Antipyrine metabolite formation and excretion in patients with chronic renal failure

Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function.Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance.The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.     

Über die Änderung der Stickstoffbilanz flüssiger Nährböden durch einige in Oberflächenwasser vorkommende Bakterien

Zusammenfassung Neun Laborstämme von im Oberflächenwasser häufig vorkommenden Bakterienarten wurden in nitrit- oder (und) nitrathaltigen flüssigen Nährböden kultiviert und die Stickstoffbilanz des Nährbodens vor und nach der Kultur ermittelt. Die Bestimmung des organisch gebundenen Stickstoffs, Ammonium-, Nitrit- und Nitratstickstoffs ergab bei acht Stämmen (Serratia marcescens, Escherichia coli, Cloaca clocacae, Klebsiella spec.,Proteus vulgaris, P. mirabilis, Bacillus subtilis undB. cereus) verschieden hohe Reduktionsleistungen, aber nur unwesentliche Veränderungen des Gesamt-Stickstoffgehaltes. Nur beiPseudomonas fluorescens wurde die Bilanz mit einem Wert von nahezu 4400 mg/l (69,7%) stark negativ. Die in diese Kulturen eingebrachten hohen Mengen an Nitrat-Stickstoff wurden bis zum gasförmigen Stickstoff umgesetzt.Der Deutschen Forschungsgemeinschaft danken wir für die Bereitstellung der Mittel zur Durchführung der Arbeit.     

Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory

Background

The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed.

Methods

The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence.

Results

In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method.

Conclusion

With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.     

Identification of variables for aerobic bacterial density at clinically relevant skin sites

In studies on efficacy testing of topical antimicrobial products, randomisation of test areas and a well-balanced gender ratio are not always standard. Our aim was to generate an evidence-based skin flora map using a systematic review of the literature supplemented by in vivo tests to identify variables that impact on microbial density. Ten out of 83 evaluated studies were reviewed. Microbial density was higher on sebaceous-rich and wet skin sites. In the in vivo study the forehead, upper back, lumbar area, and abdomen of 180 subjects were sampled with a standardised swab method. The highest aerobic microbial density was found on the forehead (mean log?? cfu/cm2 = 3.69 ± 1.00), followed by the upper back (3.00 ± 0.90), the abdomen (2.98 ± 0.74), and the lumbar area (2.35 ± 0.70). The difference between all four skin sites was significant (P < 0.001; analysis of variance). On the forehead, we found significantly more micro-organisms on the medial compared to the lateral side (P = 0.002; t-test), on the upper back we found more micro-organisms cranially than caudally (P = 0.006). Males carried significantly more micro-organisms on all sites (P < 0.001). Randomisation of the test areas is essential to obtain representative results in studies on the density of skin flora or the efficacy of skin antiseptics. A well-balanced gender ratio is also strongly recommended for any study population.