.v. administration, the terminal elimination half-life, the apparent volume of distribution and the total plasma clearance were determined to be 3.72 h, 1.52 l/kg and 565 ml/min, respectively. From the tablet and drop formulations the systemic availabilities were calculated to 73 and 81%, respectively; the mean transit times were determined to be 6.8 and 5.4 h, respectively. Both sustained-release dosage forms investigated are bioequivalent.

Adult↗
PubMed1984

[The effect of 4 different antacids on the gastrointestinal tract and mineral metabolism].

In a double-blind, randomized study, six healthy women were given four different antacids containing aluminium, magnesium or calcium, for a period of seven days, respectively. The antacids investigated were Trigastril 50 Del, Maaloxan Suspension, Kompensan-S forte Suspension and Solugastril 50 Gel. All the antacids tested led to a significant increase in the stool frequency and accelerated stool transit time. The sodium-containing agent produced a significantly greater acceleration as compared with the other antacids. No changes in the sodium, potassium or calcium blood levels were seen prior to and after administration of the various antacids. All preparations reduced phosphate concentrations (significant only with Solugastril an Trigastril). In the case of Maaloxan with a high content of magnesium, the magnesium concentration was increased mildly, but significantly. Irrespective of the dose of aluminium employed, all the antacids resulted in a significant increase in aluminium concentration of between 23 and 36 micrograms/l. All the antacids significantly reduced the excretion of phosphate in the urine. The preparation with a high level of magnesium produced the greatest excretion of magnesium, the preparation containing calcium the greatest excretion of calcium, in 24-hour urine. The results show that the effects on the weight of the stools, the transit time, the consistency of the stools, and on the mineral balance, depends upon the composition of the respective antacid.

Aluminum↗
PubMed1984

[Electrolyte excretion following administration of various diuretics in healthy females].

The fractional water and electrolyte excretion was measured in healthy women after an intake of different thiazides in combination with spironolactone. The combination of 100 mg spironolactone either with 5 mg bendrofluazide or with 10 mg butizide increased significantly the diuresis over the whole day. The greatest effect was between the fourth and the eighth hour. The combination of 100 mg spironolactone with 20 mg furosemide augmented diuresis only in the first two hours. All tested drugs induced a significantly increased excretion of sodium, whereas potassium excretion did not change. Magnesium excretion correlated with sodium excretion.

Bendroflumethiazide↗
PubMed1983

[Effect of a plant extract combination preparation on gastrointestinal transit time and bile acid excretion].

The effect of a plant extract containing Rhizoma curcumae, Fructus silybi mariani, Herba chelidonii, Aloe, Radix podophylli paltati, Radix gentianae and Cortex chinae on the evacuation of feces and on the metabolism of bile acids was investigated with 8 healthy women for a period of 14 days. In the preliminary period there was a stoolweight of 105 +/- 16 g/day. Under treatment the weight of stool rose to 422 +/- 104 g/day. Frequency of stools increased from 1.1 +/- 0.2 evacuations/day to 3.3 +/- 1.1 evacuation/day. Transit time decreased from 64 +/- 20 hours to 18 +/- 4 hours. Elimination of bile acid amounted to 549 +/- 397 mumol/day. It increased under treatment to 908 +/- 832 mumol/day. No changes were found in the laboratory blood tests. The concentration of potassium in the blood also remained constant.

Bile Acids and Salts↗