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Biomedical subjects

M Schürer

Publications and source records attributed to M Schürer.

18 recordsLinked to original sources

New injectable aqueous carbamazepine solution through complexing with 2-hydroxypropyl-beta-cyclodextrin: tolerability and pharmacokinetics after intravenous injection in comparison to a glycofurol-based formulation.

The poor water solubility of the antiepileptic drug (AED) carbamazepine (CBZ) is generally considered an absolute contraindication to parenteral administration in epileptic patients. However, the water solubility of CBZ can be largely enhanced through formation of an inclusion complex with an amorphous cyclodextrin derivative, 2-hydroxypropyl-beta-cyclodextrin (HP beta CD). We studied tolerability and pharmacokinetics of an aqueous CBZ:HP beta CD solution after intravenous (i.v.) administration in dogs. For comparison, a conventional glycofurol-based solution of CBZ was used. We also administered a commercial liquid formulation of CBZ orally (p.o.). Infusion of CBZ:HP beta CD solutions or HP beta CD "placebo" formulations i.v. was well tolerated by the animals. In contrast, infusion of CBZ:glycofurol solutions and glycofurol placebo solutions induced marked behavioral and cardiovascular adverse effects. Pharmacokinetic studies indicated that glycofurol inhibited CBZ metabolism by decreasing formation of the major CBZ metabolite CBZ-10,11-epoxide (CBZ-E). With infusion of CBZ:HP beta CD 10 ml/min for 12-15 min, resulting in a CBZ dose of CBZ 5 mg/kg body weight, peak CBZ plasma levels of approximately 3.6 micrograms/ml were obtained. This relatively low peak concentration is primarily due to the rapid elimination of CBZ in dogs [half-life (t1/2) < 1 h]. Comparison of peak plasma levels determined after p.o. administration of CBZ to dogs with peak CBZ levels previously determined after p.o. administration in humans indicated that about four times higher doses are needed in dogs to attain the same peak plasma levels as in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Hydroxypropyl-beta-cyclodextrin

[The solubility and bioequivalence of silymarin preparations].

Seven silymarin products (pharmacies only), two of them with two batches each, were analysed for their ingredients, in particular silibinin (CAS 22888-70-6) and tested in vitro for their liberation of active agents. Founded on the results of these tests three products were checked for bioequivalence. Therefore, a typical phase I 3 fold crossover study was performed showing one product (Legalon) to be qualified by an approx. 2 fold higher silibinin availability compared to the two other preparations.

Adult

[A densitometric method for the assessment of myocardial perfusion using digital subtraction angiography].

The aim of the method presented is the quantitative description of the perfusion of the myocardium. In the framework of the invasive diagnostics of the coronary heart disease with catheterization of the left heart, ventriculography and coronarography in Seldinger's technique in 50 patients (35 of them well to be evaluated) subsequently DSA-investigations of the left coronary artery (LCA) were performed by means of the DVI-2 CV system (Philips) and densitometrically evaluated with the help of the analytic processing unit (APU). In injection by hand of 4 and 6 ml, respectively, visotrast 370 in each case 10-15 DSA-pictures in LAO 60 degrees-projection were possible. For a differentiated evaluation the total myocardium was subdivided into 12 partial areas. The densitometric analysis consisted in the calculation of time-density curves over all areas and their description by suitable parameters: density maximum (DMAX) and its moment TMAX, elevation of the curve SLOPE at 50% of DMAX, the elevation time AZEIT as well as measure for the exponential decrease of the curve after the maximum LAMBDA. For special questioning the parameters of the 12 areas were concentrated according to the main supply areas of the anterior interventricular branch (RIVA), the circumflex branch (RCX) and the apex of the heart, respectively. In the interobserver comparison the statistical analysis of the results showed deviations lower than 10% (except LAMBDA). Significant correlations were found between the body-weight and the applied quantity of contrast remedies, respectively, and the parameters DMAX and AZEIT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Kidney function in the course of compensatory hypertrophy following unilateral nephrectomy in the Wistar rat].

