Study of human isoursodeoxycholic acid metabolism

BACKGROUND/AIMS: The aim of this study was to examine the metabolism of isoursodeoxycholic acid (isoUDCA) in humans. METHODS: IsoUDCA was synthesized of >99% purity and administered orally for 1 week, 3 x 250 mg/day, to six healthy male subjects. Bile acids were extracted from duodenal bile, serum, and 24-h urine samples collected before and at the end of the study period, separated into groups of conjugates, and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. RESULTS: IsoUDCA was tolerated without any side effect. Liver function tests did not change. Bile acid concentrations (mean+/-SEM) increased from 11.9+/-1.87 to 15.3+/-1.37 mmol/l in bile (n.s.), and from 3.4+/-0.10 to 6.8+/-0.43 micromol/l in serum (p<0.05). Urinary excretion of bile acids increased from 5.3+/-0.29 to 82.2+/-7.84 micromol/24 h (p<0.01). All changes were due to significant increases of isoUDCA and UDCA in bile, serum and urine, and of 3-dehydro-UDCA, the 3-oxo intermediate of isomerization, in bile and in serum. The relative enrichments of isoUDCA, UDCA, and 3-dehydro-UDCA, were: in bile, 2.2%, 25.7%, and 0.7%; in serum, 24.7%, 23.5%, and 6.1%; and in urine, 83.7%, 2.0%, and 2.4%. Whereas 78% of serum isoUDCA was unconjugated, 93-94% of biliary and urinary isoUDCA was conjugated with N-acetylglucosamine. CONCLUSIONS: This study indicates good tolerance and significant intestinal absorption of orally administered isoUDCA. IsoUDCA is extensively isomerized, probably both by intestinal and hepatic enzymes to yield UDCA which became the major biliary compound. In vitro, using the human hepatoblastoma cell line Hep G2, isoUDCA was found to be cytoprotective towards ethanol-induced cell injuries.     

Psychological comorbidity in patients with alarming chest pain symptoms]

About 1/3 of patients with chest pain undergoing coronary arteriography (CA) have no coronary artery disease (CAD). Individuals with non-CAD chest pain may be younger and more likely to be female; they may express higher degrees of neuroticism. Are those features stable enough to justifi; exclusion from CA if present? To investigate this issue, data on psychodiagnostic parameters (depression, anxiety, somatic complaints) were obtained in patients before this were referred to CA. Inclusion criteria were a chief complaint of chest pain with episodes of angina-like pain at rest, suspicious enough to warrant cardiac catherisation; and no prior history of CAD or other organic heart disease. The sample consisted of 77 patients, recruited from 89 eligible patients. 12 patients were excluded because CA findings were missing for multiple reasons. CA was conducted by Judkins technique. Patients were labeled as CAD (-) if no stenosis were detectable. In 50 (65%) of cases CA findings were positive and in 27 (35%) findings were negative. CAD+ were significantly older (p < 0.05); the superiority in both groups were male. Prevalence of emotional disorders was markedly more pronounced in both groups in comparison to the normal population and to a group of male myocardial infarction survivors. However, those features did not discriminate between the groups. Long acting chest pain was predictive for high degrees of emotional disability (relative risk 5.33; 95% Kl 1.6-61.6; p < 0.012). Chest pain at rest is a major source of anxiety, depression and subsequent somatic preoccupation despite its ischaemic or functional origin. It leads to clinically relevant adjustment disorders in a significant proportion of chest pain patients and triggers emotional disstress. These factors may thus have less impact on risk stratification than expected.     

The integration of process and cost modeling—A powerful tool for business planning

Recent developments in modeling can eliminate much experimental laboratory work and can provide quick answers in a more cost-effective manner. This article presents a brief outline of technical cost modeling, a combination of physical modeling and cost modeling, which may be used to the mutual benefit of both the managerial decision makers and the R&D community within the materials processing field.     

