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Biomedical subjects

J Strassburger

Publications and source records attributed to J Strassburger.

16 recordsLinked to original sources

In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor.

BAY 59-7939 is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention and treatment of arterial and venous thrombosis. BAY 59-7939 competitively inhibits human FXa (K(i) 0.4 nm) with > 10 000-fold greater selectivity than for other serine proteases; it also inhibited prothrombinase activity (IC(50) 2.1 nm). BAY 59-7939 inhibited endogenous FXa more potently in human and rabbit plasma (IC(50) 21 nm) than rat plasma (IC(50) 290 nm). It demonstrated anticoagulant effects in human plasma, doubling prothrombin time (PT) and activated partial thromboplastin time at 0.23 and 0.69 microm, respectively. In vivo, BAY 59-7939 reduced venous thrombosis (fibrin-rich, platelet-poor thrombi) dose dependently (ED(50) 0.1 mg kg(-1) i.v.) in a rat venous stasis model. BAY 59-7939 reduced arterial (fibrin- and platelet-rich) thrombus formation in an arteriovenous (AV) shunt in rats (ED(50) 5.0 mg kg(-1) p.o.) and rabbits (ED(50) 0.6 mg kg(-1) p.o.). Slight inhibition of FXa (32% at ED(50)) reduced thrombus formation in the venous model; to affect arterial thrombosis in the rat and rabbit, stronger inhibition of FXa (74%, 92% at ED(50)) was required. Calculated plasma levels in rabbits at the ED(50) were 14-fold lower than in the rat AV shunt model, correlating with the 14-fold lower IC(50) of FXa inhibition in rabbit compared with rat plasma; this may suggest a correlation between FXa inhibition and antithrombotic activity. Bleeding times in rats and rabbits were not significantly affected at antithrombotic doses (3 mg kg(-1) p.o., AV shunt). Based on these results, BAY 59-7939 was selected for clinical development.

Animals↗

Application of impediometry to rapid assessment of liquid culture media.

The impedance method provides as unique opportunity to determine microbial activity and kinetics. Since the metabolic processes depend on the nature and quality of the culture medium, impediometry allows the assessment of liquid culture media. Impedance microbiology represents an approach to quantitative microbiology. We investigated the influence of pH, composition and variation of the amounts of industrially made dry media, overheating during the dissolving or sterilisation processes, and qualitative differences between batches of the same culture medium. Using glucose broth as an example, we showed that impediometry allows quantitative, microbial assessment of culture media. Inaccurate preparation of the culture medium could be detected quickly by the use of impediometry. The method is very simple to perform, requires no sample preparation, allows rapid assessment of liquid culture media, and interprets results automatically with the aid of a microcomputer.

Culture Media↗

[The use of impedance measurements in medical microbiology].

The versatility of the impedance method makes it a valuable tool in clinical microbiology. Impedance can be used to estimate total number of bacteria or to determine bacterial susceptibility to antimicrobial agents. The impedance method provides a unique opportunity to determine microbial activity and kinetics. Impedance microbiology represents a different approach to qualitative and quantitative microbiology. The method is very simple to operate, requires no sample preparation, allows rapid detection of bacterial growth, and interprets with microcomputer results automatically.

Bacterial Infections↗

[Changes in the pharmacokinetics of gentamycin during nephrotoxic therapy].

Nephrotoxicity secondary to aminoglycoside antibiotic therapy is a well-known complication in clinical medicine. We have analysed the influence of a 10-day gentamicin treatment with 3.40 mg/d on pharmacokinetic parameters and renal excretion of electrolyses and beta-NAG in 10 patients (9 female, 1 males) with UTJ. Using compartment-independent methods the following kinetic parameters at the first and 10th day of treatment were estimated: total body clearance from 100 to 80 ml/min (-20%), mean residence time from 2.7 to 3.5 h (+28%) and AUC from 6.7 to 9.4 mg/l.h (+41%). Similar results could be obtained using a linear two-compartment model: k13 is changed from 0.74 to 0.54 h-1 (-27%). Vdss approximately 16 1, k12 and k21 are not significantly influenced. There was no significant difference between the first and 10th day for renal excretion electrolyses, urine volume and osmolality with the exception of beta-NAG, which increased from 7.2 to 11.7 U/l (p less than 0.05). From the results it can be concluded that even a ten day gentamicin treatment with normal doses and serum concentrations in the therapeutic range less than 5 mg/l induce nephrotoxic effects at the glomerular and tubular side of the nephron. For quantification of the nephrotoxic effects we propose a nonlinear two-compartment model with a new pharmacokinetic parameter for renal damage. This new model allows to predict and to compare the nephrotoxic effects for different aminoglycoside antibiotics and different modes of treatment.