Unilateral nephrectomy was performed in 109 male Wistar rats, 35 animals served as controls. Determinations of glomerular filtration rate (GFR) using slope clearance of 99mTc-DTPA and of tubular function using an orally water-loading test were made. The tests were performed 2 and 5 days as well as 2, 4, 5 and 6 weeks after nephrectomy. In all examinations the GFR was more than 50% of the level of two-kidney control animals. Fractional maximum diuresis was increased in the first 2 examinations after nephrectomy from 8.9 +/- 2.1 to 15.4 +/- 4.2% of the GFR and fractional clearance of osmotically free water from 6.8 +/- 1.9 to 10.9 +/- 3.5%. In the fourth and sixth week the proximal tubular reabsorption was increased and the glomerulo-tubular balance had been recovered. However, the minimal urine osmolarity was increased to 107.8 +/- 17.7 mmol/l and the osmotic load of the nephrons remained elevated. Possible clinical implications of the results are discussed.

Animals

[Kidney function in spontaneously hypertensive rats under minoxidil treatment].

In 25 spontaneously hypertensive rats the blood pressure was lowered from 192 +/- 11.6 to 130 +/- 11.7 mm Hg and in 26 normotensive Wistar rats from 129 +/- 9.1 to 107 +/- 6.7 mm Hg by applying 1 mg/kg body weight minoxidil twice a day orally. 19 spontaneously hypertensive and 21 normotensive rats served as untreated control groups. During the treatment the glomerular filtration rate, determined by the slope clearance of Tc-99m-DTPA, remained unchanged. Under maximal water diuresis the excretion fraction of sodium was diminished compared with the control data. The Na+ and water reabsorption was increased in the proximal tubules (not an aldosterone effect) only in the treated spontaneously hypertensive rats. The potassium clearance was increased in this group, but decreased in the treated normotensive group. The different reactions of the renal tubular function to the treatment with minoxidil in spontaneously hypertensive compared with normotensive rats were discussed in connection with changes of membrane transport in essential hypertension.

Animals

Scintigraphy of lymphatic vessels in malignant melanoma of the skin before operation (en bloc excision).

An injection of 99mTc-labelled antimony sulphide colloid was used to show the lymphatic pathways in patients with malignant melanoma of the trunk skin. Using a gamma camera, optimal visualisation was obtained 15-30 min postinjection. Surprising deviations of the lymphatic pathways were found; therefore, this method makes it possible to plan continuity dissection appropriate to individual cases. Two examples are presented.

Antimony

[Bacteriologic, histologic and functional studies of the kidney in 5 days' therapy of experimental E. coli pyelonephritis with gentamycin. Comparison with 9 days' therapy].

Short-term antibiotic treatment is recommended in infections of the lower urinary tract but its effectiveness is questioned in the upper urinary tract infections. We compared a 5 and a 9 day treatment of experimental E. coli 022 pyelonephritis after unilateral nephrectomy in 127 mal Wistar rats. We used 9 mg gentamycin per kg b.w. twice daily. I131 hippurat excretion was not decreased during the 5 day treatment but was only temporarily diminished during the 9 day treatment. Histologically the severe acute pyelonephritis was decreased after the 9 day treatment but not after 5 days of treatment. Bacteriologically almost all the kidneys were sterile after the 9 day treatment but the majority of the kidneys showed the injected strain of E. coli after the 5 day treatment. The results indicated that the shortened treatment was much less effective in our acute experimental pyelonephritis.

Animals

[Studies and results of the use of nuclear medicine methods in kidney function tests].

It is sought for alternative methods for the endogenous creatinine clearance as parameters for the GFR. For this purpose served investigations with Tc-99m-Sn-DTPA. It was found a good reproducibility for the slope clearance with 3 blood takings between 60 and 120 minutes. When combined with the camera function scintigraphy a side-separated quantitative statement of the clearance equivalent is possible. The inulin clearance serves as reference method. The investigations at the gamma-camera with Tc-99m-Sn-DTPA also allow the determination of the perfusion which is particularly of interest in patients with hypertension. According to the comparison at the gamma camera a diagnostic schema is recommended.

Adult

[A method for the cryopreservation of thrombocytes].

By using dimethylsulfoxide (0.7 mol/l) a technique of cryoconservation of thrombocyte concentrates was elaborated, with own material-technological possibilities being taken into consideration. In comparison to fresh thrombocytes the results of parameters tested in vitro reveal a mean functional ability of 50%. The survival time of cells stored in this way in vivo may be compared with fresh cells. On this basis HLA-typed single-donor pools could be established for clinical application.