Extended Data Acquisition Support at GSI

The Experiment Data Acquisition and Analysis System (EDAS) of GSI, designed to support the data processing associated with nuclear physics experiments, provides three modes of operation: real-time, interactive replay and batch replay. The real-time mode is used for data acquisition and data analysis during an experiment performed at the heavy ion accelerator at GSI. The computing resources provided by dedicated Experiment Computers are insufficient for the more complex experiments performed today. To meet demands for higher data rates, more computing power and more support for data analysis during an experiment, a distributed system was conceived. The GSI High Speed Data Acquisition Network provides the hardware support for the system; it consists of a number of dedicated Experiment Computers which directly control experiments, a multi-user mainframe which performs the data analysis and data storing for all experiments, and a concentrator to connect all Experiment Computers to the mainframe. Three software sub-systems were designed, one for each component of the distributed system. An experiment may be performed either in Stand Alone Mode, using only the Experiment Computers, or in Extended Mode using all computing resources available. The Extended Mode combines the advantages of the real-time response of a dedicated minicomputer with the availability of computing resources in a large computing environment. This paper first gives an overview of EDAS and presents the GSI High Speed Data Acquisition Network. Data Acquisition Modes and the Extended Mode are then introduced.     

Untersuchungen an chemischen Konservierungsmitteln II. Mitteilung Verfahren zur Bestimmung der antimikrobiellen Wirksamkeit von chemischen Konservierungsmitteln

Zusammenfassung Untersuchungen über den Einfluß unterschwelliger, d. h. die Zellvermehrung zwar hemmender, jedoch nicht völlig verhindernder Konservierungs-mittelkonzentrationen auf die Vermehrung von Hefe haben gezeigt, daß der Verlauf von Wachs tumskurven in enger Beziehung zur angewandten Konservierungsmitteldosis steht. Ebenso besteht ein enger Zusammenhang zwischen der angewandten Konservierungs-mittelkonzentration und der schließlich erreichten Endzelldichte. Diese Beobachtungen führten zur Entwicklung verhältnismäßig einfacher Verfahren zur Konservierungs-mittelbewertung, die in der vorliegenden Arbeit beschrieben werden. Ebenso werden Beispiele für ihre praktische Anwendung gegeben.Wir danken der Deutschen Forschungsgemeinschaft für ihre Unterstützung der vorliegenden Arbeit. — An dieser Stelle sei auch FrauH. Egger unser herzlicher Dank für ihre fleißige Mitarbeit bei der Durchführung der Versuche, ausgesprochen.     

Effect of calcium and magnesium on binding of beta, gamma-methylene ATP to sarcoplasmic reticulum

Isolated sarcotubular membranes (SR) from skeletal muscle bound 3.7 nmol of beta, gamma-methylene [8-3H]ATP (AMP-PCP) per mg of membrane protein. Only one class of binding site was identified and the dissociation constant (K) for this site was 1.5 X 10(-5) M. Addition of 0.05% Triton X-100 increased the number of binding sites to 5.7 nmol/mg. ATP and ADP competitively inhibited AMP-PCP binding. The dissociation constants for ATP and ADP were 3.5 X 10(-5) M and 3.3 X 10(-6) M, respectively. Since this data was obtained in the presence of 5 mM EDTA, it was established that the sarcoplasmic reticulum has a high affinity for the metal free forms of ATP, ADP, and AMP-PCP. Magnesium concentrations in excess of 1 X 10(-4) M inhibited AMP-PCP binding. Lower concentrations of magnesium had little effect on AMP-PCP binding. The effect of calcium on AMP-PCP binding was biphasic. Calcium concentration between 1 X 10(-6) and 1 X 10(-4) M inhibited AMP-PCP binding. Inhibition was maximal at 1 X 10(-5) M. Calcium concentration above 1 X 10(-4) M facilitated analogue binding. Possible sites of magnesium and calcium actions are discussed.     

Effect of surface roughness on low-cycle fatigue behavior of type 304 stainless steel

The effects of surface roughness on the low-cycle fatigue life of Type 304 stainless steel at 593°C in air have been investigated. It is observed that, at a strain rate of 4 × 10⁻³ s⁻¹ and a total strain range of 1 pct, the fatigue life (N _f cycles) decreases with an increase in surface roughness. Information on crack growthvs strain cycles has been generated, as a function of surface roughness, by the measurement of striation spacing on fractured surfaces of specimens tested to failure. Crack propagation follows the Ina ∞N (wherea is the crack length afterN strain cycles) relation for longer specimen fatigue lives (N_f > 2700 cycles) and departs from Ina ∞N for shorter fatigue lives. A quantitative estimate is made of the number of cycles N_o(r) to generate a crack length equal to 0.1 mm (≈ 1 grain diam). The initial surface roughness significantly affects only the initiation component of specimen life time. The effect of roughness on crack initiation is described byN ₀ (R) = 1012R^−0.21, whereR is the surface roughness (root-mean-square value) in microns.