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Biomedical subjects

U Wenzel

Publications and source records attributed to U Wenzel.

At least 19 recordsLinked to original sources

Morphologic and functional consequences of immune-mediated mesangiolysis: development of chronic glomerular sclerosis.

The i.v. injection of a rabbit anti-rat thymocyte serum (ATS) induces mesangiolysis in rats, followed by a mesangioproliferative glomerulonephritis (4 to 7 days after antibody). This proliferative lesion disappears 4 to 6 wks after antibody. In order to induce an antibody-mediated sclerotic glomerular disease, uninephrectomized rats received ATS twice at 6-wk interval. At 6 months after the first antibody injection, albuminuria, arterial blood pressure, and inulin clearances were evaluated and renal morphologic studies were performed. At the time of evaluation, mean arterial blood pressure and inulin clearances were not different between animals that received the antibody and uninephrectomized controls. Rats that were injected with antibody, however, had significantly higher albuminuria compared with that of controls. Glomeruli of rats with ATS revealed expansion of the glomerular mesangial matrix and focal sclerosis. A semiquantitative morphologic analysis revealed an increased incidence of glomerular lesions and a higher glomerular damage index in kidneys of nephritic rats. These data demonstrate that the repetitive injection of ATS to unilaterally nephrectomized rats induces a model of chronic glomerular sclerosis.

Albuminuria

A rat model of progressive chronic glomerular sclerosis: the role of thromboxane inhibition.

In order to evaluate a possible role of thromboxane A2 (TxA2) in the pathophysiology of chronic glomerular disease, we studied the effect of a 12-wk combined treatment with the thromboxane receptor blocker Daltroban (D) and the thromboxane synthesis inhibitor UK 38485 (UK) on glomerular function and morphology in a rat model of chronic progressive glomerular injury. The glomerular lesion was induced in unilaterally nephrectomized rats by the repeated i.v. injection of an antibody directed against mesangial cells. Control rats were uninephrectomized. Three months after the first antibody injection before D and UK treatment, albuminuria (35.8 +/- 3.6 mg/24 h) and glomerular TxB2 formation (146 +/- 20 pg/mg of protein/min) were significantly higher compared with control values (albuminuria, 14.3 +/- 3.5 mg/24 h; TxB2, 59 +/- 16 pg/mg/min). Six months after antibody, albuminuria in nephritic rats had increased to 135 +/- 17 mg/24 h. In nephritic rats treated with D plus UK, albuminuria (44 +/- 12 mg/24 h), however, was significantly (P less than 0.001) inhibited. Quantitative morphological analysis (glomerular damage index) 6 months after antibody revealed significantly (P less than 0.001) increased glomerular lesions in nephritic rats (0.353 +/- 0.095) compared with that in uninephrectomized controls (0.045 +/- 0.014). The treatment of rats with D and UK significantly (P less than 0.001) reduced the glomerular damage index (0.101 +/- 0.004) in nephritic rats. D plus UK treatment reduced glomerular TxB2 formation but increased prostaglandin E2 and 6-keto prostaglandin F1 alpha release by isolated glomeruli. This study demonstrates that interventional treatment with D and UK ameliorates albuminuria and glomerular morphological lesions in a rat model of immunologically induced progressive glomerular injury.

Albuminuria

The platelet activating factor receptor antagonist WEB 2170 improves glomerular hemodynamics and morphology in a proliferative model of mesangial cell injury.

