Mitteilungen der Gesellschaft für Informatik 186. Folge

Ohne Zusammenfassung     

Investigation of the influence of design parameters on the flow performance of single and double disk viscous micropumps

This paper investigates the effect of radius ratio, and channel aspect ratio on the flow performance of newly introduced single and double disk viscous micropumps. A lubrication solution for the flow field, which accounts for both radius and channel aspect ratios either in single or double disk micropumps was developed and compared with available experimental data and with an approximate solution which estimates for the flow rate only in single disk pump and neglects channel aspect ratio. Additionally, a number of 3D numerical models for single and double disk micropumps were built and analyzed using the finite volume method. Pressure and drag shape factors were introduced to describe the effects of radius and channel aspect ratios on the flow rate. The values of these factors for the whole range of studied parameters are found analytically and numerically. The error in estimating the flow rate was found to be less than 10% for r ₁ /r ₂ > 0.2, and less than 7% for the studied range of h/w. Also, the lubrication solution was found to be in good agreement with the numerical and experimental results.     

Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.     

PHR2 of Candida albicans encodes a functional homolog of the pH-regulated gene PHR1 with an inverted pattern of pH-dependent expression

Deletion of PHR1, a pH-regulated gene of Candida albicans, results in pH-conditional defects in growth, morphogenesis, and virulence evident at neutral to alkaline pH but absent at acidic pH. Consequently, we searched for a functional homolog of PHR1 active at low pH. This resulted in the isolation of a second pH-regulated gene, designated PHR2. The expression of PHR2 was inversely related to that of PHR1, being repressed at pH values above 6 and progressively induced at more acidic pH values. The predicted amino acid sequence of the PHR2 protein, Phr2p, was 54% identical to that of Phr1p. A PHR2 null mutant exhibited pH-conditional defects in growth and morphogenesis analogous to those of PHR1 mutants but manifest at acid rather than alkaline pH values. Engineered expression of PHR1 at acid pH in a PHR2 mutant strain and PHR2 at alkaline pH in a PHR1 mutant strain complemented the defects in the opposing mutant. Deletion of both PHR1 and PHR2 resulted in a strain with pH-independent, constitutive growth and morphological defects. These results indicate that PHR1 and PHR2 represent a novel pH-balanced system of functional homologs required for C. albicans to adapt to environments of diverse pH.     

Minimal invasive therapy of aneurysms of the superficial femoral artery and the popliteal artery

Percutaneous stent placement has been described for treatment of aneurysms as an alternative to surgical therapy. Literature reports of percutaneous minimal invasive therapy of peripheral aneurysms shall be reviewed and compared with our own results. Six male patients (51-69 years) with femoropopliteal occlusions related to aneurysms were treated percutaneously. In two cases Wallstents and in four cases polyester-covered nitinol stents were applicated. A clinical investigation including doppler-ultrasound was performed 24 hrs, 1, 3, 6, 12 and 24 months after the intervention. Stent placement succeeded in all cases. No adjunctive surgical treatment was necessary. Ankle-brachial-index (ABI) improved from 0.22 +/- 0.2 before to 0.74 +/- 0.2 24 hours after the intervention. One patient was lost for follow-up (Wallstent). A decrease of ABI and additional intraarterial angiography revealed stent-graft occlusion within one month (n = 2) and within three months (n = 1). One of these cases was successfully recanalized with local fibrinolysis therapy. In three patients patency of the stent persisted for 24 (+/- 2) months follow-up with three-vessel-supply of the calf. These results warrant further investigations for this minimal invasive method of percutaneous stent deployment as an alternative to surgical bypass treatment of femoropopliteal aneurysms. Time of hospitalization was reduced. At this time, surgical treatment of peripheral vascular aneurysms is gold standard.     

A convenient method to discriminate between cytochrome P450 enzymes and flavin-containing monooxygenases in human liver microsomes

Liver microsomes are a frequently used probe to investigate the phase I metabolism of xenobiotics in vitro. Structures containing nucleophilic hetero-atoms are possible substrates for cytochrome P450 enzymes (P450) and flavin-containing monooxygenases (FMO). Both enzymes are located in the endoplasmatic reticulum of hepatocytes and both need oxygen and NADPH as cofactors. The common method to distinguish between the two enzyme systems is to use the thermal inactivation of FMO and to inhibit P450 completely with carbon monoxide, N-octylamine or N-benzylimidazole. In the literature no indication could be found that the heat inactivation of FMO does not affect any of the human P450 enzymes or that the overall P450 inhibitors inhibit the different human P450 enzymes sufficiently and do not affect the FMO. The effect of N-benzylimidazole and heat inactivation was tested on specific activities of seven P450 enzymes in human liver microsomes, 1A2, 2A6, 2C9, 2C19, 2D6, 3A4/5, and 2E1, using methoxyresorufin O-demethylation, coumarin 7-hydroxylation, (S)-warfarin 4-hydroxylation, (S)-(+)-mephenytoin 4-hydroxylation, dextrometorphan O-demethylation, oxidation of denitronifedipine, and chlorzoxazone 6-hydroxylation respectively. The sulfoxidation of methimazole (MMI) was used as a specific probe for the determination of FMO activity. Methimazole sulfoxidation was compared with the well known assay for FMO metabolism, the formation of N,N-dimethylaniline (DMA) N-oxide, to be confirmed as an exclusively FMO mediated reaction. The participation of P450 and FMO in the sulfoxidation of four sulfur containing peptides, ametryne; terbutryne, prometryne and methiocarb was investigated using human liver microsomes. All four reactions were demonstrated to be catalysed predominantly by cytochrome P450.