Blood Platelets

[Suitability of bone scintigraphy for the determination of bone reaction or regeneration following endosseous implantation of alloplastic materials with special reference to bioactive materials].

A programme for the investigation of the behaviour of bioactive and bioinactive implant materials by the osseous bed was enlarged by the scanning. This one allows a follow-up of bone processes in vivo. The implants were inserted into the patellar surface of the right and left femur of rabbits. The bone regeneration after defect formation without implant serves as standard of comparison. The scintigrams were taked down with 99m-Tc-EHDP. The bone scanning provides differentiate statements about the temporal process incorporation. Its non-specificity allows no separation between the behaviour of bioactive and bioinactive materials in biologic surroundings. The scintigraphic findings can be interpreted below employment of the results of the other tests and previously known material qualities.

Animals

[Relation between the density and maturity of red blood cells in the perinatal period in the rat].

Relations between 59Fe incorporation into red blood cells (rbc) and their density was examined in rats during ontogenesis (20th, 21st, 22nd gestational day, 1st, 21st day of life, adults). The incorporation of 59Fe in rbc of different density was measured 24 or 96 h after application. The density separation was carried out by centrifugation of rbc in phthalate esters of known density. The density of rbc increased during ontogenesis (median density 1.093 kg/l on the 20th gestational day and 1.102 kg/l in adult rats). The erythropoietic activity, in terms of 59Fe-incorporation into peripheral rbc, is higher in newborn rats (60-70%) than in adults (30-50%). 59Fe incorporation into pregnant rats and their fetuses is similar to adult nonpregnant rats. In fetuses a relatively high incorporation of 59Fe was found in comparison to their mother. The relationship between density and maturity of rbc is postnatally more evident than in the prenatal period. (59Fe enrichment in cells of low density prenatally: 2.6 +/- 0.5, postnatally: 8.4 +/- 0.5 (1st day of life), 5.8 +/- 0.8 (21st day of life) 28.5 +/- 5.6 (adult male rats). These findings may reflect a simultaneous formation of rbc at different sites or different clonal origin during prenatal period of ontogenesis.

Age Factors

[Effect of hypoxia on the relationship of density and maturity of erythrocytes of newborn, young and adult rats].

Adult male, juvenile and pregnant rats were exposed to repeated hypoxia 8 h daily for 3-9 days in a low pressure chamber (altitude of 5000 m, pO2 = 11.3 kPa and 6000 m, respectively, pO2 = 9.89 kPa). The density distribution curves of the red blood cells (RBC) and the incorporation of 59Fe into cells of different density were determined. In the ontogenesis the density of RBC increases (median density on the first day of life 1.100 kg/l; on the 21st day of life 1.102 kg/l, adult rats 1.103 kg/l). The density difference between the 1st and 4th quartile in which 50% of the cells range was 0.010 kg/l for newborn and juvenile animals and 0.004 kg/l for adult ones. Exposure to hypoxia led iN the animals of the investigated age groups to a rise of the proporborns, 0.004 for juveniles, and 0.002 kg/l for adult rats. The cumulative distribution curves of 59Fe incorporation and density of RBC can be described by the equation (formula: see text). The value alpha characterizes the relation between density, on the one hand, and the maturity and age of cells, on the other. For control and hypoxic animals the following values for alpha have been calculated: for newborns 0.515 and 0.520, for juveniles 0.829 and 0.596 (p less than or equal to 0.01), and for adult rats 0.875 and 0.823. Juvenile animals from in regard to density similar heterogenic cells as newborns after hypoxia. It may be that ontogenetically older cell forming sites or clones are reactivated.

Aging

[Intraoperative detection of parathyroid tissue by semiconductor electrodes (author's transl)].

With miniature semiconductor electrodes of high sensitivity and special shape it is possible to charakterize diverse tissues during operation. The measured radioactivity of phosphorus reflects its enrichment and storage in the parathyroid tissue. The findings of 5 patients in whom clinically hyperparathyroidism was strongly suspected and who underwent surgery are reported. We have successfully localized parathyroidea adenomas in 3 patients, in 2 cases no adenoma could be found the storage of phosphorus 32 was normal. In all measurements we achieved a complete agreement with histological findings.

Adenoma