Rats were treated with the platelet activating factor receptor antagonist WEB 2170 (15 mg/kg/day) in three different protocols to evaluate a possible role of platelet activating factor in an experimental proliferative model of glomerular disease. The glomerular immune injury was initiated by the i.v. administration of a rabbit anti-rat thymocyte antiserum. Anti-rat thymocyte antiserum induces a proliferative glomerulonephritis with reduction of glomerular filtration rate (614 +/- 94) compared with controls (1,120 +/- 192 microL/min/100 g body wt) when studied at day 7. Treatment of rats with WEB 2170 over 8 days (starting at day -1; protocol 1) ameliorated the loss in glomerular filtration rate (936 +/- 82 microL/min/100 g body wt) in nephritic rats at day 7; however, it had no effect on controls (1,142 +/- 104 microL/min/100 g body wt). Interventional treatment with WEB 2170 (starting at day 4 after anti-rat thymocyte antiserum; protocol 2) also improved glomerular function when glomerular filtration rate was already reduced (410 +/- 41 microL/min/100 g body wt) at day 4. The platelet activating factor receptor antagonist given at day 7 after induction of disease (protocol 3) did not improve impaired glomerular filtration rate. Preinterventional and interventional treatment with WEB 2170 reduced the infiltration of polymorphonuclear granulocytes in glomeruli. Interventional treatment with WEB 2170 also reduced glomerular morphologic damage in nephritic glomeruli. The data demonstrate a beneficial effect of the platelet activating factor receptor antagonist in this animal model of proliferative glomerulonephritis which suggests that platelet activating factor might play an important role in the mediation of this disease.

Animals

[Automatic, electronic determination of resting time in small laboratory animals and the effect of psychopharmaceuticals].

The free movements of a small laboratory animal on the bottom of a cage, containing capacitive sensors, are measured as electrical signals which are then amplified, classified in a classification device and counted. With reference to the class of the highest sensitivity and by the choice of appropriate device parameters, signals are only counted during the time in which animal movements are below a level defined as rest. By this, the resting time can be determined which expresses the time in which animals are in the defined rest during the whole test time. The ED50, namely the doses after which the resting time increases by 50% during the first 10 min of the exploration phase of mice has been determined of diazepam, chlordiazepoxide, haloperidol, droperidol, fluphenazine, butaperazine, 7-fluorobutaperazine, and chlorpromazine and it was compared with the ED 50 determined in the contact bottom plates motimeter according to Knoll et al. in mice and in the catalepsy test according to Wirth et al. in rats. respectively. The method of resting time determination has proved as to be striking more sensitive (5- to 10-fold) than the other methods.

Animals

[Movement profile analysis--automatic registration and evaluation of the movement patterns of small animals].

A method is described, in which small laboratory animals are freely moving in the field of analogous capacitive sensors. The electrical signals induced by animal movements which, according to amplitude and polarity, contain informations on intensity and direction of movements are conveyed to a classification device and classified according to well-defined classes. By measuring during a fixed time (e.g. 10 min) or for a previously determined number of signals (e.g. 2000) a distribution of class frequencies, the movement profile, is obtained. Parameters of movement profile of mice in the orientation phase and factors of influence are reported on. The method allows the continuously automatic registration of movement profiles.

Animals

[The effect of drugs on electronically determined movement profile (movement profile analysis)].

In the movement profile analysis, movements of small laboratory animals, according to both intensity and direction (amplitude and polarity), are electronically measured by means of capacitive sensors. The electrical signals are amplified, classified into 13 classes in a classification device and depicted as frequency distribution. The obtained distribution corresponds to a Gaussian distribution if normal control mice are used (normal movement profile, MP). The normal MP is characteristically changed by drugs. By centrally depressing drugs (droperidol, chlorpromazine, diazepam, medazepam) distribution classes of weak movements are dose-dependently increased while classes of strong movements are decreased. Stimulating drugs (dexphenmetrazine, methamphetamine, caffeine) gave opposite changes of the MP. A certain time after a stimulating drug the change of the MP can turn to the MP of depressing drugs obviously as the result of exhaustion of the animal. After low doses of echinoramine I a MP with the characteristics of a depressing drug was found, after high doses the MP was that of a stimulating drug, perhaps as the result of subtoxic effects. After apomorphine (1, 5, and 10 mg/kg) no clear dose-dependence could be found. The movement profile analysis can be useful in the specified analysis of movements-influencing drugs.

Animals

[Direct compression nitrazepam tablets].

Tablets of nitrazepam were made by direct compression. The influence of different dry binders and other adjuvants on the physical parameters of the tablets and their texture (scanning electron microscope: SEM) were examined. Changes in the physical parameter can be explanded if the texture is known.