Electrolytes↗

Improved specificity in gentamicin bioassay.

An optimized bioassay for determination of gentamicin concentrations in serum of patients is presented. It was possible to enhance the exactness and representibility of the bioassay by means of a standardized methodical process, a suitable arrangement of the assay and reading at fifteen-fold enlargement. A systematic arrangement of the assay with randomized blocks is a safeguard against larger errors during the assay. The standard deviations in 5 culture plates for each serum sample amounted to about 0.3 mg/l envolving thus variation coefficients under 10%. The specificity of the bioassay was determined by means of the analytical procedure. The determination of gentamicin in blood serum, as it is generally known, may be masked in depencence on the concentration by heparin, vitamins, sodium chloride and sodium phosphate. Our model assays have revealed that for recognition of trouble factors in determination of gentamicin the evaluation by means of the parallel-line-assay according to the four point method should be performed. Inactivation of gentamicin for example by influence of phosphate cannot be recognized when evaluation is determined by linear regression. The bioassay, as a simple and economic method for control of treatment and pharmacokinetic investigations is available for any clinical and bacteriological laboratory.

Biological Assay↗

Bacteriuria screening and antimicrobial susceptibility testing of aerobic bacteria by an electrochemical method.

A method is described for detecting significant bacteriuria and determination of minimal inhibition concentrations (MIC's) of aerobically growing bacteria by using electrochemical electrodes to measure changes of oxygen tensions in liquid nutrient media resulting from bacterial growth. Urine specimens (n = 577) were screened electrochemically, parallel investigations were performed by standard culture methods and by photometrical measurements. All the specimens showing significant bacteriuria in standard culture were selected within 3.5 h by the electrochemical technique. An oxygen index OI was introduced which quantitatively reflects changes in oxygen tension of nutrient media during growth. OI shows good agreement with extinction and light scattering indices, respectively. On the basis of OI as a parameter of inhibited and uninhibited growth a correlation between OI and MIC's of aerobically growing bacteria was found. The electrochemical method provides an useful aid for rapid, preliminary antimicrobial susceptibility testing and definite bacteriuria screening. The application of this method in bacteriological urine diagnostics significantly reduces laboratory work and costs, and can be recommended for the screening of urine specimens to exclude negative specimens from further processing.

Anti-Bacterial Agents↗

[Fast physiochemical methods for the detection of bacteria in the urine].

Physiochemical methods permit quantitative determinations of bacteria within 3 to 6 hrs and offer possibilities of automation in clinical bacteriology. The results photometrical bacteriuria-screening and electrochemical rapid method of oxygen partial pressure measurements in culture medium in comparison with conventional culture urine processing are presented. The method of impedance measurements is introduced in brief. At present time, electrochemical measurement of oxygen partial pressure is recommended for rapid bacteriuria screening.

Bacteriological Techniques↗

In vitro sorption of aluminum complex to guinea pig stratum corneum.

The sorption of aluminum complexes to guinea pig stratum corneum has been studied using our previously described fluorometric and atomic absorption spectrophotometric procedures. The sorption, desorption, and binding properties of the two aluminum systems most often used in topically applied antiperspirants, aluminum chloride and aluminum chlorohydrate, Al2(OH)5Cl . 2H2O were examined as a function of aluminum concentration, sorption time, state of hydration, and for various delipidized tissue specimens. The results indicate rapid uptake of aluminum species in both systems from aqueous solutions for partially hydrated tissue, reaching 50% saturation levels in about 30 min. Pseudo-equilibrium sorption isotherms follow a Langmuir-type sorption behavior over the 10(-4) M to 5 x 10(-3) M aluminum concentration range for both systems reaching plateau sorption capacities. At higher aluminum concentrations, however, the aluminum chlorohydrate isotherm exhibits a long linear increase in sorption following this initial plateau. Sorption of the various aluminum species depends on the hydration state of the tissue with increases in sorption of 2- to 3-fold over tissue prehydration time periods of 0-96 hr. Desorption studies indicate significant reversibility of aluminum chloride sorption from partially hydrated tissue but little desorption from fully hydrated tissue. In contrast, little desorption is observed with aluminum chlorohydrate regardless of tissue hydration levels. These differences are interpreted in terms of the inherent physical-chemical properties of the species contained in these two aqueous aluminum (III) ion systems.

Absorption↗