Drug Compounding

[The crystallography behavior of carbamazepine under compression pressure].

In the present paper the crystallographic behavior of the carbamazepine modifications I, II and III were studied under various conditions by means of X-ray powder diffraction, IR-spectroscopy and differential-scanning-calorimetry. It was found that the crystal lattice of the carbamazepine modification I is relative stable to the applied pressure forms, whereas modification II under similar conditions undergoes a polymorphic transformation into carbamazepine modification III, the extent of which depends on compression pressure and storage time of the tablets. In the compression samples of carbamazepine modification III neither IR-spectroscopically nor X-ray-diffractionally an influence of the pressure could be found on growing up of the enantiotrophic modification I.

Calorimetry, Differential Scanning

[The polymorphism of drugs in powders and tablets. 1. The preparation and characterization of polymorphic modifications of phenobarbital].

The characterisation of three phenobarbital modifications by thermic examination procedures (DSC, DTA) is being described. Modification I was obtained by thermic treatment of the brands (modification II) from Hungary and the GDR. The spray product prepared, consisting of very fine hollow spheres, was identified as modification III. Besides the particle size distribution the form of the particle was determined by scanning electron microscopy (REM). The best results regarding saturation solubility and speed of dissolution were found for the spray product.

Chemistry, Pharmaceutical

[The polymorphism of drugs in powders and tablets. 4. The effect of the polymorphism of drugs on the physical properties and drug release of phenobarbital tablets].

Four products of phenobarbital (I, II1, II2, III) are manufactured into tablets with the dry binders Avicel PH 101 or Heweten 40 using different pressures by direct tabletting. The physical properties of the resulting tablets are different according to the modification of phenobarbital, the binders used and the pressure during tabletting. The dissolution behaviour of the drug may be changed by the different technological and physical parameters.

Chemical Phenomena

[The effect of ion pair formation on the pharmacokinetics of drugs. 2. The effect of hexylsalicylic acid on the pharmacokinetics of quinine].

The influence of the hexylsalicylic acid (2) on the pharmacokinetic of the quinine (1), was studied using rabbits. It could be observed that after i.v. application the mean resistance time (MRT) of 1 was increased by means of ion-pair-formation with 2. But the AUC of 1 was not influenced. After rectal application of the combination 1/2 an acceleration of the 1 absorption could be pointed out. The kinetic parameters of 2 were not increased significantly if 1 was applicated simultaneously.

Administration, Rectal

[Phase transformation of carbamazepine by the milling process].

In the present paper the interconversion behavior of the carbamazepine modifications I, II and III under various grinding conditions (variation of milling aggregates, milling times and frequencies) were studied. Mechanical treatment of different crystal forms led to a uniform grinding product, which is characterized crystallographically as modification III. The kinetic of phase transformations were determined by means of various quantitative methods such as a IR-spectral, a X-ray-powder diffractional and a thermoanalytical one. The results obtained by different analytical methods accorded quite well.

Carbamazepine

[The in vitro liberation behavior of quinidine from drug forms with prolonged release by various liberation methods].

The liberation behaviour of the following preparations were tested using two models: Chinidin-Duriles (Astra, Sweden), Chinidin-longo (VEB Isis-Chemie Zwickau, GDR), Chinidin-retard-Isis (VEB Isis-Chemie Zwickau, GDR). The received data were estimated by multivariate statistical methods. It was found, that the three tested preparations are different in their liberation behaviour. Moreover it was shown, that there are differences between the two apparatus. Nevertheless both methods are able to characterize the liberation behaviour of the three preparations.

Chemistry, Pharmaceutical

[Improvement of the solubility of problem drugs. 1. Production of iomeglamic acid fused and solidified products].

The insoluble X-ray diagnostic iomeglamic acid could be converted to a more soluble modification by melting and solidifying it in liquid nitrogen. The amorphous state is proved by X-ray diffraction and differential thermal analysis. During storage, recristallisation of the product appears. By means of the proved amorphous state, it seems possible to determine the amount of the amorphous state, which makes the drug more soluble from solid dispersions.

Chemistry, Pharmaceutical